A peer-reviewed journal of medical science, social science in

Transcription

Indexed in MEDLINE,
PubMed, and PubMed Central
National Library of Medicine
PRSRT STD
US POSTAGE
PAID
PORTLAND OR
PERMIT NO 1452
Volume 17 No. 4 — Fall 2013
500 NE Multnomah St, Suite 100
Portland, Oregon 97232
Change Service Requested
Fall 2013
Volume 17 No. 4
A peer-reviewed journal of medical science,
social science in medicine, and medical humanities
Original Research & Contributions
4 Comparative Effectiveness Topics from a
Large, Integrated Delivery System
14 Challenges in Evaluating All-Cause Hospital
Readmission Measures for Use as National
Consensus Standards
19 Hypovitaminosis D Correction and HighSensitivity C-Reactive Protein Levels in
Hypertensive Adults
THE PERMANENTE JOURNAL
22 From the Patient’s Perspective: Is There a
Need to Improve the Quality of Informed
Consent for Surgery in Training Hospitals?
27 How Asking Patients a Simple Question
Enhances Care at the Bedside: Medical
Students as Agents of Quality Improvement
Special Reports
32 Making Hospitals Safer for Older Adults:
Updating Quality Metrics by Understanding
Hospital-Acquired Delirium and Its Link to Falls
37 Preventing Falls in the Geriatric Population
41 Establishing a Portfolio of Quality-Improvement Projects in Pediatric Surgery through
Advanced Improvement Leadership Systems
Review Articles
47 Deep Brain Stimulation for the Treatment
of Severe, Medically Refractory ObsessiveCompulsive Disorder
52 Evaluating the State of Quality-Improvement
Science through Evidence Synthesis: Insights
from the Closing the Quality Gap Series
62 Probiotics and Liver Disease
68 Antivascular Endothelial Growth Factor Antibody for Treatment of Glioblastoma Multiforme
Editorial
80 Integrating Naturopathy:
Can We Move Forward?
Narrative Medicine
Follow @PermanenteJ
Printed on acid free paper.
The Permanente Journal
Fall 2013
Volume 17 No. 4
ISSN 1552-5767
84 The Power of Reflective Writing:
Narrative Medicine and Medical Education
See inside for additional content
as well as articles found only online
www.thepermanentejournal.org
Fall 2013/ Volume 17 No. 4
PermanenteJournal
The
Mission: The Permanente Journal advances
knowledge in scientific research, clinical
medicine, and innovative health care delivery.
Circulation: 25,000 print readers per
quarter, 6700 eTOC readers, and 1 million
Internet hits in 2012 from 150 countries.
ON THE COVER
“Autumn Foliage” by
Lynne D Calonico, PhD,
was taken in Central
Park in New York City,
using a 35mm Pentax
K20D, 16-45mm zoom,
1/90 sec, f 4.0.
Dr Calonico is a
Psychologist with the
Kaiser Permanente
Sacramento Outpatient
Child and Adolescent
Psychiatry Clinic.
Photography, especially
nature photography,
has been an avocation since her undergraduate
years. She also worked for several years during
the predigital era doing light microscopy and
transmission electron microscopy.
93 LETTERS TO THE EDITOR
95 BOOK REVIEW
96 CME EVALUATION FORM
www.thepermanentejournal.org
ISSN 1552-5767
Follow @PermanenteJ
ORIGINAL RESEARCH
& CONTRIBUTIONS
4 Comparative Effectiveness Topics from
a Large, Integrated Delivery System.
Kim N Danforth, ScD; Carrie D
Patnode, PhD; Tanya J Kapka, MD;
Melissa G Butler, PharmD, PhD;
Bernadette Collins, PhD; Amy
Compton-Phillips, MD; Raymond J
Baxter, PhD; Jed Weissberg, MD, FACP;
Elizabeth A McGlynn, PhD; Evelyn P
Whitlock, MD
An electronic survey requesting
nominations of comparative effectiveness
research questions was sent to 792
clinical and operational leaders in Kaiser
Permanente—83% of whom had direct
clinical roles. From 181 individuals, 320
research questions were nominated.
Questions most frequently addressed
cardiovascular and peripheral vascular
disease; obesity, diabetes, endocrinology, and
metabolic disorders; or service delivery and
systems-level questions. Ninety-five highpriority research questions were identified.
These inform the national discussion
regarding comparative effectiveness research,
engaging real-world stakeholders in setting
a health care research agenda.
14 Challenges in Evaluating All-Cause
Hospital Readmission Measures for
Use as National Consensus Standards.
Alexis Morgan, MPH; Adeela Khan,
MPH; Taroon Amin, MA, MPH, PhD(c)
Through the evaluation of measures for
endorsement, several overarching issues
in measuring all-cause readmissions were
identified, including statistical modeling
and the usability of the measures for
quality improvement and accountability.
Additionally, it was decided that, for
the first time, quality monitoring and
accountability of readmissions will take
place at the health plan level. Measuring
at various levels of accountability reinforces
the idea that multiple stakeholders have
a responsibility and a role to reduce
readmissions. These measures can help
reduce the substantial financial and
emotional stress that readmissions place
on the health care system.
19 Hypovitaminosis D Correction and
High-Sensitivity C-Reactive Protein
Levels in Hypertensive Adults.
Nathan Carlson, MD; Robert Mah,
MD; Maria Aburto; Mark Jason Peters,
MD; Meagan V Dupper, MD; Lie Hong
Chen, DrPH
One hundred eight subjects who were
vitamin D insufficient or deficient
completed this study. The mean 25-OHvitamin D level was 20.07 ng/mL before
treatment and 43.92 ng/mL after
treatment. Posttreatment vitamin D levels
were in the normal range for 91% of
the subjects. No statistically significant
changes in hs-CRP level were detected
after the vitamin D treatment was
administered and a posttreatment vitamin
D level above 30 ng/mL was confirmed.
22 From the Patient’s Perspective: Is There
a Need to Improve the Quality of
Informed Consent for Surgery in Training Hospitals? Shamir O Cawich, DM;
Alan T Barnett, DM; Ivor W Crandon,
FRCS; Samantha D Drew; Georgiana
Gordon-Strachan, BSc, PhD
A postoperative survey was administered
to all consecutive able and willing adult
patients who underwent the presurgical
informed consent process with surgical
residents over a 5-week period. There
were 210 surveys completed. Forty-five
patients believed that they were instructed to sign the consent document
with minimal discussion. At termination of
the consent process, only 70% of the 210
patients reported that they signed the
consent form voluntarily. Overall, 67%
of patients thought the current informed
consent process was unsatisfactory.
27 How Asking Patients a Simple Question Enhances Care at the Bedside:
Medical Students as Agents of Quality
Improvement. Hope Olivia Ward;
Sarah Kibble; Gney Mehta; Marc
Franklin; Joshua Kovoor; Aled Jones,
BN (Hons), PhD; Sukhmeet Panesar,
BSc (Hons), MBBS; Andrew CarsonStevens, MBBCh, MPhil
Medical students have traditionally played
a passive role in the delivery of health
care. Using the Model for Improvement
to adapt the Ask One Question concept
for local use, medical students at Cardiff
University (United Kingdom) asked 120
patients one question. On a simple but
effective level, Ask One Question reflects
good manners and is a demonstrable
competency of patient-centered practice.
It is a vehicle for enabling students to seek
improvements in health care and initiate
relevant actions to improve the patient
experience at the bedside.
Special Report
32 Making Hospitals Safer for Older
Adults: Updating Quality Metrics
by Understanding Hospital-Acquired
Delirium and Its Link to Falls.
Eric A Lee, MD; Nancy E Gibbs, MD;
Linda Fahey, RN, NP, MSN; Teri L
Whiffen, RN, BSN, MHA
Because of reduced “reserve capacity,”
hospitalized older adults are at high risk
of developing geriatric syndromes such
as delirium and falls. Patients who experience geriatric syndromes in the hospital
are more likely to have a longer length
of stay, higher risk of readmissions, and
worse medical outcomes. Incident delirium in hospitalized geriatric patients has
been shown to be preventable by intervening in established risk factors. Prevention of hospital-related falls has not been
consistently demonstrated. Analysis from
Kaiser Permanente data demonstrated
a correlation with delirium and hospitalrelated falls.
The Permanente Journal/ Fall 2013/ Volume 17 No. 4
Books published by
Permanente authors:
Going Prepared: A Unique
Church-Based Approach to
Crisis Prevention for Short-Term
Missions Teams
Lee Jacobs & Steve Vereb
ISBN 978-1609577360
Maitland, FL: Xulon Press; 2010
Paperback: 142 pages
$14.99
Anyone Can Intubate (5th Ed):
A Step-by-Step Guide to Intubation and Airway Management
Christine Whitten, MD
ISBN-10: 0929894189
ISBN-13: 978-0929894188
San Diego, CA: Mooncat Publications; 2013
$39.99
Brochert’s Crush Step 2:
The Ultimate USMLE Step 2
Review, 4th Edition
Theodore X O’Connell, MD
and Mayur Movalia, MD
ISBN-10: 1455703117
ISBN-13: 978-1455703111
Philadelphia, PA: Elsevier/
Saunders; 2013
$28.96
Tarascon Palliative
Medicine Pocketbook
Bates D Moses, MD
ISBN-13: 978-1-4496-3421-6
Burlington, MA: Jones & Bartlett
Learning: Tarascon Publishing; 2013
$19.95
ANNOUNCEMENT:
CME Credits Now Available for Reviewers
The Permanente Journal is happy to announce
the availability of Continuing Medical Education
credits for completing manuscript reviews for
The Permanente Journal. Physicians are now eligible
to receive up to 15 AMA PRA Category 1 Credits
per year (3 AMA PRA Category 1 Credits per
manuscript). With this change, we have launched
our new For Reviewers home page on our Web site:
www.thepermanentejournal.org/reviewers.html.
PermanenteJournal
The
If you are a Permanente author and would like your book
cited here, send an e-mail to max.l.mcmillen@kp.org.
For information and/or rates for placing an
announcement here, please contact amy.r.eakin@kp.org.
CME credits are
available online at
www.thepermanentejournal.org.
The mail-in CME form can
be found on page 96.
S pecial Report
37 Preventing Falls in the Geriatric
Population. Aimee Lee, MD; Kuo-Wei
Lee, MD; Peter Khang, MD, MPH, FAAFP
Falls are all too common in the geriatric
population, and they have devastating
consequences. They are the leading cause
of injury and death by injury in adults over
age 65 years. As patients age, they may
experience stiffened joints, decreased
muscle strength, and impaired neurologic
feedback. These changes, in combination
with other risk factors, increase the likelihood of falls. The strongest independent
risk factors for falls are previous falls,
weakness, gait and balance impairments,
and use of psychoactive medications.
Special Report
41 Establishing a Portfolio of QualityImprovement Projects in Pediatric
Surgery through Advanced
Improvement Leadership Systems.
Betsy T Gerrein, DNP, CPNP; Christina E
Williams, MS; Daniel von Allmen, MD
Formal quality-improvement (QI) projects
require that participants are educated in
QI methods. However, orchestrating a
portfolio of projects that addresses the
strategic mission of the institution requires an extension of basic QI training to
provide the division or business unit with
the capacity to successfully develop and
manage the portfolio. Advanced Improvement Leadership Systems is a program to
help units create a meaningful portfolio.
Review articleS
47 Deep Brain Stimulation for the Treatment
of Severe, Medically Refractory
Obsessive-Compulsive Disorder.
Mark Sedrak, MD; William Wong, MD;
Paul Wilson, MD; Diana Bruce, PA-C,
MSHS; Ivan Bernstein, PA-C, MSPAS,
MPH; Suketu Khandhar, MD; Conrad
Pappas, MD, PhD; Gary Heit, MD, PhD;
Eric Sabelman, PhD
Deep brain stimulation is a rapidly expanding therapy initially designed for the
treatment of movement disorders and
pain syndromes. Psychiatric diseases can
be refractory and severe, leading to high
medical costs, significant morbidity, and
even death. Whereas surgery for psychiatric disease used to include destructive
procedures, deep brain stimulation allows
safe, reversible, and adjustable treatment
that can be tailored for each patient.
Soul of the healer
Original Visual Art
40 “Okavango Sunset”
David Clarke, MD
79 “Arctic Ice Pack”
Carol S Gee, MD
89 “Boatbuilding On The Aspetuck”
Phillip LaBorie
52 Evaluating the State of QualityImprovement Science through Evidence
Synthesis: Insights from the Closing the
Quality Gap Series.
Kathryn M McDonald, MM; Ellen M
Schultz, MS; Christine Chang, MD, MPH
The Closing the Quality Gap series from
the Agency for Healthcare Research and
Quality summarizes evidence for eight
high-priority health care topics, providing
insight into the “state of the science” of
quality improvement (QI). Patient-focused
and systems-focused strategies were
generally more effective than clinicianfocused strategies. Topic reviewers
observed heterogeneity in outcomes used
for QI evaluations, weaknesses in study
design, and incomplete reporting.
62 Probiotics and Liver Disease.
Vishal Sharma, MD, DM; Shashank
Garg, MD; Sourabh Aggarwal, MD
Intestinal microbiota play an important
role in health and disease. The gut-liver
axis provides for an interaction between
bacterial components like lipopolysaccharide and hepatic receptors. This review focuses on changes in gut microbiota in the
context of liver disease and possible roles
of probiotics, prebiotics, and synbiotics in
liver disease.
68 Antivascular Endothelial Growth Factor
Antibody for Treatment of Glioblastoma
Multiforme. Joseph A Hanson; Frank P
K Hsu, MD, PhD; Arun T Jacob, MD;
Daniela A Bota, MD, PhD; Daniela
Alexandru, MD
Current first-line therapy for glioblastoma
multiforme (GBM) includes surgery with
adjuvant radiation therapy and cytotoxic
chemotherapy, but virtually all tumors
recur. Given the highly vascular nature of
GBM and its high expression of vascular
endothelial growth factor and other angiogenic factors, recent investigation has
turned to bevacizumab, an antivascular
endothelial growth factor monoclonal
antibody, for treatment of recurrent GBM.
COMMENTARY
75 Choosing Wisely and Beyond: Shared
Decision Making and Chronic Kidney
Disease. Phillip Tuso, MD
Nephrologists have multiple opportunities
to discuss treatment options with patients
throughout the course of their disease.
However, despite these opportunities
most patients beginning dialysis have not
experienced shared decision making with
their physicians. The shared decision-making process may help patients understand
the importance of being prepared to start
dialysis and the benefits of maximal conservative management.
EDITORIAL
80 Integrating Naturopathy: Can We Move Forward?
Charles R Elder, MD, MPH, FACP
Although acupuncture and chiropractic
care have achieved some measure of
acceptance within mainstream medicine,
the integrative role for naturopathy
has yet to be well specified. This essay
provides a discussion of the potential
benefits of naturopathic medicine, as
well as an overview of current obstacles
to its integration. Action steps toward
improving communication between
allopathic and naturopathic physicians
are suggested.
NARRATIVE MEDICINE
84 The Power of Reflective Writing:
Narrative Medicine and Medical
Education.
Samir Johna, MD; Ahmed Dehal, MD
Even before technology gained the upper
hand, patients were healed by physicians
when most of the remedies were useless
if not harmful, and when remedies were
driven by theories that did not stand the
test of time. To some extent, the art of
fostering the sacred physician-patient relationship might have played a major role
in the dramatic healing process.
86 Boatbuilding On The Aspetuck: An
Artist’s Thoughts About Art, Aging, and
Anxiety. Phillip LaBorie
I’m not a practicing psychologist; I don’t
have a degree in psychiatry; and I’m not
an expert in gerontology; but having
been up the creek without a paddle a few
times, I can draw some conclusions about
art, aging, anxiety, and how the Aspetuck
figures into this mélange.
90 Illness and Death in the Universe.
Carlos Franco-Paredes, MD, MPH
My mother’s unexpected death unmercifully uncovered the landscape of our human frailties in the cosmic immensity and
eliminated my Machiavellian stand in this
complex world. Sadness eventually transitioned into the rationalization that our
predicament of life and death deserves
to be viewed through the lens of our
biologic heritage in a larger and highly
dynamic natural scene.
ONLINE
ONLY
See page 2 for additional content
from The Permanente Journal
available online only.
92 “(858) 457-137”
Eric Blau, MD, and Li Huai
1
ONLINE
ONLY
Available at: www.thepermanentejournal.org/issues/2013/fall.html
CLINICAL MEDICINE
cOMMENTARY
ECG Diagnosis: Acute Pericarditis.
Kevin P Masek, MD; Joel T Levis, MD, PhD,
FACEP, FAAEM
Acute pericarditis is an inflammation of
the pericardium that can result in chest
pain, pericardial friction rub, and serial
electrocardiogram changes. The most
common causes of pericarditis are viral
or idiopathic in developed countries, and
tuberculosis in developing countries. Patients
must have two of the following four clinical
criteria for diagnosis: typical pericardial chest
pain, pericardial friction rub, widespread
ST-segment elevation or PR depression, and
new or worsening pericardial effusion on
echocardiography.
Image Diagnosis: A 16 Year Old with Chest Pain after Blunt Trauma.
Minh Van Le, MD; Clifford Swap, MD
A short time spent volunteering in a small,
rural Kenyan hospital required me to revive
dormant medical skills. Much could be done
despite markedly limited resources. Major
contrasts with my experiences in the US,
especially the harsh living conditions, types
of illnesses, and more advanced disease at
presentation, left indelible memories.
Nursing Research & Practice
A 16-year-old male developed chest pain immediately after he was tackled in a football
game one hour before presenting to the
Emergency Department. Examination of the
chest wall revealed tenderness to palpation
of the right proximal clavicle with a depression of the clavicular head.
“Wherever You Go, Remember Africa”: Memories of a Medical Experience in Kenya.
George F Longstreth, MD
Image Diagnosis: Pericardial Cyst.
Jonathan Kei, MD, MPH
A 50-year-old woman presented to the
Emergency Department with 5 days of
diffuse abdominal pain and constipation.
An acute abdominal series was obtained
to rule out a bowel obstruction during
her workup. The upright chest image of
the acute abdominal series demonstrated
a smoothly rounded mass at the right
cardiophrenic angle.
IN OUR NEXT ISSUE
REVIEW ARTICLE
Investigation of Women with Postmenopausal Uterine
Bleeding: Clinical Practice Recommendations. Malcolm G Munro, MD, FRCS(c), FACOG; The Southern California Permanente Medical Group’s
Abnormal Uterine Bleeding Working Group
Commentary
Twelve Essential Tools for Living the Life of Whole Person Health Care.
Marilyn Schlitz, PhD; Elizabeth Valentina
In the study of whole person health care,
a series of interviews were conducted with
heath care experts who are at the leading
edge of the new model of medicine, which
led to a series of simple tools: examine your
worldview, take an integral perspective,
develop healing relationships, listen deeply
for healing wisdom, cultivate lovingkindness, model optimal health, develop a
support system, create healing rituals, set
intentions for optimal healing, stay informed,
re-center yourself throughout the day, and
death makes life possible.
Announcement:
CME Credits Now
Available for
Reviewers
See inside back cover
for details.
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Copyright © 2013 The Permanente Journal
2
PermanenteJournal
The
Editor-in-Chief: Tom Janisse, MD, MBA
Associate Editor-in-Chief: Lee Jacobs, MD
Senior Editors
Vincent Felitti, MD Preventive Medicine, Book Reviews
Gus Garmel, MD, FACEP, FAAEM Clinical Medicine
Arthur Klatsky, MD Original Articles
Scott Rasgon, MD Corridor Consult
Associate Editors
Maher A Abbas, MD, FACS, FASCRS
Surgery
Mikel Aickin, PhD
Biostatistics
Marthie Baker, MS, MA, RN
Nursing Research
Ricky Chen, MD
Medicine in Society
Carrie Davino-Ramaya, MD
National Practice Guidelines
Charles Elder, MD
Integrative Medicine
Robert Hogan, MD
Family Medicine,
Health Information Technology
Eric Macy, MD
Research
Ruth Shaber, MD
Patient Care Program
Gordon and Betty Moore Foundation
Amit Shah, MD
Public Health
John Stull, MD, MPH
Spirit of Medicine Dialogues
KM Tan, MD
Continuing Medical Education
Calvin Weisberger, MD
Cognitive Clinical Medicine
Winston F Wong, MD, MS
Community Benefit, Disparities
Improvement and Quality Initiatives
Scott S Young, MD
Care Management Institute
EDITORIAL & PUBLISHING OFFICE
Merry Parker
Managing Editor & Publisher
Lynette Leisure
Creative Director
Amy Eakin
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Max McMillen, ELS
Editor & Staff Writer
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Ian Kimmich
Editorial & Publishing Assistant
The Permanente Press
Tom Janisse, MD, MBA, Publisher
The Permanente Journal is published
by The Permanente Press
Editorial BOARD
Richard Abrohams, MD
Internal Medicine and Geriatrics, The Southeast
Permanente Medical Group, Atlanta, Georgia
Fábio Ferreira Amorim, MD, PhD
Professor of Medicine, Escola Superior de Ciências da
Saúde in the Department of Research and Scientific Communication, Brasilia, Brazil
Stanley W Ashley, MD
Chief Medical Officer, Brigham and Women’s Hospital;
Frank Sawyer Professor of Surgery, Harvard Medical
School; Attending Surgeon, Gastrointestinal Cancer Center,
Dana Farber Cancer Institute; Chief, General Surgery, Harvard Vanguard Medical Associates, Boston, Massachusetts
Thomas Bodenheimer, MD
Professor, Dept of Family and Community Medicine,
University of California, San Francisco
Brian Budenholzer, MD
Associate Clinical Professor in the Department of Family
Medicine at the Brody School of Medicine at East Carolina University, Greenville, North Carolina
Alexander M Carson, RN, PhD
Associate Dean of Research and Enterprise at the Institute
of Health, Medical Sciences and Society at Glyndwr
University in Wrexham, Wales, UK
Rita Charon, MD, PhD
Professor of Clinical Medicine; Founder and Director of the
Program in Narrative Medicine at the College of Physicians
and Surgeons of Columbia University, New York City
Dan Cherkin, PhD
Senior Research Investigator, Group Health Cooperative,
and Affiliate Professor, Dept of Family Medicine and
School of Public Health—Health Services, University
of Washington, Seattle
Marilyn Chow, RN, DNSc, FAAN
Vice President, Patient Care Services, Kaiser Foundation
Health Plan; Associate Clinical Professor, Dept of
Community Health Systems, School of Nursing,
Robert R Cima, MD, FACS, FASCRS
Associate Professor of Surgery, Division of Colon and Rectal Surgery; Vice Chairman, Department of Surgery, Mayo
Clinic, Rochester, Minnesota
Ellen Cosgrove, MD
Vice Dean, Academic Affairs, University of Washington
School of Medicine, Seattle, Washington
Quentin Eichbaum, MD, PhD, MPH, MFA, MMCH, FCAP
Assistant Dean for Program Development; Associate
Director of Transfusion Medicine; Associate Professor of
Pathology; Associate Professor of Medical Education and
Administration; Director, Fellowship Program in Transfusion
Medicine; Member, Vanderbilt Institute for Global Health;
Vanderbilt University School of Medicine, Nashville, Tennessee
Linda Fahey, RN, NP, MSN
Regional Manager, Quality and Patient Safety, Patient Care
Services, Kaiser Permanente, Southern California, Pasadena
Adrianne Feldstein, MD, MS
Associate Medical Director, Quality Services, Kaiser Permanente Northwest; Investigator, Center for Health
Research, Portland, Oregon
Richard Frankel, PhD
Professor of Medicine and Psychiatry, University of Indiana
School of Medicine, Indianapolis
Carol Havens, MD
Family Practice and Addiction Medicine, Director
of Clinical Education, The Permanente Medical Group,
Oakland, California
James T Hardee, MD
Internal Medicine, Colorado Permanente Medical Group;
Associate Clinical Professor of Medicine, University of
Colorado School of Medicine, Westminster
Arthur Hayward, MD
Internal Medicine and Geriatrics, CMI Clinical Lead for
Elder Care; Assistant Clinical Professor, Division of General
Medicine, Dept of Internal Medicine, Oregon Health
Sciences University, Portland
Catherine Hickie, MBBS
Director of Clinical Training, Bloomfield Hospital, Greater
Western Area Health Service; Conjoint Senior Lecturer in
Psychiatry, University of New South Wales, Australia
Thomas E Kottke, MD
Medical Director for Population Health, HealthPartners;
Consulting Cardiologist, HealthPartners Medical Group;
Senior Clinical Investigator, HealthPartners Institute for
Education and Research; Professor of Medicine, University of Minnesota, Minneapolis
Tieraona Low Dog, MD
Director of Education, Program in Integrative Medicine,
University of Arizona; Clinical Assistant Professor,
Department of Medicine, Clinical Lecturer, University
of Arizona College of Pharmacy, Tucson
Lewis Mehl-Madrona, MD, PhD
Core Faculty, Clinical Psychology Program, Union
Institute and University; Director of Education and
Training, Coyote Institute, Brattleboro, Vermont
Michel M Murr, MD, FACS
Professor of Surgery, Director of Bariatric Surgery, University
of South Florida Health Science Center, Tampa, Florida
Sylvestre Quevedo, MD
Director of Health Policy, Healthy Humans; Adjunct
Faculty, Stanford Geriatrics Education Center, Stanford
University, Palo Alto, California
Cheryl Ritenbaugh, PhD, MPH
Professor and Associate Head for Research, Department
of Family and Community Medicine, The University of
Arizona, Tucson
Ilan Rubinfeld, MD, MBA, FACS, FCCP
Director, Surgical Intensive Care; Associate Program
Director, General Surgery Residency; Henry Ford Hospital,
Detroit, Michigan; Assistant Professor of Surgery, Wayne
State University School of Medicine, Detroit, Michigan
Kate Scannell, MD
Internal Medicine and Rheumatology, and Director
of Ethics, The Permanente Medical Group, Oakland,
California; Assistant Clinical Professor, Dept of Medicine,
Marilyn Schlitz, PhD
Ambassador for Creative Projects and Global Affairs, and Senior Scientist, Institute of Noetic Sciences, Petaluma, California
Audrey Shafer, MD
Associate Professor, Dept of Anesthesia, Co-Director,
Biomedical Ethics & Medical Humanities Scholarly Concentration, Stanford University School of Medicine, Palo Alto, California
Mark Snyder, MD
Specialist Leader, Electronic Medical Record
Implementation and Physician Adoption; Deloitte
Consulting, LLP, McLean, Virginia
Swee Yaw Tan, MBchB (Edin), MRCP (UK), ACSM, FAMS
Senior Consultant Cardiologist, National Heart Centre,
Adjunct Assistant Professor Duke National University of
Singapore Graduate Medical School, Singapore
William L Toffler, MD
Professor of Family Medicine; Director of Predoctoral
Education, Oregon Health and Sciences University, Portland
Paul Wallace, MD
Senior Vice President and Director, Center for
Comparative Effectiveness Research, The Lewin Group,
Falls Church, Virginia
3
Original RESEARCH & CONTRIBUTIONS
Comparative Effectiveness Topics from a Large, Integrated Delivery System
Kim N Danforth, ScD; Carrie D Patnode, PhD; Tanya J Kapka, MD; Melissa G Butler, PharmD, PhD; Bernadette Collins, PhD;
Amy Compton-Phillips, MD; Raymond J Baxter, PhD; Jed Weissberg, MD, FACP; Elizabeth A McGlynn, PhD; Evelyn P Whitlock, MD
Perm J 2013 Fall;17(4):4-13
http://dx.doi.org/10.7812/TPP/13-036
Abstract
Objective: To identify high-priority comparative effectiveness questions directly
relevant to care delivery in a large, US integrated health care system.
Methods: In 2010, a total of 792 clinical and operational leaders in Kaiser Permanente
were sent an electronic survey requesting nominations of comparative effectiveness
research questions; most recipients (83%) had direct clinical roles. Nominated questions were divided into 18 surveys of related topics that included 9 to 23 questions for
prioritization. The next year, 648 recipients were electronically sent 1 of the 18 surveys
to prioritize nominated questions. Surveys were assigned to recipients on the basis of
their nominations or specialty. High-priority questions were identified by comparing the
frequency a question was selected to an “expected” frequency, calculated to account
for the varying number of questions and respondents across prioritization surveys. Highpriority questions were those selected more frequently than expected.
Results: More than 320 research questions were nominated from 181 individuals.
Questions most frequently addressed cardiovascular and peripheral vascular disease;
obesity, diabetes, endocrinology, and metabolic disorders; or service delivery and
systems-level questions. Ninety-five high-priority research questions were identified,
encompassing a wide range of health questions that ranged from prevention and
screening to treatment and quality of life. Many were complex questions from a systems
perspective regarding how to deliver the best care.
Conclusions: The 95 questions identified and prioritized by leaders on the front lines
of health care delivery may inform the national discussion regarding comparative effectiveness research. Additionally, our experience provides insight in engaging real-world
stakeholders in setting a health care research agenda.
Introduction
Comparative effectiveness research has
been proposed as a way to address the
health care questions that are most relevant to patients, clinicians, and policymakers. Comparative effectiveness research is
commonly defined as research designed
to inform health care decision making
through comparing the effectiveness, benefits, and harms of alternative strategies
to diagnose, treat, or manage a clinical
condition.1 Currently, limited information exists regarding the effectiveness,
benefits, and harms associated with many
clinical practices. Furthermore, available
research may not address the questions
most relevant to practicing clinicians
because studies may have included nonrepresentative patient groups in nonrepresentative settings (eg, academic medical
centers), or have made comparisons to a
placebo or untreated group. Comparative
effectiveness research, in contrast, compares different strategies for preventing,
diagnosing, treating, or managing a clinical condition in real-world settings with
respect to their effectiveness, benefits, or
harms. This type of research further seeks
to determine what works best for whom,
recognizing potential treatment response
heterogeneity among populations. Thus,
as the number of treatment and prevention options increases, and as appreciation
of potential differences among individuals
and populations grows, comparative effectiveness research has emerged as one
way to improve the quality, efficiency,
and value in health care.2
For comparative effectiveness research
to reach its potential in improving and
transforming health care, efforts will
need to focus on the questions of greatest
relevance to patients, clinicians, administrators, and policymakers. Integrated
health care delivery organizations are well
situated to identify important research
questions whose answers could improve
the everyday delivery of health care.3
These settings include large groups of
nonresearch and research clinicians who
care for patients in a population-based
model of care, health system administrators who manage the health care systems
in which these patients are seen, and the
members or patients themselves. Given
the breadth of questions that comparative
effectiveness research can address, identifying and prioritizing questions with the
greatest clinical significance is essential
and should include the perspective of
practicing leaders and clinicians.
In 2009, Congress directed the Institute
of Medicine (IOM) to identify national
priorities for comparative effectiveness
research to inform funding decisions by
government agencies awarding grants
under the American Recovery and Reinvestment Act.4 When putting together its
Kim N Danforth, ScD, is a Research Scientist for the Department of Research and Evaluation, Kaiser Permanente Southern California in Pasadena.
E-mail: kim.n.danforth@kp.org. Carrie D Patnode, PhD, is a Research Associate for the Center for Health Research-Northwest, Kaiser Permanente Northwest
in Portland, OR. E-mail: carrie.d.patnode@kpchr.org. Tanya J Kapka, MD, is a Research Associate for the Center for Health Research-Northwest, Kaiser
Permanente Northwest in Portland, and Lead Clinician at Virginia Garcia Memorial Health Center in Hillsboro, OR. E-mail: tkapka@vgmhc.org.
Melissa G Butler, PharmD, PhD, is an Assistant Investigator for the Center for Health Research-Southeast, Kaiser Permanente Georgia in Atlanta.
E-mail: melissa.g.butler@kp.org. Bernadette Collins, PhD, is a Consulting Practice Leader for the Division of Research in Oakland, CA. E-mail: bernie.collins@kp.org.
Amy Compton-Phillips, MD, is the Associate Executive Director for The Permanente Federation in Oakland, CA. E-mail: amy.l.compton-phillips@kp.org.
Raymond J Baxter, PhD, is the Senior Vice President of Community Benefit, Research and Health Policy for Kaiser Foundation Health Plan and Hospitals
in Oakland, CA. E-mail: raymond.j.baxter@kp.org. Jed Weissberg, MD, FACP, is the Senior Vice President, Hospitals, Quality and Care Delivery Excellence
for Kaiser Foundation Health Plan and Hospitals in Oakland, CA. E-mail: jed.weissberg@kp.org. Elizabeth A McGlynn, PhD, is the Director for the Kaiser
Permanente Center for Effectiveness and Safety Research in Pasadena, CA. E-mail: elizabeth.a.mcglynn@kp.org. Evelyn P Whitlock, MD, is a Senior
Investigator for the Center for Health Research-Northwest, Kaiser Permanente Northwest in Portland, OR. E-mail: evelyn.whitlock@kpchr.org.
4
list of the top 100 questions in comparative effectiveness, the IOM obtained input
from a diverse group of stakeholders via
interactive, mailed, and online mechanisms.1 Nominated topics were reviewed
and prioritized by the IOM committee,
with additional topics added by the committee to diversify the portfolio.1,5 Many
questions on the IOM’s list involved issues
concerning health care delivery systems,
racial and ethnic disparities, functional
limitations and disabilities, and cardiovascular and peripheral vascular disease.
There have been several other efforts
that engaged practicing clinicians or patients in identifying and prioritizing health
care research questions, but most do not
publish the actual questions prioritized.
Instead, these efforts have focused on
describing the methods of generation and
prioritization of research questions.6 As a
result, it is unclear how well the questions
that have been published or otherwise
made widely available reflect the views
of those on the front lines of health care
delivery, who are key stakeholders and
anticipated consumers of comparative
effectiveness research.
In its report to Congress, the IOM recommended a “continuous evaluation of
research topic priorities.”1 We conducted
a survey of clinical and operational leaders
within Kaiser Permanente (KP) to obtain
their input on the comparative effectiveness research questions of particular importance to them. KP serves approximately
nine million patients across the country and
has been cited as one example of a large,
preventive health care delivery system in
national health care discussions. Thus,
questions of high priority to KP leaders on
the front lines of care delivery and health
care decision making may be relevant to
others. Additionally, it has been advocated
that the questions generated by these types
of surveys be published so that they are
available to others.6
The aim of this article is to report
the high-priority comparative effectiveness research questions identified and
prioritized by practicing clinical and
operational leaders in a large, diverse,
integrated delivery system—along with
the process used to engage them—to
inform the national discussions on comparative effectiveness research.
Methods
Study Setting
The KP Center for Effectiveness and
Safety Research was established to promote and facilitate interregional research
on effectiveness and safety involving the
8 KP Regions: Colorado, Georgia, Hawaii,
Mid-Atlantic States (District of Columbia,
Maryland, Virginia), Northern California,
Northwest (Oregon and Washington),
Ohio, and Southern California. KP is an
integrated health care organization that
provides comprehensive services to its
members, including preventive, primary
care, specialty, emergency, and hospital
services. More than 15,000 physicians
are employed by KP, and together the 8
Regions serve about 9 million members
with diverse geographic, racial/ethnic,
and socioeconomic characteristics. The
work presented here was conducted as
part of KP operational activities and was
determined not to be research by the
institutional review board.
Surveys of Clinical and
Operational Leaders
To elicit comparative effectiveness
research questions and subsequently
prioritize them, we sent 2 surveys approximately 10 months apart to approximately
800 clinical and operational leaders in
KP who were identified through input
from national and regional executive
leadership. Figure 1 displays the flow of
identification and prioritization process.
Nomination of Questions
Figure 1. Project overview.
CER = comparative effectiveness research.
In Fall 2010, we e-mailed a link to
the KP Survey of Critical Topics in Comparative Effectiveness to 792 clinical
and operational leaders asking them to
nominate up to 5 comparative effectiveness research questions within their areas
of expertise. Recipients were invited to
provide the specific comparative effectiveness research question and any relevant
background information, including specific
populations, interventions, outcomes, and
comparators of interest. Survey recipients
were identified in multiple ways, including
5
using existing distribution lists of clinical leaders in and across KP Regions for
specific clinical specialties (eg, breast
cancer, urology, cardiovascular disease,
behavioral health), as well as lists of
those involved in developing national
KP clinical practice guidelines, working
in quality improvement, or working in
technology and products. Most survey
recipients had direct clinical roles (83%);
the remaining represented nonclinical
roles such as executive leaders, experts
in medical technology, and those in fields
such as laboratory medicine.
Each nominated question was reviewed
by the research team, and questions that
were clearly not comparative effectiveness were excluded. For example, questions focused on establishing disease
registries or clinical guidelines without
mention of a specific comparative effectiveness research question were
excluded. In making this determination,
we used a broad definition guided by
the IOM’s definition of comparative
effectiveness research.1 Questions with
multiple but distinct parts were separated
(eg, if one part focused on prevention
and another on treatment of a disease,
they were separated into two questions).
Likewise, nearly identical questions posed
by different nominators were combined
into a single research question.
Each question was reviewed by 2 team
members to classify the question according to its content area from a listing of
43 possible codes. We assigned up to 3
clinical and 4 cross-cutting nonclinical
(eg, pharmacology, service delivery)
categories to each question. Clinical categories were adapted from the list used
by the IOM7 and were modified after
pilot testing. Cross-cutting themes largely
reflected overarching interests of the
delivery organization, concerns among
health care reformers, and clinical issues
that did not fit into the more focused
clinical conditions. Because the research
team was particularly interested in questions related to cost, cost-effectiveness,
and resource allocation, any question
that contained this domain, either specifically in the question or in the background
information provided by the nominator,
was coded in this category. Additionally,
a “main” classification was selected for
each question from one of the clinical
or cross-cutting classifications, favoring
Table 1. Prioritization survey groups, number of questions, and recipients
Survey
no.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Total
a
6
Survey title
Chronic Diseases and Chronic Disease Management
(includes Renal Diseases)
Cardiovascular Disease (Miscellaneous Topics)
Cardiovascular Disease (Pharmacy Topics)
Cardiovascular Disease (Surgery and Device Topics)
Ears, Nose, and Throat Disorders and Ophthalmology
Gastrointestinal System Disorders
Geriatrics
Health Systems
Infectious Diseases and Respiratory Diseases
Mental Health/Psychiatric Disorders and Addiction Medicine
Obesity, Diabetes, Endocrinology, and Metabolic Disorders
Oncology and Hematology
Pain Management
Palliative and End-of-Life Care/Dementia
Pediatrics
Prevention, Health Promotion, and Screening
Surgery, Procedures, and Anesthesia
Women’s Health
Number of
questions on
each survey
22
Number of
stakeholders
sent each survey
42
15
18
15
9
9
11
23
17
15
21
17
19
14
19
13
21
10
288
36
36
34
26
29
36
46
36
40
36
32
36
34
39
38
38
34
648a
Twenty-six additional individuals were sent an invitation to complete a survey; however, the e-mail invitation was redirected back
to us as undeliverable, likely indicating that they were no longer with the organization.
clinical areas unless the question primarily focused on a cross-cutting issue. Differences in classifications were resolved
through informal discussion or team
meetings. A final review of all questions
was done by 1 team member (TJK) to
ensure consistency of coding decisions
across questions.
Prioritization of Questions
In the second phase of the project,
we took the comparative effectiveness
research questions generated by the KP
comparative effectiveness research survey
and further engaged KP stakeholders
to prioritize among questions in broad
clinical and systems-level categories. After
omitting the research questions that were
not clearly comparative effectiveness
research and combining and splitting the
questions as appropriate, a total of 288
questions remained. To facilitate prioritization, we divided the 288 questions into
18 groups of related topics (eg, obesity
and diabetes). We believed that splitting
the questions into smaller, more manageable lists of related topics would better
facilitate prioritization rather than prioritizing across the full list of 288 questions.
On the basis of this process, 18 electronic
prioritization surveys were developed that
included a range of 9 to 23 nominated
research questions each (Table 1). The
cardiovascular disease questions (n = 48)
were separated into 3 surveys to make
them more manageable for prioritization.
In contrast, certain content areas received
few nominations, and we elected to create
more heterogeneous prioritization surveys
containing these questions.
Because 10 months elapsed between
nomination and prioritization, we updated the respondent list with input from
national and regional KP leadership, including adding researchers with relevant
expertise to the survey recipients. All of
the original nominators and a random
sample of the remaining group of original
recipients were included in the updated
list. The resulting 648 individuals were
assigned to receive a particular prioritization survey based on their specialty area
or whether they had nominated a question on that survey. Generally, recipients
were sent only 1 prioritization survey, but
there were a few exceptions (eg, someone
nominated multiple questions that ended
up on different prioritization surveys).
The number of individuals sent a particular
prioritization survey ranged from 26 to 46.
Within each survey, we asked participants to choose the 5 research questions
that they believed should have the highest
priority for comparative effectiveness research in their set of grouped topics (without ranking them). Because the number
of nominated questions and the number
of survey respondents varied substantially across surveys, we sought a metric
that would standardize the meaning of
“highly prioritized” across content areas.
Therefore, to identify highly prioritized
questions, we calculated an “expected”
number of times a question would be
selected or “voted for” if all the questions
were judged to be of equal importance
and each reviewer selected 5 questions
(no. of survey respondents multiplied by
5 potential votes/total no. of questions on
the survey). For example, the pediatrics
survey had 19 survey questions and 16 respondents, making the expected votes per
question if all questions were judged to be
of equal importance as follows: (16∙5)/19
= 4.2. We then compared the number of
times a question was actually selected (or
“voted” for) with the expected number
of votes to identify high-priority topics.
The a priori goal as stated at the
outset by leaders initiating the survey
was to generate a list of approximately
100 highly prioritized questions, which
equated to approximately one-third of
questions from each of the 18 surveys.
Table 2. First tier of high-priority comparative effectiveness research questions from surveys of clinical and operational
leaders in Kaiser Permanente (n = 12)a
Survey topic area
Chronic diseases
and chronic disease
management
Geriatrics
Health systems
Mental health,
psychiatry, and addiction
medicine
Obesity, diabetes,
endocrinology, and
metabolic disorders
Oncology and
hematology
Pain management
Pediatrics
Surgery, procedures,
anesthesia, and imaging
Question/Objective
Clinical effectiveness of alternatives to the physician’s office visit in managing patients with hypertension and diabetes. Looking
at quality metrics in these areas, and comparing performance on the basis of number of office visits per year, and the number and
quality of telephone calls, vs HealthConnect messages. What is the most effective methodology, and does it vary by patient age?
Compare the effectiveness (including resource utilization, workforce needs, net health care expenditures, and requirements for
large-scale deployment) of new remote patient monitoring and management technologies (eg, telemedicine, Internet, remote
sensing) and usual care in managing chronic disease.
Would patients with chronic conditions (ie, diabetes, coronary artery disease, heart failure) receive more effective and efficient
care delivery when care is delivered in a chronic care clinic when compared with traditional primary care clinic?
What is the comparative effectiveness of different staffing models in the care of frail/functionally disabled seniors?
1. Traditional primary care physician-led primary care.
2. Geriatric care team with strong emphasis on registered nurse support.
3. Geriatric care team with strong emphasis on nurse practitioner support.
Compare strategies to promote shared decision making by patients considering preference sensitive interventions vs usual
care on decision outcome (screening choice, treatment choice, knowledge, treatment-preference concordance, and decisional
conflict) with regard to various chronic conditions, including cancers. Possible strategies to compare include benefit designs and
incentives; physician recommendation and “prescription”; and use as a “medical management” technique promoted by a health
plan, payer, or employer. b
Does colocation of behavioral health specialists (ie, social worker with a master of social work, licensed clinical social worker,
psychologist, psychiatrist) in an adult primary care setting lead to improved patient outcomes including depression, anxiety,
physical symptoms, physical disability, disease remission/modification (diabetes, hypertension, obesity, cardiovascular disease),
quality of life, decreased absenteeism, prescription substance use, mental and physical function, satisfaction with the provider,
and cost. Costs of care may include utilization of Emergency Department services, outpatient services, specialty psychiatry
services, and total outpatient clinic visits.b
Compare the effectiveness of case management approaches to standard individual psychotherapy in psychiatric patients with
intermittent but persistent affective or anxiety disorders. Case management would include more flexible visits (eg, more frequent
but shorter visit frequency based on symptom acuity, group visits, telephone visits, novel visits such as Internet chats).
Compare the effectiveness of use of team-based approach of registered nurse (or other nonphysician) linked to a specific
physician and his/her panel, with time for 3 to 20 contacts, to improve a HbA1C > 9%, compared with usual care.
Compare the effectiveness of management strategies for localized prostate cancer: active surveillance, androgen ablation,
external beam radiotherapy, brachytherapy, radical retropubic prostatectomy, laparoscopic prostatectomy, robotic-assisted
laparoscopic prostatectomy. Outcomes include quality of life, survival, recurrence, side effects, and cost.b
Compare the effectiveness of treatment of chronic pain by cognitive behavioral and physical therapy treatment programs vs
primary care treatment in an adult population.b
Compare the effectiveness of the most common treatment modalities applied to symptoms associated with autism spectrum
disorders, including physical therapy, occupational therapy, speech therapy, and applied behavior analysis-based strategies:
stratified by the number of hours per week each is applied. The outcome would be measured on the basis of “effectiveness per
hour” by modality, as measured by comparative pre- and postfunctional assessment by population.b
Compare the efficacy and morbidity of radical retropubic prostatectomy vs robotic prostatectomy for localized prostate cancer.
Questions are listed in alphabetical order by survey topic area. Questions are listed as nominated, except for slight editing for style and combining questions
on the same topic or separating out multipart questions on different topics.
b
Survey question was a combination of separately nominated but nearly identical questions.
a
7
Table 3. Second tier of high-priority comparative effectiveness research questions from surveys of clinical and operational
leaders in Kaiser Permanente (n = 46)a
Survey Topic Area
Cardiovascular
disease:
miscellaneous topics
Cardiovascular
disease: pharmacy
Cardiovascular
disease: surgery/
device/stent
Chronic diseases
and chronic disease
management
Ear, nose, and throat
and ophthalmology
Gastrointestinal
disorders
Geriatrics
Health systems
Question/Objectives
Effectiveness of modeling: compare the decreased heart attacks and strokes from cardiovascular disease prevention program using the best
results in the literature vs results from using a medical economic program (Archimedes) [software capable of modeling human physiology,
diseases, behaviors, interventions, and health care systems] with direction to introduce principles of efficiencies and effectiveness to optimize
outcome at controlled cost. Observational results from Archimedes are available; a comparable observational result would need to be chosen.
Compare the effectiveness of advanced virtual care technologies for the home-based treatment of congestive heart failure vs conventional
physical visits plus unilateral phone-based follow-up, for reducing unscheduled Emergency Department visits and hospitalizations in patients
with severe disease.
Compare effectiveness of treating to target low-density lipoprotein cholesterol vs application of high-dose/high-potency statins for preventing
cardiovascular events and mortality in persons with atherosclerotic cardiovascular disease or diabetes. Compare the effectiveness of using
atorvastatin (Lipitor), 80 mg, vs rosuvastatin (Crestor), 40 mg (nonformulary), for patients who have coronary artery disease.b
Compare the effectiveness of a “bundle of medications” for cardiovascular disease prevention with “usual care” of titration of blood pressure
and lipids to target in individuals with high risk of cardiovascular disease.
Compare the effectiveness of warfarin vs dabigatran (and other future oral anticoagulants) in 1) stroke prevention in atrial fibrillation patients,
2) intracranial hemorrhage, 3) gastrointestinal hemorrhage, 4) deep vein thrombosis or pulmonary embolism, 5) myocardial infarction rates,
6) gastrointestinal symptoms, 7) medication adherence, and 8) orthopedic prophylaxis.
Compare the effectiveness of treatment strategies for asymptomatic carotid stenosis including optimal medical management, carotid
endarterectomy, and carotid artery stenting.
Define the precise clinical settings in which percutaneous transluminal coronary angioplasty/stenting is superior to aggressive medical therapy
for stable coronary disease. Need to include patients of different ages and with different comorbidities.b
Compare the benefit of coronary artery bypass grafting vs aggressive medical therapy for coronary artery disease in patients who are being
referred to surgery for control of angina.
Compare the effectiveness of strategies for managing peripheral arterial disease in a patient population including screening programs,
surveillance and tracking systems for monitoring known disease, and surgical and medical management options for treating advanced disease.
Compare how chronic disease care gaps are resolved using the current model of health care delivery (primary care physician using an office
face-to-face visit to address a care gap such as ordering a routine dual-energy x-ray absorptiometry, or DEXA, for primary screening) vs a systems
approach where the DEXA request is generated from a list of all patients who need a DEXA and the DEXA order is prioritized on the basis
of risk of hip and other fragility fractures. You could easily substitute any care gap such as Pap smear [Papanicolaou test], mammogram, or
immunizations. The comparison is on face-to-face visits vs a systems approach that automatically requests the appropriate test.
Address adherence to medications using a systematic approach to cover not just traditional barriers, but also mental/behavioral, cultural,
literacy, and other personal issues. Identify those with adherence issues around crucial medications (PHASE [Preventing Heart Attacks
and Strokes Everydayc] medications, for example, that impact outcomes) in that population, take a systematic patient-centered approach
addressing all of the myriad of issues with tested interventions, and look at the impact on adherence and outcomes. Compare with similar
population where adherence is identified and not addressed in a systematic way.
Compare clinical outcomes (rate of complications, admissions to the hospital, mortality) of different models following stable in-center dialysisdependent patients. More than once a month, once a month (currently required by Centers for Medicare and Medicaid Services), or less
frequently, depending on clinical need. Use of physician extenders for in-center assessment vs a nephrologist’s visit.
What is the most reliable method for calculating intraocular lens power following LASIK [laser-assisted in situ keratomileusis] in patients?
What is the comparative effectiveness of fecal immunochemical test alone annually, fecal immunochemical test plus flexible sigmoidoscopy
every 5 years, or colonoscopy every 10 years with regard to death of colon cancer? Consider using a data-based national registry of all Kaiser
Permanente patients screened and comparing outcomes.b
What is the comparative effectiveness of health care provider home visits for the homebound frail/functionally disabled and the palliative care
patient when compared with traditional clinic-based care?
Compare effectiveness of providing geriatric primary care for frail/end-of-life members ages 85 years and older vs usual primary care.
Compare satisfaction scores for patients seen in a clinic setting vs virtual visits.
Among patients with mental health diagnoses seen in primary care practices, what is the effectiveness of components of integrated care services when
compared with each other or with programs incorporating multiple components of integrated care, in leading to improved mental health outcomes?
Compare the effectiveness of different benefit design, utilization management, and cost-sharing strategies in improving health care access and
quality in patients with chronic conditions.
Compare the use of systematic care coordination for a population who is high risk for utilization and cost vs a population of similar risk without
systematic care coordination. Use the special needs plan model of care implemented in California, Colorado, and Georgia, and compare with
nonspecial needs plan Regions with similar members to see any differences in outcomes—utilization, cost, and quality.
Compare the effectiveness of dissemination and translation techniques to facilitate the use of comparative effectiveness research by patients,
clinicians, payers, and others. How do we foster the adoption of proven strategies for diagnosis, treatment, and care into practice? What
methodologies (electronic medical records, alerts, phone calls, incentives, etc) for translating findings into practice work the best and foster
improved health outcomes at lower cost?
(continued on next page)
8
(continued from previous page)
Infectious diseases and
respiratory disorders
Mental health, psychiatry,
and addiction medicine
Obesity, diabetes,
endocrinology, and
metabolic disorders
Oncology and
hematology
Pain management
Palliative and
end-of-life care
Pediatrics
Prevention, screening,
and health promotion
Surgery, procedures,
anesthesia, and imaging
Compare the effectiveness of preventing inpatient infections by performing daily chlorhexidine bed baths vs standard bathing.
Compare the effectiveness of two weeks vs four weeks of intravenous antibiotics for treatment of Staphylococcus aureus bacteremia
in patients with an identified transient source such as a catheter, abscess, or cellulitis.
Compare the effectiveness of a noninvasive approach (serial lactate levels) to early goal-directed therapy for sepsis care with the
current invasive approach. Study outcomes to be assessed would include overall mortality rates and costs of care (equipment and
nursing care).b
Compare the effectiveness of inhaled corticosteroids plus adherence encouragement techniques compared with inhaled corticosteroids
plus long-acting β-agonists for treatment of persistent asthma uncontrolled on a regimen of medium-dose inhaled corticosteroids alone.
Compare the effectiveness of inpatient drug and alcohol residential treatment vs outpatient chemical dependency program for
substance abuse in long-term sobriety from drugs and alcohol.
Does tight glycemic control improve outcomes and reduce cost of care of hospitalized patients?
Compare the effectiveness of insulin pen devices vs insulin vial and syringe in type 2 diabetes.
Compare the effectiveness and cost-effectiveness of conventional medical management of type 2 diabetes in adolescents and adults
vs conventional therapy plus intensive educational programs or programs incorporating support groups and educational resources.
What strategies are effective in getting large populations to eat a high-nutrition, low-calorie diet? Compare the effectiveness of financial
incentives vs targeted advertising vs no intervention, to get patients to eat high-nutrition, low-calorie diets to treat obesity.
Compare the effectiveness of treatments of metabolic syndrome and obesity: Mediterranean diet and exercise program with weekly group
exercise sessions vs daily online interactive support/encouragement regarding diet/exercise (with or without quarterly group meetings in person).
Comparative effectiveness and safety of bariatric surgery vs medications such as oral and/or injectable in the management of diabetic
patients with HbA1C above 8% and with body mass index over 35 kg/m2.
Compare the effectiveness in treatment outcomes in patients with a specific type of cancer that compares patients in whom a genetic
biomarker is used to influence treatment options vs patients in whom the genetic biomarker is not useful.
Compare the effectiveness of patients with chronic pain participating in a patient education/therapy program vs usual care through
appropriate specialists and interventions without this additional training program.
Compare the effectiveness of different nonnarcotic therapies used in the management of chronic pain/fibromyalgia.
Evaluate the effectiveness of a coordinated pain policy in decreasing “drug-seeking behavior” in the Emergency Department and
patient satisfaction.
Alzheimer disease/dementia: compare the effectiveness of screening and diagnostic strategies, as well as pharmacologic and
nonpharmacologic treatments in treating the cognitive decline and slowing the functional decline of people with Alzheimer disease
and other dementias, and managing behavioral disorders in home and institutional settings.b
Comparative effectiveness of medical and nonmedical interventions in the behavioral symptoms of dementia.
What treatments make a real difference in the quality of life for patients with Alzheimer disease?
Compare the effectiveness of a palliative care consult on all patients living in long-term-care facilities vs no consult for decreasing
hospital admissions, decreasing odds of dying in a hospital, decreasing overall cost of care in the last two months of life, and patient
and family satisfaction.
Compare the effectiveness of pediatric health screening questionnaires with physician conversation, health education classes, online
handouts, online videos, and online interactive courses in improving outcomes for key health behaviors and risks such as sexually
transmitted infections/pregnancy prevention, depression, firearm safety, and obesity.
Compare the effectiveness of programs to prevent or to treat child obesity, as differentiated by degree of participation required and
target areas of behavior change (reduce sugar-sweetened beverages, increase physical activity, decrease screen time, increase
consumption of fruits and vegetables), on behavior change.
What, if any, treatment makes a difference in the outcomes of children with autism spectrum disorder?
It has been said that there is no survival benefit for a population screened for prostate cancer (prostate specific antigen and digital rectal
examination) compared with an “unscreened” population. The benefit in terms of reducing morbidity via screening is controversial. Screening
for prostate cancer does result in a significant stage shift. Does this stage shift reflect a true reduction in morbidity, or is it simply time-lag bias?
Compare the effectiveness of yearly health visit/interaction with a clinician on the quality of life of a patient vs no visit or interaction at all.
Study the impact of shared decision making in Kaiser Permanente on elective surgeries in a systematic approach over a large
population to utilization, cost, risk management, and functional status and quality of life outcomes. Use a systematic intervention around
shared decision making for a large group of members vs usual surgical consent and care in Kaiser Permanente. Although this has been
studied in selected areas and some companies have implemented this approach (one example is Health Dialog, a care management/
decision support system [in Boston, MA]), this has not been rigorously studied in our own system in large populations as yet so we
might see or demonstrate the impact. The hypothesis is that such an intervention in our system would reliably lead to even lower
surgical rates, fewer bad outcomes, and less cost in risk management for a large number of elective surgeries, resulting in increased
capacity, fewer direct and indirect costs, and better outcomes for members in terms of functional status and quality of life.
Questions are listed in alphabetical order by survey topic area. Questions are listed as nominated, except for slight editing for style and combining questions on the same topic or
separating out multipart questions on different topics.
b
c
PHASE is a cardiovascular risk reduction program that uses low-cost and generic medications and clinical interventions to reduce heart attacks, implemented at a systems level.
DEXA = dual energy x-ray absorptiometry.
a
9
We compared the observed number of
votes with the expected number for each
survey and categorized the questions
into 3 tiers on the basis of the ratio of
observed-to-expected votes; a cut-point
of greater than the number of expected
votes was used to identify high-priority
questions because it yielded about 33%
of nominated questions. The first tier
consisted of questions receiving 2 or
more times as many votes as expected;
the second tier, those receiving 1.5 to 2
times the number of expected votes; and
the third, those receiving more than the
expected number but less than 1.5 times
the expected number of votes.
Results
Nomination of Questions
Of the 792 individuals invited to nominate topics, 181 responded with at least
1 topic nomination (23% response rate).
Most individuals (56%) nominated 1 topic,
but 21% nominated 2 topics, and 23%
nominated 3 or more. The nominators
represented 50 distinct clinical specialties
or areas of health system leadership.
A total of 326 research questions
were received; 16 were dropped from
prioritization because they were not comparative effectiveness research questions.
After separating out distinct questions
in a multiple-question nomination or
combining nearly identical topics into a
single question, there were 288 research
questions for prioritization (Table 1).
Questions on cardiovascular
and peripheral vascular disMany of the
ease were the most frequent
high-priority
(n = 48 questions), followed
topics raised
by health systems (n = 23);
complex,
chronic diseases and chronic
systems-level
disease management (n = 22);
questions
obesity, diabetes, endocrinology, and metabolic disorders
about how
(n = 21); and surgery, proceto deliver the
dures, anesthesia, and imagbest care.
ing (n = 21). When question
content was examined using
the “main” topic classification according to our team’s rating, independent of
prioritization survey, similar results were
observed. However, prevention, health
promotion, and screening (n = 19) questions also were identified as a common
focus of questions.
10
Prioritization:
95 High-Priority Questions
The overall prioritization survey response rate was 31%, ranging from
11% for the geriatrics survey to 53% for
the oncology and hematology survey.
Ninety-five questions were identified as
high-priority questions on the basis of a
comparison of the observed-vs-expected
number of votes (Tables 2 to 4). There
were 12 questions in the top tier, 46 in
the second tier, and 37 in the third tier.
Of the 12 research questions in the top
priority tier, 9 were questions from a systems perspective about the way in which
care is delivered. For instance, questions
focused on the comparative effectiveness
of face-to-face vs remote management
of patients (including different types of
remote management); care provided in
specialty clinics vs primary care; and
the use of different staffing models (eg,
linking nurses to a specific physician or
emphasizing the role of nurses in care
provision). In contrast, the other 3 top-tier
questions focused on what specific care
was best in particular clinical instances:
2 questions focused on treatment and
management of prostate cancer, and 1
on treatment of autism. The prostate
cancer questions both focused on localized prostate cancer and were related
but not identical. One question proposed
comparing a wide range of management
and treatment methods, whereas the other
focused on comparisons between radical
retropubic vs robotic prostatectomy. The
high-priority research questions in the second- and third-priority tiers represented
a mix of broad systems-level and specific
clinical questions (eg, comparisons of 2
drugs for a particular clinical condition).
The most common clinical categories
among the high-priority questions were
cardiovascular and peripheral vascular
disease (19%); obesity, diabetes, endocrinology, and metabolic disorders (14%);
and oncology and hematology (14%).
Frequent cross-cutting, nonclinical areas
were service delivery and systems-level
issues (40%); pharmacology/pharmacy
(34%); and prevention, health promotion,
and screening (22%). Health information
technology, which tended to include
questions related to the electronic
medical record, was also mentioned
somewhat frequently (14%). Additionally,
issues related to cost or cost-effectiveness
were coded as occurring in most (62%)
of the 95 high-priority research question
nominations.
Discussion
The nominated and high-priority questions identified in this study ranged from
prevention and screening to treatment and
quality of life, reflecting the broad spectrum of issues encountered by practicing
clinicians and administrators in a large
health system. Questions addressed common health conditions facing our nation,
including cardiovascular disease, obesity,
and cancer, as well as topics related to
health disparities, such as health literacy.
Many of the high-priority topics raised
complex, systems-level questions about
how to deliver the best care.
Half of the 12 top-priority topics identified by our survey were the same or
largely similar to questions on the IOM
list. Overall, results from the 95 highpriority questions identified in our survey
echoed some common themes from the
IOM report, including health systems,
chronic disease management, behavioral
health integration into primary care, optimal cardiovascular disease management
strategies, and concerns about better management of patients with chronic pain.
In fact, despite favoring clinical areas in
our determination of the “main” focus of
a question, service delivery and systemslevel questions were still the second most
common main topic area.
The IOM prioritized system-level questions highly as well, with topics about
health care delivery systems being the
most common primary or secondary topic
among its top 100 comparative effectiveness research questions.1 However, the
systems-level questions identified by KP
leaders tended to be somewhat broader
than those raised in the IOM’s report. For
instance, the high-priority questions in KP
raised questions about staffing models
(eg, primary care vs specialty care) or how
care is delivered (eg, remote medicine vs
in-person visit). In contrast, questions in
the top quartile of the IOM’s list focused
more on comparisons of specific strategies for particular conditions. These
comparisons encompassed wide-ranging
options (eg, primary prevention vs clinical
interventions), but tended to focus more
on the content of care rather than broad
approaches to delivering care.
These differences between the IOM and
KP lists may reflect differences in who was
involved in nominating and prioritizing
questions. Nearly all our respondents had
direct patient care roles and practiced in
an integrated delivery system, in contrast
to the IOM respondents. Additionally, the
processes themselves were different. For
instance, the IOM solicited nominations
from a wide group of stakeholders, started
with many more nominated questions,
and then prioritized them through several rounds of voting,7 whereas we used
a single round of prioritization among
clinical and operational leaders in KP.
The IOM also deliberately included ques-
tions of key significance to vulnerable
subpopulations as part of its prioritization
process.1 Although we did not specifically
seek out those types of questions, several
nominated questions fell into that category,
such as questions on health literacy and
intimate partner violence, one of which
was included among the 95 high-priority
questions. Thus, the questions generated
here are complementary to those of the
IOM and reinforce the importance of
certain questions and areas, such as care
coordination, delivery, and management.
We designed the survey process
around practical considerations, including respondent burden, which limited
the information we collected. Although
a large number of clinicians were invited
to participate in the study, we did not
randomly sample all staff in direct care-
delivery roles. Instead, those invited to
participate were intended to represent
clinical and administrative leadership
roles. Thus, the sample may not be fully
reflective of all caregivers in our system
or in general. Additionally, survey respondents were not equally inclusive across
different specialties and did not include
some specialties (eg, dentists).
We also grouped questions into 18
separate prioritization surveys instead
of asking recipients to review all nominated questions to decrease respondent
burden. Even in a prioritization survey,
we did not ask recipients to rank all
questions but rather to select their top
5 questions. Despite trying to minimize
the time required to complete the surveys through these methods, response
rates were relatively low, and thus the
Table 4. Third tier of high-priority comparative effectiveness research questions from surveys of clinical and operational leaders
in Kaiser Permanente (n = 37)a
Survey Topic Area
Cardiovascular
disease:
miscellaneous
topics
Cardiovascular
disease: pharmacy
Chronic diseases
and chronic disease
management
Ear, nose, and
throat and
ophthalmology
Gastrointestinal
disorders
Health systems
Infectious diseases
and respiratory
disorders
Mental health,
psychiatry, and
addiction medicine
Question
Compare the effectiveness of ultrafiltration vs intravenous diuretics for patients admitted with heart failure and volume overload (alternative:
compare the effectiveness of intermittent ultrafiltration vs diuretics for outpatients with severe heart failure and volume overload).
Compare the outcomes specified as death or cardiovascular event between patients presenting with chest pain and unchanged or normal
electrocardiogram and normal troponin levels, and who are in low to intermediate pretest probability; treated either by admission, observation, and
early stress test, or by being placed on a regimen of β-blockers, aspirin, statins, and as-needed nitrates and sent home for outpatient stress testing.b
Compare results and cost-effectiveness of conventional risk stratification (via stress testing, nuclear, etc) vs immediate computed tomographic
angiography in patients who present to the Emergency Department with chest pain.
Compare the effectiveness of computerized, individualized risk, and benefit assessment vs usual care (guidelines-driven treatment without
computer models) for preventing cardiovascular events and mortality among people with atherosclerotic cardiovascular disease or diabetes.
Compare the effectiveness of warfarin (consistently maintained at an international normalized ratio of 2.0-3.0) plus aspirin, 81 mg, in adult patients
with known coronary artery disease (who have a history of coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction,
etc) and an indication for thromboembolic prophylaxis (ie, atrial fibrillation) vs warfarin alone. Study outcomes should include myocardial infarction
(fatal and nonfatal), coronary revascularization, stroke, and mortality as well as safety outcomes of major and minor bleeding.b
Compare effectiveness of one vs two years of dual antiplatelet therapy post coronary stenting with drug-eluting stents for preventing recurrent
myocardial infarctions, death, bleeding, and readmission for angina.
Determine the incremental benefit of adding lipid-lowering agents to high-dose/high-potency statins for preventing cardiovascular events and
mortality in persons with atherosclerotic cardiovascular disease or diabetes.
Compare the effectiveness of care programs using patient-reported outcomes with those programs without patient-reported outcomes.
Compare effectiveness of antibiotic prophylaxis regimens for routine cataract surgery to prevent the devastating complication of endophthalmitis.b
Compare effectiveness of screening for diabetic retinopathy by traditional means (face-to-face provider visits) vs photos reviewed by provider vs
computer-read photo screening.
What is the optimal follow-up period after an adenomatous polyp has been removed during a colonoscopy?
What is the value of upper endoscopy in the evaluation of gastroesophageal reflux disease?
Compare the effectiveness of specialty clinical consults using traditional visits vs telemedicine visits.
Compare the effectiveness of real-time identification of uncontrolled asthma status linked to real-time notification of uncontrolled status to patients
and asthma specialists to usual outreach asthma care management.
Compare the effectiveness of treatment of community-acquired pneumonia with macrolides vs without macrolides.
Compare the effectiveness of strategies to implement consistent treatment protocols for common mental disorders.
What, if any, treatment makes a difference in the outcomes of adults with autism spectrum disorder?
Compare the effectiveness of usual care (a reactive behavioral model) vs a care management program (an integrated, proactive medical model
that engages patients) for patients using the Emergency Department for alcohol/substance abuse-related problems.
(continued on next page)
11
nominated and prioritized topics may
not be representative of KP clinicians and
leaders as a whole. Low response rates
were also a problem in the high-profile
IOM process, in which about 9% of those
e-mailed responded with nominations.1
Overall, the limitations due to how we
grouped the questions and conducted the
study, along with the low response rates,
are important to consider when assessing
the internal and external generalizability
of the results. Issues in particular disease
areas may be underrepresented or overrepresented given the number of individuals
invited to participate and responders in that
area. However, we surveyed a wide range
of clinical and operational leaders, whose
responses correspondingly reflected the
wide spectrum of issues faced by leaders
in an integrated delivery system. Although
different prioritization methods or a higher
response rate (and therefore a different
group of responders) may have yielded dif-
ferent high-priority questions, we believe
that the questions identified here are still
likely to represent questions of practical,
clinical importance given that they were first
nominated and then prioritized by a diverse
group of clinicians and administrators.
Given the number of nominations we
received, it was out of scope for this project to include more objective information
regarding the underlying disease burden
or to qualify nominated questions as
clearly unanswered (by searching for inprocess or published research). Thus, we
cannot confirm whether the nominators’
questions represented needed research or
instead indicated lack of dissemination of
existing research findings or recommendations for practice. In other work, we
have found that about 25% of the time,
publicly nominated research questions
are already addressed through recent
systematic reviews (Michelle Eder, PhD,
oral communication, 2012 May 14).a
Another limitation is that we were
not able to determine why highly prioritized questions were selected. We
collected ratings from the nominators
and prioritizers regarding the potential
impact of the question on health care
quality, efficiency, or equity. However,
questions were generally rated highly on
all these domains, which did not enable
us to discriminate the reason for the
priority. Additionally, we did not include
patients in our surveys. However, their
perspective is being obtained by the
Patient-Centered Outcomes Research
Institute, which is currently asking patients to nominate research questions.
This research institute also is encouraging studies to include patients and other
stakeholders in the research process by
making their involvement part of the
criteria for funding decisions, as well
as including patients in the review of
submitted proposals.8
(continued from previous page)
Oncology and
hematology
Pain management
Palliative and endof-life care
Pediatrics
Prevention,
screening, and
health promotion
Surgery,
procedures,
anesthesia, and
imaging
Women’s health
Evaluate whether ductal carcinoma in situ needs treatment.
Standard follow-up with or without positron emission tomography scan for follow-up for lymphoma, with death as endpoint. When is positron
emission tomography needed?
Compare hospice care vs usual medical care for patients with Stage 4 (advanced) cancer, with respect to survival, quality of life, and health care costs.
Does a multidisciplinary breast cancer clinic improve care for patients with breast cancer compared with a “traditional” nonintegrated care system?
Compare outcomes in acute lumbar radiculopathy treated with oral steroid vs no steroid.
Compare the effectiveness of a trigger-based vs a referral-based palliative care program.
Does the presence of an inpatient palliative care service improve care for patients with cancer?
Would a video-based tool describing end-of-life choices for dementia, made available via Internet or kiosk/checkout at physician’s office compared
with usual option of advance directive written brochure (Your Life/Your Choices class) increase the number of patients with an advance directive or
(physician’s orders for life-sustaining treatment) in patients with early dementia?
How important is it that patients have a registered visit to assess their progress on attention deficit disorder/attention deficit with hyperactivity
disorder medication at various intervals after beginning their medication? Would a documented phone call that may not be a telephone advice visit,
in our medical record, be a legitimate option?
Compare the effectiveness of a program of incenting patients to stop smoking vs usual smoking cessation care, to test whether providing
incentives to members who stop smoking is a more effective strategy.
Compare the effectiveness of traditional behavioral interventions vs economic incentives in motivating behavior changes (eg, weight loss, smoking
cessation, avoiding alcohol and substance abuse) in children and adults.
Compare the cost and outcomes of benign gynecology hysterectomy methods: vaginal, laparoscopic, abdominal.
Are there any short- or long-term benefits/risks from the use of steroid injections or hylan G-F 20 (Synvisc) in treating knee arthritis?
Compare the effectiveness of having surgery vs not having surgery for arthroscopy.
Compare the effectiveness of the use of INFUSE bone morphogenic protein, a proprietary product from Medtronic, to alternative biologics/growth
factors like allograft, human-derived demineralized bone matrix, and synthetic (ie, ceramic) bone graft substitutes.
Conduct a prospective trial comparing elective cesarean delivery vs induced vaginal delivery for pregnant women who are 41 or more weeks’
gestation with an unfavorable Bishop score and high fetal vertex presentation. Look at maternal and neonatal morbidity and overall length of stay.
Compare the effectiveness of induction of labor using extraordinary levels of oxytocin over routine methods of induction for all matched pregnancies.
Compare rates of thrombosis between different forms of hormone replacement therapy for menopause.
Compare the effectiveness of screening methods for improving identification of intimate partner violence in female Health Plan members: routine
universal screening vs screening of patients with intimate partner violence risk factors.
Questions are listed in alphabetical order by survey topic area. Questions are listed as nominated, except for slight editing for style and combining questions on the same topic or separating out
multipart questions on different topics.
b
a
12
A range of quantitative and qualitative methods have been used to obtain
stakeholders’ input on research needs and
priorities. These methods have included
semistructured, rating, and forced-ranking
surveys, iterative Delphi or modified
Delphi techniques, focus groups, citizens’
juries and consumer panels (in the case
of engaging the public at-large), and deliberative democracy and other facilitated
consensus-building methods.9 Each of
these methods has different strengths and
weaknesses, and their most appropriate
application depends on context (eg, the
intended focus of the research, its intended uses, and the available resources
to support the engagement). Our method
was a broad-based initial effort to engage
real-world health care leaders in a large
population-based system that has an integrated research and quality-improvement
capability, with the potential for further
development. As other organizations
deliberate processes for eliciting research
needs and priorities, an essential step is
for them to think about the ultimate implications and uses of the results. They
may wish to draw on existing work, such
as the Agency for Healthcare Research
and Quality’s prioritization of topics by
reviewing existing evidence (eg, prevalence, mortality, variations in treatment,
existing studies).7,10
Conclusion
In conclusion, by seeking input from
practicing clinicians and operational
leaders in a large health system providing comprehensive care, we obtained a
wide range of questions reflecting the
diverse health issues facing patients,
clinicians, and health care systems. The
95 high-priority questions presented here
represent issues of importance to those
on the front lines of health care delivery,
who are key stakeholders and anticipated
consumers of comparative effectiveness
research. Thus, these questions may help
inform the national discussion regarding
comparative effectiveness research and
health care. v
Research Associate, Kaiser Permanente
Center for Health Research, Portland, OR
a
Disclosure Statement
This study was funded through Kaiser
Permanente internal operating funds provided
by the Kaiser Permanente Center for Effectiveness and Safety Research. The author(s) have
no other conflicts of interest to disclose.
Acknowledgment
We gratefully acknowledge the contributions and support provided by: Joe Selby,
MD, Executive Director, Patient-Centered
Outcomes Research Institute, Washington,
DC; the Kaiser Permanente National Research
Council; and the Kaiser Foundation Research
Institute, Oakland, CA.
Kathleen Louden, ELS, of Louden Health
Communications provided editorial assistance.
References
1. Committee on Comparative Effectiveness
Research Prioritization, Institute of Medicine of
the National Academies. Initial national priorities for comparative effectiveness research:
report brief [monograph on the Internet].
Washington, DC: Institute of Medicine of the
National Academies; 2009 Jun 30 [cited 2013
Aug 14]. Available from: www.iom.edu/~/
media/Files/Report%20Files/2009/ComparativeEffectivenessResearchPriorities/CER%20
report%20brief%2008-13-09.pdf.
2. Federal Coordinating Council for Comparative
Effectiveness Research. Report to the President
and the Congress. Washington, DC: US
Department of Health and Human Services;
2009 Jun 30.
3. Dubois RW, Graff JS. Setting priorities for
comparative effectiveness research: from
assessing public health benefits to being
open with the public. Health Aff (Millwood)
2011 Dec;30(12):2235-42. DOI: http://dx.doi.
org/10.1377/hlthaff.2011.0136
4. American Recovery and Reinvestment Act of
2009, Pub L No. 111-5 (Feb 17, 2009).
5. Iglehart JK. Prioritizing comparative-effectiveness research—IOM recommendations. N Engl
J Med 2009 Jul 23;361(4):325-8. DOI: http://
dx.doi.org/10.1056/NEJMp0904133
6. Stewart RJ, Caird J, Oliver K, Oliver S. Patients’
and clinicians’ research priorities. Health Expect
org/10.1111/j.1369-7625.2010.00648.x
7. Committee on Comparative Effectiveness
Research Prioritization, Institute of Medicine of
the National Academies. Initial national priorities for comparative effectiveness research.
Washington, DC: Institute of Medicine of the
National Academies; 2009.
8. Patient-Centered Outcomes Research Institute
[homepage on the Internet]. Washington, DC:
Patient-Centered Outcomes Research Institute;
c2013 [cited 2013 Aug 14]. Available from:
www.pcori.org.
9. O’Haire C, McPheeters M, Nakamoto E, et
al; Oregon Evidence-based Practice Center;
Vanderbilt Evidence-based Practice Center.
Engaging stakeholders to identify and prioritize
future research needs. Methods future research
needs report number 4. Publication No.
11-EHC044-EF [monograph on the Internet].
Rockville, MD: Agency for Healthcare Research
and Quality; 2011 Jun [cited 2013 Aug 14].
Available from: http://effectivehealthcare.ahrq.
gov/ehc/products/200/698/MFRNGuide04-Engaging_Stakeholders--6-10-2011.pdf.
10. Whitlock EP, Lopez SA, Chang S, Helfand
M, Eder M, Floyd N. AHRQ series paper 3:
identifying, selecting, and refining topics for
comparative effectiveness systematic reviews:
AHRQ and the effective health-care program.
J Clin Epidemiol 2010 May;63(5):491-501.
DOI: http://dx.doi.org/10.1016/j.jclinepi.2009.03.008
Joy
When, after so many efforts, you have at last arrived at a certainty, your joy is one of the greatest which can be felt by a human soul.
— Louis Pasteur, 1822-1895, French chemist and microbiologist
13
Challenges in Evaluating All-Cause Hospital Readmission Measures for Use as National Consensus Standards
Alexis Morgan, MPH; Adeela Khan, MPH; Taroon Amin, MA, MPH, PhD(c)
Perm J 2013 Fall;17(4):14-18
Abstract
Context: The National Quality Forum (NQF) aims to improve
the quality of health care for all Americans through fulfillment of
its three-part mission. The NQF uses its formal Consensus Development Process to evaluate and endorse consensus standards,
including performance measures, best practices, frameworks,
and reporting guidelines.
Objective: To understand the opportunities and challenges
in endorsing measures addressing all-cause readmissions to
hospitals for use as national voluntary consensus standards for
accountability and quality-improvement purposes.
Design: Report of standards development process.
Main Outcome Measures: The Consensus Development Process was used to evaluate 3 candidate standards using the NQF
Measure Evaluation Criteria. A 21-member steering committee
rated each standard according to the criteria and made initial
endorsement recommendations for all measures.
Results: Through the evaluation of measures for endorsement,
several overarching issues in measuring all-cause readmissions
were identified, including statistical modeling and the usability
of the measures for quality improvement and accountability.
Additionally, it was decided that, for the first time, quality monitoring and accountability of readmissions will take place at the
health-plan level. Measuring at various levels of accountability
reinforces the idea that multiple stakeholders have a responsibility and a role to reduce readmissions.
Conclusions: These NQF-endorsed measures are a major
step in promoting better understanding of readmissions and
a reduction in hospital readmission rates, when appropriate.
These measures can help reduce the substantial financial and
emotional stress that readmissions place on the health care
system, and patients will be able to communicate hospital-level
performance on this important quality indicator.
Introduction
The National Quality Forum (NQF) is a not-for-profit
membership organization created to develop and to implement a national strategy for health care quality measurement
and accountability. Membership consists of national, state,
regional, and local groups representing consumers, public
and private purchasers, health care professionals, provider
organizations, health plans, accrediting bodies, labor unions,
suppliers, and other organizations involved in health care
research or quality measurement and improvement. The
NQF has focused on several areas and aims to improve the
quality of health care in the US through fulfillment of its
three-part mission:
1.setting national priorities and goals for performance improvement
2.endorsing national consensus standards for measuring and
publicly reporting on performance
3.promoting the attainment of national goals through education and outreach programs.
To achieve quality health care across the continuum, there is
a need for robust measures that specifically address outcomes
of care provided in our nation’s health care system. Before
the start of this project, the NQF had endorsed more than 100
outcome measures through various Consensus Development
Process projects, including the multiphase Patient Outcomes
Project. However, many gaps remain, including those related
to all-cause readmissions.
The private and public sector spends billions of dollars
each year on hospital readmissions, with one-fifth of Medicare
beneficiaries readmitted to a hospital within 30 days. Medicare
payments for unplanned readmissions alone cost the Centers
for Medicare & Medicaid Services (CMS) $17.4 billion in 2004.1
Although patients who are privately insured are less likely to
experience a readmission than those with public health insurance, the cost of readmitting commercially insured patients is
higher because of higher commercial payment rates.2 In 2008,
8% of patients who were privately insured in New York State
were readmitted, costing private payers $568.9 million, or 15.2%
of the state’s total readmissions cost.3
To curb spending across the public and private sector on
avoidable readmissions, lawmakers, purchasers, and health plans
have proposed incentives to reduce unplanned readmissions
through public reporting, making it clear that readmissions, as
an outcome indicator of quality, is important to patients.4-7 The
Patient Protection and Affordable Care Act,8 which enacted the
Hospital Readmissions Reduction Program under Medicare,
began penalizing hospitals for high rates of readmissions in
Fiscal Year 2013. Condition-specific and/or all-cause readmission measures will be used across several federal programs,
including the National Patient Safety Initiative, the Hospital
Readmission Reduction Program, and the community-based
Care Transition Program to better understand and ultimately
reduce unplanned hospital readmission rates across the country.
Alexis Morgan, MPH, is a Senior Project Manager in Performance Measurement at the National Quality Forum in Washington,
DC. E-mail: amorgan@qualityforum.org. Adeela Khan, MPH, is a Project Manager in Performance Measurement at the National
Quality Forum in Washington, DC. E-mail: akhan@qualityforum.org. Taroon Amin, MA, MPH, PhD(c), is the Senior Director of
Performance Measurement at the National Quality Forum in Washington, DC. E-mail: tamin@qualityforum.org.
14
To support these initiatives, there is an important need to
endorse consensus-based performance measures for all-cause
readmissions that can be used across various quality reporting
and accountability applications.
Methods
Consensus Development Process
In October 2011, the Department of Health and Human
Services requested that the NQF launch a Consensus Development Process project to identify and endorse cross-cutting,
noncondition-specific quality measures (candidate consensus
standards) that addressed all-cause hospital readmissions.
As part of the NQF’s maintenance of endorsed performance
measures, consensus standards related to all-cause hospital
readmissions and endorsed before June 2009 were evaluated
in this same project. Endorsement maintenance provides the
opportunity to update and to harmonize specifications, ensuring that the best available measures are endorsed and the NQF
portfolio of voluntary consensus standards remains current.
Submitted measures were developed using national guidelines for publicly reported outcome measures and following the
technical guidance set forth by the NQF guidance for outcome
measures.9 Candidate consensus standards were evaluated for
their suitability on the basis of the four NQF Measure Evaluation
Criteria (Table 1) and by using the NQF’s Consensus Development Process.10
The Consensus Development Process is intended to consider
the interests of stakeholder groups from across the health care
industry. The NQF’s Consensus Development Process is designed
to satisfy the requirements of a voluntary consensus standardssetting organization as defined by the National Technology
Transfer and Advancement Act11 and as implemented by the
Office of Management and Budget Circular A-119.
For the All-Cause Readmissions Consensus Development
Process Project, a 21-member steering committee and the Consensus Standards Approval Committee, composed of clinical and
methodologic experts from public and private health care sectors,
evaluated the submitted candidate consensus standards (Table 2).
Statistical Modeling
Although the NQF’s Measure Evaluation Criteria do not
require, or prefer, a specific statistical modeling approach, all
measures submitted to the NQF must be tested to ensure that
they are reliable and valid. Additionally, the risk adjustment
used must be evidence based, relying on intrinsic patient factors.
Each measure developer submitted different methods to
capture a readmission. To control for differences in patient casemix, measures used various approaches to logistic regression
modeling. One particular approach used was hierarchical linear
modeling, which helps to correct for the shared variance seen
in hierarchically structured data. In other words, hierarchical
linear modeling would account for the fact that patients who are
nested in hospitals may not be independent of each other since
patients would be treated by similar physicians in that hospital.
Hierarchical linear modeling using a Bayesian estimator results
in two coefficient estimates of the regression model for each
level (patient and hospital).12
Table 1. National Quality Forum: measure evaluation criteriaa1
Criterion
Importance to
measure and report
Scientific acceptability
of measure properties
Feasibility
Usability
a
1
Description
Extent to which the specific measure focus is evidence
based, important to making significant gains in health
care quality, and improving health outcomes for a
specific high-priority (high-impact) aspect of health care
where there is variation in or overall less-than-optimal
performance
Extent to which the measure, as specified, produces
consistent (reliable) and credible (valid) results about
the quality of care when implemented
Extent to which the required data are readily available
or could be captured without undue burden and can be
implemented for performance measurement
Extent to which intended audiences (eg, consumers,
purchasers, providers, policymakers) can understand
the results of the measure and find them useful for
decision making
Effective until November 2012. Evaluation subcriteria are not included in this table.
National Quality Forum: Measure evaluation criteria and guidance summary tables—effective
for projects beginning after January 2011 [monograph on the Internet]. Washington, DC:
National Quality Forum; 2012 [cited 2013 August 21]. Available from: www.qualityforum.org/
WorkArea/linkit.aspx?LinkIdentifier=id&ItemID=69376.
Generalized Bayesian estimators13 can be used to account for
the simultaneous relationships and shared variance among hierarchical levels by computing a weighted combination of the two
levels.12 Furthermore, classic estimation theories do not assume
prior knowledge of a distribution for variables in the regression
model. In contrast, Bayesian estimation may be used to predict
hospital performance from a common prior distribution, such
as performance from a previous year, or from the grand mean
of the population of all hospitals.
Results
Of the candidate consensus standards (Table 2), 2 measures,
1789: Hospitalwide all-cause unplanned readmission measure
and 1768: Plan all-cause readmissions, were subsequently endorsed by the NQF Board of Directors.
Throughout the review process, several challenges to measuring and endorsing all-cause hospital readmissions were identified, and important overarching themes were noted throughout
the evaluation.
Statistical Modeling
Stakeholders raised concerns that the risk-adjusted rates using hierarchical linear modeling with Bayesian estimators to
predict performance for low-volume hospitals would be adjusted
toward the mean performance of all hospitals. This shrinkage
toward the mean could potentially cause bias for small-volume
hospitals, which would seem to have average rates. However,
others argued that if the measures did not use a Bayesian estimation technique, hospitals with small volumes would have
large confidence intervals around their performance score that
would overlap with the average performance of all hospitals.
This would result in performance scores for low-volume hospitals
that would not allow for statistically significant and practically
meaningful differences in performance.
15
It was broadly recognized that shrinkage toward the mean
should theoretically be less of a concern since there is a greater
sample size per hospital for all-cause readmissions than condition-specific readmissions.
Hospital Volume
Major concerns also were raised about the lack of risk adjustment for hospital volume. Experts noted that growing literature
demonstrates a relationship between hospital volume and quality
performance. Two principal hypotheses have been advanced to
explain the relationship. The first hypothesis is that physicians
(and hospitals) develop more effective skills if they treat more
patients (higher volumes), and the second hypothesis is that physicians (and hospitals) achieving better outcomes receive more
referrals and thus accrue larger volumes.14,15 This relationship
would demonstrate that including volume, as a covariate, would
improve the risk adjustment models performance. However, in
developing risk adjustment models for performance measures,
there should be consideration on why conceptually stakeholders
should expect a priori differences in hospital performance on
all-cause readmissions rates based on their patient volume and
whether such differences are justified. A systematic review to
understand what is known about how volume and outcomes are
associated, and by what causal pathways they might be related,
did not determine that any specific factor was able to explain
outcome differences between high- and low-volume hospitals.16
The review found that no longitudinal studies address the important question of how much of the variability, especially among
low-volume hospitals, is due to chance.
Usability for Quality Improvement
Throughout the Consensus Development Process, questions
surrounded the usability and implementation of an all-cause
readmission measure using Medicare claims data. Physicians
expressed concern about the inability to produce strategies
for effective performance evaluation and quality-improvement
activities because of the timeliness of reporting by the CMS and
others. Delays in receiving performance results means hospitals
are unable to produce strategies for improvement, effectively
making it difficult for consumers to make timely and informed
decisions when selecting a physician. As such, there was consensus that if these measures are to be used for public reporting, accountability, or payment, the CMS and other users must provide
timely feedback to hospitals to support rapid-cycle improvement.
Equally as important, timely reporting of quality performance
will help to inform consumers about higher-quality hospitals.
The CMS has indicated that they are working to develop
methods to provide timely feedback and information on all readmissions, through the CMS dry run, hospital-level results will be
shared with hospitals to better understand the performance on the
number of readmissions, the patient risk factors, comorbidities,
and the name of the hospital where the patient was readmitted.
Table 2. Patient outcomes: all-cause readmissions expedited review of submitted measures
Measure ID no./title
0329
Risk-adjusted
30-day all-cause
readmission ratea
Measure description
The existing NQF-endorsed measure provides a means for determining the risk-adjusted readmission rate for a
selected adult target population and can be applied for any desired timeframe. Readmission rate is defined as the
percentage of acute inpatient discharges during the measurement period followed by an acute inpatient admission
for any diagnosis to any hospital within 30 days.
We are proposing to change the measure and offer a risk factor approach. This method allows for calculation of
a risk-adjusted readmission rate for use in two different ways: 1) retrospective analysis of hospital (or other study
population) performance determination and 2) in a real-time electronic health record environment, analysis to
determine the readmission risk factor for each inpatient admission.
Measure steward
UnitedHealth
Group
1768
Plan all-cause
readmissions
For members age 18 years and older, the number of acute inpatient stays during the measurement year that
were followed by an acute readmission for any diagnosis within 30 days and the predicted probability of an acute
readmission. Data are reported in the following categories:
1. Count of Index Hospital Stays (denominator)
2. Count of 30-Day Readmissions (numerator)
3. Average Adjusted Probability of Readmission
4. Observed Readmission (numerator/denominator)
5. Total Variance
Note: For commercial insurance plans, only members age 18 to 64 years are collected and reported; for Medicare,
only members age 18 years and older are collected, and only members age 65 years and older are reported.
This measure estimates the hospital-level, risk-standardized rate of unplanned, all-cause readmission after
admission for any eligible condition within 30 days of hospital discharge (RSRR) for patients age 18 years and older.
The measure reports a single summary RSRR, derived from the volume-weighted results of 5 different models, 1 for
each of the following specialty cohorts (groups of discharge condition categories or procedure categories): surgery/
gynecology, general medicine, cardiorespiratory, cardiovascular, and neurology. The measure also indicates the
hospital standardized risk ratios for each of these 5 specialty cohorts.
We developed the measure for patients age 65 years and older using Medicare fee-for-service claims and
subsequently tested and specified the measure for patients aged 18 years and older using all-payer data. We used
the California Patient Discharge Data, a large database of patient hospital admissions, for our all-payer data.
National
Committee for
Quality Assurance
1789
Hospitalwide allcause unplanned
readmission
measure
Centers for
Medicare &
Medicaid Services
a
Maintenance measure.
NQF = National Quality Forum.
16
Of note, the usability of the health plan-level measure was
also a point of discussion. The measure was seen as useful for
holding health plans responsible for readmissions, recognizing
that responsibility for effective care coordination is not solely
the job of the hospital or physician.
Risk Adjustment and Socioeconomic Status
Measures submitted for this project were not risk adjusted
for a patient’s socioeconomic status. In accordance with the
NQF guidance, inclusion of socioeconomic status factors in
risk-adjustment models is inappropriate because it assumes that
differences in outcomes based on those factors are acceptable.
Risk adjustment for socioeconomic status may conceal disparities in care by race or ethnicity. The NQF guidance advises that
distinctions among population groups should be emphasized to
acknowledge disparities, and that including items such as race
or ethnicity in a risk-adjustment model would mask differences
based on these characteristics.17
Although the steering committee agreed that the NQF guidance was appropriate, there was concern regarding evidence
indicating that a patient’s socioeconomic status may affect his/
her posthospitalization recovery owing to inaccessibility of
community resources.18,19 As such, hospitals argue that they
cannot be solely responsible for readmissions because multiple
factors influence their patients’ likelihood of being readmitted.20
Many methodologic challenges inhibit including socioeconomic
status as a variable in a measure, since it is especially complex
to interpret what this variable is correcting for in a predictive
model. To overcome this challenge, some agreed that to support fair and appropriate comparisons, hospital performance
on this measure could be reported in like comparison groups
(eg, disproportionate-share hospitals). Doing so would highlight
disparities in care and improve policy decisions, specifically
potential unintended consequences such as the removal of
community-level resources from vulnerable communities.
However, it should also be noted that stratification, by disproportionate-share hospitals in particular, might be inappropriate
since payments to disproportionate-share hospitals are dependent
on Medicaid eligibility and coverage, which vary across states.
Also, there is no evidence to suggest that disproportionate-share
hospitals should perform a priori differently than do nondisproportionate-share hospitals, or that the difference seen is justifiable.
Recognizing that measuring readmissions without adjustment for
socioeconomic status holds a hospital partially responsible for
coordination and collaboration across care transitions, neither
readmissions measure seeks to isolate simply the hospitals’ role,
but rather seeks to encourage shared accountability for care
transitions. In short, developers of both measures recognized
that readmissions are not a quality issue solely for hospitals but
also for communities and for local health systems.
Discussion
The NQF process resulted in endorsement of both a health
plan- and hospital-level 30-day all-cause hospital readmission
measure. To address many of the overarching issues identified
throughout the Consensus Development Process, the NQF developed guidance language to reflect the multiple perspectives
voiced during the discussion, particularly related to the hospitallevel measure (1789). This language sought to reinforce the
multifactorial nature of readmissions and the importance of
hospital-community collaboration to reduce readmission rates.
The NQF board provided the following guidance language
for measure 1789:
Multiple factors affect readmission rates and other
measures including: the complexity of the medical
… neither
condition and associated therapies; effectiveness
readmissions
of inpatient treatment and care transitions; patient
measure seeks
understanding of and adherence to treatment plans;
to isolate
patient health literacy and language barriers; and the
availability and quality of postacute and communitysimply the
based services, particularly for patients with low
hospitals’
income. Readmission measurement should reinforce
role, but
national efforts to focus all stakeholders’ attention
rather seeks
and collaboration on this important issue.21
to encourage
The NQF acknowledges the concerns raised by physhared
sicians and hospitals on the potential negative impact
accountability
to hospitals that disproportionately treat patients with
for care
complex social comorbidities. Ultimately, an all-cause
transitions.
readmission measure provides an opportunity to highlight important quality outcomes that are important
to patients. v
The author(s) have no conflicts of interest to disclose.
Acknowledgment
Kathleen Louden, ELS, of Louden Health Communications provided
editorial assistance.
References
1. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients
in the Medicare fee-for-service program. N Engl J Med 2009;360(14):
1418-28.
2. Steiner C, Barrett M, Hunter K. Hospital readmissions and multiple emergency department visits, in selected states, 2006-2007. Healthcare Cost
and Utilization Project statistical brief #90 [monograph on the Internet].
Rockville, MD: Agency for Healthcare Research and Quality; 2010 May
[cited 2013 Jun 5]. Available from: www.hcup-us.ahrq.gov/reports/statbriefs/sb90.pdf.
3. Chollet D, Barrett A, Lake T; Mathematica Policy Research. Reducing
hospital readmissions in New York State: a simulation analysis of alternative
payment incentives [monograph on the Internet]. New York: NYS Health
Foundation; 2011 Sep [cited 2013 Jun 5]. Available from: http://nyshealthfoundation.org/uploads/resources/reducing-hospital-readmissions-paymentincentives-september-2011.pdf.
4. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to
reduce 30-day rehospitalization: a systematic review. Ann Intern Med 2011
Oct 18;155(8):520-8. DOI: http://dx.doi.org/10.7326/0003-4819-155-8201110180-00008
5. Corrigan JM, Martin JB. Identification of factors associated with hospital
readmission and development of a predictive model. Health Serv Res 1992
Apr;27(1):81-101.
6. Ashton CM, Del Junco DJ, Souchek J, Wray NP, Mansyur CL. The association
between the quality of inpatient care and early readmission: a meta-analysis
of the evidence. Med Care 1997 Oct;35(10):1044-59. DOI: http://dx.doi.
org/10.1097/00005650-199710000-00006
7. Halfon P, Eggli Y, Prêtre-Rohrbach I, Meylan D, Marazzi A, Burnand B.
Validation of the potentially avoidable hospital readmission rate as a routine
indicator of the quality of hospital care. Med Care 2006 Nov;44(11):97281. DOI: http://dx.doi.org/10.1097/01.mlr.0000228002.43688.c2
8. The Patient Protection and Affordable Care Act of 2010. Public Law 111148, 111th Congress, 124 Stat 119, HR 3590, enacted 2010 Mar 23.
17
9. Guidance for evaluating the evidence related to the focus of quality
measurement and importance to measure and report [monograph on the
Internet]. Washington, DC: National Quality Forum; 2011 Jan [cited 2013
Jun 6]. Available from: www.qualityforum.org/WorkArea/linkit.aspx?LinkIde
ntifier=id&ItemID=70941.
10. Consensus development process [Web page on the Internet]. Washington,
DC: National Quality Forum; c2013 [cited 2013 Jun 6]. Available from:
www.qualityforum.org/Measuring_Performance/Consensus_Development_
Process.aspx.
11. National Technology Transfer and Advancement Act of 1995, Pub. L. No.
104-113, 110 Stat. 775 (1996 Mar 7).
12. Woltman H, Feldstain A, MacKay JC, Rocchi M. An introduction to hierarchical linear modeling. Tutor Quant Methods Psychol 2012;8(1):52-69.
13. Berger JO. Statistical decision theory and Bayesian analysis. 2nd Ed. New
York: Springer-Verlag; 1985.
14. Flood AB, Scott WR, Ewy W. Does practice make perfect? Part I: the
relation between hospital volume and outcomes for selected diagnostic categories. Med Care 1984 Feb;22(2):98-114. DOI: http://dx.doi.
org/10.1097/00005650-198402000-00002
15. Flood AB, Scott WR, Ewy W. Does practice make perfect? Part II: the relation between volume and outcomes and other hospital characteristics. Med
Care 1984 Feb;22(2):115-25. DOI: http://dx.doi.org/10.1097/00005650198402000-00003
16. Hewitt M. Interpreting the volume-outcome relationship in the context of
health care quality: workshop summary. Washington, DC: The National
Academies Press; 2000. p 4-10.
17. Weissman JS, Betancourt JR, Green AR, et al. Commissioned paper: healthcare disparities measurement [monograph on the Internet]. Washington,
DC: National Quality Forum; 2012 Feb [cited 2013 Jun 6]. Available from:
www.qualityforum.org/WorkArea/linkit.aspx?LinkIdentifier=id&Item
ID=67965.
18. Arbaje AI, Wolff JL, Yu Q, Powe NR, Anderson GF, Boult C. Postdischarge
environmental and socioeconomic factors and the likelihood of early
hospital readmission among community-dwelling Medicare beneficiaries.
Gerontologist 2008 Aug;48(4):495-504. DOI: http://dx.doi.org/10.1093/
geront/48.4.495
19. Joynt KE, Orav EJ, Jha AK. Thirty-day readmission rates for Medicare beneficiaries by race and site of care. JAMA 2011 Feb 16;305(7):675-81. DOI:
http://dx.doi.org/10.1001/jama.2011.123
20. Joynt KE, Jha AK. Thirty-day readmissions—truth and consequences. N
Engl J Med 2012 Apr 12;366(15):1366-9. DOI: http://dx.doi.org/10.1056/
NEJMp1201598
21. NQF endorses all-cause unplanned readmissions measure [press release on
the Internet]. Washington, DC: National Quality Forum; 2012 Apr 24 [cited
2013 Aug 15]. Available from: www.qualityforum.org/News_And_Resources/Press_Releases/2012/NQF_Endorses_All-Cause_Unplanned_Readmissions_Measures.aspx.
Nature and Kind Nurses
Their situation too, when sick, in the family of a good farmer, where
every member is emulous to do them kind offices, where they are
visited by all the neighbors, who bring them the little rarities which
their sickly appetites may crave, and who take by rotation the
nightly watch over them, when their condition requires it, is without
comparison better than in a general hospital, where the sick, the dying,
and the dead are crammed together in the same rooms, and often in the
same beds. The disadvantages, inseparable from general hospitals, are
such as can never be counterposed by all the regularities of medicine
and regimen. Nature and kind nursing save a much greater proportion
in our plan way, at a smaller expense, and with less abuse.
— Thomas Jefferson, 1743-1826, American Founding Father, author, and third President of the United States
18
Hypovitaminosis D Correction and High-Sensitivity C-Reactive Protein Levels in Hypertensive Adults
Nathan Carlson, MD; Robert Mah, MD; Maria Aburto; Mark Jason Peters, MD; Meagan V Dupper, MD; Lie Hong Chen, DrPH
Perm J 2013 Fall;17(4):19-21
Abstract
Context: Hypovitaminosis D has been implicated as a possible risk factor for the development of cardiovascular disease.
High-sensitivity C-reactive protein (hs-CRP) has been one of the
most extensively studied biomarkers for cardiovascular inflammation as an indicator of disease and event risk, independent
of traditional risk factors. To date, it is unclear if correction of
hypovitaminosis D leads to a reduction of hs-CRP in human
subjects.
Objectives: To assess laboratory validity of 25-hydroxyvitamin D (25-OH-vitamin D) and hs-CRP measurements and to
determine whether hs-CRP levels in adults with well-controlled
hypertension and comorbid low vitamin D levels changed after
hypovitaminosis D correction to a serum 25-OH-vitamin D level
greater than 30 ng/mL.
Design: Prospective study using an unblinded design.
Results: One hundred eight subjects who were vitamin D
insufficient or deficient completed this study. The mean 25-OHvitamin D level was 20.07 ng/mL before treatment and 43.92
ng/mL after treatment. Posttreatment vitamin D levels were in
the normal range for 91% of the subjects. No statistically significant changes in hs-CRP level were detected after the vitamin
D treatment was administered and a posttreatment vitamin D
level above 30 ng/mL was confirmed.
Conclusion: We did not detect a statistically significant difference in hs-CRP after correction of hypovitaminosis D. Twelve
weekly oral doses of 50,000 IU of ergocalciferol corrected the
hypovitaminosis D in more than 90% of cases.
Introduction
Hypovitaminosis D has been implicated as a possible, underappreciated risk factor for the development of cardiovascular
disease.1 For example, among the Framingham Offspring cohort
with hypertension, a twofold increased risk of cardiovascular
events was found in patients deficient in vitamin D.2
There are possible mechanisms by which vitamin D reduces
vascular damage. Experimental observations indicate that vitamin
D suppresses the renin gene as well as having direct vascular
effects such as modulating smooth muscle cell proliferation,
inflammation, and thrombosis. Vitamin D inhibits cholesterol
uptake in macrophages, and a vitamin D-deficient-environment
leads to foam cell development in patients with diabetes.3
In small clinical trials, vitamin D supplementation has promoted improved blood pressure measurements, left ventricular
hypertrophy, and inflammatory cytokine levels.2,4 However, to
date, it is not known if correction of this deficiency leads to any
improved clinical outcome.5 Short courses (8 to 12 weeks) of
vitamin D supplementation in deficient individuals, even at doses
of 50,000 international units (IU) weekly, have not been shown
to result in vitamin D toxicity. Some investigations suggest that a
daily oral vitamin D intake up to 2000 IU (100 μg) is safe in the
adult population.6
There are barriers to optimal trials of vitamin D supplementation in cardiovascular disease prevention. Randomizing patients
with moderate to severe vitamin deficiency to a long-term placebo arm could be considered unethical once hypovitaminosis
is identified in an individual. Also, a primary prevention trial of
vitamin D supplementation would require a very large sample.
Therefore, it seems reasonable to search for surrogates that might
identify subgroups most likely to benefit from hypovitaminosis
D correction.
The most extensively studied biomarker of inflammation in
cardiovascular diseases is C-reactive protein, for which standardized high-sensitivity assays are now widely available.1 In both
primary and secondary prevention trials involving statins, the
“greatest clinical event reduction has been noted in patients who
achieved low-density lipoprotein cholesterol levels below 70 mg/
dL and high sensitivity C-reactive protein (hs-CRP) levels under
2 mg/L (and to a greater degree with hs-CRP levels < 1 mg/L).”7
Up to 14% of major cardiovascular events occur in patients
who have none of the traditional risk factors.8 It would be of
great benefit to determine whether correction of vitamin D deficiency in selected patients would push elevated hs-CRP levels
down to the lowest tertile and thus potentially add another
anti-inflammatory weapon against some of the major causes of
death in the US.
Methods
Subjects and Data
The study design and methods were approved by the Southern
California Permanente Medical Group institutional review board.
Informed consent was obtained. This study was a prospective
study using an unblinded design. Patients were identified in the
Kaiser Permanente (KP) electronic medical record database at
the KP Fontana Medical Center in California.
Nathan Carlson, MD, is a Family Physician and Faculty of the Family Medicine Residency Program at the Fontana Medical Center in CA.
E-mail: nathan.d.carlson@kp.org. Robert Mah, MD, is a Family Medicine Resident at the Fontana Medical Center in CA. E-mail: robert.x.mah@kp.org.
Maria Aburto is a Research Assistant at the Fontana Medical Center in CA. E-mail: maria.x.aburto@kp.org. Mark Jason Peters, MD, is a Family
Medicine Physician at the Oceanside Medical Offices in CA. E-mail: jason.m.peters@kp.org. Meagan V Dupper, MD, is a Community Medicine
Fellow at the Fontana Medical Center in CA. E-mail: meagan.v.dupper@kp.org. Lie Hong Chen, DrPH, is a Biostatistician in Research and
Evaluation for the Southern California Permanente Medical Group in Pasadena, CA. E-mail: lie.h.chen@kp.org.
19
Table 1. Baseline characteristics (N = 108) Characteristic
Age, mean (SD), years
Female sex, n (%)
Ethnicity, n (%)
Non-Hispanic white
Hispanic
Non-Hispanic black
Non-Hispanic others
Declined to state
Framingham Risk Score, median (range), %
Prestudy weekly vitamin D dietary intake,
median (range), IU
Value
64.5 (4.74)
68 (62.96)
40 (37.04)
16 (14.81)
21 (19.44)
4 (3.70)
27 (25.0)
5.5 (1-20)
822 (0-8939)
IU = international units; SD = standard deviation.
Subjects were advised not to take any calcium or other vitamin D supplements during the study period and to report any
illnesses. Inclusion criteria were as follows: 1) age 55 years or
older, 2) a diagnosis of hypertension (based on 2 blood pressure measurements of ≥ 140/90 mm Hg), 3) blood pressure
controlled with medication and lifestyle therapies (< 140/90
mm Hg), and 4) a serum 25-hydroxyvitamin D (25-OH-vitamin
D) level below 30 ng/mL (the Medical Center’s laboratory
standard). Subjects were excluded if they had any of the following: 1) a preexisting diagnosis of vitamin D deficiency, 2)
uncontrolled or secondary hypertension, 3) any of a number
of other cardiovascular conditions, 4) treatment with statin
medication, 5) long-term corticosteroid use, 6) cancer, 7)
abnormal serum calcium levels or parathyroid disease, or 8)
infection (viral, bacterial, or other) within 1 month preceding
the collection of blood samples for hs-CRP analysis.
Table 2. Comparison of clinical measurements
Variable
Measure 1
Measure 2
Vitamin D,b mean (SD), ng/mL
Pretreatment
20.07 (5.06)
20.11 (5.35)
Posttreatment
43.92 (11.53)
37.14 (9.56)
High-sensitivity C-reactive protein, median (range), mg/L
Pretreatment
2.50
2.60
(0.20-12.80)
(0.10-21.60)
Posttreatment
2.80
2.60
(0.10-13.10)
(0.10-28.30)
Difference
p valuea
0.04 (3.46)
6.78 (5.68)
0.956
< 0.001
0.1
(−21.20-4.00)
0.2
(−15.20-4.90)
0.819
0.606
for C-reactive protein.
serum 25-hydroxyvitamin D.
SD = standard deviation.
a
b
Table 3. Comparison of measurements before and after treatment of
hypovitaminosis
Variable
Vitamin D, (serum
25-hydroxyvitamin D), ng/mL
High-sensitivity C-reactive
protein, mg/L
SD = standard deviation.
20
Before treatment,
mean (SD)
After treatment,
mean (SD)
20.06
(4.92)
1.36
(0.57)
40.53
(10.20)
1.31
(0.60)
Difference
Mean (SD) p value
20.47
< 0.001
(9.97)
−0.05
0.055
(0.28)
Past blood pressure measurements were assessed to ensure
good control at the onset of the study. An initial testing of
calcium, 25-OH-vitamin D and hs-CRP levels was conducted.
There was a repeated test of serum hs-CRP and 25-OH-vitamin
D levels 2 weeks later. Those found to have normal calcium
levels and vitamin D deficiency then received 12 weekly oral
doses of 50,000 IU of ergocalciferol. Weekly telephone calls
reminded participants to take their prescribed vitamin D supplements. After 12 weeks of supplementation, subjects returned
for measurement of their 25-OH-vitamin D and hs-CRP levels,
with repeated tests (the fourth blood measurement) performed
approximately 2 weeks later.
A poststudy interview confirmed compliance with the regimen
and verified that there were no illnesses, injuries, medication
changes, or unauthorized vitamin supplementation during the
study period. After completion of the study, each subject was
provided a monetarily small gift card to partially compensate
them for time and travel expenses.
Statistical Analysis
Paired t tests were used to examine the change of hs-CRP and
25-OH-vitamin D values. The Wilcoxon signed rank sum test
was used if a non-normal distribution was observed. Pearson/
Spearman correlation coefficient, linear regression, and analysis
of covariance assessed the associations between log-transformed
measurements of hs-CRP and 25 OH-vitamin D, controlling for
baseline demographics and reported dietary vitamin D intake.
Significance level was defined as p < 0.05. The software SAS
Enterprise Guide was used for all analyses (version 4.3, SAS
Institute Inc, Cary, NC).
Results
A total of 327 adult hypertensive subjects were screened
for vitamin D deficiency, and 142 (43%) of the subjects had
low serum vitamin D levels (< 30 ng/mL). Analysis included
108 patients who completed all aspects of the study. The
main reason that subjects failed to complete the study was
failure to undergo the required blood tests in a timely manner. The mean age of the study subjects was 64.5 years. This
study was composed of 37% white, 19.4% African-American,
and 14.8% Hispanic individuals. The remainder declined to
state their racial background. Women made up 63% of the
participants (Table 1).
There was no statistically significant difference between the
first and second measurements of pretreatment vitamin D, or
pretreatment and posttreatment hs-CRP. There was, however, a
significant difference between the first and second posttreatment
measurements of vitamin D (< 0.001). The first posttreatment
measurements were, on average, 6.8 ng/mL higher than the
second measurement of posttreatment vitamin D. The 2 measurements of pretreatment vitamin D, pretreatment hs-CRP, and
posttreatment hs-CRP were statistically similar, with a p-value
range from 0.61 to 0.96 (Table 2).
There was no significant difference of median hs-CRP levels
between pretreatment and posttreatment values (Table 3). After
log transformation, there was no significant decrease between
log-transformed pretreatment and posttreatment hs-CRP levels
(p = 0.055). The average log-transformed hs-CRP level decreased
from 1.37 to 1.31 mg/L (Figure 1).
The results indicated that 12 weeks of treatment were sufficient
to correct vitamin D deficiency. The average vitamin D level increased from 20 ng/mL to 40.5 ng/mL. No significant changes in
hs-CRP level were found because of a large variation of hs-CRP
values. The posttreatment hs-CRP level may be associated with
the initial degree of vitamin D deficiency. This is supported by
a trend toward significance (p = 0.056) (Figure 2).
Discussion
Our main finding in this study was that correction of hypovitaminosis D had no statistically significant effect on hs-CRP
levels in patients with hypertension and with no other major
disease states. We did confirm that a 12-week treatment with
ergocalciferol was effective treatment for hypovitaminosis D.
However, these data suggest that such gains may be fleeting and
that ongoing oral vitamin D supplementation is likely required
to maintain normal serum vitamin D levels.
Our study has a number of limitations. First, this was a pilot
study with limited power to discern subtle changes in hs-CRP.
We estimate that 1441 subjects would be needed to observe a
significant change at the 0.05 level with 80% power, assuming
that the observed results were similar in a larger study. Second,
the patients in the study were predominantly women and the
mean age was age 64.5 years, possibly limiting the application
of data to other populations. Third, the exclusion criteria were
restrictive. Fourth, the study follow-up period of 12 weeks for
most subjects precluded study of effects on hs-CRP with prolonged supplementation. Finally and importantly, although hsCRP itself has been linked to risk of cardiovascular events, this
study did not evaluate the clinical effect that the replacement of
vitamin D would have directly on cardiovascular risk reduction
via other mechanisms.
It is noteworthy that 43% of the eligible participants who had
their initial screening blood drawn for this study met laboratory
criteria for vitamin D insufficiency or deficiency. This suggests
that lower blood levels of vitamin D appear to be common even
among residents of “sunny Southern California.” In any case,
the clinical significance of hypovitaminosis D in cardiac disease
remains unclear. v
Acknowledgment
Kathleen Louden, ELS, of Louden Health Communications provided
editorial assistance.
References
Figure 1. Log-transformed high-sensitivity C-reactive protein
(hs-CRP) levels (mg/L) before and after vitamin D treatment.
1. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum
25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and
cardiovascular mortality. Arch Intern Med 2008 Jun 23;168(12):1340-9.
DOI: http://dx.doi.org/10.1001/archinte.168.12.1340
2. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of
cardiovascular disease. Circulation 2008 Jan 29;117(4):503-11. DOI: http://
dx.doi.org/10.1161/CIRCULATIONAHA.107.706127
3. Oh J, Weng S, Felton SK, et al. 1,25(OH)2 vitamin D inhibits foam cell
formation and suppresses macrophage cholesterol uptake in patients with
type 2 diabetes mellitus. Circulation 2009 Aug 25;120(8):687-98. DOI:
http://dx.doi.org/10.1161/CIRCULATIONAHA.109.856070
4. Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 2003 May;89(5):552-72. DOI: http://dx.doi.org/10.1079/
BJN2003837
5. Heaney RP. Long-latency deficiency disease: insights from calcium and
vitamin D. Am J Clin Nutr 2003 Nov;78(5):912-9.
6. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations,
and safety. Am J Clin Nutr 1999 May;69(5):842-56.
7. Lavie C, Milani RV, Verma A, O’Keefe JH. C-reactive protein and
cardiovascular diseases—is it ready for primetime? Am J Med
Sci 2009 Dec;338(6):486-92. DOI: http://dx.doi.org/10.1097/
MAJ.0b013e3181c61b66
8. Canto JG, Kiefe CI, Rogers WJ, et al; NRMI Investigators. Number of
coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA 2011 Nov 16;306(19):2120-7. DOI: http://dx.doi.
org/10.100/jama.2011.1654
Figure 2. Nearly significant correlation of pre-25-OH-vitamin D
and post high-sensitivity C-reactive protein level.
21
From the Patient’s Perspective: Is There a Need to Improve the Quality of Informed Consent for Surgery in Training Hospitals?
Shamir O Cawich, DM; Alan T Barnett, DM; Ivor W Crandon, FRCS; Samantha D Drew; Georgiana Gordon-Strachan, BSc, PhD
Perm J 2013 Fall;17(4):22-26
Abstract
Objective: This study was performed to evaluate the presurgical informed consent
process at a training hospital in Jamaica.
Methods: A postoperative survey was administered to all consecutive able and willing
adult patients who underwent the presurgical informed consent process with surgical
residents during a 5-week period. Information was collected on patient demographics
and patients’ perception and satisfaction with the informed consent process.
Results: There were 210 surveys completed. Patients were unaware of the training
status of the physician involved with their presurgical informed consent process in 48%
of cases. Nineteen (9%) patients were instructed to sign a consent document without
any discussion. An attempt was made to secure a signature after some discussion with
the remaining 191 patients. Patients reported that details of the operation were discussed
74% of the time; potential benefits of the surgery, 72% of the time; potential morbidity,
84% of the time; potential mortality, 19% of the time; predicted postoperative course,
49% of the time; projected recovery, 26% of the time; and other treatment options, 33%
of the time. Forty-five patients believed that they were instructed to sign the consent
document with minimal discussion. At termination of the consent process, only 70% of
the 210 patients reported that they signed the consent form voluntarily. Overall, 67% of
patients thought the current informed consent process was unsatisfactory.
Conclusion: The current informed consent process in use in the surgical training
program at the University Hospital of the West Indies requires improvement to meet
expected ethical and legal standards.
Introduction
For medical care to be effective, patients must make important decisions
about their management. Most patients
do not have the requisite medical training
necessary to make autonomous decisions
about their care. They rely on their attending physicians to share accurate and
relevant information with them that will
empower them with the ability to choose
from several therapeutic options and to
make rational decisions about their care in
their own best interest. This is the process
of informed consent.
Physicians have a legal and ethical
responsibility to complete this process
before any physical investigations or
therapeutic interventions are performed
in their patients.1-3 Three criteria must be
satisfied for the process of informed consent to be effective and valid: 1) capacity,
2) autonomy, and 3) disclosure.4-6
Capacity is the clinical term that refers
to a patient’s ability to understand all
information relevant to decision making
and any reasonably foreseeable consequences of the patient’s decision.3-5 The
determination of capacity is a complex,
multidimensional task requiring physicians to determine whether patients
have properly received, understood, and
retained information relative to the specific scenario or decision.4,7 Its complexity
was best summed up by the US Supreme
Court as “not only a factual but rational
understanding” of facts.8
Autonomy is the second criterion for
effective, valid informed consent. AngloAmerican law protects the individual’s
right to independent choice and freedom
from unwanted intrusion on one’s liberty
and self. The process of informed consent
is intended to uphold this principle by
requiring a capable individual to grant
permission for procedures without any
element of force, deceit, or coercion.1,4,5
It is a delicate process that may be easily
affected by patient factors such as confidence, cognition, and affect.9,10 Clinicians
may introduce subtle coercion through their
demeanor and body language. Situational
duress may arise when patients believe
that they have no choice but to accept the
treatment offered by health care professionals. This may occur when patients believe
that their options are limited by insurance
benefits, managed health care restrictions,
and even attitudes and/or opinions from
health care professionals that may stifle their
perceptions of alternatives.
For disclosure, the third criterion for
informed consent, each patient must be
furnished with sufficient relevant and
updated information to enable him/her
to make a decision. Although there is no
clear guideline, there are two US landmark
legal precedents that are instructive on the
content of disclosure.
In 1960, the Kansas Supreme Court outlined information that physicians would be
required to provide to their patients during
the process of informed consent (Natanson
v Kline, 1960).11 This Professional Standard
of Disclosure included information on the
nature and purpose of proposed treatment,
potential risks and benefits of treatment,
and alternative treatments along with their
risks and benefits.11 In the second land-
Shamir O Cawich, DM, is a Lecturer in the Department of Clinical Surgical Sciences at the University of West Indies in Port
of Spain, Trinidad and Tobago. E-mail: socawich@hotmail.com. Alan T Barnett, DM, is a Lecturer in the Department of
Surgery at the University of West Indies in Kingston, Jamaica. E-mail: alanbarnett@gmail.com. Ivor W Crandon, FRCS, is a
Lecturer in the Department of Surgery at the University of West Indies in Kingston, Jamaica. E-mail: ivorcrandon@gmail.com.
Samantha D Drew is a House Officer in the Department of Surgery at the Southampton General Hospital, United Kingdom.
E-mail: sddrew@hotmail.com. Georgiana Gordon-Strachan, BSc, PhD, is a Lecturer in the Department of Surgery at the
University of West Indies in Kingston, Jamaica. E-mail: ggstrachan@gmail.com.
22
mark case (Canterbury v Spence, 1972), a
Washington, DC, circuit court ruled that a
practitioner is obliged to disclose what “a
reasonable person would want to know
about a treatment before undergoing it.”12
Although both the Natanson and
Canterbury precedents serve as guides
in modern medicine,3-6 many physicians
still experience difficulty with the depth
of disclosure. On one hand, physicians
may want to volunteer all available
information so they are not vulnerable
to litigation.6 On the other hand, many
clinicians suggest that patients may become apprehensive and anxious when
excessive information is volunteered,13,14
although this remains unproved.
In the end, the physician obtaining
consent is ultimately responsible for the
content of disclosure. In 1957, a United
Kingdom court (Bolam v Friern, 1957)15
ruled that a physician will not be found
negligent once a body of responsible physicians finds his/her practice competent.
On the basis of this Bolam principle, many
surgeons inform their patients of risks that
occur with greater than 1% frequency.6
This, however, is only a guide. In 1992,
an Australasian court ruled that a physician
was negligent for not discussing a complication with a risk of 0.007% during consent
for surgery (Rogers v Whitaker, 1992).16 Additionally, in a recent study of the standards
of consent achieved in British hospitals,
16% of clinical negligence solicitors felt
that patients should be informed about
complications with a 1:1,000,000 risk.17
These considerations serve to remind
us that the process of informed consent is
a difficult, complex, and multidimensional
task. Yet it is important because it sets the
stage for physician-patient bonding and
developing trust-based relationships.18,19
There is an additional dimension of complexity in postgraduate surgical training. On
one hand, surgical residents may not always
impart complete or accurate information to
fulfill the patient’s needs for decision making. On the other hand, it is paramount for
them to engage in the process of informed
consent before any procedure in preparation for independent practice.
Anecdotal patient reports at a training
hospital in Jamaica suggested that patients
were becoming increasingly dissatisfied
with the informed consent process performed by surgical residents. Therefore,
we sought to document the views on the
process by performing a patient survey
to evaluate their views on the informed
consent process.
Methods
The University Hospital of the West
Indies in Mona, Jamaica, is a fully accredited training institution providing
postgraduate surgical education in the
Caribbean region.20,21 In this setting, any
patient requiring a surgical procedure was
admitted to the hospital and managed by
a surgical team. Each team was headed by
at least one attending/consultant surgeon,
who managed several surgical residents
at various stages in their training. A single
resident was given the responsibility to
secure informed consent from the patients before any operative procedure.
The decision to designate a resident to
this process was made by the attending/
consultant surgeon heading the respective
surgical team. Consultant supervision was
not routine during this process.
Approval was obtained from the hospital
ethics committee to interview patients for
this study without the knowledge of the
physicians obtaining informed consent.
We identified all consecutive adult patients
admitted by the surgical services over 5
weeks from October 3, 2011, to November
7, 2011. Any patient who required a surgical
procedure during hospitalization was considered a potential candidate for this study.
Patients were excluded from this study
if they were younger than age 16 years;
deemed incompetent to hold a rational conversation for whatever reason (eg, confused,
tracheal intubation with sedation); unable to
sign their own consent form for whatever
reason; or unwilling to participate in the
study. Patients younger than age 16 years
were excluded from this study as they were
younger than the age at which they could
legally give informed consent.
Any patient older than age 65 years was
considered “elderly” in keeping with the
definition proposed by the World Health
Organization. Any patient between age 16
and 65 years was considered a “younger”
patient. Permission to participate in this
study was sought from any patient who
met the inclusion criteria. Independent
investigators interviewed the candidates
using a standardized questionnaire that
sought information regarding patients’
level of satisfaction with the process of
informed consent and their perception
of disclosure on the need for operation,
details of the procedure, risks, complications, and benefits of the operation
(Postgraduate Surgical Training: Improving the Quality of the Process of Informed
Consent for Surgery in Training Hospitals
questionnaire available at: www.thepermanentejournal.org/files/Fall2013/AuthorQuestionnaire.pdf). Interviews were held
either on the third postoperative day or
on the day of discharge (whichever was
first) so the patients would be sufficiently
recovered to allow them to reflect on the
informed consent process in relation to
their hospital experiences.
In this study, we used Weiser’s22 standardized definition of major surgery that
included “any intervention occurring in a
hospital operating theatre involving the
incision, excision, manipulation, or suturing of tissue, usually requiring general/regional anaesthesia or profound sedation.”
This was a patient-based questionnaire
study. Therefore, information on the
individual physicians securing informed
consent (age, sex, level of training, etc)
was not recorded. Data from incomplete
questionnaires were not included in the final analysis. Data were analyzed using the
Statistical Package for the Social Sciences
(SPSS) version 12.0 (SPSS, Chicago, IL).
Results
During the study period,
… only 146
263 consecutive patients were
(70%)
of 210
admitted for a range of operapatients were
tive procedures. After excludgiven the option
ing 53 patients who met the
exclusion criteria, there were
to grant consent
210 patients interviewed,
by signing a
including 83 men (40%) and
consent form of
127 women (60%). A total
their own free
of 74 minor and 136 major
will and after all
operations were performed.
their questions
The questionnaires were
were answered.
completed fully by all the
patients interviewed.
All patients had informed consent taken
by surgical residents at different levels of
training. Patients were unaware of the
training status of the physician involved
with their presurgical informed consent
process 48% (101/210) of the time. As this
was a patient-based questionnaire study,
there was no accurate information on the
23
Table 1. Responses of patients who thought
an attempt was made at securing informed
consent (n = 191)
Information discussed during
informed consent
Details of the operation
Potential benefits of the surgery
Potential morbidity
Potential mortality
Predicted postoperative course
Projected recovery
Other treatment options
Patients who
agreed, no. (%)
141 (74)
138 (72)
160 (84)
47 (19)
93 (49)
50 (26)
63 (33)
age, sex, level of training, or identity of
the consent-seeking surgical residents.
Nineteen patients (9%) reported that
they were instructed to sign a consent form
without any discussion. The remaining
191 patients thought that an attempt was
made at securing their informed consent,
and their responses are shown in Table 1.
In addition to the 19 patients who were
instructed to sign a consent form without
any discussion whatsoever, an additional
45 patients reportedly were told that it was
mandatory for them to sign a consent document, although they still had unanswered
questions after what they considered inadequate discussion. At the termination of the
discussion, only 146 (70%) of 210 patients
were given the option to grant consent by
signing a consent form of their own free will
and after all their questions were answered.
In the overall group, 141 (67%) of 210
patients thought that the current practice of
securing informed consent was unsatisfactory and needed substantial improvement.
Subgroup analysis revealed that the level
of patient satisfaction with the process of
informed consent was greater in patients
having minor operations (97%; 72/74)
compared with major operations (91%;
124/136; p = 0.15); in men (95%; 79/83)
compared with women (92%; 117/127; p =
0.57); and in elderly patients (97%; 33/34)
compared with younger patients (93%;
163/176; p = 0.47). However, none of these
trends achieved statistical significance.
There was also no discernible relationship between patient satisfaction with the
informed consent process and individual
operative procedures.
Because this was a patient-based study,
we solicited recommendations from the
patients as stakeholders on methods to
improve the process of informed consent.
24
They volunteered the following recommendations: consent-seeking physicians
should deliberately solicit questions before
consent document is signed (37%); there
should be better attention to analgesia before the discussion (34%); patients should
be asked whether they wish to sign a consent document voluntarily (31%); and there
should be more detailed discussion before
the consent document is signed (52%).
More than 50% of the patients desired
better disclosure in the following areas: cost
of treatment in 3% of cases (n = 7); expected
postoperative recovery in 11% of cases (n =
24); success rates of intended treatment in
16% of cases (n = 33); operative risk in 34%
of cases (n = 72); details of the operation in
38% of cases (n = 79); and details about the
operating surgeons in 52% cases (n = 109).
Discussion
Most postgraduate training programs
mandate surgical residents to pass through
a series of clinical rotations in which they
actively participate in patient care. The
training program at the University Hospital of the West Indies is similar,21 in that
surgical residents are expected to secure
informed consent before each procedure
without specific training in this process.
The findings of this study suggest that
the current standard of informed consent in
this setting is unsatisfactory in 67% of cases.
We acknowledge that this finding is based
on the patient’s subjective recall of the consent process, which could be influenced by
several external factors. Nevertheless, we
believe that an unsatisfactory mark in 67%
of cases is indicative of a failing process
that requires urgent attention.
It is a common misconception that the
purpose of informed consent is to secure
the patient’s signature on a written consent form to act as security if the need
arises. This misconception may have been
the reason that 64 patients thought that
they were forced to sign a consent document without being allowed to ask questions. There is simply no excuse for the
fact that patients reportedly were denied
their autonomy 31% of the time. Surgical
residents must be reminded that the real
purpose of the informed consent process
is to provide the patient with meaningful
information to empower them to make
proper decisions. As such, the validity of
the informed consent process depends
more on the quality of clinician-patient
interaction than on documentation.4-6
We cannot comment on the overall
adequacy of disclosure since the study
included a heterogenous case mix and the
details for each individual procedure varied
widely (indications, expected benefits, morbidity, mortality, etc). However, the finding
that 52% of patients desired more detailed
disclosure before the consent document
was signed is instructive. In the end, the
patients are stakeholders in the process and
their recommendations on methods to improve the process should be taken seriously.
Fortuitously, the patients were able to
identify specific pitfalls in the process.
Although there may be inherent bias in
patient perceptions based on physicianpatient interaction, therapeutic outcomes,
and patient-related factors, we believe that
understanding patient perceptions and attitudes provided valuable insight to areas
that needed improvement.
More than 50% of patients (52%) suggested increased disclosure of details about
the operating surgeon. Several health professionals at our institution oppose this on the
basis that the Jamaican populace is generally
aware that the University Hospital of the West
Indies is a teaching hospital where patients
benefit by gaining access to highly trained
academic physicians, experimental therapies,
and cost subsidization.23 In turn, by virtue of
their attendance, patients are expected to facilitate medical education through “implied”
consent to treatment by surgical residents.24
On the other hand, it is our duty as
medical educators to uphold ethical principles.23 Regardless of their knowledge of
the background of the University Hospital
of the West Indies, patients do not waive
their right to autonomy when they enter a
teaching institution.25-28 In addition, several authorities have found that patients are
more accepting of residents’ involvement
if their autonomy is preserved through
the process of informed consent.28,29 Even
after patients are made aware of residents’
involvement, they usually remain willing
to allow residents to partake in their care
with appropriate supervision.30 Therefore,
we support the divulgence of surgeon details because we believe this is in keeping
with good ethico-legal practice governing
patient interaction during training.
The other patient suggestions of increased disclosure on the cost of treat-
ment, expected postoperative recovery,
success rates, operative risk and procedural details are reasonable. In fact, these are
legal requirements in Anglo-American law
and are fully supported by the Natanson,11
Canterbury,12 and Bolam15 precedents.
The study design did not allow us
to determine whether there were a few
individuals who repeatedly failed at the
consent process. Therefore, we did not
target specific physicians for remedial action. Nevertheless, we were able to take a
more general approach on the basis of our
results; we implemented specific changes
in our practice to improve the standard of
informed consent. They are described here.
Practice Changes
The five changes we implemented in
practice to improve informed consent
were as follows:
1.formal training on informed consent
2.introduction to the physician giving
consent
3.use of a consent checklist
4.implementation of a two-stage consent process
5.aids to improve understanding and
recall.
Formal Training
We introduced formal lectures on
informed consent into the training curriculum to expose surgical residents to the
nuances of the process. This should be
done in the first training year in the hope
that the surgical residents would become
proficient at an early stage.
Introduction to the
Physician Giving Consent
In this study, 48% of patients were
unaware of the training status of the physician who discussed informed consent with
them. This unfamiliarity is inappropriate
because this is the primary process that
secures the physician-patient relationship.
We currently train our surgical residents
that the first step during any consultation, inclusive of the process of informed
consent, should be a clear introduction.
Use of a Consent Checklist
To ensure that the relevant information
is relayed to the patients, we introduced a
checklist (see Sidebar: Standard objectives
of informed consent process). Anecdotal
experience with local culture has shown
that it is common practice for our patients
to “go along with” the medical team’s
suggestions because “they know best.”
Therefore, we make it a point to instruct
residents to avoid the temptation to truncate the process at this point and stress to
these patients that they must make their
own decisions after complete disclosure.
Implementation of a
Two-Stage Consent Process
We firmly believe that patients should
have sufficient time to process information
in a comfortable environment. Additionally,
there are existing data suggesting that 75%
of clinical negligence solicitors (attorneys)
believe that consent should be obtained
2 weeks before an elective procedure.17
Therefore, we now commence the process
in the outpatient clinic as a part of a 2-step
consent process, with the second step being
performed at the time of elective admission
for surgery. Whenever possible, Step 1 is
performed by the attending surgeon, and it
is stressed that it is an ongoing process that
continues and strengthens at every point of
physician-patient interaction.
Adequate disclosure requires the physician who is obtaining consent to have a
certain level of maturity. Obviously, the
physician must be sufficiently knowledgeable about the pathology and procedure
for proper disclosure. Several authors
suggest that only senior surgeons who
can perform the operation should take
consent.6,31 We believe that it is important for surgical residents to perform
this duty and learn this skill during their
training, although it is apparent that they
require increased supervision and focused training first. Therefore, whenever
possible, we now reserve the second
stage of the process for ward rounds
so that residents can take consent with
supervision by the attending surgeon.
Aids to Improve
Understanding and Recall
Several aids, including visual aids,
diagrams, videos, written/printed material, and the Internet, have been used to
increase patient understanding and recall.4,6,32 One advantage is that patients can
voluntarily access this information away
from the stressful hospital environment
in circumstances under their control.6,33
We now encourage the surgical residents
to use drawings and to document written
facts on a separate sheet of paper for the
patients to keep and to review on his/her
own time. Although this practice is encouraged, we remain cognizant that these
aids are meant to facilitate but not replace
physician-patient dialogue.
The final responsibility to uphold the
doctrine of informed consent is solely
that of the attending surgeons. As medical
educators, we must remember that we
are preparing our surgical residents for
independent practice in the community.
As such, we must ensure that they adhere
to ethical and legal guidelines when they
interact with patients.
Study Limitations
There were several limitations to this
study, some of which have been mentioned already. This study was a patientbased questionnaire study performed in
a single institution over a limited period.
Therefore, the results may not be extrapolated to other institutions.
Standard Objectives of informed Consent Process
1. Explain the nature of the illness in simple lay terms
2. Explain the reason for the proposed operation and the benefit it is intended to provide
3. Discuss any available alternative treatments and compare them with the treatment you are offering
4. Explain the details of the operative procedure (illustrations and diagrams are useful)
5. Discuss success and failure rates of the operation
6. Discuss the potential complications and risks of the operation and anesthesia
7. Discuss any possible residual effects of the treatment or anesthesia
8. Explain the anticipated in-hospital and long-term postoperative recovery period
9. Discuss the duration of hospitalization and any incapacitation that may result
10. Explain any other residual effects from the procedure
11. Explain the methods you intend to use to reduce unwanted side effects or complications in the postoperative hospitalization period
12. Encourage questions from the patient and relatives
13. Ask the patient to sign an informed consent form
14. Ask your witness to sign the informed consent form
25
Second, the study relies on subjective
data from patients on their perceptions
of the informed consent process. We are
cognizant that these impressions may
be affected by the in-hospital course,
presence of complications, interpersonal
relationships established with consentseeking physicians, and finances. In
retrospect, one method to strengthen the
study would have been to correlate our
results with these objective data.
Third, the study methods did not allow for accurate data collection on the
physicians seeking consent. It would
have been instructive to record the relationship between patients’ subjective
assessment of the informed consent process and the consent-seeking physcians’
level of training, sex, age, and ethnicity.
Another method to strengthen the study
could have been to analyze the results of
“secret shopper” surveys or observations
from health care workers who may have
witnessed the consent process.
Last, although independent interviewers were used to collect data, the face-toface interview method could have influenced patients’ responses. The interviews
were deliberately held on Day 3 or the
day of hospital discharge to allow patients
time to reflect on the consent process. Additionally, it was hoped that there would
have been sufficient recovery in the way
of pain control, mobilization, and return
of self-sufficiency to allow patients to
focus on the questions about the consent
process. On the other hand, longer intervals between the informed consent process and interviews could have clouded
patients’ recall of the process.
Conclusions
The current practice of informed
consent in this teaching-hospital setting
requires improvement to meet the ethical
and legal demands of modern medicine.
We have attempted to improve our practice by targeting education, increasing
supervision, and creating a checklist
for this process. A further study will be
performed with the recommendations in
effect to determine the improvement, if
any, provided by these interventions. v
The author(s) have no conflicts of interest
to disclose.
26
Acknowledgment
19.
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org/10.1097/00006534-199405000-00031
How Asking Patients a Simple Question Enhances Care at the Bedside: Medical Students as Agents of Quality Improvement
Hope Olivia Ward; Sarah Kibble; Gney Mehta; Marc Franklin; Joshua Kovoor; Aled Jones, BN (Hons), PhD;
Sukhmeet Panesar, BSc (Hons), MBBS; Andrew Carson-Stevens, MBBCh, MPhil
Perm J 2013 Fall;17(4):27-31
Abstract
Medical students have traditionally played a passive role in
the delivery of health care. The Institute for Healthcare Improvement Open School members and leaders initiated the Ask One
Question project in December 2011. Through a commitment to
the project, students are learning to assume a unique position
in health care settings, as both learners and caregivers. They
are improving care at the bedside by asking a simple question:
“How can I improve your stay today?” Using the Model for
Improvement to adapt the Ask One Question concept for local
use, medical students at Cardiff University (United Kingdom)
asked 120 patients. A content analysis of those responses identified 89 issues across 4 broad areas for improvement, including
communication issues (uncertainty about their care management
and desire for more time with their health care professional);
practical issues (assistance with tasks made difficult because of
ill health); wider organizational and National Health Services
requests; and medical needs (requiring medical or nursing
intervention). A medical student, a clinical colleague, or the
hospital organization could act on those issues. Actions ranged
from attending to simple tasks (eg, finding spectacles) or basic
care needs (eg, giving a drink) to suggestions requiring wider
institutional change. On a simple but effective level, Ask One
Question reflects good manners and is a demonstrable competency of patient-centered practice. It is a vehicle for enabling
students to seek improvements in health care and initiate relevant
actions to improve the patient experience at the bedside.
Introduction
Patients all too often feel ignored and report that their health
care has been fragmented and not holistic.1 The quality of patient
care has raised considerable political and public concern in the
UK,2 fueling efforts to achieve a patient-centered culture within
the National Health Services (NHS). The recent Francis Inquiry
in the UK revealed that patients and their caregivers were failed
at many levels and, among many recommendations, called for
better health care leadership and patient-centered care.3,4 These
are qualities that can be exhibited by medical students, who are
an untapped resource for improving health care quality.5
Medical students have more flexibility and time to spend
with patients than employed staff. However, medical students
in the UK typically interact with patients for learning purposes
only—for example, they obtain medical histories, perform physical examinations, and observe encounters between patients and
more senior health care staff—and often assume a passive role
in health care delivery and its improvement.6 Moreover, the effects of the “hidden curriculum,” defined as “a set of influences
that function at the level of organizational structure and culture,”
can shape the moral and ethical attitudes of medical students
during their professional training.7 As a result, students in the
early stage of their courses are reportedly more empathic and
patient-centered than those in the later stages of their training.6,8,9
The Institute for Healthcare Improvement (IHI) Open School
is an interdisciplinary community that has a mission to advance
health care improvement and patient safety competencies in
the next generation of health professionals.10 It encourages the
set-up of chapters where students, supported by faculty, engage
with each other about issues related to quality improvement in
health care. The Ask One Question project was initiated by IHI
Open School members and leaders in December 2011, challenging students to ask patients, “What can I do to improve your
stay?” Pilot work undertaken by early adopters of the project in
Denmark, Wales, and the US suggests the majority of patients
responded to this question with basic care requests, for example
hydration, nutrition, and comfort.11,12
This article describes work undertaken by medical students at
the IHI Open School chapter at the School of Medicine at Cardiff
University in Wales, UK, who sought to adapt and develop the
Ask One Question concept and identify opportunities for medical students to make active contributions to health care delivery
and its improvement.
Methods
The concept of Ask One Question is simple—ask all patients,
“What can I do to improve your stay?” Using the Model for Improvement,13 a series of small tests of change were undertaken between
October 1, 2012 and December 1, 2012, to adapt the concept in
terms of content (ie, identify the most appropriate question) and
execution (ie, identify how and in what situations students can ask
Hope Olivia Ward is a Third-Year Clinical Medical Student at Cardiff University in Wales, United Kingdom. E-mail: WardHO@cardiff.ac.uk. Sarah Kibble
is a Third-Year Clinical Medical Student at Cardiff University in Wales, United Kingdom. E-mail: KibbleSL@cardiff.ac.uk. Gney Mehta is a Third-Year
Clinical Medical Student at Cardiff University in Wales, United Kingdom. E-mail: MehtaGV@cardiff.ac.uk. Marc Franklin is a Third-Year Clinical Medical
Student at Cardiff University in Wales, United Kingdom. E-mail: franklinM1@cardiff.ac.uk. Joshua Kovoor is a Third-Year Clinical Medical Student at
Cardiff University in Wales, United Kingdom. E-mail: KovoorJ@cardiff.ac.uk. Aled Jones, BN (Hons), PhD, is a Senior Lecturer at the School of Nursing
and Midwifery Studies in the College of Biomedical and Life Sciences at Cardiff University in Wales, United Kingdom. E-mail: JonesA97@cardiff.ac.uk.
Sukhmeet Panesar, BSc (Hons), MBBS, is an Honorary Fellow at the Centre for Population Health Sciences at the University of Edinburgh in Scotland,
United Kingdom. E-mail: sukhmeet.panesar@surgicalmatrix.com. Andrew Carson-Stevens, MBBCh, MPhil, is a Clinical Lecturer in Health Care
Improvement at the Cochrane Institute for Primary Care and Public Health at Cardiff University in Wales, United Kingdom. E-mail: andypcs@gmail.com.
27
the question). Five clinical medical students (HW, SK, GM, MF,
JK) from Cardiff University participated in the project.
Students approached inpatients for different clinical specialties
including general medicine, trauma and orthopedics, and general
surgery. Students typically seek guidance from senior clinical
staff to identify suitable patients for them to work with before
obtaining histories and performing physical examinations. Patients
participated if they agreed to be involved in student learning. At
baseline for the first test of change, students asked the question
(“What can I do to improve your stay?”) at the end of their interaction with the patient. Each student collected the following data:
the patient’s gender, specialty of his/her responsible clinician,
time of day (morning, afternoon, evening), the patient’s response,
and the actions they undertook for the patient. No confidential or
patient-identifying data were recorded, in line with local clinical
governance arrangements. Table 1 summarizes key moments from
the iterative trial and learning Plan-Do-Study-Act cycles. Team
reflection (by all coauthors) informed this process.
With support from faculty advisors (AJ, ACS), approval to
undertake this work was sought and granted from the Dean
of Medical Education and hospital executives at a local health
board, as well as from managers on wards where the project
was undertaken. Students with limited clinical experience reported difficulty determining when it was appropriate to act
on patients’ wishes. For this reason, all students participating
in the Ask One Question project were encouraged to liaise with
the appropriate nursing or medical staff to assess whether an
intervention was appropriate.
Outcome measures for the project were the number of patients
assisted, responses by patients, and actions undertaken by students. ACS and SSP undertook a content analysis of responses
by independently coding them and developing a coding framework based on a random sample of the free text in the “patient
response” and “action by student” fields. The coding framework
was applied to all reports with strong agreement between the
2 reviewers (observed kappa statistic = 0.92, 95% confidence
interval = 0.87-0.97). Discrepancies in coding were resolved
through wider team discussion with HW and SK.
Results
Over the course of this short pilot project, a total of 120
patients (72 men and 48 women) were assisted: 82 requested
the students’ help for a total of 89 issues; 38 patients made no
requests. The issues identified fell into 4 broad categories:
• communication issues (n = 40): a spectrum of communication
problems resulting in uncertainty in terms of discharge date
and details about care management and prescribed medicines,
as well as requests for more time with health care professionals (physicians and nurses) and family
• practical issues (n = 32): minor requests for assistance with a
task made difficult because of ill health
• wider organizational and NHS requests (n = 10): concerns
and ideas relevant for feedback to the wider organization
• medical needs (n = 7): symptomatic relief or management
that required medical or nursing intervention.
An overview of patients by gender and clinical specialty
are summarized in Table 2. The issues highlighted by patients
are further broken down by category and subcategory, with
examples, in Table 3.
Students or other staff fulfilled 61 of the 82 requests from
patients. Of those requests, 27 were fulfilled by medical students
acting independently, 15 by medical students acting with ad-
Table 1. Plan-Do-Study-Act cycles
Learning from
previous cycles
Cycle 1
Pilot work led by early
adopter sites asked, “What
can I do to improve your
stay?”
Cycle 2
Patients appeared confused
about why we were asking
about improving their care.
Cycle 3
Establish a trusting rapport
with patients before asking
the question.
Cycle 4
Giving feedback to clinical
teams.
28
Plan
Do
Study
Act
Determine the relevance
of the question for
patients in Wales.
Ask ten patients the
original question.
Many patients had no request and
seemed to not want to burden us with
their requests.
Patients also appeared confused about
why we were asking the question.
Modified question to “If
there were one thing I
could do to improve your
stay, what would it be?”
Introduce the Ask One
Question campaign to
patients and ask for their
help.
Briefly talk about
the purpose of
the study with ten
patients.
The focus shifted to the patient helping
us; time spent talking about the project
allowed a rapport to be developed,
which resulted in longer conversations
about their stay and more specific
responses to the question.
Continued to share details
of the Ask One Question
campaign with patients,
thus building rapport with
patients.
Determine the most
appropriate time to ask
the question.
Ask the question
before, during, and
after history taking.
The best time was immediately
following history taking or physical
examination.
Propose that future
students ask patients at
the end of the consultation.
Refer patients’
responses to appropriate
staff when necessary
and collate results to see
common requests.
Give feedback to
different members
of the clinical team.
Ward staff were unsure about what we
were doing.
Introduce the Ask One
Question campaign to
ward staff before talking to
patients.
Table 2. Overview of patients by gender and clinical
specialty
Characteristic
General medicine
Trauma and orthopedics
General surgery
Total
Men
55
3
14
72
Women
36
1
11
48
Total
91
4
25
120
vice or assistance from professional health care staff, and 19 by
other staff members without student involvement. Twenty-one
requests were not able to be immediately fulfilled at the bedside
(Table 4). We estimate the time taken to fulfill each task ranges
from seconds to minutes (certainly no longer than 5 minutes),
depending on the complexity of the request.
Discussion
Key Findings
Through asking and reporting responses to a simple question—“What can I do to improve your stay?”—we demonstrated
that medical students can make small improvements in patients’
experiences of hospital-based care. The contribution made by
participating students contrasts with the traditionally passive role
of medical students in the clinical environment, which is largely
focused on students’ meeting prescribed learning objectives
rather than making contributions to patient care.
We have also demonstrated that to ask one question is appropriate at the end of a clinical encounter such as history taking
or physical examination. Learning generated by successive small
tests of change indicated patients were more likely to request
assistance if the student first explained the purpose of Ask One
Question. Hesitation and uncertainty about accepting the initial
offer of assistance is a possible indicator that patients do not
normally receive such offers from medical students.
Communication issues concerning physicians and nurses,
such as the patient not understanding their medical conditions
or plans for discharge, were most commonly discussed. The
remainder of patient requests largely involved seeking assistance
with practical and medical issues. In cases where the student did
not feel competent to manage requests directly, it was possible
to relay the information to junior physicians (residents) or nurses
and to ensure a discussion took place to address the necessary
issues. Issues that were beyond the immediate responsibility of
the clinical team, eg, noisy bins and doors and lack of Wi-Fi,
were reported back to the Director of Patient Experience at the
health board. This feedback is currently being used in conjunction with patient satisfaction surveys and other sources to direct
future interventions by the health board.
Practicalities and Opportunities for Improvement
This project highlighted that the Ask One Question approach
varied with the severity of the patient’s illness and the patient’s
previous relationship with the student (eg, several previous encounters or none). Although Ask One Question provided a means
for identifying immediate opportunities to improve the patients’
experiences at the bedside, it also gave rise to an opportunity to
have a more in-depth conversation with them about their clinical
care experiences and opportunities to improve on this.
For the preliminary testing of this concept, student participants
were largely directed to patients for learning purposes by their
senior clinical colleagues. Unfortunately this sample did not include patients who were acutely ill or those with communication
Table 3. Patients’ requests by category
Category
Communication issues
(n = 40)
Practical issues
(n = 32)
Wider NHS and
organizational requests
(n = 10)
Medical needs
(n = 7)
Subcategory
More time with health care professional
Care management uncertainty
Discharge uncertainty
More family contact
Medication uncertainty
Support and reassurance
Comfort
Request for item
Hydration
Noise
Nutrition
Noise
Recreation
Complaint
Comfort
Hygiene
Request for item/logistics
Request for medical assistance
Care management uncertainty
No request (n = 38)
Example
“The doctors should come around more often.”
“I didn’t understand what the doctors said on the ward rounds.”
“When am I going home?”
“I would like to see my family more.”
“Am I meant to be on this warfarin when I go home?”
“Can you hold my hand during this test?”
Move table closer to patient.
“Can you get my phone out of the bag?”
Refill water jug.
Turn TV volume down.
“All my meals are cold!”
Doors bang at night.
Access to Wi-Fi.
“It takes staff too long to respond to patients.”
More comfortable bed.
“The toilets here are in bad condition.”
Pass a sick bowl.
New onset of pain.
“I think this bandage was meant to come off this morning.”
n
10
10
8
5
4
3
13
9
8
2
2
2
2
2
1
1
4
2
1
38
NHS = National Health Services.
29
Table 4. Responsibility taken for actions informed by patients’ requests
Actions
Achieved by student
Achieved by student with advice or
assistance from medical and nursing staff
Achieved by other members of staff
Not fulfilled
Description of actions
Passing items to patients, conversing with patients during procedures to distract them,
turning on lights.
Students often needed assistance with tasks such as locating items (eg, extra pillows
and blankets) and finding family members on the ward.
Patients wanted to speak to the physician about their medications, discharge plan, or
investigations. Students were able to alert physicians to patients’ requests and facilitate
discussions on ward rounds.
“My meals are cold when they get to me.” “I wish there was Wi-Fi in the hospital.” “The
bin is noisy and keeps me awake at night.” These requests were discussed with the
Director of Patient Experience.
No request
barriers. Further work is currently underway between stroke
survivors and IHI Open School chapter members in Cardiff to
identify generic opportunities to improve the care experience
of those enduring communication difficulties.
Relationship with the Literature
Ask One Question brings medical students and patients together as partners to achieve patient-centered care at the bedside.
In recent years, the Picker Institute has pioneered the concept
of patient-centered care that is associated with improved health
status, defined as “understanding and respecting patients’ values,
preferences and expressed needs.”14,15
The demands on health care professionals inherent within busy
health care systems can sometimes be a barrier for providing care
with empathy.16 Medical students are in the privileged position of
being able to spend more time with patients, and the students’
emotional skill set must be nurtured.17 Ask One Question has the
potential to encourage rapport with patients and shift emphasis
from administering care to a patient to building a relationship
with a person. The emphasis on “persons” rather than “patients”
is firmly in keeping with the professional duties and values
of modern physicians, who should aim to respect patients as
individuals.18 Including Ask One Question as part of early professionalism training at health care schools could assist
students to focus on delivering patient-centered care
Ask One Question
beginning early in their careers.
has the potential
Medical students traditionally take on a passive
to encourage
role in the hospital, with an emphasis on learning
rapport with
rather than getting involved in patient care. It is
patients and shift
recognized that in the later years of professional
preparation contact with patients is essential for
emphasis from
recognizing patterns of presenting complaints,
administering
acknowledging the clinical relevance of basic
care to a patient
sciences, and improving professional and comto building a
munication skills.19 In traditional curricula, senior
relationship with a
physicians have used patients solely as “teaching
person.
material”20; however patients also have a role as
teachers themselves. Many patients are experts in
their own condition and have personal narratives about their
health care experiences.19 If patients are used as teachers of
medical students in their own right, it stands that students
should develop patient-centered attitudes as a benefit of the
30
n
27
15
19
21
38
relationship. Ask One Question extends the relationship with the
patient by offering a two-way relationship, where the student
not only learns from patients but also offers to help alleviate
issues that trouble them at the bedside. By collating and aggregating individual answers, students can assist hospitals to
gain invaluable information about opportunities to improve
the patient experience.
Ask One Question serves as a commitment to the improvement philosophy that everyone in health care has two jobs
when they go to work every day—to do their work and to
improve it.21 In 2009, the Check a Box. Save a Life. campaign
motivated thousands of students to raise awareness and
lead efforts to implement the World Health Organization
Surgical Safety Checklist at their places of work and study.5
Medical students are an undervalued resource in health care
organizations, and when educational providers such as the
IHI Open School provide medical students with the skills
and knowledge to lead improvement, they can lead change
in health care.10,22,23
Implications for Practice, Policy, and Education
and Further Work Needed
Asking patients “What can I do to improve your stay?” is good
manners and requires no additional professional training or funding. Educators might wish to consider this a demonstrable competency of professional etiquette with patients during examinations.
Although assessment drives learning in modern practice, medical
schools should advocate the integration of this practice into students’ professional encounters with patients and seek methods to
evaluate whether this is being done reliably with every patient.
The top five actions that all medical students can routinely
consider to assist patients at their bedside are to: 1) ensure
patients have water; 2) ensure table and its contents are within
reach; 3) ensure they are warm; 4) open curtains after closing
them; and 5) adjust the bed safely, as needed. As Ask One Question continues to spread across the globe, it will be interesting
to pool the learning and empirically expand this list of actions
that all health care students can use to improve the patient
experience at the bedside.
Ask One Question can be a vehicle for identifying existing
excellence in care as well as for identifying opportunities to
improve care. Further work should consider how health care
schools could reinforce the professional benefits from Ask One
Question and how health care organizations can systematize
this practice among their workforce, regardless of discipline or
position, at every patient encounter, every time.
Conclusion
Medical students bring a fresh pair of eyes to the health care
system where qualified professionals might accept problems as
the norm. Ask One Question is a vehicle for enabling students
to seek improvements and initiate relevant actions to improve
the patient experience of health care at the bedside. Ask One
Question is an opportunity for educators to champion and ensure demonstrable competencies of patient-centered practice are
present among tomorrow’s health care professionals. v
Acknowledgments
The authors thank Vignesh Rajasundaram for assisting in data collection.
Leslie Parker, ELS, provided editorial assistance.
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Am J Med Qual 2009 Sep-Oct;24(5):447-8. DOI: http://dx.doi.
org/10.1177/1062860609343389
More About Love
I think health care is more about love than about most other things. If there isn’t at the core
of this two human beings who have agreed to be in a relationship where one is trying to help
relieve the suffering of another, which is love, you can’t get to the right answer here.
— Donald Berwick, MD, b 1946, former Administrator of the Centers for Medicare and Medicaid Services and former President and Chief Executive Officer of the Institute for Healthcare Improvement.
31
credits available for this article — see page 96.
Special Report
Making Hospitals Safer for Older Adults: Updating Quality Metrics by Understanding Hospital-Acquired Delirium and Its Link to Falls
Eric A Lee, MD; Nancy E Gibbs, MD; Linda Fahey, RN, NP, MSN; Teri L Whiffen, RN, BSN, MHA
Perm J 2013 Fall;17(4):32-36
Abstract
The medical care of hospitalized geriatric patients must differ from the care of younger
adults. Because of reduced “reserve capacity,” hospitalized older adults are at high risk
of development of geriatric syndromes such as delirium and falls. Geriatric syndromes
often lead to functional decline and dependence. Patients who experience geriatric
syndromes in the hospital are more likely to have a longer length of stay, higher risk of
readmissions, and worse medical outcomes. Incident delirium in hospitalized geriatric
patients has been shown to be preventable by intervening in established risk factors.
Prevention of hospital-related falls has not been consistently demonstrated. Analysis from
Kaiser Permanente data demonstrated a correlation with delirium and hospital-related
falls. We propose that age-specific quality metrics should be made to reduce the risk
of the development of geriatric syndromes in hospitalized older adults. By preventing
delirium, we believe that health care practitioners can reduce hospital-related falls in
geriatric patients and improve the quality of care delivered to hospitalized older adults.
An illustrative fictional case study is presented.
Case Study
A man, age 75 years, was admitted to the
hospital after a 1-week history of increasing
dyspnea. Before admission, the patient was
receiving no medications and had no clinically significant medical history. He did not
drink alcohol or have a history of tobacco
use. He was still employed and walked up
to 3.2 km (2 mi) daily without difficulty. In
the Emergency Department (ED), the patient
received a diagnosis of congestive heart
failure. After an indwelling urinary catheter
was placed, diuresis was initiated in the ED.
At hospital admission, furosemide
therapy was continued for diuresis.
Lisinopril treatment was started because
of systolic dysfunction, omeprazole was
added for routine stress ulcer prophylaxis,
and temazepam was ordered as needed for
relief of insomnia. For patient comfort and
convenience, the patient rested in bed during the first 48 hours, and the indwelling
urinary catheter was left in place. On hospital Day 3, his anticipated day of discharge,
the patient experienced sudden confusion.
In his agitated state, the patient got out of
bed and fell. His radiographs showed no
evidence of fracture. A workup for delirium
revealed pyuria, and a ceftriaxone regimen
was begun. Cultures later showed growth
of Escherichia coli in the blood and urine.
On Day 6 of hospitalization, Clostridium difficile diarrhea developed and the
patient was treated with metronidazole.
The patient was sent to a skilled nursing
facility on Day 9, where he remained for
60 days. He was forced to retire from work
because of continued impaired cognition
and reduced physical stamina.
Alternative with
Updated Quality Metrics
If quality metrics had been updated to
meet age-specific concerns, this case scenario would have had different treatments
and outcomes. The indwelling urinary
catheter would not have been inserted
for comfort and convenience, the patient
would have been mobilized at admission
to the ED and hospital, and omeprazole
and temazepam would not have been
prescribed. Subsequently, bacteremia and
C difficile colitis would likely have been
avoided, and the patient would probably
have been able to continue working.
The Aging Population and
the Aging Medical Paradigm
The first cohort of baby boomers officially became “seniors” in 2011. The fastest
growing segment of our patient population
is people over the age of 85 years. Geriatric
patients are more likely to have substantial
renal and hepatic insufficiency, reduced
cardiac output, increased body fat, and
reduced lean body mass compared with
those younger than age 65 years. Because
of these physiologic changes, hospitalized older adults adapt to environmental
and internal insults differently from their
younger counterparts. The manifestation of
reduced reserve capacity in older adults is
a geriatric syndrome, which often portends
increased health care utilization and functional dependency on others. Hospitalized
older adults are most vulnerable to the
development of geriatric syndromes.
Incident (hospital-acquired) delirium
is common in older adults, occurring in
nearly one-sixth of all older adults hospitalized for medical reasons.1 Risk factors for
incident delirium are shown in Table 1.
Hospital-acquired delirium is associated
with increased length of stay and risk of
unplanned readmission.2,3 Four percent of
all symptoms of delirium resolve at the
time of hospital discharge.4 Only 18% of
patients have all symptoms of delirium
resolve 6 months after hospital discharge.4
Historically, delirium was once considered
a self-limiting occurrence. However, there
is more evidence that delirium is indeed
Eric A Lee, MD, is the Assistant Chief of Internal Medicine at the West Los Angeles Medical Center and former Chair of the Southern California
Permanente Medical Group Geriatric Hospital Safety Committee in Los Angeles. E-mail: eric.a.lee@kp.org. Nancy E Gibbs, MD, is the Regional
Coordinating Chair for Geriatrics and Continuing Care for Kaiser Permanente Southern California in Pasadena. E-mail: nancy.e.gibbs@kp.org.
Linda Fahey, RN, NP, MSN, is the Regional Director of Quality and Patient Safety for Patient Care Services for Kaiser Permanente Southern
California in Pasadena. E-mail: linda.x.fahey@kp.org. Teri L Whiffen, RN, BSN, MHA, is a Quality and Patient Safety Consultant for Patient
Care Services for Kaiser Permanente Southern California in Pasadena. E-mail: teri.l.whiffen@kp.org.
32
more insidious. Dementia, with inexorable
cognitive decline, may be a sequela of
delirium.5 Eventual return to the patient’s
predelirium cognitive status should no
longer be assumed.
Falls in the community also occur frequently in older adults. Thirty percent of
community-dwelling adults over age 65
years of age fall, and 50% of communitydwelling adults over age 80 years fall, many
repeatedly.6 Of all falls that occur in the
community, 10% lead to a major injury,
including fractures, soft-tissue injury, and
subdural hematomas.7 The psychological
consequences of falls are dramatic; there is
a 20% to 55% prevalence rate of fear of falls
in community-dwelling older adults, and
the prevalence is higher in those who have
already experienced a fall.8 Not surprisingly, the attributable risk of a fall leading
to nursing home placement is 10%.9
The Centers for Medicare & Medicaid
Services designated that falls occurring
during hospitalization are a “never event.”10
However, in contrast to falls in the community, the epidemiology and risk factors
for this never event are incompletely
characterized in the literature. To comply
with the Centers for Medicare & Medicaid
mandate to prevent falls during hospitalization of an older adult, the risk factors must
be clearly defined. One reasoned approach
to preventing falls in the hospital is to apply
our knowledge of preventing falls in the
community (risk factors shown in Table 1).
Geriatric syndromes should not be
considered inevitable events. Inouye et
al1 demonstrated that incident delirium in
older adults hospitalized for medical reasons could be decreased by 50% through
a multiple risk factor reduction approach.
Tinetti and colleagues6 demonstrated that
30% of falls in older adults living in the
community also could be lowered by
reducing multiple risk factors.
At our institution, 40% of all hospitalized
patients are older than 65 years. Complications caused by geriatric syndromes
lead to increased length of stay and
number of readmissions.3 The medical
paradigm—treating the disease leading
to hospitalization in isolation—must be
retired. Hospital care of the geriatric patient must be viewed comprehensively,
combining our medical paradigm with the
additional focus on preventing iatrogenically acquired geriatric syndromes.
This idea has been proposed since
1995, when Landefeld et al11 published
their landmark findings of the Acute Care
for Elders Unit. Older patients hospitalized
in this special unit were, compared with
controls, more likely to have improved
function, less likely to have worse function,
and less likely to be sent to a nursing home
after hospital discharge. To our knowledge, there are only two comprehensive
approaches to maintain or to improve
the functional status of hospitalized older
adults, including the Acute Care for Elders Unit and delirium prevention. Given
similarities in both interventions, the Acute
Care for Elders Unit and delirium prevention have been combined in at least one
community health care system.12
Preventing delirium can improve function and thereby make hospitals safer for
older adults through improved age-specific
care. This is a seemingly simple task since
delirium and falls share many of the same
risk factors (Table 1). In 1995, Tinetti
et al13 demonstrated that two common
ambulatory geriatric syndromes (falls and
incontinence) shared similar risk factors
and proposed that we should unify our
approach to geriatric syndromes. If we
intervened on risk factors for one geriatric
syndrome, we could prevent the occurrence of another geriatric syndrome. Indeed, delirium prevention has been shown
to prevent falls in the hospital.14
Applicability of The Joint
Commission Quality Metrics in
the Hospitalized Older Adult
The Joint Commission Accountability
Measures of 2011 are based on the classic medical paradigm for patients of all
ages hospitalized for medical reasons.
Of these possible 25 metrics (in the areas
of heart attack care, heart failure care,
pneumonia care, venous thromboembolism prophylaxis, and stroke care),
only 1 metric addresses the prevention
of functional decline (stroke care—assessed for rehabilitation).15 The emphasis
on ß-blocker use (myocardial infarction
care) is certainly an important metric of
quality. However, what impact will an
angiotensin-converting enzyme inhibitor/
angiotensin receptor blocker have in a
95 year old with new-onset heart failure
due to systolic dysfunction and with no
hypertension?
Similarly, the accountability metrics
for pneumonia 16,17 (antibiotic selection, blood culture attainment before
antibioitic administration) are actively
ordered and routinely performed by
seasoned hospital-based physicians.
However, they fail to redirect attention to
ameliorate physical function that would
improve outcomes in older adults, yet
are often neglected by the physician. Are
these quality metrics the most important
considerations in older adults at high
risk of functional dependence caused by
hospitalization?
These quality metrics should be culled
by accrediting commissions carefully.
Putting focus on the medical paradigm
without consideration of functional outcomes has substantial opportunity cost,
with the vulnerable older adult population most at risk. Hospital physicians and
leaders must assume that all older adults
are at high risk of geriatric syndromes,
and they should proactively focus on
preventing them from occurring. By
modifying quality metrics to address the
needs of our aging population, we can
make hospitals safer for older adults.
Proposed Age-Specific Quality
Metrics for Older Adults
The authors propose better agespecific care by revising quality metrics
that address functional outcomes of
hospitalized medical patients. These
quality metrics should be modeled to
target risk factors for incident delirium
and falls. In addition, these three additional quality metrics satisfy the four
Table 1. Risk factors for incident delirium during
hospitalization and falls in the community
Risk factor
Restraints (immobility)
Urinary catheter
Malnutrition
Polypharmacy
(> 3 medications added)
High-risk medications
Iatrogenic event
Use of sedative-hypnotics
Cognitive impairment
Lower extremity weakness
Gait and balance disorders
Acute illness
Delirium in
hospital
X
X
X
X
Falls in
community
X
X
X
X
X
X
X
X
X
X
X
X
33
accountability criteria for processes of
care as cited by the custodians of The
Joint Commission.16 We proposed quality
metrics for older patients as shown in the
Sidebar: Proposed age-specific quality
metrics for older adults.
Preventing Deconditioning/
Improving Mobility
More than 80% of the time (nearly
20 hours per day) during hospitalization is spent in bed. Only 4% of the
time (less than 1 hour per day) during
hospitalization is spent standing or walking.18 Length of stay has been shown to
improve with early and progressive mobilization.19,20 Poor mobilization during
hospitalization is associated with poor
functional outcomes in older adults. Immobility is an established risk factor for
delirium, and lower extremity weakness
is an established risk factor for falls in
the community.6 Concerted efforts to mobilize older adult patients must be made
even though they are fatigued because of
an acute illness. Improved mobility must
start from the time the patient arrives
in the ED, at minimum by encouraging
the use of a bedside commode or assisting the patient to the bathroom (rather
than giving a bedpan or urinal). Nursing administration must recognize that
mobilization of older patients is of equal
importance to medication administration
and grooming.
Preventing Catheter-Related
Urinary Infections
The indwelling urinary catheter can be
considered a one-point restraint and hinders
free mobility.21 Up to 40% of the time, the
presence of an indwelling urinary catheter
goes unrecognized by the hospital physician.22 The rate of bacterial colonization is
5% per day in a patient with an indwelling urinary catheter, and 4% of all Foley
catheter-related urinary tract infections can
lead to bacteremia.23 Up to 1.4% of all
indwelling urinary catheters placed in the
ED, operating room, or hospital wards may
lead to a traumatic urethral injury.24 Unlike
other minor procedures that commonly
lead to adverse outcomes, the insertion
of an indwelling urinary catheter does not
require informed consent. Consequently, its
indications are often not known by ED or
hospital physicians. The indications for an
indwelling urinary catheter are as follows:25
• Acute urinary retention or obstruction
• Incontinence in a patient at the end of
life for comfort or with a perineal wound
• Critical monitoring of the fluid input
and output in the care of the incontinent patient
• Perioperative setting.
If an indwelling urinary catheter is
placed, an attempt to remove it should
be made as soon as possible because of
the patient’s risk of reduced mobility and
increased risk of catheter-related urinary
infections.
Proposed Age-Specific Quality Metrics for Older Adults
1. Prevent deconditioning/improve mobility in previously ambulating patients
a. Establish patient’s functional status
i. one month before admission
ii.at hospital admission
iii.at discharge
b.Define processes to improve physical function
i. percentage of time patient is out of bed for meals and while awake
ii.percentage of time patient has a physical therapy evaluation and continued physical therapy care
iii.percentage of time patient demonstrates increase in ambulation (time and distance) within 48, 72,
and 96 hours of admission
2. Prevent catheter-related urinary tract infections
a. percentage of time patient has a urinary catheter with an approved indication
b. percentage of time patient without an approved indication has urinary catheter removed within 36 hours of insertion
3. Prevent adverse drug events by minimizing polypharmacy
a. percentage of time patients received an anticholinergic agent from the following classes:
i.antispasmodic gastrointestinal agents
ii.skeletal muscle relaxants (with the exception of carisoprodol [Soma] because of risk of withdrawal)
iii.H1 antihistamine (unless used for prevention or treatment of an allergic reaction)
iv.tricyclic antidepressants (unless used for treatment of depression)
b. percentage of time patient received a proton pump inhibitor without an approved indication
c. percentage of time patient received a benzodiazepine or nonbenzodiazepine hypnotic
34
Preventing Adverse Drug Events
by Minimizing Polypharmacy
The indications for all medications
should be scrutinized during hospitalization. When a clinician prescribes a new
medication during the hospitalization of
an older adult, the safest option should
always be chosen and the number of new
medications initiated should be minimized
because the substrate of the hospitalized
older adult is different.26 Hospital-based
physicians should feel comfortable stopping outpatient medication regimens.
Indeed, the chance of an adverse drug
event during the hospitalization of an
older adult taking 8 or more medications
is greater than 85%.27 Medications can be
safely stopped in older adults, with improved functional outcomes in the outpatient setting.28 Reduction in polypharmacy
should target three classes of medications:
anticholinergics, proton pump inhibitors
(PPIs), and benzodiazepine and nonbenzodiazepine hypnotics.
Anticholinergic Agents
The use of anticholinergic agents is a
known risk factor for delirium and falls in
the community. Reports have been published that up to 27% of all communitydwelling older adults use medications
with some anticholinergic activity.29 Alzheimer disease is thought to be partially
caused by a cholinergic deficiency and
hence the use of anticholinergic agents
can deteriorate cognitive function in patients with dementia. The use of anticholinergics is an established risk factor for
delirium.30 In addition, because anticholinergics may lead to symptomatic orthostatic
hypotension, they are a risk factor for falls
in the hospital. The use of medications
with some anticholinergic activity may
be unavoidable (ie, furosemide, atenolol,
nifedipine). However, many commonly
used anticholinergics have minimal to no
demonstrable efficacy (skeletal muscle
relaxants such as cyclobenzaprine and
antispasmodic gastrointestinal agents
such as dicyclomine), whereas others
have safer alternatives (H1 blockers such
as diphenhydramine and hydroxyzine).
Finally, tertiary tricyclic agents are often
used for off-label purposes (tertiary tricyclic antidepressants such as amitriptyline
and imipramine) to treat neuropathy and
insomnia and should be discontinued
during hospitalization.
Proton Pump Inhibitors
Stress ulcer prophylaxis is overused
in the hospital setting. The indications
for stress ulcer prophylaxis are limited to
critically ill patients only.31 Unfortunately,
hospital-based physicians now prescribe
PPIs in the noncritical hospitalized patient
without indication. The number needed
to harm is 111 for a hospital-acquired
pneumonia.32 The number needed to
harm is 533 for C difficile diarrhea.33 The
number needed to prevent a stress ulcer
in a noncritical hospitalized patient is 730
for any acid suppression medication.34 In
older adults, the broad indications for PPIs
may include the following:35
• Patients on mechanical ventilation
therapy
• Patients hospitalized in the intensive
care unit with a coagulopathy
• Treatment of proven or suspected upper gastrointestinal bleeding
• Continuation of treatment of a recently
diagnosed peptic or duodenal ulcer
• Treatment of a preexisting esophagitis
or esophageal stricture
• Use of aspirin or other nonsteroidal
anti-inflammatory drug during hospitalization.
Benzodiazepine and
Nonbenzodiazepine Hypnotics
The use of sedative-hypnotics are a classic risk factor for falls in the community and
hospital-acquired delirium. A nonpharmacologic sleep protocol consisting of relaxing
music, a back rub, and a warm drink was
shown to reduce the rate of sedativehypnotic use from 54% to 31%.36 Benzodiazepine use has been demonstrated to
increase length of stay. Previously thought
to be safe, Z class nonbenzodiazepines
have been recently targeted as a high-risk
medication as well,37 with evidence that they
increase risk of injurious falls and confusion.
In hospitalized patients, zolpidem use has
been shown to be a risk factor for falls in
the hospital. The authors concluded that 55
inpatients administered zolpidem might lead
to 1 additional fall.38
Application of Approaches:
Putting Medical Knowledge
into Clinical Practice
On the basis of internal interregional
data review that showed a clear association between hospital-related falls and
delirium, Kaiser Permanente (KP) Southern
California (KPSC) Region’s Falls Prevention
Team targeted the prevention of delirium
as an additional area of its focus. Delirium
prevention principles were incorporated
into education about falls and interventions
used by a multidisciplinary team, which
included nurses, nursing assistants, physical therapists, pharmacists, and physicians.
The Confusion Assessment Method
tool39 is being used to screen for delirium
in KPSC intensive care units. Currently,
hospital units from two medical centers
are testing the effectiveness of early identification of delirium by using the Confusion Assessment Method tool in medicalsurgical units. KPSC has made a concerted
effort to reduce outpatient prescribing of
anticholinergic agents in older adults for
the past three years, reducing the number of high-risk medications prescribed
on an ambulatory basis that might have
been otherwise unnecessarily continued
in the hospital setting. Through physician
education, partnership with patient and
family members on the dangers of sedativehypnotics, and the use of hospital admission order sets that exclude their use in
older adults, the attempt to systematically
reduce the use of benzodiazepines and Z
class nonbenzodiazepines has been made.
For 2013, minimizing the prescriptions for
sedative-hypnotic drugs in the ambulatory
setting for older adults has been made into
a major quality initiative throughout the
Southern California Permanente Medical
Group, likely reducing the chance that
such medications are prescribed at hospital
admission. In addition, the potentially inappropriate use of PPIs in the hospital setting
is being scrutinized in different KPSC Medical Centers, with pharmacists contacting
hospital-based physicians about potentially
inappropriate use. In all Medical Centers,
the multidisciplinary team has partnered
with family members to individualize care
that would optimize mobility for hospitalized older adults.
A pilot program using pedometers has
begun at the KP Fontana Medical Center in
Fontana, CA, to increase early and cumulative ambulation during hospitalization.
These interventions, along with encouraging the use of patients’ hearing aids and
eyeglasses and bringing familiar objects
and pictures from home, are the KPSC
Region’s attempts to make our hospitals
safer for older patients.
Conclusion
Quality metrics are a powerful strategy to institute change
and will allow hospitalists to
learn and apply the principles
of geriatrics. Proactively focusing on preventing geriatric
syndromes by targeting the
shared risk factors for delirium
and falls can reduce length
of stay, minimize unplanned
readmissions, maximize functional independence, and
keep our hospitals safer for
older adult patients. v
… minimizing
the prescriptions
for sedativehypnotic drugs in
the ambulatory
setting for older
adults … likely
reduces the
chance that such
medications
are prescribed
at hospital
admission …
The author(s) have no conflicts
of interest to disclose.
Acknowledgments
We wish to thank Jeffrey Brettler, MD,
Assistant Area Medical Director, Kaiser Permanente West Los Angeles; Gloria Blackburn,
RN, former Chief Nursing Executive, Kaiser
Permanente West Los Angeles (retired); and
Howard Fullman, MD, Area Medical Director,
Kaiser Permanente West Los Angeles, for their
support, encouragement, and sponsorship of
programs that have improved the quality of
care for older members at Kaiser Permanente
West Los Angeles. We thank Michael Kanter,
MD, Regional Medical Director for Quality and Clinical Analysis, Kaiser Permanente
Southern California; and Patti Harvey, RN,
MPH, CPHQ, Vice President, Kaiser Foundation Health Plan Southern California Region
for their thoughtful critique, suggestions, and
support to disseminate quality-improvement
interventions programs for older members
in Kaiser Permanente Southern California.
Additional thanks to our national and regional
nursing leaders and colleagues: Marilyn Chow,
RN, PhD, FAAN, Vice President, National Patient Care Services; Lisa Shilling RN, MPH, Vice
President Healthcare Performance Improvement; Jerry Spicer RN, MPA, Vice President
Patient Care Services Southern California and
Hawaii; Lorraine Woo, Senior Quality and
Safety Project Manager, National Patient Care
Services; Rebecca Gambatese, MPH; Helena
Gurascier, MS, Utility for Care Analysis; and
Douglas Lenaburg, RN, MSN, Senior Director,
Clinical Operations, Southern California Patient
Care Services for their sponsorship, support,
and commitment to ensuring safe quality
care for our Kaiser Permanente patients and
families. A special thanks to Joel Handler,
MD, Intensive Care Unit physician, Kaiser
Permanente Orange County and the National
Kaiser Permanente Hypertension Lead, who
implemented the first delirium prevention program in Kaiser Permanente Southern California
35
and helped spur the creation of our Kaiser
Permanente Southern California committee that
focused on improving functional outcomes of
hospitalized older adults.
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catheters: a one-point restraint? Ann Intern Med
2002 Jul 16;137(2):125-7. DOI: http://dx.doi.
org/10.7326/0003-4819-137-2-200207160-00012
22. Saint S, Wiese J, Amory JK, et al. Are physicians aware of which of their patients have
indwelling urinary catheters? Am J Med 2000
Oct 15;109(6):476-80. DOI: http://dx.doi.
org/10.1016/S0002-9343(00)00531-3
23. Saint S, Lipsky BA. Preventing catheter-related
bacteriuria: should we? Can we? How? Arch
Intern Med 1999 Apr 26;159(8):800-8. DOI:
http://dx.doi.org/10.1001/archinte.159.8.800
24. Chavez AH, Coffield KS, Kuykendall SJ, et al.
Incidence of Foley catheter-related urethral
injury in a tertiary referral center [abstract]. J
Am Coll Surg 2009 Sep;209(3 Suppl):S129-30.
DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2009.06.325
25. Lo E, Nicolle L, Classen D, et al. Strategies to
prevent catheter-associated urinary tract infections in acute care hospitals. Infect Control Hosp
Epidemiol 2008 Oct;29 Suppl 1:S41-50. DOI:
http://dx.doi.org/10.1086/591066
26. Inouye SK. AGS Henderson lecture—Delirium:
applying research to transform care at the
bedside [PowerPoint on the Internet]. New York,
NY: The American Geriatrics Society; 2010.
Available from: http://unmhospitalist.pbworks.
com/f/Delirium+Inouye+AGS+lecture.pdf.
27. Onder G, Petrovic M, Tangiisuran B, et al.
Development and validation of a score to assess
risk of adverse drug reactions among in-hospital
patients 65 years or older: the GerontoNet
ADR risk score. Arch Intern Med 2010 Jul
12;170(913):1142-8. DOI: DOI: http://dx.doi.
org/10.1001/archinternmed.2010.153
28. Garfinkel D, Mangin D. Feasibility study of a
systematic approach for discontinuation of
multiple medications in older adults: addressing polypharmacy. Arch Intern Med 2010
29. Ness J, Hoth A, Barnett MJ, Shorr RI, Kaboli
PJ. Anticholinergic medications in communitydwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and
adverse drug events. Am J Geriatr Pharmacother 2006 Mar;4(1):42-51. DOI: http://dx.doi.
org/10.1016/j.amjopharm.2006.03.008
30. Inouye SK. Delirium in older persons. N Engl
J Med 2006 Mar 16;354(11):1157-65. DOI:
http://dx.doi.org/10.1056/NEJMra052321
Erratum in: N Engl J Med 2006 Apr
13;354(15):1655. DOI: http://dx.doi.
org/10.1056/NEJMx060018
31. Cook DJ, Fuller HD, Guyatt GH, et al; Canadian
Critical Care Trials Group. Risk factors for gastrointestinal bleeding in critically ill patients. N Engl
J Med 1994 Feb 10;330(6):377-81. DOI: http://
dx.doi.org/10.1056/NEJM199402103300601
32. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER.
Acid-suppressive medication use and the risk
for hospital-acquired pneumonia. JAMA 2009
org/10.1001/jama.2009.722
33. Howell MD, Novack V, Grgurich P, et al.
Iatrogenic gastric acid suppression and the risk
of nosocomial Clostridium difficile infection.
Arch Intern Med 2010 May 10;170(9):78490. DOI: http://dx.doi.org/10.1001/
archinternmed.2010.89v
34. Herzig SJ, Vaughn BP, Howell MD, Ngo LH,
Marcantonio ER. Acid-suppressive medication
use and the risk for nosocomial gastrointestinal tract bleeding. Arch Intern Med 2011
35. Yachimski PS, Farrell EA, Hunt DP, Reid AE.
Proton pump inhibitors for prophylaxis of
nosocomial upper gastrointestinal tract
bleeding: effect of standardized guidelines on
prescribing practice. Arch Intern Med 2010
36. McDowell JA, Mion LC, Lydon TJ, Inouye SK. A
nonpharmacologic sleep protocol for hospitalized older patients. J Am Geriatr Soc 1998
Jun;46(6):700-5.
37. HEDIS DAE 2013 [table on the Internet].
Washington, DC: National Committee for Quality
Assurance; updated 2013 [cited 2013 Aug 30].
Available from: www.ncqa.org/portals/0/HEDISQM/HEDIS%202011/NDC/Table%20DAE-A.doc.
38. Kolla BP, Lovely JK, Mansukhani MP, Morgenthaler TI. Zolpidem is independently associated
with increased risk of inpatient falls. J Hosp
Med 2013 Jan;8(1):1-6. DOI: http://dx.doi.
org/10.1002/jhm.1985�
39. Inouye SK, van Dyck CH, Alessi CA, Balkin S,
Siegal AP, Horwitz RI. Clarifying confusion: the
confusion assessment method. A new method
for detection of delirium. Ann Intern Med
1990 Dec 15;113(12):941-8. DOI: http://dx.doi.
org/10.7326/0003-4819-113-12-941.
Special Report
Preventing Falls in the Geriatric Population
Aimee Lee, MD; Kuo-Wei Lee, MD; Peter Khang, MD, MPH, FAAFP
Perm J 2013 Fall;17(4):37-39
Introduction
The word “fall” does not usually strike
fear in the hearts of most people. But
it should. Falls are all too common in
the geriatric population, and they have
devastating consequences. They are the
leading cause of injury and death by injury
in adults over the age of 65 years.1 One
of 3 community-dwelling older adults falls
each year, with 24% of those who fall sustaining serious injuries and 6% sustaining
fractures.2 In the year 2000, falls cost the
US health care system more than $19 billion, a number that is expected to increase
to $54.9 billion by 2020.3 A person who
falls may subsequently experience pain,
hospitalization, surgical intervention,
admission to a nursing home, decreased
overall functional ability, poorer quality
of life, or a fear of falling.
Risk Factors for Fallsa
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
a
previous falls
decreased strength
gait/balance impairments
use of psychoactive medications
visual impairment
polypharmacy
depression
dizziness
orthostasis
functional limitations
age > 80 years
female sex
low body mass index
urinary incontinence
cognitive impairment
arthritis
diabetes
undertreated pain
Risk factors in bold indicate strongest independent
risk factor.
Fear of Falling
Fear of falling is a defined geriatric
syndrome that may contribute to further
functional decline in an already frail patient. When people experience something
unpleasant, their natural response is an
aversion to that experience. People may
begin to limit their activities after a fall
or as they become weaker and less agile
with increasing age. This leads to a more
sedentary lifestyle and physical atrophy,
which further predisposes them to falls.
Successful encouragement to maintain or
increase physical activity may promote the
ability to avoid falling or to catch oneself
before a fall.
Why Patients Fall
Normal gait and balance requires freely
moving joints; muscles contracting at the
right time with the appropriate strength;
and accurate visual, vibratory, and proprioceptive input. As patients age, they
may experience stiffened joints, decreased
muscle strength, and impaired neurologic
feedback. These changes, in combination
with other risk factors, increase the likelihood of falls. The strongest independent
risk factors for falls are previous falls,
weakness, gait and balance impairments,
and use of psychoactive medications. The
risk of falling increases with the number
of risk factors present (see Sidebar: Risk
Factors for Falls). One study showed that
a patient with 4 risk factors has a 78%
chance of falling.4
Screening for Falls
The most important first step that clinicians can take in preventing falls is to ask
about history of falls. In 2010, the American and British geriatrics societies released
Actions to be Taken for
Patients at High Risk for Falls
1.Ask about history of falls and patient’s
assessment of his/her functional ability.
2.Review medications and medical
history.
3.Perform gait assessment; physical
examination (especially neurologic,
cardiac); assessment of orthostatic
vital signs; visual acuity examination;
cognitive evaluation; examination
of feet and footwear; home safety
evaluation.
updated clinical practice guidelines for fall
prevention in older adults. The guidelines
state that all patients age 65 years or older
should be asked yearly about previous
falls.5 Patients who report a fall or gait
and balance difficulties should undergo
an in-office assessment such as the Timed
Up and Go test (Figure 1).
Timed Up and Go Test
This is a quick and easy test that can
be performed by a trained health care
team member in ambulatory care settings
within a few minutes. The patient should
wear regular footwear, use their usual
walking aid if needed, and start by sitting
back in a chair with armrests. The patient
is timed while s/he rises from the chair,
walks three meters, turns around, walks
back to the chair, and sits back down.
Postural stability, gait, stride length, sway,
and steppage should be observed. Kaiser
Permanente uses the operational value of
14 seconds or less. (The normal value is 10
seconds or less; and 20 seconds or more is
considered abnormal.) If the result of the
Aimee Lee, MD, is a Graduate of the Geriatrics Fellowship in the Department of Geriatrics, Palliative Medicine, and Continuing
Care at the Los Angeles and West Los Angeles Medical Centers in CA. She currently works in primary care and telemedicine at
Banner Health. E-mail: aimee.lee@bannerhealth.com. Kuo-Wei Lee, MD, is the Geriatrics Program Director in the Department
of Geriatrics, Palliative Medicine, and Continuing Care at the Los Angeles and West Los Angeles Medical Centers in CA. E-mail:
kuo-wei.x.lee@kp.org. Peter Khang, MD, MPH, FAAFP, is the Physician in Charge of the Department of Geriatrics, Palliative
Medicine, and Continuing Care at the Los Angeles and West Los Angeles Medical Centers in CA. E-mail: peter.s.khang@kp.org.
37
Preventing Falls in the Geriatric Population:
Physician Pocket Reference
Risk Factors for Falls
Previous falls
Decreased strength
Gait/balance impairments
Use of psychoactive
medications
Visual impairment
Polypharmacy
Depression
Dizziness
Orthostasis
Functional
limitations
Age > 80 years
Female sex
Low body mass index
Urinary incontinence
Cognitive impairment
Arthritis
Diabetes
Undertreated pain
Screening for Falls
• Ask about a fall history every year.
• If a patient reports a fall or gait and balance problems, perform an in-office
gait evaluation such as the Timed Up and Go test.
Timed Up and Go Test
• Observe postural stability, gait, stride length, sway, and steppage.
• A normal time is 14 seconds or less.
Ask the patient to:
1. rise from the chair
2. walk three meters
3. turn around
4. walk back to the chair
5. sit back down
Risk Assessment
Ask about
history of falls
patient’s assessment of his/her
functional ability
Review
medications
medical history
Perform
gait assessment
physical exam (esp neurologic, cardiac)
assessment of orthostatic vital signs
visual acuity exam
cognitive evaluation
examination of feet and footwear
home safety evaluation
Ambulatory Interventions
1. Exercise/physical therapy programs
aimed at improving balance, gait,
and strength
2. Withdrawal or minimization of use of
psychoactive medications
3. Management of postural
hypotension
4. Management of foot problems
5. Changes in footwear
6.
7.
8.
Modification of home environment
Patient and caregiver education
Vitamin D supplementation in
deficient or high fall risk patients
9. Expedited cataract surgery (selected
patients)
10. Dual chamber cardiac pacing
(selected patients)
Hospital Interventions (based on Schmid Fall Risk Assessment)
1. Appropriate reorientation strategies
7. Patient and family education about
2. Access to patient’s hearing aids or
fall risk
glasses
8. Early and frequent mobilization
3. Call bell
9. Nonslip footwear
4. Access to patient’s personal items
10. Elimination of barriers to transfer or
5. Use of patient’s walking aids
ambulation
6. Frequent comfort rounds
11. Minimization of use of restraints
12. Use of bed alarm when necessary
Figure 1. Physician Pocket Reference.
This pocket reference is available to download and print at: www.thepermanentejournal.org/files/Fall2013/PreventingFallsPhyscianPocketReference.pdf.
Timed Up and Go test is abnormal, targeted interventions selected from Table 1
and a comprehensive risk assessment may
be warranted.
Risk Assessment
and Interventions
In community-dwelling adults, use of
multifactorial assessments and interventions has led to a decrease in fall rates
by 25% to 40%.4,6 (see Sidebar: Actions
to be Taken for Patients at High Risk for
Falls.) Depending on the results of this
risk assessment, appropriate multifactorial
interventions for preventing ambulatory
falls may include any or all of the following (Figure 1):
1.exercise/physical therapy programs
aimed at improving balance, gait,
and strength
2.withdrawing or minimizing psychoactive medications
3.management of orthostatic hypotension
4.management of foot problems
Table 1. Interventions for abnormal results of the Timed Up and Go test
Observation
Difficulty rising from
chair
Staggering or reported
dizziness upon rising
Significance
Proximal muscle
weakness
Possible orthostasis
Pill-rolling tremor,
stooped posture,
shuffling/festinating gait
Increased sway,
magnetic gait
Possible parkinsonism
Path deviation
Slow, antalgic gait
Possible normal
pressure hydrocephalus
Possible peripheral
neuropathy,
cerebrovascular disease
Pain from osteoarthritis,
peripheral neuropathy,
podiatric disorders
CT = computed tomography; PT = physical therapy.
38
Intervention
PT referral for lower extremity strengthening
Check orthostatic vital signs; review
medications that may contribute to
orthostasis
Consider neurology referral
Ask about urinary incontinence and memory
issues. If these are highly suspected,
consider head CT
Consider neuropathy workup, examination
of feet, PT referral for assistive device
Pain control, examination of feet
5.changes in footwear
6.modification of home environment
7.patient and caregiver education
8.vitamin D supplementation in patients with vitamin D deficiency or
high risk of fall
9.expedited cataract surgery
(selected patients)
10.dual chamber cardiac pacing
(selected patients).
There is insufficient evidence to support use of these interventions in the
long-term-care setting or for patients with
dementia.5 To reduce the risk of fall-related fractures, patients should be screened
for osteoporosis at the appropriate age
and the relevant medications should be
prescribed if necessary.
Fall Prevention in Hospitals
Physicians and other health care team
members should be aware that in hospitals,
nurses perform fall prevention assessments
for every patient using standardized tools.
Tools for assessing risk for falls include:
the Morse Fall Scale, the Hendrich II Fall
Risk Model, the Briggs Risk Assessment
Form, and the Conley Risk Assessment
Tool, among others. Kaiser Permanente
uses the Schmid Fall Assessment Tool. It involves evaluation of the patient’s mobility,
mentation, toileting, fall history, and use of
psychoactive medications. A score of three
or more indicates an increased risk for falls
requiring the following interventions:
1.appropriate reorientation strategies
2.access to patient’s hearing aids or
glasses
3.call bell
4.access to patient’s personal items
5.use of patient’s walking aids
6.frequent comfort rounds
7.patient and family education about
fall risk
08.early and frequent mobilization
09.nonslip footwear
10.elimination of barriers to transfer
or ambulation
11.minimization of use of restraints
12.use of bed alarm when necessary.
Conclusion
Given the devastating effects falls have
on patients and the increased burden on
family members and the health care system,
screening and assessment for fall risk are
paramount priorities. Screening may be easily
performed in the ambulatory and hospital
settings, with simple interventions producing meaningful results. Physicians should
coordinate with other health care team
members to provide effective multifactorial
interventions to their patients (see Sidebar:
Online Resources for More Information).
With each fall that is prevented, the patient,
their family members, the health care team,
and the health care system all benefit. v
to disclose.
Acknowledgment
Leslie Parker, ELS, provided editorial
assistance.
References
1. Injury prevention & control: data & statistics
(WISQARS) [Web page on the Internet].
Atlanta, GA: Centers for Disease Control and
Prevention, National Center for Injury Prevention and Control; updated 2013 Sept 20 [cited
2013 Sept 25 ]. Available from: www.cdc.gov/
injury/wisqars/.
2. Tinetti ME, Speechley M, Ginter SF. Risk
factors for falls among elderly persons living in the community. N Engl J Med 1988
Dec 29;319(26):1701-7. DOI: http://dx.doi.
org/10.1056/NEJM198812293192604
3. Costs of falls among older adults [monograph
on the Internet]. Atlanta, GA: Centers for Disease Control and Prevention, National Center
for Injury Prevention and Control, Division of
Unintentional Injury Prevention; updated 2013
Sept 20 [cited 2013 Sept 25 ]. Available from:
www.cdc.gov/HomeandRecreationalSafety/
Falls/fallcost.html.
4. Tinetti ME, Kumar C. The patient who
falls: “It’s always a trade-off.” JAMA 2010
Jan 20;303(3):258-66. DOI: http://dx.doi.
org/10.1001/jama.2009.2024
5. Prevention of falls in older persons. Clinical
practice guidelines [monograph on the
Internet]. New York, NY: American Geriatrics
Society; 2010 [cited 2012 Aug 12]. Available from: www.americangeriatrics.org/
health_care_professionals/clinical_practice/clinical_guidelines_recommendations/2010/.
6. Tinetti ME, Baker DI, McAvay G, et al. A
multifactorial intervention to reduce the
risk of falling among elderly people living
in the community. N Engl J Med 1994
org/10.1056/NEJM199409293311301
Suggested Reading
• Schmid, NA. 1989 Federal Nursing Service
Award Winner. Reducing patient falls: a
research-based comprehensive fall prevention
program. Mil Med 1990 May;155(5):202-7.
• Gongoll R, editor. Progress, challenges and
next steps. Proceedings of the 2007 California
Fall Prevention Summit; 2007 Dec 5-6;
Long Beach, CA. Los Angeles, CA: The Fall
Prevention Center of Excellence, University of
Southern California; 2009.
• Chang JT, Ganz DA. Quality indicators for falls
and mobility problems in vulnerable elders. J
Am Geriatr Soc 2007 Oct;55 Suppl 2:S32734. DOI: http://dx.doi.org/10.1111/j.15325415.2007.01339.x
• Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA 2007
Jan 3;297(1):77-86. DOI: http://dx.doi.
org/10.1001/jama.297.1.77
• Moncada LV. Management of falls in older
persons: a prescription for prevention. Am Fam
Physician 2011 Dec 1;84(11):1267-76.
• Rubenstein LZ, Solomon DH, Roth CP, et al. Detection and management of falls and instability
in vulnerable elders by community physicians.
J Am Geriatr Soc 2004 Sep;52(9):1527-31.
DOI: http://dx.doi.org/10.1111/j.15325415.2004.52417.x
• Tinetti ME, Williams CS. Falls, injuries
due to falls, and the risk of admission to
a nursing home. N Engl J Med 1997 Oct
30;337(18):1279-84. DOI: http://dx.doi.
org/10.1056/NEJM199710303371806
Online Resources for More Information
For patients and their families:
NIHSeniorHealth is a Web site that provides aging-related health information in an easyto-understand format. It was developed by the National Institute on Aging (NIA) and the
National Library of Medicine (NLM). http://nihseniorhealth.gov/falls/aboutfalls/01.html.
For clinicians:
American Geriatrics Society, British Geriatrics Society Clinical Practice Guideline. www.americangeriatrics.org/health_care_professionals/clinical_practice/clinical_guidelines_recommendations/prevention_of_falls_summary_of_recommendations.
Sympathy
The most effective therapeutic weapon at the disposal of a physician in the care of the aged is sympathy.
— Richard A Kern, MD, 1891-1982, Allergist and Professor of Medicine at Temple University
39
SOUL OF THE HEALER
“Okavango Sunset”
photograph
David Clarke, MD
The Okavango River begins in Angola and flows for 1000 miles before emptying into the
Kalahari Desert in Botswana, where it supports abundant wildlife and spectacular sunsets.
Dr Clarke is President of the Psychophysiologic Disorders Association and an Assistant
Director at the Oregon Health & Science University Center for Ethics.
40
Special Report
Establishing a Portfolio of Quality-Improvement Projects in Pediatric
Surgery through Advanced Improvement Leadership Systems
Betsy T Gerrein, DNP, CPNP; Christina E Williams, MS; Daniel von Allmen, MD
Perm J 2013 Fall;17(4):41-46
Abstract
Formal quality-improvement (QI) projects require that participants are educated in
QI methods to provide them with the capability to carry out successful, meaningful work.
However, orchestrating a portfolio of projects that addresses the strategic mission of the
institution requires an extension of basic QI training to provide the division or business unit
with the capacity to successfully develop and manage the portfolio. Advanced Improvement
Leadership Systems is a program to help units create a meaningful portfolio. This program,
used by the Division of Pediatric General and Thoracic Surgery at Cincinnati Children’s
Hospital Medical Center, helped establish a portfolio of targeted QI projects designed to
achieve outstanding outcomes at competitive costs in multiple clinical areas aligned with
the institution’s strategic goals (improve disease-based outcomes, patient safety, flow, and
patient and family experience). These objectives are addressed in an institutional strategic
plan built around 5 core areas: Safety, Productivity, Care Coordination and Outcomes,
Patient and Family Experience, and Value. By combining the portfolio of QI projects with
improvements in the divisional infrastructure, effective improvement efforts were realized
throughout the division. In the 9 months following the program, divisional capability
resulted in a 16.5% increase (5.7% to 22.2%) of formally trained staff working on 10 QI
teams. Concurrently, a leadership team, designed to coordinate projects, remove barriers,
and provide technical support, provided the capacity to pursue this ongoing effort. The
Advanced Improvement Leadership Systems program increased the Division’s efficiency
and effectiveness in pursing the QI mission that is integral at our hospital.
Introduction
The Institute of Medicine reports from
the late 1990s and early 2000s document
the substantial problems with quality in
the US health care system. In those studies, medical errors resulted in the deaths
of an estimated 44,000 to 98,000 people
each year.1,2 This realization led health
care systems to reevaluate how care is
provided and to seek processes for improving patient safety. For the last decade,
Cincinnati Children’s Hospital Medical Center (CCHMC) focused its efforts on transforming the organizational culture from a
traditional approach, in which errors are
expected and accepted as inevitable and
care is based on practitioner preference, to
one in which the focus is on learning from
errors and care is driven by evidence and
outcomes. The ultimate goal is to achieve
an organization where safety and quality
improvement (QI) become an integral part
of the way medicine is practiced rather
than periodic initiatives responding to suboptimal care. CCHMC invested resources
to develop the appropriate educational
training for faculty, nursing leaders, and
administrators who would undertake the
QI work. As an academic medical center, CCHMC has a strategy for building
improvement capability that focuses on
advancing the scholarship of health care
improvement through rigorous methods
and QI research.3
Two broad concepts emerged from
this strategy regarding an organization’s ability to successfully achieve
sustained improvement results. The
concept of capability refers to the presence of “knowledgeable and skilled
human resources to lead the design
of improvement initiatives to achieve
measurable results, execute (ie, develop,
test, measure, and implement changes)
the improvement efforts, and sustain
the results.”4 The concept of capacity is
defined as “organizational resources that
enable it to initiate and sustain a transformation effort.”4 Previous publications
describe the educational training courses
at CCHMC that are necessary to build the
proper capability required for successful
transformation.4,5
As trained QI leaders proliferated
across the organization, it became apparent that there was also a need for a guiding structure for leaders of the academic
divisions to coordinate and manage a QI
portfolio of work. These leaders held the
responsibility of directing work to meet
the strategic goals of improving diseasebased outcomes and transforming care
systems across the organization. Across
CCHMC, many divisional leaders had
undergone extensive training in improvement science, yet it was clear that many
divisions lacked the necessary capacity
to achieve the results required by the
organization’s strategic initiatives. To
address this deficit, CCHMC created an
educational program called Advanced
Improvement Leadership Systems (AILS).
This course helps divisional leaders in the
institution address the institutional objectives to achieve outstanding outcomes at
a competitive cost, manage a portfolio of
projects to achieve goals in multiple strategic areas and to deliver on the CCHMC
strategic plan goals through effective
alignment.4 AILS is a six-month training
and development program for Division
Directors responsible for developing
and aligning their divisional goals with
Betsy T Gerrein, DNP, CPNP, is a Pediatric Nurse Practitioner and Program Lead for the Division of Pediatric General and Thoracic Surgery at Cincinnati
Children’s Hospital Medical Center in OH. E-mail: betsy.gerrein@cchmc.org. Christina E Williams, MS, is an Account Manager and Quality Improvement
Consultant at Cincinnati Children’s Hospital Medical Center in OH. E-mail: christina.williams@cchmc.org. Daniel von Allmen, MD, is the Director of the
Division of Pediatric General and Thoracic Surgery at Cincinnati Children’s Hospital Medical Center in OH. E-mail: daniel.vonallmen@cchmc.org.
41
Establishing a Portfolio of Quality-Improvement Projects in Pediatric Surgery through Advanced Improvement Leadership Systems
the organization’s overall strategic goals
to improve disease-based outcomes,
patient safety, and patient flow.4 This
article describes our work using the
AILS model to establish a coordinated
portfolio of successful QI projects in
the Division of Pediatric General and
Thoracic Surgery.
Methods
The AILS model consists of a series
of five educational half-day sessions that
are outlined below.4 QI leadership teams
consisting of four to ten people participate
in the process. The Division of Pediatric
General and Thoracic Surgery QI Leadership Team includes the Division Director,
the nurse practitioner (NP) team leader, the
Business Director, a QI consultant, and a
lead decision support analyst. Each of the
five sessions focused on an educational
theme with deliverables for each team due
before and after each session. The session
themes were as follows (Figure 1):
1.Assessing the current state (divisional
readiness, existing projects)
2.Safety and productivity (identify key
safety processes)
3.Care coordination and outcomes (understand the chronic care model)
4.Patient and family experience/managing your system of work (portfolio,
dashboard)
5.Execution of system’s goals (report on
work completed and plan for execution).
At each of the five learning sessions,
a combination of didactic material presentations and individual group work is
completed.
The Division of Pediatric General and
Thoracic Surgery is a large division with
7 subspecialties (bariatric, colorectal,
fetal, general surgery, hemangiomas/
vascular malformations, transplantation,
and trauma), each with different needs
and different populations. There are 21
surgeon faculty members and 21 NPs.
At the onset of the AILS course, 5.7% of
faculty and NPs had received formal QI
methodology training.
Given the diversity of the conditions
and patient populations treated in the
Division, the decision was made to select
a single disease treated by most Division
members and to address multiple aspects
of the disease management (a so-called
vertical process) and a non-disease-specific process affecting all diseases treated
in the Division (a so-called horizontal
process). Appendicitis management was
Figure 1. Roadmap of Advanced Improvement Leadership Systems.
AILS = Advanced Improvement Leadership Systems; CCHMC = Cincinnati Children’s Hospital Medical Center;
FY = fiscal year; ID = identify; QI = quality improvement.
Reprinted with permission from Cincinnati Children’s Hospital Medical Center.
42
selected as the vertical process on the
basis of the frequency of the diagnosis
(500 to 600 patients per year) and the
availability of literature suggesting clinical
best practice. A treatment guideline was
developed for perforated appendicitis and
agreed on by the faculty, with primary
objectives of reducing the number of
patients treated with interval appendectomy and reducing the number of patients
discharged on an antibiotic regimen.
Data gathered included adherence to the
guideline and a balancing measure of
readmissions because of abscess within
30 days of treatment.
The horizontal process selected addresses communication of the care plan
with the family, a known correlate to
have an impact on patient and family
satisfaction. Through extensive analysis of
patient and staff satisfaction survey data,
a common theme was noted regarding
basic communication of the care plan to
the various members of the care team
and, equally important, to the patient
and family. To address this opportunity,
the process of morning rounding by the
care team was studied. Baseline data were
obtained, followed by sequential tests of
change designed to result in a clear care
plan communicated to the entire team
for each patient on the service at the end
of rounds each morning. A second effort
was undertaken to facilitate the transfer
of the care plan to the bedside caregivers
and the patient and family. Nurses and
family members were integrally involved
in the testing and implementation of the
redesigned process. The approach of selecting a vertical and horizontal problem
was designed to engage the majority of
faculty, surgical fellows, and NPs in the
work and increase their exposure to the
QI process and methodology. Subsequently, additional targeted education
efforts are now in place to ensure appropriate capability for strategic faculty and
staff training on the basis of prioritized
improvement initiatives.
Through this process, 6 NPs participated in the Rapid Cycle Improvement Collaborative educational program; and 2 surgeons and 1 nurse manager participated
in the Intermediate Improvement Science
Series course. Rapid Cycle Improvement
Collaborative is a project-focused education process in which a small team learns
improvement science methods and works
to solve a specific problem in a 120-day
learning collaborative. The Intermediate
Improvement Science Series is a more
comprehensive 6-month leadership
course that teaches participants leadership skills and offers extensive training
in improvement science methods. Our
Rapid Cycle Improvement Collaborative
teams worked on appendicitis care and
patient and family satisfaction, while our 3
Intermediate Improvement Science Series
teams completed QI projects specific to
the Colorectal Center.
The process of increasing the capability
of the Division presents challenges both to
the institution, to provide training, and to
the clinicians, to invest a substantial time
commitment to complete the training. The
Rapid Cycle Improvement Collaborative
and Intermediate Improvement Science
Series courses are heavily supported
with coaches, lecturers, and consultants
representing a substantial investment by
the institution in the QI effort. Similarly,
the clinicians involved in each project are
supported during their work, but care is
taken not to overstretch the clinical care
resources required to provide for the clinical volume. In addition, “initiative fatigue”
is a potential barrier that also limits the
speed at which training and overall improvement work can occur.
Results
Through participation in the AILS program, the Division of Pediatric General
and Thoracic Surgery used its multidisciplinary QI leadership team to effectively
manage a portfolio of projects that align
and deliver on the CCHMC’s 2015 strategic
plan. Figure 2 (available in color at: www.
thepermanentejournal.org/files/Fall2013/
Timeline.pdf) illustrates the body of
ongoing improvement work in the Division. Each arrow represents an individual
project, which is color-coordinated to
correspond with the surgical subspecialty
program identified at the bottom of the figure. Each project is aligned with one of the
five CCHMC’s care delivery domains that
form the core of the institution’s strategic
plan—Safety, Productivity, Care Processes
and Outcomes, Patient and Family Experience, and Value—which are indicted in a
circle on the left side of each arrow. The
QI leadership team (meeting weekly after
completion of the AILS program) operates
in a way that integrates improvement,
transparently shares data, reports on QI
team status, and delivers care for surgical
patients at the population level.
The Division of Pediatric General and
Thoracic Surgery’s strategic goals for
Fiscal Year 2013 were operationally set
around delivering both the best clinical
outcomes and the best value for patients
undergoing surgical services care. For the
clinically oriented outcome work, the key
measures were percentage of patients
receiving evidence-based care for patients
with perforated appendicitis, cost of care
for perforated appendicitis, patient and
family satisfaction, percentage of patients
in the Bowel Management Program who
successfully achieved fecal continence,
and percentage of reliable remote followup with patients in this program. Figure 3
(available at: www.thepermanentejournal.
org/files/Fall2013/Dashboard.pdf) shows
the Care Delivery System Dashboard that
helps the Division of Pediatric General
and Thoracic Surgery use data to drive its
decision making. Our organization’s value
initiative, aligning strongly with both
organizational priorities and the Institute
for Healthcare Improvement priorities,6
aims to reduce the cost of providing
surgical services. The following results
of the active QI teams demonstrate the
high-level accomplishments obtained in
the first nine months after conclusion of
the AILS program.
Results of Active Improvement Teams
Appendicitis Evidence-Based
Care Guideline
The team increased the percentage of
patients treated with an evidence-based
guideline for treatment of perforated appendicitis from 5% to 88%.
Patient and Family
Experience Rounds Redesign
The team increased the percentage of
NPs, nurses, and families that reported a
consistent care plan (at least 4 of the 5
equally weighted elements) each morning
for general surgery patients on 2 surgical
inpatient units from 50% to 90%. The care
Figure 2. Division of Pediatric General and Thoracic Surgery Quality Improvement Capability
and Capacity Building Timeline.
HVMC = Hemangioma and Vascular Malformation Center; Pectus Bar SSI = surgical site infection after pectus excavatum
correction; QI = quality improvement.
43
plan elements were as follows: 1) changes
to medications or antibiotics; 2) tests (ie,
laboratory tests, x-rays) or procedures
(ie, operating room, drain placement); 3)
starting, stopping, continuing, or changing intravenous fluids; 4) diet or nutrition
plan; and 5) predicted date of discharge.
Anorectal Malformation
Follow-up Process
The team increased the reliability of
remote contact and collection of outcomes
data for patients in the Bowel Management Program from 50% to 96%.
directors) working on 10 improvement
teams actively engaged in successful QI
work. This rapid growth in capability
required substantial financial commitment on the part of the Division and time
commitment on the part of the clinicians.
Anorectal Malformation Outcomes
Division Quality Improvement
Capability
In the 9 months following the AILS
formal curriculum, Division capability
achieved a 16.5% increase—from 5.7% to
22.2%—of formally trained staff (physicians, registered nurses, NPs, and business
Discussion
During the past ten years, the Division of Pediatric General and Thoracic
Surgery, along with the entire institution, accumulated a number of Division
members trained in improvement science
methods. Although this provided some
The team increased the percentage
of patients in the Bowel Management
Program (first-time program participants
only) who successfully achieved fecal
continence by the end of the 4-week
program from 36% to 85%.
Figure 3. Care delivery system dashboard, Fiscal Year 2013, Quarter 2.
AI = active improvement; CCHMC = Cincinnati Children’s Hospital Medical Center; D = Division-specific measure; Dir = director; exam = examination; FTE = full-time employee; FY = Fiscal Year;
FW = future work; IP = improvement priority; MD = physician; Mng = manager; MO = monitor; N/A = not available; NIH = National Institutes of Health; OSHA = Occupational Safety and Health
Administration; OR = operating room; Q = quarterly; QI = quality improvement; QIC = quality improvement consultant; RVUs = relative value units; SA = semiannual; SD = strategic domain measure; S2D2 = same day consult / same day surgery; TBD = to be determined; wRVUs = work relative value unit; Y = yearly; YTD = year to date; # = number; ↑ = increase; ↓ = decrease.
44
capability—knowledgeable and skilled
human resources able to lead the design
of improvement initiatives to achieve
measurable results—the Division lacked
sufficient improvement capacity—organizational resources that enable sustaining
a transformative effort.3 Completing the
AILS program demonstrated to divisional
leadership that it lacked sufficient improvement capacity across the microsystem, mesosystem, and macrosystem
levels.7-9 Before participating in AILS, the
Division of Pediatric General and Thoracic
Surgery lacked both the organization and
infrastructure to change the culture and
behavior across the entire Division to
one in which QI efforts are aligned with
institutional goals and are prioritized for
completion. Creation of the infrastructure,
at the leadership level, in the Division allows for both oversight and accountability
to accomplish strategic goals. The AILS
program resulted in divisional success with
both improvement capability and capacity.
The AILS process produced a clear
roadmap demonstrating the Surgery Division’s needs, both skilled resources and
proper infrastructure, to create a microsystem environment where QI initiatives
achieve measurable results. Whereas the
Division of Pediatric General and Thoracic
Surgery lacked sufficient support resources to initiate its QI knowledge and skills
before the AILS program, completing this
process enabled the Division to focus on
proper development of QI leaders, effective and efficient utilization of resources,
and maximization of human resources
to help ensure success. Before the AILS
program, few improvement projects were
initiated, fewer were completed, and virtually none entered the sustain phase of
an adopted improvement. In many cases,
limited projects were initiated by clinicians
without the time or support to see the
projects to completion. The addition of a
QI consultant to the Division along with
project prioritization, and the leadership
management and oversight precipitated
by the AILS process, dramatically increased the throughput and sustainability
of the work. The structure allows busy
clinicians to focus on their clinical work
while still directing strategic QI work.
CCHMC uses an institutionally developed system-level key driver diagram
(Figure 4) to aid QI efforts by ensuring
that all projects are aligned to strategic
goals. Aim statements for specific projects
under way replace the list of interventions
on a conventional key driver diagram
(Figure 4). In this way, systematic segmentation of strategic goals permits development of a portfolio of aligned projects to
improve quality. Ultimately, the Division
of Pediatric General and Thoracic Surgery
developed the following infrastructure
components to frame its QI through the
output of AILS:3
• Build improvement capability beyond
acquisition of knowledge and skills,
moving toward action-oriented improvement that achieves critical results
and accelerates transformation
• Identify key safety, productivity, patient
and family experience, outcomes, and
critical clinical processes to improve
child health as a multidisciplinary
leadership team
• Manage a system of work with a strong
governance structure, transparent data
Figure 4. Care processes and outcomes for system-level key driver diagram for Fiscal Year 2013.
APN = advanced practice nurse; MD = physician; PFE = patient and family experience; RN = registered nurse;
≈ = approximately; shaded boxes = what we are working on currently.
45
driving decisions, and a comprehensive
map of the Surgery Division’s QI project
portfolio to plan and execute its QI work.
Conclusion
AILS enabled the Division of Pediatric
General and Thoracic Surgery to create a
multidisciplinary QI leadership team to
accelerate managing a portfolio of projects that align and deliver on the medical
center’s strategic plan. Moreover, after the
AILS program, the leadership team now
conducts operations in a way that integrates improvement to advance
child health as a multidisciplinary
The structure
team effort. Additionally, followallows busy
ing AILS, the Division of Pediatric
clinicians
General and Thoracic Surgery
to focus on
mapped out QI capability planning across seven subspecialty
their clinical
programs with quarterly and
work while
yearly goals for Fiscal Year 2013
still directing
and beyond, launched five Rapid
strategic QI
Cycle Improvement Collaborative
work.
teams, and trained three students
in the Intermediate Improvement
Science Series program. Figure 3 displays
the Division of Pediatric General and
Thoracic Surgery care delivery system
dashboard, which has been critical to
achieving a more integrated approach to
maintaining and aligning the Surgery Division’s QI projects to advance organizational
strategic initiatives.3 The AILS program
helped clarify the Division of Pediatric
General and Thoracic Surgery’s QI aims,
boundaries, and core processes across
domains of safety, productivity, outcomes
and clinical excellence, patient and family experience, and value.3 Figure 4 is an
example of a high-level diagram outlining
the incorporation of the core objectives
into the appendicitis improvement work.
The AILS program highlighted the need
for a multidisciplinary leadership team that
works together to overcome challenges
and barriers in achieving QI goals by executing work in a coordinated, intentional
manner. The Division of Pediatric General
and Thoracic Surgery now possesses the
necessary components—proper infrastructure, clear governance, and coordination—
to achieve and to sustain results. v
to disclose.
Acknowledgments
Special thanks to John Gaskey, MHA, who
participated in the Advanced Improvement
Leadership Systems training, to Alicia Vincent,
who has contributed greatly to building capability and capacity for improvement in our
Division, and to Uma Kotagal, MBBS, MSc,
and Geraldine Kaminski, MS, DA, who developed and taught the Advanced Improvement
Leadership Systems process and supported
and mentored us in this important work.
Communications provided editorial
assistance.
References
1. Institute of Medicine: Committee on Quality
of Health Care in America. Kohn LT, Corrigan
JM, Donaldson MS, editors. To err is human:
building a safer health system. Washington,
DC: National Academy Press; 2000.
2. Institute of Medicine: Committee on Quality of
Health Care in America. Crossing the quality
chasm—a new health system for the 21st
century. Washington, DC: National Academy
Press; 2001.
3. Margolis P, Provost LP, Schoettker PJ, Britto MT.
Quality improvement, clinical research, and
quality improvement research—opportunities for integration. Pediatr Clin North Am
2009 Aug;58(4):831-41. DOI: http://dx.doi.
org/10.1016/j.pcl.2009.05.008
4. Kaminski GM, Schoettker PJ, Alessandrini
EA, Luzader C, Kotagal U. A comprehensive
model to build improvement capability in
a pediatric academic medical center. Acad
Pediatr 2013. [Forthcoming]. DOI: http://dx.doi.
org/10.1016/j.acap.2013.02.007
5. Langley GJ, Nolan KM, Nolan TW, Norman CL,
Provost LP. The improvement guide: a practical
approach to enhancing organizational performance. 2nd ed. San Francisco, CA: Jossey-Bass
Publishers; 2009.
6. Berwick DM, Nolan TW, Whittington J. The
triple aim: care, health, and cost. Health Aff
(Millwood) 2008 May-Jun;27(3):759-69. DOI:
http://dx.doi.org/10.1377/hlthaff.27.3.759
7. Batalden PB, Nelson EC, Mohr JJ, et al.
Microsystems in health care: part 5. How
leaders are leading. Jt Comm J Qual Saf 2003
Jun;29(6):297-308.
8. Godfrey MM, Nelson EC, Wasson JH, Mohr JJ,
Batalden PB. Microsystems in health care: part
3. Planning patient-centered services. Jt Comm
J Qual Saf 2003 Apr;29(4):159-70.
9. Nelson EC, Godfrey MM, Batalden PB, et al.
Clinical microsystems, part 1. The building
blocks of health systems. Jt Comm J Qual
Patient Saf 2008 Jul;34(7):367-78.
Modeling the Way
A leader who models the way is one who shares beliefs about leading; breaks projects into steps; sets personal example; talks about guiding values; follows through on promises; and sets clear goals and plans.
— The Leadership Challenge, James M Kouzes and Barry Z Posner
46
Review article
Deep Brain Stimulation for the Treatment of Severe, Medically Refractory Obsessive-Compulsive Disorder
Mark Sedrak, MD; William Wong, MD; Paul Wilson, MD; Diana Bruce, PA-C, MSHS; Ivan Bernstein, PA-C, MSPAS, MPH;
Suketu Khandhar, MD; Conrad Pappas, MD, PhD; Gary Heit, MD, PhD; Eric Sabelman, PhD
Perm J 2013 Fall;17(4):47-51
Abstract
Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment
of movement disorders and pain syndromes. The therapy includes implantation of electrodes
in specific targets of the brain, delivering programmable small and safe electric impulses,
like a pacemaker, that modulates both local and broad neurologic networks. The effects are
thought to primarily involve a focus in the brain, probably inhibitory, which then restores
a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to
high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric
disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation
offers new hope for these unfortunate patients, and the preliminary results are promising.
Historic Review
of Psychiatric Surgery
Surgical interventions for the treatment
of psychiatric illness began in 1932, when
Antonio Egas Moniz observed that an extensive bilateral frontal lobe lesioning in a
monkey produced a tame, calm animal.1
He then extended this result to humans
in 1936 and developed the first somatic
therapy of the modern era for psychiatric
conditions—the frontal lobotomy. He
was corecipient of the 1949 Nobel Prize
for this work. James Papez formulated
the so-called Papez Circuit at about the
same time based on his work involving
feline rabies infections. The Papez Circuit
defined a core circuit of neuroanatomical
connections that were thought to underlie
emotional behaviors.2 Many of these structures have been studied since those times,
in vast detail, and found to be excellent
targets for surgical therapy.
From the beginning, psychiatric surgery
has been exalted and celebrated but also
mired in ethical, moral, and scientific
controversy. These swings reflect not only
the complex social currents of the time but
also the evolving scientific milieu and the
personalities of the prominent advocates
of psychiatric surgery. In Moniz’s time,
the bilateral frontal lobotomy promised
“salvation” and stood in contrast to bleak
alternatives, which included lifetime
institutionalization under inhumane
conditions. Less attention, therefore, was
focused on the obvious adverse sequelae
of loss of frontal initiative and personality changes caused by these nonspecific
ablative procedures. These procedures
reached their pinnacle with Freeman’s
cavalier application of orbital frontal
leucotomies in the mid-1960s.3 The emergence of successful pharmacologic agents
for the treatment of psychiatric illnesses
was the final force driving orbital frontal
leucotomies from favor.
A subsequent somatic therapy, electroconvulsive therapy, did little to increase
enthusiasm for nonpharmacologic somatic
therapies.4 Despite the loss of interest in
ablative surgical interventions for psychiatric diseases, centers in Europe and in
the US continued to refine indications,
techniques, and targets for psychosurgery. Ultimately, these centers helped
define criteria for surgical intervention
and localize targets of ablation. The Massachusetts General Hospital group refined
cingulotomy for refractory obsessivecompulsive disorder (OCD), and a group
at the Catholic University of Leuven in
Belgium refined capsulotomy for the same
indications.5,6 Remarkably, both groups
independently defined similar indications
for surgery. They both discovered that the
interventions improved OCD. Appropriate
surgical candidates were defined as those
who had failed all somatic therapies,
inclusive of multiple trials of pharmacologic agents and appropriate behavioral
therapies.
The use of these approaches, particularly in the US, was hampered by a vigorous debate about the potential misuse of
psychiatric somatic therapies as an instrument of social control, based on fears of
mind control by the government amidst
the prevailing social climate. These fears
were reinforced with the publishing of
Ervin and Marks’ Violence and the Brain,7
which proposed the use of these therapies
for control of what was then perceived as
sociopathic behaviors arising from aberrant neural processes.8-10 These concerns
led to the State of California adopting
legislation to regulate somatic therapies
for psychiatric diagnosis, inclusive of
psychiatric surgery.11
As technology evolved, stereotactic
radiosurgery, an incisionless technique,
first came into significant use in the 1970s
Mark Sedrak, MD, is the Director of Stereotactic and Functional Neurosurgery for The Permanente Medical Group and a Neurosurgeon
at the Redwood City Medical Center in CA. E-mail: mark.f.sedrak@kp.org. William Wong, MD, is a Psychiatrist at the Redwood City
Medical Center in CA. E-mail: william.t.wong@kp.org. Paul Wilson, MD, is the Chief of Psychiatry and a Psychiatrist at the Redwood
City Medical Center in CA. E-mail: paul.wilson@kp.org. Diana Bruce, PA-C, MSHS, is Physician Assistant in Functional Neurosurgery at
Redwood City Medical Center in CA. E-mail: diana.m.bruce@kp.org. Ivan Bernstein, PA-C, MSPAS, MPH, is a Physician Assistant in
Functional Neurosurgery at the Redwood City Medical Center in CA. E-mail: Iivan.p.bernstein@kp.org. Suketu Khandhar, MD, is the
Director of Movement Disorders for The Permanente Medical Group and a Neurologist at the Sacramento Medical Center in CA.
E-mail: suketu.m.khandhar@kp.org. Conrad Pappas, MD, PhD, is a Neurosurgeon at the Sacramento Medical Center in CA.
E-mail: conrad.pappas@kp.org. Gary Heit, MD, PhD, is the Former Director of Stereotactic and Functional Neurosurgery for
The Permanente Medical Group in Redwood City, CA. E-mail: garyheit@gmail.com. Eric Sabelman, PhD, is a Bioengineer in
Functional Neurosurgery at Redwood City Medical Center in CA. E-mail: eric.sabelman@kp.org.
47
REVIEW article
Figure 1. Diffusion tensor image demonstrating connections between prefrontal cortex
regions and the ventral portion of the anterior limb of the internal capsule (ALIC) and
the adjacent ventral capsule ventral striatum (VC/VS). Yellow box in upper left corner is
a 3x3mm voxel seed point. Tractography was set at threshold of 0.15 and minimal fiber
length of 15mm. Intense orbitofrontal connections are seen. Other fiber pathways include
dorsolateral prefrontal cortex, supplementary motor, sensorimotor, uncinate fasciculus,
inferior occipitofrontal fasciculus, thalamus, and various dorsal mesencephalic pathways.
Figure 2. Frontal section
through the target area, giving the topographic relations
between internal capsule,
nucleus accumbens, and bed
nucleus of stria terminalis.
Target point: 3 mm rostral CA,
7 mm right lateral of midline.
3-4 mm ventral of AC-PC line.
Green: rostral edge of bed
nucleus of stria terminalis.
White: caudal part of anterior
limb of internal capsule.1
1. Sturm V, Lenartz D, Koulousakis A,
et al. The nucleus accumbens: a
target for deep brain stimulation in
obsessive-compulsive- and anxietydisorders. J Chem Neuroanat 2003
Dec;26(4):293-9.
DOI: http://dx.doi.org/10.1016/j.
jchemneu.2003.09.003
48
and involved ablating either the anterior
limb of the internal capsule (capsulotomy)
or the posterodorsal cingulum bundle (cingulotomy), which connects the cingulate
cortex with orbitofrontal and dorsolateral
convexities (Figure 1).12,13 This procedure
has had a response rate of up to 64% in
individuals with OCD. Enlargement of the
initial ablative zone in a second procedure,
however, is often required to achieve the
64% response rate and can lead to major
complications including altered frontal
lobe functioning (disinhibition and abulia)
as well as radiation necrosis.14 Although
outcomes reflected an impressive long-term
response in an otherwise intractable disease
and desperate population, the irreversible
nature of the intervention and the historic
misapplication of other ablative psychiatric
surgeries limited the adoption of stereotactic
radiosurgery for psychiatric indications.
Psychiatric surgery, however, has taken
on new vigor with the introduction of
a minimally invasive, reversible somatic
therapy: deep brain stimulation (DBS).
DBS has evolved and gained in popularity
through its safe application in the treatment
of Parkinson disease, essential tremor, and
dystonia.15,16 Both the efficacy and complication rate for the DBS implantation procedure
are now well defined, derived from outcomes of tens of thousands of DBS implantations performed worldwide for movement
disorders.17 Serious complications with
long-lasting, severe neurologic sequelae or
death occur at a rate between 0.5% and 1%.
Remaining complications, such as stroke
or intracranial hemorrhage without lasting
symptoms, skin erosions, seizures, device
failure, and infection, have been reported
to occur at rates of 3% to 15%.18
The relative safety of DBS coupled with
identification of potential efficacious therapeutic targets has led to trials of its effectiveness in treatment-refractory OCD.6,19,20 The
results of these trials led to the US Federal
Drug Administration’s Humanitarian Device
Exemption approval of DBS for treatmentrefractory OCD in 2009.21
Obsessive-Compulsive
Disorder and Deep Brain
Stimulation
OCD is categorized as an anxiety disorder and is marked by recurrent obsessive thoughts and compulsive behaviors.22
Affecting about 1% to 3% of the adult
Review article
population, it is one of the most common
anxiety disorders.23 In 50.6% of these patients, OCD is classified as severe.24 OCD
can be extremely disabling because of
the time the affected individual spends
performing compulsive behaviors and the
mental energy required to distract oneself
from obsessive thoughts. In a 2000 World
Health Organization mental health report,25
OCD was estimated to be the 11th leading
cause of nonfatal burden in the world,
accounting for 2.5% of total global years
lost to disability. Moreover, many other
research reports cite OCD as the fourth-
most common mental illness, after phobias,
substance abuse, and major depression.
Conventional treatments for OCD are
well established.26 Cognitive-behavioral
therapy, including exposure and ritual
prevention, and medications, particularly
serotonin reuptake inhibitors, are first-line
treatments. In a naturalistic clinical study,
over one-third of participants receiving
recommended doses of serotonin reuptake inhibitors did not perceive substantial
long-term benefit from pharmacotherapy.27 Treatment of OCD rarely results in
complete remission.
OCD exacts a huge toll on patients and
is a heavy economic burden. Between
10% and 27% of OCD patients attempt
suicide at least once in their lifetime.28
Total annual cost of OCD was estimated
to be $8.4 billion, constituting 5.7% of the
total mental health care cost in 1990. This
includes both direct and indirect costs.
Direct costs are for outpatient services
by physicians and other professionals,
hospital care, supported housing and
administrative costs, and private health
insurance. These accumulate to $2.1
billion. Indirect costs, reflecting lost
Table 1. Outcomes of deep brain stimulation for obsessive-compulsive disorder
Jadad
score
3
0
Doubleblind
Yes
No
Started/
finished, n
6/4
3/3
Final
observation, mo
21
33-39
Nuttin3
4
Yes
6/4
21
fMRI, PET
Sturm4
Abelson5
Greenberg6
0
3
4
No
No
Yes
4/4
4/4
10/8
30-34
10
36
fMRI, PET
PET
Jiménezb7
Mallet8
0
4
Yes
Yes
1/1
18/16
3
Nuttin9
4
Yes
6/6
21
Study
Nuttin1
Gabriëls2
Cerebral
blood flow
fMRI, PET
PET
Clinical
scales
POMS
BPRS, POMS,
Y-BOCS
CGI, Y-BOCS
GAF, HDRS
HDRS,
Y-BOCS
GAF
GAF, CGI,
MADRAS,
MDRS, MINI,
Y-BOCS
CGI, Y-BOCS
DBS
location
AL/IC
AL/IC
Adverse
effectsa
AL/IC,
DMNT
Right NA
AL/IC
AL/IC,
VC/C
ITP
STN
AL/IC
Improved,
n (%)
3 (75)
2 (67)
Recovered,
n (%)
3(75)
Mild dizziness
Seizure,
hypomania,
relapse with
battery failure
15 major
including a brain
hemorrhage; 22
minor
4 (100)
3 (75)
2 (25)
1 (25)
4 (50)
1 (100)
10 (62)
1 (100)
4 (25)
3 (50)
other than minor surgical effects.
b
In this study, one patient with obsessive-compulsive disorder and another with treatment resistant depression underwent DBS.
AL/IC = anterior limbs of internal capsule; BPRS = Brief Psychiatric Rating Scale; DBS = deep brain stimulation; CGI = Clinical Global Impressions; DMNT = dorsa-medial nucleus
of the thalamus; fMRI = functional magnetic resonance imaging; GAF = Global Assessment of Scale; HDRS = Hamilton Depression Rating Scale; ITP = inferior thalamus peduncle;
MADRS = Montgomery-Asberg Depression Rating Scale; MDRS = Mattis Dementia Rating Scale; MINI = Mini International Neuropsychiatric Interview; mo = month; NA = nucleus
accumbens;
PET = positron-emission tomography; POMS = Profile of Mood States; STN = subthalamic nucleus; Y-BOCS = Yale-Brown Obsessive-Compulsive Scale.
a
1. Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B. Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder.
Lancet 1999 Oct 30;354(9189):1526. DOI: http://dx.doi.org/10.1016/S0140-6736(99)02376-4
2. Gabriëls L, Cosyns P, Nuttin B, Demeulemeester H, Gybels J. Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and
neuropsychological outcome in three cases. Acta Psychiatr Scand 2003 Apr;107(4):275-82. DOI: http://dx.doi.org/10.1034/j.1600-0447.2003.00066.x
3. Nuttin BJ, Gabriëls LA, Cosyns PR, et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 2003 Jun,52(6):1263-74;
DOI: http://dx.doi.org/10.1227/01.NEU.0000064565.49299.9A
4. Sturm V, Lenartz D, Koulousakis A, et al. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. J Chem Neuroanat 2003
Dec;26(4):293-9. DOI: http://dx.doi.org/10.1016/j.jchemneu.2003.09.003
5. Abelson JL, Curtis GC, Sagher O, et al. Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 2005 Mar 1;57(5):510-6. DOI: http://dx.doi.org/10.1016/j.
biopsych.2004.11.042
6. Greenberg BD, Malone DA, Friehs GM, et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 2006
Nov;31(11):2384-93. DOI: http://dx.doi.org/10.1038/sj.npp.1301165
Erratum in: Neuropsychopharmacology 2006 Nov;31(11):2394. DOI: http://dx.doi.org/10.1038/sj.npp.1301201
7. Jiménez F, Velasco F, Salín-Pascual R, et al. Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder. Acta Neurochir Suppl 2007;
97(Pt 2):393-8. DOI: http://dx.doi.org/10.1007/978-3-211-33081-4_44
8. Mallet L, Polosan M, Jaafari N, et al; STOC Study Group. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 2008 Nov 13;359(20):2121-34.
Erratum in: N Engl J Med 2009 Sep3;361(10):1027. DOI: http://dx.doi.org/10.1056/NEJMoa0708514
9. Nuttin BJ, Gabriëls LA, Cosyns PR, et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 2008 Jun;62(6 Suppl 3):966-77.
DOI: http://dx.doi.org/10.1227/01.neu.0000333764.20575.d6.
Modified and reprinted under the auspices of the Creative Commons Attribution Lecense from Lakhan SE, Callaway E. Deep brain stimulation for obsessive-compulsive disorder and
treatment-resistant depression: systematic review. BMC Res Notes 2010 Mar 4;3:60. DOI: http://dx.doi.org/10.1186/1756-0500-3-60
49
REVIEW article
productivity of individuals dying from
or otherwise suffering from the disorder,
were estimated at $6.2 billion, or 73.8%
of the total cost of OCD.29 According
to one survey, 21.8% of severe OCD
patients undergo psychiatric
hospitalization during a year
… a 38.7%
of treatment.30 Of these, more
decrease in
than 50% are hospitalized more
Y-BOCS scores at
than once, and more than 10%
12 months. This
experience 5 or more hospilevel of symptom
talizations. The average cost
reduction is
per hospitalization is approxiequivalent to
mately $12,500. Approximately
full response as
28% of OCD patients receive
inappropriate treatment (no
defined by the
serotonin reuptake inhibitors
Expert Consensus
or behavior therapy), such that
Panel on OCD.
for each of them about $4000
per year is spent on nonproductive outpatient provider costs and
$1500 per year is spent on ineffective
medication. This amounts to approximately $2 billion per year for ineffective
treatment.31 In a retrospective analysis of
claims data from a large, prepaid health
plan, Koran et al found that OCD patients
had 63% higher mean annual costs for
nonpsychiatric (ie, medical) visits, and
56% higher costs for laboratory and radiology services compared with patients
with no psychiatric visits.32
Abnormalities in so-called corticostriatal-thalamic-cortical loops seem to
be involved in the pathophysiology of
OCD.33 Recent diffusion tensor magnetic
resonance imaging tractography data
demonstrate rich interconnections between
these systems in the anterior limb of the
internal capsule target area.34,35 Connections between the orbitofrontal cortex,
medial prefrontal cortex (anterior and
rostral cingulate gyrus), caudate, ventral
striatum, anterior cingulate nucleus accumbens, bed nucleus of the stria terminalis,
and thalamus are central to OCD (Figure
2). Numerous studies have demonstrated
associated abnormal metabolic activity in
these regions, with normalization following
successful somatic therapies inclusive of
DBS.20,34,36,37 Acute DBS has been shown to
increase perfusion to the orbitofrontal cortex, anterior cingulate, striatum, pallidum,
and thalamus.19 Interestingly, normalization
of subsystems in this network is seen with
any effective treatment for OCD, be it behavioral or pharmacologic intervention or
50
the aforementioned somatic intervention.36
Results of DBS for the treatment of
severe OCD have been published for at
least 9 studies (Table 1). Six of these studies were double-blind. In the double-blind
studies, improvement rates ranged from
25% to 100%. Pooled together, 22 out of
43 (51%) study participants responded.38
More specifically, Abelson et al reported on 4 patients with medically intractable OCD who participated in a doubleblind crossover stimulation paradigm in
the anterior limb of the internal capsule,
the site of prior ablative brain targeting
and interventions.20 Yale-Brown Obsessive
Compulsive Scale (Y-BOCS) score, used
to measure OCD symptom severity in
all active-stimulation patients, decreased
from 30 to 10 (a decrease from severe to
mild symptom intensity) during each of
the ON-STIM testing periods; researchers
and patients were blinded to ON and
OFF stimulation status. Greenberg et al19
reported 3-year follow-up data for 9 OCD
patients with stimulating leads implanted
in the anterior limb of the internal capsule.
Eight patients had been followed up for
at least 36 months. Mean Y-BOCS score
decreased from 34 (severe) at baseline to
22 (moderate) at 36 months (p < 0.001).
Four of 8 patients had a 35% decrease
in Y-BOCS at 36 months; in 2 patients,
scores declined between 25% and 35%.
Depression and anxiety improved, as
did functioning in self-care, independent
living, work, school, and social domains.
These data led to a multicenter DBS
trial conducted by Medtronic.6 Deep brain
stimulating leads were implanted in a total
of 29 patients, with a 38.7% decrease in
Y-BOCS scores at 12 months. This level
of symptom reduction is equivalent to
full response as defined by the Expert
Consensus Panel on OCD. A responder is
a subject with a 25% reduction in Y-BOCS
score. These data were used to obtain a
Humanitarian Device Exemption from
the Federal Drug Administration that was
approved in 2009.39 Since then, a number
of small studies have been done using
DBS in a variety of targets.38,40 Stronger
research designs using blind or crossover
protocols are problematic because stimulation produces rapid and marked clinical
effects.41 Patients feel the dramatic effects
of stimulation immediately, breaking the
on and off blinding spontaneously and
making crossover studies impractical—
a testament to the dramatic effects of DBS.
Conclusion
DBS is established as a safe, reversible,
adjustable, efficacious, evidence-based
treatment for severe, refractory OCD. Patients with severe, refractory OCD suffer
from high morbidity, and the illness exacts
an enormous toll on their well-being.
Considerable resources are devoted to
reducing their suffering. The emergence
of DBS as a highly effective treatment
for this population offers them hope of a
much higher quality of life as well as more
effective and efficient use of their financial
resources. The Permanente Medical Group
is uniquely situated to define and develop
the appropriate scope of application of this
promising intervention. v
to disclose.
Acknowledgment
Leslie Parker, ELS, provided editorial
assistance.
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Inherently Mysterious
One of the reasons that [the brain] remains so mysterious is that it is governed by both mechanical and
quantum principles. As a result, the brain is inherently indeterminate, unpredictable, and uncertain.
— Richard Restak, b 1942, American neurologist, neuropsychiatrist, author, and professor
51
Review article
Evaluating the State of Quality-Improvement Science through Evidence
Synthesis: Insights from the Closing the Quality Gap Series
Kathryn M McDonald, MM; Ellen M Schultz, MS; Christine Chang, MD, MPH
Perm J 2013 Fall;17(4);52-61
Abstract
Context: The Closing the Quality Gap series from the Agency for Healthcare Research
and Quality summarizes evidence for eight high-priority health care topics: outcomes
used in disability research, bundled payment programs, public reporting initiatives,
health care disparities, palliative care, the patient-centered medical home, prevention
of health care-associated infections, and medication adherence.
Objective: To distill evidence from this series and provide insight into the “state of
the science” of quality improvement (QI).
Methods: We provided common guidance for topic development and qualitatively
synthesized evidence from the series topic reports to identify cross-topic themes, challenges, and evidence gaps as related to QI practice and science.
Results: Among topics that examined effectiveness of QI interventions, we found improvement in some outcomes but not others. Implementation context and potential harms
from QI activities were not widely evaluated or reported, although market factors appeared important for incentive-based QI strategies. Patient-focused and systems-focused
strategies were generally more effective than clinician-focused strategies, although the
latter approach improved clinician adherence to infection prevention strategies. Audit
and feedback appeared better for targeting professionals and organizations, but not
patients. Topic reviewers observed heterogeneity in outcomes used for QI evaluations,
weaknesses in study design, and incomplete reporting.
Conclusions: Synthesizing evidence across topics provided insight into the state of
the QI field for practitioners and researchers. To facilitate future evidence synthesis,
consensus is needed around a smaller set of outcomes for use in QI evaluations and a
framework and lexicon to describe QI interventions more broadly, in alignment with
needs of decision makers responsible for improving quality.
Introduction
The quality of health care in the US is
widely recognized as needing improvement. Indeed, as many as 50% of all
patients, on average, may receive suboptimal care.1-3 Yet quality is improvable,
and efforts to make improvements are
widespread.1,4,5
Just as medical science focuses on treating ailments and supporting the health
of the human body through medical,
surgical, pharmacologic, and preventive interventions, the science of quality
improvement (QI) focuses on “treating”
quality gaps and supporting optimal
performance of the health care system
through improvement interventions and
quality monitoring. A key question for
both medical and improvement science is
how altering one part of a system—either
the human body or the health care system—produces desired results. Additional
questions relate to how interventions
interact with the surrounding environment and circumstances (the context of
change) and how delivery of the intervention (implementation of change) has an
impact on effectiveness. Many of the tools
of medical research that were tailored to
answer such questions have also been
applied to improvement science, including systematic reviews and meta-analyses.
In 2004, the Agency for Healthcare
Research and Quality (AHRQ) launched
a collection of systematic reviews on QI
strategies related to high-priority chronic
conditions (eg, diabetes, asthma, hypertension), practice areas (eg, prevention of
health care-associated infections, antibiotic prescribing behavior), and processes
(eg, care coordination) identified by the
Institute of Medicine.6-12 AHRQ followed
this collection with a new series of eight
evidence reports—Closing the Quality
Gap: Revisiting the State of the Science—
to continue the focus on improving the
quality of health care, including current
efforts to reward high-quality care through
measurement and reporting as well as key
tenets of health care reform legislation
passed under the Patient Protection and
Affordable Care Act.13 In addition, through
two cross-topic synthesis projects,14,15 the
new series of reports also sought to illuminate broader lessons about the state
of QI science by aggregating evidence
in a qualitative way across the sample of
topics included in the series.
This article builds on that synthesis,
summarizing the “state of the science”
for the effectiveness, implementation
decision factors, and evidence base of
the QI field on the basis of findings from
the most recent Closing the Quality Gap
series of topic reports.
Methods
Series Topics
The Closing the Quality Gap series included eight topics selected by leaders in
AHRQ for their relevance to high-priority
populations, settings, and processes,4 and
to provisions of the Affordable Care Act
(Table 1). Selected topics were also ripe
for systematic review and expected to yield
Kathryn M McDonald, MM, is a Senior Scholar and Executive Director of the Center for Health Policy/Center for Primary Care
and Outcomes Research at Stanford University in CA. E-mail: kathryn.mcdonald@stanford.edu. Ellen M Schultz, MS, is a Project
Coordinator at the Center for Health Policy/Center for Primary Care and Outcomes Research at Stanford University in CA.
E-mail: emschultz@stanford.edu. Christine Chang, MD, MPH, is a Medical Officer at the Center for Outcomes and Evidence
of the Agency for Healthcare Research and Quality in Rockville, MD. E-mail: christine.chang@ahrq.hhs.gov.
52
Review article
Evaluating the State of Quality-Improvement Science through Evidence Synthesis: Insights from the Closing the Quality Gap Series
actionable evidence for patients, practitioners, health systems, and policy makers.
We mapped these topics to three
core approaches (“3 Is”) for achieving
improvements, as noted by health care
systems researcher Victor Fuchs,16 who
said that real reform “requires changes in
the organization and delivery of care that
provide physicians with the information,
infrastructure, and incentives they need
to improve quality and control costs.” In
today’s complex health care system, these
leverage points for improvement apply
beyond the physician to include other
clinicians, systems managers, and patients
themselves. The set of topics selected for
the series address each of these three core
approaches (see Table 1).
Topic Reviews
Each topic was reviewed by a team
from an AHRQ Evidence-based Practice
Center (EPC) using a standard methods
guide. 17 Complete details of review
methods for each topic are available in
the individual topic reports.18-25 A brief
summary is presented here. In conjunc-
tion with topic-specific technical expert
panels, team members of each EPC developed a set of key questions to guide their
review. The EPC teams searched a wide
variety of literature databases, including at
a minimum MEDLINE, and an average of
25 years of literature for each topic (range,
5 to 65 years). They identified relevant
articles through multiple rounds of review
and abstracted detailed information from
each included study. All studies were
evaluated for quality and potential bias
using a standard protocol. Likewise, when
reported and applicable, evaluations of
strength of evidence across studies also
followed standard methods.17
Cross-Topic Synthesis
Results presented in this article are
based on the eight series topic review
reports.18-25 We initially provided common
guidance to each topic review team for
the series to facilitate cross-topic synthesis. Then we reviewed the evidence
presented in the reports, including tables
and text, to identify cross-cutting themes,
take-home lessons, common challenges,
Table 1. Closing the Quality Gap series topics and primary focus for leverage to
improve quality of care
Topic
Focus
Information: Providing information about outcomes used in evaluating health care quality
Disability outcomes18
Identify outcomes measures used in quality-focused research
involving people with disabilities
Incentives: Influencing improvement through payment changes and quality monitoring
Bundled payment20
Examine the influence on organizations of adopting payment bundling
as an approach for paying for care (contrasted with fee-for-service
models), and how organizational response to such new incentives
either enhances or deters health care quality, including efficiency
Public reporting23
Understand how public reporting of health care quality information
affects behaviors of people and organizations in ways that potentially
improve the quality of care received by patients
Infrastructure: Changing delivery infrastructure to improve quality of care
Disparities22
Examine the benefits and harms of quality-improvement interventions
aimed specifically at reducing disparities in care
Palliative care19
Examine the impact on health care quality of various aspects of
palliative care, including palliative care delivered in hospice and
nursing homes
Patient-centered medical Understand whether and how implementation of a comprehensive
home (PCMH)25
PCMH improves care overall for the full population of patients served
by a health care organization
Health care-associated
Examine effectiveness of quality-improvement efforts aimed at
infections (HAI)21
improving adherence with evidence-based HAI-prevention strategies,
including at ambulatory surgical centers, dialysis centers, and longterm care facilities
Medication adherence24
Address both the efficacy and effectiveness of interventions designed
to improve medication adherence for adults with chronic conditions,
including system and policy-level interventions
and evidence gaps as they relate to the
science of QI. Thus, this synthesis is based
on comparisons across the series topic
reports rather than on primary studies
reviewed in those reports. We did not
perform quantitative meta-analyses, but
instead focused on qualitative synthesis
to provide insight into the field of QI. Additional discussion of topic-specific findings and implications for key stakeholder
audiences may be found in the series
summary report15 and an accompanying
methods report.14
Key Questions
We developed a set of series key questions to guide evidence synthesis across
series reports. These key questions focus
on the “state of the science” for three core
aspects of QI: effectiveness, implementation decision factors, and evidence. The
key question areas are as follows:
1.What is the state of the evidence for the
effectiveness of QI activities? What outcomes have been examined in evaluating effectiveness? What is known about
the benefits and harms of particular
types of QI strategies or targets?
2.What is the state of the science for
factors of likely importance to those
individuals and organizations deciding
whether and how to implement QI
interventions? What is known about
the role of context and implementation
approaches/challenges in QI activities?
What is known about the impact of QI
activities on disparities or vulnerable
populations?
3.What is the state of QI and implementation science evidence? What gaps exist
in the quality of evidence or in methods
for evidence synthesis?
We summarized evidence of effectiveness—both benefits and potential
harms—for the series topics (excluding
disability outcomes, which focused on
use of outcomes and did not address effectiveness) and considered the role of
outcomes choice in effectiveness evaluations. We also examined evidence of effectiveness for QI strategies by type, using
a taxonomy of improvement strategies
developed for the first Closing the Quality
Gap series.10 We grouped these strategies by the intervention target—patients,
clinicians, or systems/organizations—to
further analyze evidence of effectiveness.
53
REVIEW article
Table 2. Summary of key findings for intervention-focused series topicsa
Mixed or no evidence
of improvement
Mixed impact on quality measures (variable
magnitude and direction of effects)
Topic
Bundled
payment
Evidence of improvement
Small decreases in health care
spending (≤10%) and health care
utilization (5%-15% reduction)
Public
reporting
Hospital-level reporting shows
decreased mortality
Health plan and long-term-carelevel reporting shows improved
pain, pressure ulcers, patient/family
satisfaction
Clinicians and health care
organizations responded to public
reporting by offering new services,
changing policies, and by increasing
quality-improvement activities
Few patients use public reports to make
health care decisions; reports lack
relevance or clarity or are unavailable
when needed
Disparities
A single study showed reduced disparity
in HbA1c testing among black vs white
patients with a disease management
and patient education program
Limited evidence of amplified effects
of collaborative care and languageconcordant patient education
strategies in vulnerable populations
Interventions targeting:
Pain: improved pain-related outcomes
Coordination: improved patient/family
satisfaction
Communication/decision making:
improved health care utilization
Insufficient evidence for changes in
disparity after quality-improvement
interventions; few studies addressed the
research question
Palliative care
Patient-centered
medical home
(PCMH)
Health careassociated
infection (HAI)
Medication
adherence
Small improvements in patient and
staff experiences (satisfaction with
care, perception of coordination)
Decreased use of Emergency
Department by older adults
Small positive effects on delivery of
preventive services
Some combinations of strategies
show improved adherence to best
practices and lower infection rates
Adherence improved with policylevel change decreasing patients’
out-of-pocket costs and several other
patient-focused strategies
Potential harms or unintended
consequences
Single-setting bundled payment programs
resulted in care shifting to other settings
Few studies addressed other potential harms
Overall, evidence of no harm outweighed
evidence of harm
Mixed results and low-quality evidence about
impact of public reporting on patient access
Some evidence that public reporting in longterm care led to changes in coding practices
and readmitting patients before reporting
assessment
Evidence refuted claims that public reporting
leads surgeons or health care organizations
to withdraw from the market or that public
reporting is associated with declines in quality
of unmeasured aspects of care (crowding out)
No studies addressed potential harms
Interventions targeting:
Pain: no improvement in QOL or health
care utilization
Coordination: no improvement in QOL,
symptoms, or health care utilization
Communication: no improvement in patient/
family satisfaction or health care utilization
No interventions using only clinicianfocused strategies were effective
No decrease in hospital admissions for
older adults
No evidence of cost-savings with PCMH
Not examined
Organizational change and clinician
education alone did not improve adherence
or infection rates
Insufficient evidence to draw conclusions
about improvements in cost savings or
return on investment
Decreasing patients’ costs did not improve
adherence with inhaled corticosteroids
Only a subset of studies showing improved
adherence also improved other diseasespecific clinical outcomes
Studies of medication adherence
interventions rarely examined impacts on
health care utilization or costs; evidence is
inconclusive
No studies addressed potential harms
Limited evidence from two studies found that
when program costs were considered, the
overall cost of care was greater for the PCMH
intervention
No other evidence on potential harms from
PCMH reported in included studies
Few studies addressed potential harms
a
The disability outcomes report did not evaluate the effectiveness of quality-improvement interventions and therefore is not included in this table.
HbA1c = glycosylated hemoglobin; QOL = quality of life.
54
Review article
To examine the state of the science regarding factors likely to inform implementation decisions, we summarized findings
from each report that relate to the context
of QI implementation or evaluation, implementation approaches and challenges,
and the impact of QI efforts on health
disparities or on vulnerable populations.
Finally, we evaluated the state of the science on the basis of the entire evidence
base, summarizing common challenges
encountered by the EPCs and identifying
gaps in the evidence and in systematic
review methods applied to improvement
and implementation science.
Results
Key Question 1: Effectiveness of
Quality-Improvement Strategies
Table 2 summarizes key findings about
the effectiveness of QI efforts for each
of the seven series topics that evaluated
interventions. Authors of all seven topics
found mixed results, with evidence of
benefit for some outcomes but not for
others. For example, the bundled payment
review found evidence that the impact
of payment bundling on quality of care
depended on the quality measure evaluated (Table 2). The medication adherence
review authors found variability in how
adherence was defined, and they noted
that only a subset of studies reporting
improved adherence also showed improvements in other outcomes.
Six reports sought information about
potential harms associated with QI interventions (Table 2). Potential harms were
evaluated most often for the incentivebased interventions (bundled payment,
public reporting), whereas harms were
rarely addressed in the literature reviewed
for the infrastructure-focused intervention topics (disparities, patient-centered
medical home, health care-associated
infections, medication adherence). Although the potential for harm from public
reporting was widely discussed, the review authors found only limited evidence
examining whether harm actually occurred and concluded that evidence of no
harm outweighed evidence of harm. The
bundled payment review found consistent
evidence that single-setting bundled payment programs resulted in care shifting
to other settings, but few other potential
harms were examined. The review authors noted that most current bundled
payment programs are now administered
across settings, which is expected to reduce incentives for care shifting.
The disability outcomes review identified 71 different outcomes measures used
in evaluating health care for disabled
populations. Many of these assessed similar concepts, including health, quality of
life, functioning, and patient experience,
but used different definitions, tools, and
measurement scales. The review authors
also noted that researchers’ perspec-
tive—whether trained and practicing
in medicine, rehabilitation, or social
services—had a profound impact on the
ways in which care and life goals were
conceptualized for people with disabilities, influencing their choice of outcomes
for evaluation.18
Across the series topics, most QI interventions were multifaceted, using more
than one type of improvement strategy
(Table 3). There was greater evidence
of effectiveness for systems-focused
strategies than for either clinician- or
patient-focused strategies. However, most
evidence of systems-focused strategies
related to organizational change, which
can encompass many different kinds of
activities.10 For most topics examined,
clinician-focused strategies were generally less effective than patient-focused
strategies, with the exception of interventions aimed at improving clinician
adherence to strategies to prevent health
care-associated infections. Among the
patient-focused strategies, patient education often showed benefit.
In contrast, evidence of effectiveness
was mixed for patient and clinician
reminder systems and for audit and
feedback strategies (Table 3). The latter
strategies can be patient-focused when
aimed at influencing consumers’ decisions
about where to seek care, such as through
public reporting of quality information.
These strategies can be clinician-focused
Table 3. Effectiveness of quality-improvement interventions by strategy type and targeta
Strategy type
Target: Patients
Education
Promotion of self-management
Reminder system
Audit and feedback
Target: Clinicians
Education
Reminder system
Facilitated relay of clinical data
Audit and feedback
Target: Systems
Organizational change
Financial, incentives, regulation, and policy
Audit and feedback
Bundled
payment
Public
reporting
Disparities
Palliative
care
HAI
Medication
adherence
■
□
■
■
□
□
□
■
■
■
□
□
□
□
□
■
■
□
■
PCMH
□
■
□
■
■
□
■
■
□
■
■
■
■
The disability outcomes report did not evaluate the effectiveness of quality improvement interventions and therefore was not included in this table.
HAI = health care-associated infection; PCMH = patient-centered medical home; ■ = intervention type has been examined, and there is evidence of effectiveness;
□ = intervention type has been examined, but there is no evidence of effectiveness.
a
55
REVIEW article
when aimed at motivating clinicians to
make changes in their practice on the
basis of their performance on quality
measures. Alternatively, the strategies can
be system-focused if intended to influence organizations’ practices or motivate
QI efforts.�Four reports found evidence
related to audit and feedback strategies,
showing that they were not
effective when targeting
… conclusions were
patients but were generbased on moderate
ally effective when targeting
or high strength
clinicians and organizations.
Differences in outcomes
of evidence
seen across topics may rewere: reducing
flect topic-specific differthe patient’s
ences in the locus of control,
out-of-pocket
contextual factors, variable
costs improved
adaptation of intervention
medication
components, interaction
adherence, hospitalbetween intervention comlevel public
ponents, and underlying
reporting decreased
barriers to improved permortality rates, and
formance. Reviews typically
public reporting
found limited details about
the presumed mechanism of
stimulated
an intervention for influencimprovement in
ing behavior (sometimes recompetitive markets
ferred to as the logic model),
and among low
limiting synthesis-based inperformers …
sights about which interventions are effective and why.
Key Question 2: QualityImprovement Implementation
Decision Factors
Many of the reports examined three
key drivers of QI implementation decisions: the role of context, implementation approaches and challenges, and
the impacts of QI efforts on vulnerable
populations or health care disparities
(Table 4). In assessing contextual factors to determine reasons for amplification or dampening of the effect
of an intervention, both the bundled
payment and public reporting reviews
found evidence that these incentivebased strategies were more effective
when financial pressures were greater,
such as in competitive markets (public reporting), and in for-profit or
financially stressed hospitals (bundled
payment). Other reports of contextual
factors varied greatly in the type of
factors examined and their use in the
primary studies, ranging from economic
56
considerations to patient characteristics
(disease severity, age, insurance coverage, health needs) and organizational
characteristics (leadership, change,
resource availability). All five series reports that examined the role of context
in some manner (Table 4) found that
information on contextual factors was
often lacking, incompletely described, or
noted only anecdotally.
Aside from a specific focus on implementation in two reports (health careassociated infections, bundled payment),
and explicit exclusion of implementation
studies in the public reporting review
(because of lack of outcomes available
in relevant studies), the remaining five
reviews had limited coverage of implementation approaches and challenges
(Table 4). Two reports noted challenges
related to clinician resistance to interventions (bundled payment, palliative care)
and two reports identified resource issues
(disparities, patient-centered medical
home). Several reports (patient-centered
medical home, health care-associated
infections, medication adherence) sought
information about approaches used to
enable implementation (eg, toolkits, collaborative learning).
Four reports examined the impact
of QI efforts or choice of evaluation
outcomes on health disparities or vulnerable populations (Table 4). Although
the available literature was limited, the
disparities report found some promise for
reducing disparities in health outcomes
among racial minorities using collaborative care and targeted patient education
interventions. Racial and ethnic minorities
were the most widely studied vulnerable
populations across the topics.
Key Question 3: State of QualityImprovement Evidence
The EPC teams conducting the topic
reviews encountered several common challenges that limited their ability to synthesize
evidence across studies and to address
their research questions. Many of these
challenges stemmed from limitations in the
primary studies. Members of the EPCs for
all eight topics observed great heterogeneity in choice and definition of outcomes
used for QI evaluations. They also noted
study design weaknesses and incomplete
reporting of key details such as intervention
design and its theoretical basis, contextual
factors and impact on outcomes, intervention components, and comparators.
Across the series, just a handful of conclusions were based on moderate or high
strength of evidence (the confidence that
a conclusion reflects a true effect). They
were as follows: reducing the patient’s
out-of-pocket costs improved medication adherence (moderate strength of
evidence), hospital-level public reporting decreased mortality rates (moderate
strength of evidence), and public reporting stimulated improvement in competitive markets and among low performers
(high strength of evidence). The strength
of evidence for most other research questions addressed across the series topics
was low or inconclusive.
These limitations in the primary studies
created challenges in adapting systematic
review methods to the QI literature. The
heterogeneity in outcomes, coupled with
the complexity of multifaceted, systemslevel interventions typical of the QI literature, limited the ability of the EPC teams
to quantitatively synthesize results across
studies. They instead summarized evidence
qualitatively, grouping evidence by particular disease groups, settings, outcomes,
or intervention components. Ambiguity
around use of key terms in the primary
studies (eg, QI itself, as well as some
topic-specific terms such as medical home
and palliative care) complicated development of search strategies. Other systematic
review challenges included assessment of
the body of evidence across heterogeneous
studies and the lack of statistical or other
approaches to synthesize across a diversity
of study designs, intervention components,
implementation factors, contextual factors,
and outcomes.
Some challenges encountered may
positively reflect characteristics of QI
evidence. Whereas heterogeneity in QI
strategies presented difficulties in synthesis
and drawing conclusions, this also reflects
the variety of strategies used in practice
that are likely to be relevant to decision
makers. Similarly, heterogeneity in outcomes offers many different lenses through
which to view quality of care. Furthermore,
despite challenges, the methodologic quality of the evidence base has improved,
as noted by the authors of the report
on health care-associated infections.21
Review article
All reports found a body of evidence to
synthesize. Most reports included various study types to complement evidence
from controlled trials, providing additional
detail that improved the usefulness of
the reports.
Discussion
This Closing the Quality Gap series systematically reviewed and synthesized evidence relating to eight QI topics. Although
far from inclusive of all QI efforts, the eight
topics included within this series represent
a sample of the range of topics, populations, settings, strategies, and improvement
targets within the broader universe of QI
science; they cover three critical leverage
points for improving care: information,
incentives, and infrastructure.16
Table 4. Summary of findings by topic on implementation decision factors
Topic
Disability
outcomes
Context
Not applicable
Implementation approaches
and challenges
Reviewers emphasize that choice of
outcomes can lead to problems if poorly
matched to population needs and values
Some survey evidence that new bundled
payment systems faced initial resistance
from clinicians
For each bundled payment study or set of
studies, topic review includes a section on
reported implementation challenges
Not examined
Bundled
payment
Some weak evidence that bundled
payment decreased health care
utilization more among for-profit
providers compared with not-for-profit
providers and at hospitals under
greater financial pressure
Public
reporting
Strong evidence that public reporting
leads to improvements in competitive
markets and among low performers
Disparities
Not examined
Reviewers noted that some interventions
required substantial programmatic and
implementation resources
Palliative care
Some evidence supported the
effectiveness of both integrative and
consultative models for delivering
palliative care
Payment models used to support
PCMH implementation varied
widely, including receipt of external
study funding, capitation payments,
enhanced fee-for-service, and a hybrid
approach. Fewer than half of studies
described their payment model
Some studies reported challenges with
clinician uptake of interventions, as well as
difficulties with recruitment or retention of
participants in QI activities
Horizon scan identified a number of
planned formative evaluations to identify
factors associated with successful
implementation. Cost to practice noted as
a factor for study
Implementation usually included formal
learning collaboratives or collaborative
program planning for practice team
for members to learn about the new
intervention (19 of 22 studies), and audit
and feedback strategies were often tied to
QI (13 of 22 studies)
QI strategy was defined as the
implementation strategy (eg, clinician
education regarding an HAI preventive
intervention). Implementation materials
were described as a contextual feature for
some interventions
Minimal or unclear information available on
implementation (eg, organizational learning
strategies, use of implementation toolkits,
or fidelity to intervention protocol)
Patient-centered
medical home
(PCMH)
Health careassociated infection
(HAI)
Medication
adherence
Wide variety of contextual factors
reported. Three most commonly
reported factors were availability of
implementation materials, unit-level
changes in responsibilities, and unitlevel leadership
Not examined
Impacts on vulnerable populations
and disparities
Disabled populations rarely included
in studies with nondisabled patients
Not examined
One study found increased disparity
between white and black or Hispanic
patients in the receipt of coronary
artery bypass graft surgery with public
reporting
Few studies have examined QI
strategies as a way to reduce health
disparities
Limited evidence suggests some
reduction in health outcome disparities
with collaborative care and targeted
patient education interventions,
particularly among racial minorities
Not examined
Not examined
Not examined
Interventions generally had a positive
impact on medication adherence
for most vulnerable populations
examined. These populations were
typically defined by race-ethnicity and
medical condition
QI = quality improvement.
57
REVIEW article
Individually, each of the series reviews
offers detailed information that can help
inform QI efforts and decisions related to
its respective topic. Viewing the evidence
together across series reports revealed
broader insights. For example, the finding
that both the incentive-based improvement topics (bundled payment and public
reporting) were sensitive to the market
context—competitiveness of the health
care market, financial pressure on delivery
organizations—suggests that particular attention should be paid to the market and
financial context of any incentive-based
improvement efforts. Context is likely also
important to consider for information and
infrastructure-based improvement efforts.
The disability outcomes reviewers ob-
Table 5. Example typology for quality-improvement interventionsa
Intervention target: The target refers to the person, people, health system, or policy to which
intervention activities are directed. Interventions may directly target providers, patients, aspects of
a health system, health policies, or some combination of these four.24
Intervention agent: An intervention agent is the person, people, or technology used to deliver the
intervention. Examples of possible intervention agents include physicians, nurses, pharmacists,
case managers, multidisciplinary teams, or family members. Some interventions may have more
than one agent delivering an intervention or a part of an intervention.24
Mode of delivery: The mode of delivery refers to the manner by which the agent delivers the
intervention. For example, interventions may be delivered face-to-face, by telephone, with print
materials, or by computer, DVD, video, or CD/audio. Like intervention target and agent, an
intervention may have more than one mode of delivery.24
Intensity of intervention: Intensity refers to the total amount of time an intervention lasts, taking
into account the duration and number of all individual sessions (eg, five 30-minute sessions or one
60-minute session).24
Duration of intervention: In contrast to intensity, the duration of an intervention is a description
of the total length of calendar time over which any series of individual sessions are delivered. Two
interventions may have the same total intensity (eg, five 30-minute sessions) but be spread out
over different total durations of time (eg, one over 1 month, another over 1 year).24
Intervention components: Frequently, multiple components are used to create a multifaceted
intervention strategy.24 One taxonomy developed for the original Closing the Quality Gap series
specifies nine types of improvement strategies:10
Clinician reminder systems
Facilitated relay of clinical data to clinicians
Audit and feedback
Clinician education
Patient education
Promotion of self-management
Patient reminders
Organizational change
Financial, regulatory, or legislative incentives
Implementation context: The circumstances under which the QI intervention is implemented.
One set of contextual factors adapted from the patient safety field26 lends structure and common
language possibilities:
Structural organizational characteristics: organization size, location, financial status, academic
status, complexity, volume, existing quality infrastructure, space/physical environment, use of
information technology, physician ownership, and the dates of study.
External factors: regulatory environment, payments and penalties, local sentinel event, marketplace
competition, competing demands.
Culture, teamwork, leadership: each of these three factors can be examined at the organizational
level or unit level.
Implementation and management tools: includes use of specific improvement strategies targeted
at clinicians or staff (such as education, audit and feedback, or financial incentives) staff education,
designated staff time to implement change, designating an internal or external person responsible
for implementation, local tailoring or use of an iterative process, help desk support, extent of project
management, implementation timeline, and implementation process (one unit at a time or all at once).
Adapted from the medication adherence review,24 the original Closing the Quality Gap series,10 and a patient
safety context report from the Agency for Healthcare Research and Quality.26
CD = compact disk; DVD = digital video disk; QI = quality improvement.
a
58
served that the professional background
of researchers influenced their conception of how to evaluate interventions
for disabled populations, highlighting
the relevance of the evaluation context,
especially choice of outcomes.
Looking across topics, the series also
found evidence supporting the effectiveness of broader types of intervention
strategies, in particular organizational
change. Although specific studies varied
with respect to the kinds of organizational
change implemented (eg, collaborative
care, patient-centered medical home,
case management) and ways in which
organizational change was combined
with other intervention strategies, these
results suggest that this is likely an important component of many effective QI
interventions.
Additional patterns of effectiveness became apparent when examining the target
for improvement strategies. Public reporting, an example of an audit and feedback
strategy, was generally effective in changing clinician and organizational behaviors,
but not patients’ behavior. Qualitative
evidence included in the public reporting
review supported this finding. Interventions that focused solely on clinicians as
a target group tended to demonstrate less
benefit, with the exception of the topic of
health care-associated infections.
The teams from the EPCs also identified
a gap in examination and reporting of
potential harm from QI activities. Although
examination of side effects of medical
therapies is expected in the medical literature, the reviews revealed that few studies
of QI efforts have addressed the potential
for unintended negative consequences.
Among the series topics, public reporting
had received the most attention toward
potential harms, but even for this topic,
the reviewers found that the potential for
harm was discussed far more often than it
was evaluated. This gap in QI evidence is
ripe for development, and it may require
guidelines for evaluating and reporting
harms that may be far-reaching or that
may occur well after the initial intervention.
In addition to these insights, synthesis
of evidence across series topics also sheds
light on the “state of the science” for the
QI field itself. The common challenges
experienced by the teams from the EPCs
highlight areas where additional methods
Review article
or conceptual development is needed.
Inconsistencies in how interventions are
described in the literature point to the
need for an underlying framework and
lexicon to describe QI interventions.
Although a framework and terminology
must be flexible enough to cover the
diverse universe of QI strategies, consistent use of a common set of terms would
help facilitate synthesis of results across
studies, as was done in the cross-topic
review presented in this article. Table 5
presents an example of a typology used
to describe improvement interventions,
adapted from the medication adherence
review.24 As Table 3 demonstrated, combining one element of this typology—the
intervention target—with the taxonomy
of improvement strategies used in the
original Closing the Quality Gap series10
provided insights that apply across topics and that were not readily apparent
without this structure. Reaching consensus
around a common framework and lexicon
for QI science requires further development, but the approach demonstrated in
this synthesis presents a useful starting
place in that endeavor.
The evidence base is growing regarding
the importance of context for quality and
patient safety topics,26-28 yet all five series
reports that examined the role of context
found that implementation context was
rarely described in the QI literature. The
teams from the EPCs recommended that
contextual factors be more frequently
and robustly measured and reported. To
accomplish this will require development
of reliable and valid measures of such factors, but at this early stage of exploration,
little is known about which contextual
factors are important to measure, and
how to do so. Thus, filling this knowledge gap will require iterative measure
development, measurement, research, and
refinement of the measures. Each of these
steps will contribute valuable knowledge
to the field. Table 5 includes a starter
set of contextual factors, adapted from
the patient safety field,26 that can help
lend structure and a common language
to future work around implementation
context. These context factors also map
well to the Consolidated Framework for
Implementation Research.29,30
This “meta” review evinces the promise
of scaling up knowledge across topics
through a structured qualitative synthesis,
in this case relying on a common conceptualization of different levers (information,
infrastructure, and incentives) for influencing behavior change to improve clinical and economic outcomes, a typology of
QI strategies and contexts (Table 5), and
attention to potential harms and vulnerable populations. To foster useful description and synthesis, we also recommend
extending a framework acronym that is
commonly applied to systematic reviews
of clinical interventions to the needs of
QI evaluation. Thus, PICOTS (population,
intervention, comparator, outcomes, timing, setting) becomes PLICCOTS, adding
“L” for logic model, and “C” for context.
The overarching question for QI studies is
then: for a defined population, what is the
logic argument for a complex intervention working better than its comparator
in a given context to produce outcomes
(of interest to QI) within a time period
and setting?
All eight reviews in this series were
limited in their ability to synthesize the
available evidence and draw conclusions
across studies in part because of the
extreme heterogeneity in the outcomes
reported and ways in which those outcomes were measured, which highlights
the need for more consistent outcomes
measurement. Developing a set of consensus-based, clearly defined, and fully
specified outcomes measures for use in
QI research would help facilitate evidence
synthesis by enhancing comparability
across studies, although use of standardized measures must be balanced with the
need to tailor choice of outcomes to the
goals of particular QI efforts or research
studies. Some efforts to develop core measure sets and harmonize quality measures
are underway31-35 and hold promise for
advancing the state of QI science if the
resulting consensus-based measures are
widely used. For example, the US Department of Health and Human Services
(HHS), as a part of the National Strategy
for Quality Improvement in Health Care,
is developing measure selection processes
with public input and the goal of aligning measures across new and existing
HHS programs and focusing on patient
outcomes and patient experience of care.
Because of this effort, multiple measures
for blood pressure control in use across
HHS were identified, and in the future
a consensus-developed set of measures
will be used across all HHS programs.34
Evidence synthesis by the
series EPCs was further hamThe evidence
pered by limitations in apbase is growing
plying study designs and sysregarding the
tematic review methods that
importance
were developed for evaluating
clinical interventions to the
of context for
kinds of multifaceted, contextquality and
dependent, systems-level interpatient safety
ventions and implementation
topics, yet
approaches typical of the QI
all five series
field. However, the topic teams
reports that
did explore various approachexamined the
es to improve the relevance of
role of context
the reports for decision makers.
found that
For example, the public reportimplementation
ing review included qualitative
context was
research to complement the
rarely described
quantitative studies, and the
patient-centered medical home
in the QI
review included a horizon
literature.
scan to inform decision makers about ongoing research.
Because of the context-dependent nature
of QI interventions, other complementary
methods may inform questions related
to policy and practice, and may provide
information for better decision making.
These methods could potentially help
address the diversity of intervention
components, implementation factors,
and context. Advances could include
qualitative research synthesis techniques,
exploration of methods to systematically
identify and assess gray literature, and exploration of methods to assess and incorporate a variety of study designs. Further
methodologic attention to meta-analytic
approaches is also needed to achieve
sufficient statistical power with relatively
few intervention units (eg, hospitals, clinics, health systems) for organization-level
interventions. Although it is beyond the
scope here to describe specific methods,
the choice of method will depend on the
anticipated use of the review, the type of
questions asked, underlying assumptions,
and breadth and depth of the proposed
review. Overall, the preponderance of low
strength of evidence findings and limited
information on additional considerations
of interest to local decision makers (eg,
context, implementation approaches/
challenges, vulnerable population impact)
59
REVIEW article
found across the eight series reports
speaks to the immaturity of the QI and
implementation science fields. In these
fields, decision-salient research questions
and standards for robust and complementary study design continue to evolve.
Although synthesizing evidence across
the series topics provided valuable insight into the state of QI science, the
eight topics in the series represent just a
sample of the QI field. Findings from this
synthesis can help guide future QI efforts
and suggest directions for future research
but do not represent conclusive evidence
of effectiveness or associations between
particular strategies and other important
factors. In addition, findings reported in
this synthesis are presented in broad terms;
much detail about the particular populations, settings, outcomes, and strategies
included in the primary studies is omitted
for the sake of highlighting conclusions
that are applicable across major portions of
the health care system. The individual topic
reports provide much greater granularity in
their findings and should be consulted to
interpret particular topic-specific findings.
Conclusion
This series synthesis highlights the value
in expanding our view from the level of
individual improvement efforts to examine effectiveness of QI strategies across
initiatives, topics, and targets. Limitations
in the literature encountered by the EPCs
point to areas in need of more rigorous
standards for study design and reporting,
methodologic weaknesses in need of
further development, and research questions ripe for exploration. The findings
also highlight common challenges limiting
much of the QI literature, in particular, the
lack of consensus around key outcomes
important for evaluating QI effectiveness,
gaps in analyzing other factors important
to decisions about implementing a particular QI strategy, and weaknesses in study
design and analytic methods. Using these
challenges and methodologic weaknesses
to generate practical and scientifically
sound solutions can help guide future
research efforts and the development of
the QI field. v
During the writing of this article, CC was
employed by the Agency for Healthcare
60
Research and Quality (AHRQ), Rockville,
MD. The author(s) have no conflicts of
interest to disclose.
This work was supported by the AHRQ
(Contract no. 290-2007-10062-I). AHRQ
did not play any role in study design, data
collection, analysis, and interpretation for the
Closing the Quality Gap systematic reviews.
The views expressed in this paper are those of
the authors and do not necessarily represent
the views of the US Department of Health
and Human Services and the Agency for
Healthcare Research and Quality.
Acknowledgments
The authors thank the author teams and
AHRQ’s task order officers from each of the
Closing the Quality Gap reports in the series
for undertaking these challenging topics and
supporting efforts to develop common approaches to allow the synthesis reported here.
�10.
�11.
�12.
�13.
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� 3. McGlynn EA, Asch SM, Adams J, et al. The
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� 4. Adams K, Corrigan JM, editors. Priority areas
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quality. Washington, DC: The National Academies Press; 2003.
� 5. Committee on Quality of Health Care in
America, Institute of Medicine. Crossing the
quality chasm: a new health system for the
21st century. Washington, DC: The National
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� 6. Bravata D, Sundaram V, Lewis R, et al. Closing
the quality gap: a critical analysis of quality
improvement strategies (vol 5: asthma care).
Technical reviews no. 9.5. Rockville, MD:
Agency for Healthcare Research and Quality;
2007 Jan. AHRQ Publication No. 04-005101-5.
� 7. McDonald K, Sundaram V, Bravada D, et al.
Closing the quality gap: a critical analysis of
quality improvement strategies (vol 7: care
coordination). Technical reviews no. 9.7.
and Quality; 2007 Jun. AHRQ Publication No.
04(07)-0051-7.
� 8. Ranji SR, Shetty K, Posley KA, et al. Closing
improvement strategies (vol 6: prevention of
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Shojania KG, McDonald KM, Wachter RM,
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reviews no. 9.1. Rockville, MD: Agency for
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Walsh J, McDonald KM, Shojania KG, et al.
Closing the quality gap: a critical analysis
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hypertension care). Technical reviews no. 9.3.
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Shojania KG, Ranji SR, Shaw LK, et al. Closing
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2004 Sep. AHRQ Publication No. 04-0051-2.
Timeline for health care reform implementation: system and delivery reform provisions
[monograph on the Internet]. New York, NY:
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Reform_040110_v5_rev%2051310.pdf.
McDonald KM, Chang C, Schultz E. Through
the quality kaleidoscope: reflections on the
science and practice of improving health care
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state of the science. Methods research reports.
and Quality; 2013 Feb. AHRQ Publication No.
13-EHC041-EF.
McDonald KM, Chang C, Schultz E. Summary
report. Closing the quality gap: revisiting the
state of the science. Rockville, MD: Agency for
Healthcare Research and Quality; 2013 Jan.
AHRQ Publication No. 12(13)-E017.
Fuchs VR. The proposed government
health insurance company—no substitute
for real reform. N Engl J Med 2009 May
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Internet]. Rockville, MD: Agency for Healthcare
Research and Quality; 2012 Apr 9 [cited 2012
Jul 26]. Available from: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guidesreviews-and-reports/?pageaction=displayprodu
ct&productid=318.
Butler M, Kane RL, Larson S, Jeffery MM,
Grove M. Closing the quality gap: revisiting the
state of the science (vol 7: quality improvement measurement of outcomes for people
with disabilities). Evidence reports/technology
assessments, no. 208.7. Rockville, MD: Agency
for Healthcare Research and Quality; 2012 Oct.
AHRQ Publication No. 12-E013-EF.
Dy S, Aslakson R, Wilson R, et al. Closing the
quality gap: revisiting the state of the science (vol
8: improving health care and palliative care for
advanced and serious illness). Evidence reports/
technology assessments, no. 208.8. Rockville,
MD: Agency for Healthcare Research and Quality;
2012 Oct. AHRQ Publication No. 12-E014-EF.
Hussey PS, Mulcahy AW, Schnyer C, Schneider
EC. Closing the quality gap: revisiting the state
of the science (vol 1: bundled payment: effects
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Healthcare Research and Quality; 2012 Nov.
McPheeters ML, Kripalani S, Peterson NB, et
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Griffin J, Walker M. Closing the quality gap:
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�26. Shekelle PG, Pronovost PJ, Wachter RM, et
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�27. Shekelle PG, Pronovost PJ, Wachter RM, et al.
Advancing the science of patient safety. Ann
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�28. Foy R, Ovretveit J, Shekelle PG, et al. The role
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Quality Forum; c2013 [cited 2013 Jan 17]. Available from: http://qualityforum.org/map/.
Toward Improvement
‘What is everyone learning?’ Asking the question that
way will help clinicians and researchers see further in
navigating toward improvement.
— Donald Berwick, MD, b 1946, former Administrator of the Centers
for Medicare and Medicaid Services and former President and Chief
Executive Officer of the Institute for Healthcare Improvement
61
Review article
Probiotics and Liver Disease
Vishal Sharma, MD, DM; Shashank Garg, MD; Sourabh Aggarwal, MD
Perm J 2013 Fall;17(4):62-67
Abstract
Intestinal microbiota play an important role in health and
disease. The gut-liver axis provides for an interaction between
bacterial components like lipopolysaccharide and hepatic
receptors (Toll-like receptors). Dysbiosis and altered intestinal
permeability may modulate this interaction and therefore
result in hepatic disorders or worsening of hepatic disorders.
Administration of health-promoting microbial strains may help
ameliorate these harmful interactions and hepatic disorders. This
review focuses on changes in gut microbiota in the context of
liver disease and possible roles of probiotics, prebiotics, and
synbiotics in liver disease.
Introduction
Humans coexist with an enormous quantity of microbial
organisms collectively termed microbiota. This very old relationship is a subject of active research. Since the mid-1990s there
has been a steady increase in the interest in and understanding
of microbiota and their functions.1 This is partly because of
new tools that have lifted the veil off organisms that cannot be
cultured by standard microbiologic techniques. The approach
to the study of microbiota has now become multidimensional
and involves methods to identify not only the organisms but
also their genes (metagenomics) and metabolic products.2 In
fact, along the lines of the Human Genome Project, the Human
Microbiome Project attempted to evaluate the entire collection
of genomes that the microbiota harbor. Human microbiota
exist at various sites on and inside the human body, including the skin, nares, oral cavity, urogenital tract, and gut. Of
course, the human gastrointestinal tract is the most heavily
colonized site, and the colon contains more than two-thirds of
the microbial load. On the whole, our gut has approximately
100 trillion (1014) microbes, which make up approximately
1 to 2 kilograms of our weight.1,3 The number of microbial
species estimated to exist in a human gut is more than 1800.
In the human gut the bacterial density gradient progressively
increases from the stomach to the colon. The vastness of the
human microbiota is evident given that the bacterial cells in
the human gut outnumber human cells by a factor of 10 and
microbial genes outnumber human genes by a factor of 100.1
There are variations in the predominant bacterial species not
only along the length of the gastrointestinal tract but also from
the lumen to the epithelium.1
Functions of Gut Microbiota
in Health and Disease
Gut microbiota perform diverse immunologic, digestive, and
metabolic functions. They are capable of producing energy by
means of specialized digestion of complex polysaccharides that
cannot otherwise be digested by humans. Colonic microbes can
produce short-chain fatty acids like acetate, butyrate, and propionate by metabolizing these polysaccharides. Although acetate
is the dominant short-chain fatty acid, butyrate is the primary
source of energy for colonocytes.4 This microbial activity is put
to clinical use in management of short bowel syndrome—the
loss of small intestinal absorptive surface can be compensated
to some extent by utilizing production of short-chain fatty acid
by colonic bacteria. This can account for energy production of
up to 1000 kcal. Even in healthy adults, microbiota can produce
varying amounts of energy (50 kcal to 200 kcal).5 This energy
harvesting is believed to vary with variations in gut microbiota.
Excessive energy harvesting has been implicated in the causation of obesity.
Gut microbiota also have an extremely important immune
function. Our gastrointestinal tracts are exposed daily to a large
number of microorganisms. However, we are able to handle this
immense microbial load without any adverse consequences. This
is predominantly a result of the colonization resistance afforded
by the flora in our intestines.6 The mechanisms involved are
complex and include the epithelium’s recognition of microbiota
as nonpathogenic and a contained, inflammatory response to
these commensals.7 This interaction occurs via the recognition of
bacterial antigens (commensalism-associated molecular patterns)
to the pattern-recognition receptors of the host (Toll-like receptors
[TLRs]). This interaction mediates the further cascade of inflammatory activation. The intracellular cytosolic pattern recognition is
mediated by the nucleotide oligomerization domains. A number
of factors prevent unwarranted activation of the inflammatory
cascade. These include the intracytoplasmic location of some of
the pattern-recognition receptors, limited expression of TLRs,
inhibitory cytokines, etc. All in all, the commensal bacteria do not
incite an uncontrolled immune response and therefore continue
to exist in a delicate equilibrium in the human gut.
The barrier function of the human gut includes physical,
chemical, and immunologic components. Antimicrobial peptides
(eg, defensins, mucins, and angiogenin 4) and secretory immunoglobulin A contribute to luminal chemical and immunologic
mechanisms to maintain the gut’s barrier function.8 However,
Vishal Sharma, MD, DM, is a Senior Research Associate at the Department of Gastroenterology, Postgraduate Institute of
Medical Education and Research, Chandigarh, India. E-mail: docvishalsharma@gmail.com. Shashank Garg, MD, is an Internist
at Sinai Hospital in Baltimore, MD. E-mail: shashgarg87@gmail.com. Sourabh Aggarwal, MD, is an Internist at the Western
Michigan University School of Medicine in Kalamazoo. E-mail: drsourabh79@gmail.com.
62
Review article
this barrier is disrupted in stressful situations like pathogenenterocyte interaction, the presence of certain drugs, inflammation, hypoxia, etc. Disruption of this barrier is an opportunity
for the previously excluded antigens and lipopolysaccharides to
enter the enterocytes and systemic circulation.8 This situation has
been described as a leaky gut and the resulting phenomenon as
metabolic endotoxemia. Metabolic endotoxemia is different from
the endotoxemia associated with septicemia, because plasma
lipopolysaccharide levels are elevated by a factor of 2 to 3
compared with the much larger increases in septicemia.9 Beyond
their digestive, immune, and barrier functions, gut microbiota
are also involved in metabolism, including synthesis of vitamins
(folate, vitamin K, and biotin), biotransformation of drugs and
xenobiotics, and metabolism of bile acids.1
Microbiota and Liver Disease
The close interaction of the gastrointestinal tract and the liver
and the fact that the nutrients absorbed by the gut first reach
the liver have fostered use of the term gut-liver axis. Cirrhosis
patients have colonic microbiota that are different from that of
healthy control subjects.10,11 Increases in Enterobacteriaceae
and Enterococcus with a reduction in Bifidobacterium species
were noted in one report. Whether these changes are a cause
or a consequence of cirrhosis is not clear.10 An earlier report
had indicated a reduced proportion of bacteroidetes and an
increase in proteobacteria and fusobacteria.11 In fact, a positive
correlation was observed between Child-Turcotte-Pugh score and
streptococcaceae.11 Another report contradicted these findings
vis-à-vis the diversity in intestinal microbiota amongst subjects
with hepatitis B virus-related cirrhosis, subjects with chronic
hepatitis B, and controls. However, there were changes in the
composition of intestinal Bifidobacterium species, indicating
dysbiosis in cirrhosis.12 Another report indicated a progressive
decrease in the ratio of Bifidobacterium to Enterobacteriaceae
accompanying progression of liver disease in a range of subjects, from healthy controls to subjects with decompensated
hepatitis B virus cirrhosis to asymptomatic carriers and subjects
with chronic hepatitis B.13 This indicates that changes in gut
microbiota seem to mirror changes in severity of disease. The
TLR 4/lipopolysaccharide interaction may be the link modulating this relationship; the role of this interaction in fibrogenesis
is increasingly recognized.14
Changes in microbiota have also been reported in nonalcoholic fatty liver disease (NAFLD), hepatic encephalopathy,
alcohol-related liver disease, and hepatocellular carcinoma. Gut
microbiota may cause NAFLD by luminal ethanol production,
causing a leaky gut and metabolic endotoxemia, or by metabolizing choline, which is no longer available for the liver.15 Also,
those who suffer from NAFLD may have a microbiota phenotype
with a better energy-harvesting capacity that increases the calorie
load to the liver. Indeed, the microbiota of obese individuals
includes a reduced level of bacteroidetes and an increased level
of firmicutes.16 The role of the inflammasome-mediated (intracytoplasmic protein complexes to sense pathogen-associated
molecular patterns) microbiota-host interaction may have a role
in the transition from NAFLD to nonalcoholic steatohepatitis.17
Regarding alcohol-related liver disease, there is evidence from
animal studies that chronic alcohol intake does lead to changes
in microbiota.18 A study in human subjects confirmed these findings and also indicated a correlation between alcohol-induced
dysbiosis and endotoxemia.19 Recent animal studies have shown
that microbial translocation begins early in the course of alcoholic
liver disease, leading to increased inflammation and eventually
cirrhosis.20 In rat models of hepatocarcinogenesis, induction of
gut dysbiosis significantly promoted carcinogenesis.21 Another
report indicates that microbiota may not be involved in initiation
of hepatocellular carcinoma but in promotion and proliferation
of hepatocellular carcinoma.22 Changes in microbiota have also
been implicated in causation of hepatic encephalopathy, but
the reports are conflicting.23-25 However, the weight of evidence
suggests some relationship between changes in microbiota and
cognition. Changes in gut microbiota may also have a role in the
pathogenesis of other complications of cirrhosis (eg, spontaneous bacterial peritonitis, hepatorenal syndrome, and cirrhotic
Table 1. Common preparations of probiotics and synbiotics
Strain
Probiotics
E coli Nissle
Lactobacillus
(many strains)
Bifidobacterium spp
Sacchromyces boulardii
VSL#3a
Synbiotic
Synbiotic 2000Forteb2
a
b
Comment
Benefits1
One of the earliest strains to be used
L rhamnosus GG is most commonly used, as it can survive
gastric and biliary secretions
Immense contemporary interest for possible anti-obesity effects
Nonpathogenic yeast inherently resistant to all antibiotics
Multistrain probiotic with 300 billion per gram of bacteria
Possible benefit in ulcerative colitis
Prevention and treatment of acute childhood
diarrhea, prevention of antibiotic-associated diarrhea
Childhood diarrhea, ulcerative colitis
Prevention of antibiotic-associated diarrhea
Ulcerative colitis, prevention of pouchitis
Mixture of 4 Lactobacillus strains and biofibers (inulin, pectin,
resistant starch, and β-glucan)
Critically ill patients
Sigma-tau: VSL Pharmaceuticals Inc; Gaithersburg, MD.
Synbiotic 2000Forte, Medipharm, Sweden.
1. Floch MH, Montrose DC. Use of probiotics in humans: an analysis of the literature. Gastroenterol Clin North Am 2005 Sep;34(3):547-70,x. DOI: http://dx.doi.org/10.1016/j.
gtc.2005.05.004
2. Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically ill trauma patients:
early results of a randomized controlled trial. World J Surg 2006 Oct;30(10):1848-55. DOI: http://dx.doi.org/10.1007/s00268-005-0653-1
63
REVIEW article
hyperdynamic circulation). It has also been suggested that microbiota are involved in the pathogenesis of cholestatic disorders
like primary sclerosing cholangitis and primary biliary cirrhosis.
The expression of TLRs is elevated in both of these conditions,
and therefore TLR tolerance declines.26 It is, therefore, apparent
that changes in microbiota coexist with many hepatic disorders
and may play a role in their causation. If this is indeed true,
modulation of colonic microbiota may be an effective strategy
for managing these diseases.
Probiotics and Related Compounds
Clinicians have traditionally modulated the microbial environment of the gut with nonabsorbable disaccharides to manage
hepatic encephalopathy related to cirrhosis. Lactulose acts not
just by lowering pH in the colonic lumen and thereby improving
excretion of ammonia but also by exerting a prebiotic effect and
promoting the growth of certain bacteria, like Bifidobacterium
and Lactobacillus.27 This approach is often termed selective gut
decontamination. Another approach is use of prebiotics, probiotics, and synbiotics. Probiotics are live microorganisms supplied
from outside the human body, usually in the form of spores in
a dosage believed to have beneficial effects.28,29 However before
a microbial strain can exert any beneficial effect in the intestine,
it must be able to tolerate the acidic gastric and the alkaline bile
juices and survive the journey from the mouth to the intestine.
Prebiotics are, on the other hand, substrates that are fermented
by the microbiota. By virtue of their promicrobiota properties,
they are believed to increase microbial diversity and increase
colonization resistance against pathogens.29 These are usually
plant fibers and consist of nondigestible carbohydrates. Synbiotics are combinations of prebiotics and probiotics. A synbiotic
composition should ideally include a probiotic strain with evidence of health benefits along with a prebiotic that promotes
growth of the coadministered probiotic strain.28
Numerous commercial preparations have flooded the market,
creating confusion about probiotics (Table 1). Probiotics cannot
be recommended as a panacea. An ideal probiotic preparation
would comprise species with a human origin, as these are likely
to be safe. Probiotics should be used only in those clinical situations where benefits have irrevocably been proven in adequate
clinical trials, and the strain and dosage should be those shown
to be beneficial. Although probiotics are generally regarded as
safe, some complications have been noted. Occasional cases of
bacteremia, endocarditis, and fungemia have been reported.30
Probiotics in Liver Disease
Hepatic Encephalopathy
Hepatic encephalopathy encompasses a broad range of neuropsychiatric disturbances that may accompany portosystemic shunting, acute liver failure, and cirrhosis. Cirrhotic encephalopathy is
Table 2. Trials of probiotics and synbiotics in minimal hepatic encephalopathy
Reference
Saji et al1
Setting
RCT; 43 children with A and
B cirrhosis and MHE
Mittal et al2
RCT; 160 subjects with
cirrhosis and MHE
Open label; 105 subjects
with Cirrhosis and MHE
Sharma et al3
Bajaj et al4
Liu et al5
Malaguarnera et al6
Nonblinded randomized trial;
25 subjects with nonalcoholic
cirrhosis and MHE
55 subjects with cirrhosis
and MHE
RCT; 60 subjects with
cirrhosis and MHE
Intervention
Lactobacillus acidophilus, L rhamnosus, Bifidobacterium
longum, and Saccharomyces boulardi; 1.25 billion spores
3 times daily for 4 weeks versus placebo
Lactulose versus L-ornithine L-aspartate versus probioticsa
110 billion colony-forming units twice daily for 3 months
Probiotics (Streptococcus faecalis, Clostridium butyricum,
Bacillus mesentricus, LAB) 1 capsule 3 times daily for
1 month versus lactulose versus both
Probiotic yogurt for 2 months versus no drug
Synbiotic preparation (Cocktail 2000; Medipharm,
Kagerod, Sweden) for 30 days versus fermentable fiber
versus placebo
Bifidobacterium longum with fructo-oligosaccharide versus
placebo for 90 days
Outcome
No change in ammonia, evoked
responses, and NCT
All improved MHE and QOL
All were equally effective in
treating MHE
Improvement NCT-A, BDT, and
DST; reduction in overt HE
Increase in nonurease producers,
reduced ammonia levels, MHE,
and endotoxemia
Reduced ammonia, improved
symbol digit test; reduced
performance on trail making tests
a
Nature of probiotics unknown.
BDT = block design test; DST = digital symbol test; HE = hepatic encephalopathy; LAB = lactic acid bacteria; MHE = minimal hepatic encephalopathy;
NCT = number connection test; QOL = quality of life; RCT randomized controlled trial.
1. Saji S, Kumar S, Thomas V. A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy. Trop Gastroenterol 2011
Apr-Jun;32(2):128-32.
2. Mittal VV, Sharma BC, Sharma P, Sarin SK. A randomized controlled trial comparing lactulose, probiotics, and L-ornithine L-aspartate in treatment of minimal
hepatic encephalopathy. Eur J Gastroenterol Hepatol 2011 Aug;23(8):725-32. DOI: http://dx.doi.org/10.1097/MEG.0b013e32834696f5
3. Sharma P, Sharma BC, Puri V, Sarin SK. An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy.
Eur J Gastroenterol Hepatol 2008 Jun;20(6):506-11. DOI: http://dx.doi.org/10.1097/MEG.0b013e3282f3e6f5
4. Bajaj JS, Saeian K, Christensen KM, et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol 2008 Jul;103(7):1707-15.
DOI: http://dx.doi.org/10.1111/j.1572-0241.2008.01861.x
5. Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis.
Hepatology 2004;39(5):1441-9. DOI: http://dx.doi.org/10.1002/hep.20194
6. Malaguarnera M, Greco F, Barone G, Gargante MP, Malaguarnera M, Toscano MA. Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal
hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci 2007 Nov;52(11):3259-65. DOI: http://dx.doi.org/10.1007/s10620-006-9687-y
64
Review article
broadly classified as overt and minimal hepatic encephalopathy
(MHE). MHE refers to the condition of that subset of patients
with cirrhosis who do not have any clinically detectable neurologic abnormality but have abnormal neuropsychometric or
neurophysiologic test results.31 Specifically, these patients have
abnormal results for 2 of 4 tests: number connection test A and
B, block design test, and digital symbol test. The traditional
therapy for hepatic encephalopathy has been antibiotics or
nonabsorbable polysaccharides. There is, however, emerging evidence that various probiotic preparations have a role
in various stages of hepatic encephalopathy, especially MHE.
Table 2 summarizes the various trials that have evaluated the
roles of prebiotics, probiotics, and synbiotics in MHE. The effect
is believed to be modulated by changes in gut microbiota: an
increase in non-urease-producing bacteria like lactobacilli and
a concomitant reduction in urease producers like Escherichia
coli and Staphylococcus aureus.
As these trials suggest, the bulk of evidence favors the use of
probiotics for MHE. A meta-analysis of 9 eligible reports indicated
a beneficial effect of prebiotics, probiotics, and synbiotics in patients with hepatic encephalopathy.32 In fact, a guideline by the
Indian National Association for Study of the Liver recommends
use of probiotics in MHE.31 The situation is less clear with regards
to probiotic preparations for overt hepatic encephalopathy. A Cochrane review of probiotics for hepatic encephalopathy could not
determine any evidence of improvement in clinically significant
outcomes, although probiotics reduced plasma ammonia levels.
However, some reports indicate that probiotics are beneficial for
overt hepatic encephalopathy; this issue needs to be addressed
in further trials before any clear recommendations can be made
regarding use of probiotics for treatment or secondary prevention
of overt hepatic encephalopathy.33
Nonalcoholic Fatty Liver Disease
Many data from animal experiments have indicated that modulating gut microbiota with prebiotics, probiotics, and synbiotic
preparations has a beneficial effect on NAFLD. Loguercio et al
first postulated the role of a gut-liver axis in causation of liver
disease and its related complications.34 They reported benefits
of a complex preparation of probiotics, prebiotics, vitamins,
and minerals in reducing aminotransferase levels in patients
with nonalcoholic steatohepatitis. The same group reported a
reduction in parameters of lipid peroxidation in NAFLD patients
with use of VSL#3 (Sigma-tau: VSL Pharmaceuticals, Inc; Gaithersburg, MD).35 Another small report, on the contrary, indicated an
increase in hepatic fat with probiotic use. Some human studies
have further evaluated the role of probiotics in NAFLD (Table 3);
this includes 1 study in a pediatric sample.36
Therefore, it is premature to recommend probiotics for treatment of NAFLD. Ongoing research may shed more light in the
future. The recent guidelines by the American Association for
Study of Liver Diseases do not recommend probiotics for NAFLD.37
Other Liver Diseases
Probiotic use has been evaluated in patients with compensated
cirrhosis with at least one major complication. A multistrain
probiotic had no benefit in these patients except for a nonsignificant trend toward reduction in serum ammonia levels in those
with elevated ammonia.38 Preoperative and postoperative use
of probiotics in cirrhosis and hepatocellular carcinoma patients
who underwent tumor resection was associated with a lower
serum TNF-α level and quicker recovery of hepatic function.39
Use of VSL#3 for 2 months in cirrhosis patients with an elevated
hepatic venous pressure gradient (>10 mm of Hg) did not reduce
hepatic venous pressure gradient, although reductions in plasma
endotoxemia and cytokines (TNF-α, interleukin 6, and interleukin 8) were noted.40 Use of E Coli Nissle strain was reported to
result in improvement in liver function, as measured by ChildPugh score, and reduction in endotoxin levels.41 Those results,
however, have not been replicated. These reports indicate the
need for large prospective trials to evaluate clinical outcomes of
patients with cirrhosis and liver disease treated with probiotics.
In a recent study, probiotic strains were used with norfloxacin
for prophylaxis of spontaneous bacterial peritonitis in patients
Table 3. Reports of probiotic use in humans with nonalcoholic fatty liver disease
Reference
Aller et al1
Loguercio et al2
Solga et al3
Vajro et al4
a
Setting
Open label, randomized; 30
subjects with NAFLD
Open label; NAFLD, alcoholic
cirrhosis, HCV, HCV cirrhosis
Interventions
500 million Lactobacillus bulgaricus and Streptococcus
thermophilus for 3 months versus placebo
VSL#3a for 3 months
Open label; 4 subjects with NAFLD
RCT; pediatric NAFLD
VSL#3, 1 sachet for 4 months
Lactobacillus rhamnosus, 12 billion CFU/day for
8 weeks
Outcomes
Improvement in transaminases
Reduction in plasma levels,
malondialdehyde, and
4-hydroxynonenal
Increased hepatic fat
Improved transaminases,
reduced lipopolysaccharide levels
Sigma-tau: VSL Pharmaceuticals, Inc; Gaithersburg, MD.
CFU = colony-forming unit; HCV = hepatitis C virus; NAFLD = nonalcoholic fatty liver disease; RCT = randomized controlled trial.
1. Aller R, De Luis DA, Izaola O, et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. Eur
Rev Med Pharmacol Sci 2011 Sep;15(9):1090-5.
2. Loguercio C, De Simone T, Federico A, et al. Gut-liver axis: a new point of attack to treat chronic liver damage? Am J Gastroenterol 2002 Aug;97(8):2144-6. DOI: http://
dx.doi.org/10.1111/j.1572-0241.2002.05942.x
3. Solga SF, Buckley G, Clark JM, Horska A, Diehl AM. The effect of a probiotic on hepatic steatosis. J Clin Gastroenterol 2008 Nov-Dec;42(10):1117-9. DOI: http://dx.doi.
org/10.1097/MCG.0b013e31816d920c
4. Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr 2011
Jun;52(6):740-3. DOI: http://dx.doi.org/10.1097/MPG.0b013e31821f9b85
65
REVIEW article
with cirrhosis. However, the authors observed no accrual benefits
of the combination compared with norfloxacin alone.42
Probiotics have also been evaluated in primary sclerosing cholangitis. Primary sclerosing cholangitis is a cholestatic liver disease
characterized by relentless fibro-inflammatory involvement of
the extrahepatic and intrahepatic biliary system. It is often seen
in association with inflammatory bowel disease. Inflammatory
bowel disease is known to be associated with dysbiosis, and
use of probiotics has been shown to be beneficial. However, the
use of a multistrain probiotic in patients with primary sclerosing
cholangitis for three months had no benefit for pruritus or liver
functions.43 Another interesting report from China evaluated
a multistrain probiotic (Lactobacillus and Propionobacterium
species) in healthy individuals and noted a decrease in urinary
excretion of aflatoxin metabolite, suggesting that probiotics may
reduce exposure to aflatoxin and may have a chemopreventive
role in hepatocellular carcinoma.44 Also, the use of synbiotics
seems to decrease bacterial infections after liver transplantation.45
In a recent randomized study, preoperative and postoperative
use of a synbiotic preparation significantly reduced infectious
complications after elective living-donor liver transplantation.46
To summarize, with the growing recognition of the roles that
changes in gut microbiota have in the causation of various liver
diseases and their complications, there is an increasing interest
in probiotics and related products for preventing and treating
hepatic disorders. For now, probiotics cannot be recommended
for treatment of most hepatic disorders—apart from minimal
hepatic encephalopathy—in clinical settings. With accumulating
evidence, however, probiotics may be used more widely to treat
other liver diseases. v
Acknowledgment
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13. Lu H, Wu Z, Xu W, Yang J, Chen Y, Li L. Intestinal microbiota was assessed
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17. Henao-Mejia J, Elinav E, Jin C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012 Feb
1;482(7384):179-85. DOI: http://dx.doi.org/10.1038/nature10809
18. Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P. Intestinal dysbiosis: a possible mechanism of alcohol-induced
endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp
Res 2009 Oct;33(10):1836-46. DOI: http://dx.doi.org/10.1111/j.15300277.2009.01022.x
19. Mutlu EA, Gillevet PM, Rangwala H, et al. Colonic microbiome is
altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 2012 May
1;302(9):G966-78. DOI: http://dx.doi.org/10.1152/ajpgi.00380.2011
20. Schaffert CS, Duryee MJ, Hunter CD, et al. Alcohol metabolites and
lipopolysaccharide: roles in the development and/or progression of alcoholic
liver disease. World J Gastroenterol 2009 Mar 14;15(10):1209-18. DOI:
http://dx.doi.org/10.3748/wjg.15.1209
21. Zhang HL, Yu LX, Yang W, et al. Profound impact of gut homeostasis
on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats. J Hepatol 2012 Oct;57(4):803-12. DOI: http://dx.doi.
org/10.1016/j.jhep.2012.06.011
22. Dapito DH, Mencin A, Gwak GY, et al. Promotion of hepatocellular
carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012 Apr
17;21(4):504-16. DOI: http://dx.doi.org/10.1016/j.ccr.2012.02.007
23. Bajaj JS, Hylemon PB, Ridlon JM, et al. Colonic mucosal microbiome differs
from stool microbiome in cirrhosis and hepatic encephalopathy and is linked
to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 2012
Sep 15;30(6):G675-85. DOI: http://dx.doi.org/10.1152/ajpgi.00152.2012
24. Bajaj JS, Ridlon JM, Hylemon PB, et al. Linkage of gut microbiome with
cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver
Physiol 2012 Jan 1;302(1):G168-75. DOI: http://dx.doi.org/10.1152/
ajpgi.00190.2011
25. Shawcross DL, Sharifi Y, Canavan JB, et al. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy,
but not mortality in cirrhosis. J Hepatol 2011 Apr;54(4):640-9. DOI: http://
dx.doi.org/10.1016/j.jhep.2010.07.045
26. Miyake Y, Yamamoto K. Role of gut microbiota in liver diseases. Hepatol
Res 2013 Feb;43(2):139-46. DOI: http://dx.doi.org/10.1111/j.1872034X.2012.01088.x
27. Panesar PS, Kumari S. Lactulose: production, purification and potential
applications. Biotechnol Adv 2011 Nov-Dec;29(6):940-8. DOI: http://dx.doi.
org/10.1016/j.biotechadv.2011.08.008
28. Ciorba MA. A gastroenterologist’s guide to probiotics. Clin Gastroenterol Hepatol 2012 Sep;10(9):960-8. DOI: http://dx.doi.org/10.1016/j.
cgh.2012.03.024
29. Bengmark S. Bioecologic control of the gastrointestinal tract: the role
of flora and supplemented probiotics and synbiotics. Gastroenterol Clin
North Am 2005 Sep;34(3):413-36, viii. DOI: http://dx.doi.org/10.1016/j.
gtc.2005.05.002
30. Snydman DR. The safety of probiotics. Clin Iinfect Dis 2008 Feb 1;46 Suppl
2:S104-11; discussion S144-51. DOI: http://dx.doi.org/10.1086/523331
Review article
31. Dhiman RK, Saraswat VA, Sharma BK, et al; Indian National Association for
Study of the Liver. Minimal hepatic encephalopathy: consensus statement
of a working party of the Indian National Association for Study of the
Liver. J Gastroenterol Hepatol 2010 Jun;25(6):1029-41. DOI: http://dx.doi.
org/10.1111/j.1440-1746.2010.06318.x
32. Shukla S, Shukla A, Mehboob S, Guha S. Meta-analysis: the effects of gut
flora modulation using prebiotics, probiotics and synbiotics on minimal
hepatic encephalopathy. Aliment Pharmacol Ther 2011 Mar;33(6):662-71.
DOI: http://dx.doi.org/10.1111/j.1365-2036.2010.04574.x
33. McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC. Probiotics for patients with hepatic encephalopathy. Cochrane Database Syst Rev. 2011 Nov
9;(11):CD008716. DOI: http://dx.oi.org/10.1002/14651858.CD008716.pub2
34. Loguercio C, De Simone T, Federico A, et al. Gut-liver axis: a new
point of attack to treat chronic liver damage? Am J Gastroenterol 2002 Aug;97(8):2144-6. DOI: http://dx.doi.org/10.1111/j.15720241.2002.05942.x
35. Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic
VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin
Gastroenterol 2005 Jul;39(6):540-3. DOI: http://dx.doi.org/10.1097/01.
mcg.0000165671.25272.0f
36. Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus
strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr 2011 Jun;52(6):740-3. DOI: http://dx.doi.org/10.1097/
MPG.0b013e31821f9b85
37. Chalasani N, Younossi Z, Lavine JE, et al; American Association for the
Study of Liver Diseases; American College of Gastroenterology; American
Gastroenterological Association. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Association
for the Study of Liver Diseases, American College of Gastroenterology, and
the American Gastroenterological Association. Am J Gastroenterol 2012
Jun;107(6):811-26. DOI: http://dx.doi.org/10.1038/ajg.2012.128
Erratum in: Am J Gastroenterol. 2012 Oct;107(10):1598. DOI: http://dx.doi.
org/10.1038/ajg.2012.217
38. Pereg D, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y.
Probiotics for patients with compensated liver cirrhosis: a double-blind
placebo-controlled study. Nutrition 2011 Feb;27(2):177-81. DOI: http://
dx.doi.org/10.1016/j.nut.2010.01.006
39. Rifatbegovic Z, Mesic D, Ljuca F, et al. Effect of probiotics on liver function after surgery resection for malignancy in the liver cirrhotic. Med Arh
2010;64(4):208-11.
40. Tandon P, Moncrief K, Madsen K, et al. Effects of probiotic therapy
on portal pressure in patients with cirrhosis: a pilot study. Liver Int
2009 Aug;29(7):1110-5. DOI: http://dx.doi.org/10.1111/j.14783231.2009.02020.x
41. Lata J, Novotný I, Príbramská V, et al. The effect of probiotics on
gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol 2007 Dec;19(12):1111-3. DOI: http://dx.doi.org/10.1097/
MEG.0b013e3282efa40e
42. Pande C, Kumar A, Sarin SK. Addition of probiotics to norfloxacin does
not improve efficacy in the prevention of spontaneous bacterial peritonitis:
a double-blind placebo-controlled randomized-controlled trial. Eur J Gastroenterol Hepatol 2012 Jul;24(7):831-9. DOI: http://dx.doi.org/10.1097/
MEG.0b013e3283537d61
43. Vleggaar FP, Monkelbaan JF, van Erpecum KJ. Probiotics in primary sclerosing cholangitis: a randomized placebo-controlled crossover pilot study.
Eur J Gastroenterol Hepatol 2008 Jul;20(7):688-92. DOI: http://dx.doi.
org/10.1097/MEG.0b013e3282f5197e
44. El-Nezami HS, Polychronaki NN, Ma J, et al. Probiotic supplementation
reduces a biomarker for increased risk of liver cancer in young men from
Southern China. Am J Clin Nutr 2006 May;83(5):1199-203.
45. Rayes N, Seehofer D, Theruvath T, et al. Supply of pre- and probiotics
reduces bacterial infection rates after liver transplantation—a randomized,
double-blind trial. Am J Transplant 2005 Jan;5(1):125-30. DOI: http://dx.doi.
org/10.1111/j.1600-6143.2004.00649.x
46. Eguchi S, Takatsuki M, Hidaka M, Soyama A, Ichikawa T, Kanematsu T.
Perioperative synbiotic treatment to prevent infectious complications in
patients after elective living donor liver transplantation: a prospective
randomized study. Am J Surg 2011 Apr;201(4):498-502. DOI: http://dx.doi.
org/10.1016/j.amjsurg.2010.02.013
Liver, noun
A large red organ thoughtfully provided by nature to be bilious with … . It was at one time considered the seat of life; hence its name—liver, the thing we live with.
— The Devil’s Dictionary, Ambrose Bierce, 1842-1913,
American editorialist, journalist, satirist, and author
67
Review article
Antivascular Endothelial Growth Factor Antibody for Treatment of Glioblastoma Multiforme
Joseph A Hanson; Frank P K Hsu, MD, PhD; Arun T Jacob, MD; Daniela A Bota, MD, PhD; Daniela Alexandru, MD
Perm J 2013 Fall;17(4):68-74
Abstract
Despite aggressive investigation, glioblastoma multiforme (GBM) remains one of the deadliest cancers, with low progression-free survival and high one-year mortality. Current first-line
therapy includes surgery with adjuvant radiation therapy and cytotoxic chemotherapy, but
virtually all tumors recur. Given the highly vascular nature of GBM and its high expression
of vascular endothelial growth factor and other angiogenic factors, recent investigation has
turned to bevacizumab, an antivascular endothelial growth factor monoclonal antibody,
for treatment of recurrent GBM. Phase 2 studies demonstrated the efficacy and safety of
bevacizumab therapy for recurrent GBM, which led to its approval by the US Food and Drug
Administration in 2009 for use in recurrent GBM. Since then, several new Phase 2 studies
and retrospective series have demonstrated that bevacizumab significantly increased sixmonth progression-free survival in patients with recurrent GBM and may do so in new-onset
GBM. The objective of this review is to provide a collective resource for these materials,
highlighting the efficacy and safety of bevacizumab and calling for increased investigation
toward its optimal application in the management of high-grade glioma.
Introduction
Glioblastoma multiforme (GBM) is
a highly aggressive tumor with a rapid
progression and poor prognosis. This
tumor comprises nearly 50% of gliomas
and 25% of all primary brain tumors.1-3
According to the most recent report from
the Central Brain Tumor Registry of the
United States, there are approximately
10,000 new cases of GBM recorded annually in the US.3 The development of GBM
is positively correlated with age, reaching
a peak in gross incidence at 45 to 64 years4
and highest per capita incidence at ages
74 to 85 years.3
Unfortunately, GBM is the most deadly
form of glioma, classified as Stage 4
infiltrative glioma by the World Health
Organization.5 The median overall survival
is poor, ranging from 9 to 19 months in
maximally treated patients,6,7 and the
1-year survival rate has been recorded at
approximately 32%.2 Survival rates have
historically increased with the advent
of new surgical techniques and chemo-
therapeutic options,2 and they continue
to slowly rise.4 GBM, however, recurs
almost universally regardless of treatment
regimen.
The extent of surgical resection is an
independent risk factor for survival, with
gross total resection increasing survival.6,8,9
However, even those patients with radiographically demonstrated resection in
excess of 98% tumor volume experience
nearly 100% recurrence, presumably
because of the persistence of quiescent
glioblastoma tumorigenic stem cells.8,10
Standard therapy for GBM involves
surgical resection to the maximal extent
possible with adjuvant radiotherapy and
chemotherapy. Initial studies examined
nitrosourea-based compounds to target
GBM because of their lipophilicity and
ability to cross the blood-brain barrier.
Large meta-analyses have revealed that
lomustine and carmustine in combination
with whole-brain radiation or stereotactic
radiotherapy yielded only modest results,
with 1-year survival up to 35%, a 6%
increase compared with radiotherapy
alone.11 Phase 2 trials for combinations of
carboplatin, procarbazine, and fluorouracil were similarly unimpressive, reaching a
1-year survival proportion of 32%.12
Temozolomide (Temodar, ScheringPlough Corp, Kenilworth, NJ) is an alkylating agent approved by the US Food
and Drug Administration (FDA) for use in
newly diagnosed GBM,13 which has been
successfully used in the treatment of GBM.
The Stupp protocol demonstrated increased
survival of 2.5 months (12.2 months to 14.6
months) with the addition of temozolomide
at dosages of 75 mg/m2/day for 7 days
during radiotherapy and not exceeding 49
days.7,14,15 Following a 4-week break in therapy, temozolomide was administered again
for 5 days in 28-day cycles for between
1 and 6 cycles. The study demonstrated
a survival benefit at 2 years of 27.2% for
patients receiving adjuvant temozolomide
after maximal surgical resection, up from
10.9% in patients with adjuvant radiotherapy
alone.7 The survival benefit at 5 years was
9.8% for patients with combination therapy
compared with 1.9% for patients who received radiation therapy alone.7,14,15
With the advent of temozolomide for
the treatment of GBM, a new gene product was identified that conferred survival
advantage. Expression of O6-methylguanine-DNA methyltransferase (MGMT), an
enzyme involved in DNA repair, was linked
to shorter survival.16 The epigenetic silencing of the MGMT expression by methylation of the promoter was linked with a
survival advantage in patients receiving
temozolomide, with an overall survival
of 18.2 months in patients with MGMT
methylation compared with 12.2 months
in patients without MGMT methylation.16
Joseph A Hanson is a Medical Student in the Departments of Neurology and Neurosurgery at the University of California
Irvine in the City of Orange. E-mail: jhanson1@uci.edu. Frank P K Hsu, MD, PhD, is a Professor in the Department of
Neurosurgery at the University of California Irvine in the City of Orange. E-mail: fpkhsu@uci.edu. Arun T Jacob, MD, is a
Neurosurgeon in the Department of Neurosurgery at Baptist Memorial Healthcare in Memphis, TN. E-mail:aruntjacob@gmail.com.
Daniela A Bota, MD, PhD, is an Assistant Professor in the Department of Neurology at the University of California Irvine in
the City of Orange. E-mail:dbota@uci.edu. Daniela Alexandru, MD, is a Neurosurgeon at the University of California Irvine
Medical Center in Orange. E-mail: danielaa@uci.edu.
68
Review article
Despite chemotherapy and radiation,
GBM universally recurs, and at recurrence
the disease rapidly becomes lethal.12 Some
of the treatments considered at recurrence were repeated surgery, repeated
irradiation, or other chemotherapies,17,18
which all have yielded less than modest
results. Because of the altered signaling pathways and frequent mutations
found in GBM, the focus of therapy has
shifted toward the use of biologics and
target-specific molecular drugs for treatment.18 Bevacizumab (Avastin, Genentech,
South San Francisco, CA) is a humanized antivascular endothelial growth
factor (anti-VEGF) immunoglobulin G1
monoclonal antibody that was granted
accelerated FDA approval in 2009 as a
single-agent therapy for use in recurrent
GBM refractory to prior chemotherapy
or radiotherapy (Figure 1).19 This review
will evaluate the theoretical mechanism
of bevacizumab and its use and efficacy
in treating glioma, to demonstrate the
benefits it yields for well-selected patients
with newly diagnosed or recurrent GBM.
Angiogenesis, Vascular
Endothelial Growth Factor,
and Glioblastoma
Angiogenesis, the process of creating
new blood vessels and vascular branches
from preexisting tissues, is a vital component of tumorigenesis; it is required for
solid tumor growth beyond a 0.125-mm
radius because of limitations in nutrient
and oxygen diffusion capacity.20 This
process requires an abundance of unique
growth factors and cell adhesion molecules, which include different isoforms
of VEGF (VEGF-A, VEGF-B, VEGF-C,
and VEGF-D) as well as platelet-derived
growth factor.21 A receptor tyrosine kinase
ligand, VEGF-A has been identified as a
key promotor of tumor angiogenesis.22 In
tumor microenvironments such as GBM,
VEGF secretion is increased to promote
abnormal angiogenesis.23 In GBM, the
highest concentrations of VEGF are
found in areas of necrosis and hypoxia
in the tumor, because VEGF production
is stimulated in tumorigenic glial cells by
hypoxia and the concomitant upregulation of hypoxia inducible factor-1.24 The
resultant vasculature is often abnormal,
creating the potential for the development
of new areas of necrosis and hypoxia, thus
Table 1. Bevacizumab for recurrent glioblastoma multiforme
Author
Friedman,32
2009
Combination
therapy
Trial
Phase 2
Irinotecan
None
Vredenburgh,34
2007
Vredenburgh,47
2012
Norden,36
2009
Bokstein,35
2007
Kreisl,39
2009
Lai,45
2011
Cohen,19
2009
Phase 2
Irinotecan
Phase 2
Phase 2
Radiotherapy,
temozolomide
Irinotecan
Phase 2
Irinotecan
Phase 2
None; irinotecan on
disease progression
Radiotherapy,
temozolomide
Phase 2
Phase 2
Irinotecan
Irinotecan
Ali,37
2008
Hasselbalch,33
2010
Nghiemphu,50
2009
Gutin,41
2009
Chamberlain,40
2010
Gilbert,38
2009
Sathornsumetee,42
2010
Case series
Irinotecan
Phase 2
Irinotecan, cetuximab
Retrospective
None; irinotecan
Phase 2
Retrospective
Hypofractionated
stereotactic radiotherapy
None
Phase 2
Irinotecan
Phase 2
Erlotinib
Use
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant
Number
85
82
35
125
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant
34
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
Adjuvant,
recurrence
85
17
48
70
Median age,
years (range)
54
(23-78)
57
(23-79)
48
(18-66)
56.2
(19-80)
54.5
(31-74)
56
(38-74)
53
(21-69)
57.4
(31.3-75.8)
6-month PFS
(95% CI)
Median
PFS
Median
OS
4.2 months
9.2 months
5.6 months
8.7 months
3%
< 70
> 70
42.6%
(29.6%-55.5%)
50.3%
(36.8%-63.9%)
46%
(32%-66%)
—
24 weeks
42 weeks
13.8 months
—
> 70
40.0%
21.9 weeks
37.4 weeks
> 50
25.0%
4.2 months
7 months
> 60
29%
(18%-48%)
—
16 weeks
31 weeks
13.6 months
19.6 months
4.2 months
—
> 70
36.0%
(25.0%-47.0%)
—
3.9 months
—
—
—
24 weeks
27 weeks
—
16 weeks
30 weeks
4.25 months
9.0 months
KPS
> 70
> 70
> 60
> 70
44
54
(23-78)
54
(21-69)
53
(32-76)
54
(23-70)
—
—
33%
(19%-48%)
—
20
56
—
65.0%
—
12.5 months
50
64
(36-70)
57
> 60
42.0%
1 month
8.5 months
Median:
80
> 70
37%
(24-50%)
29.2%
(13.0%-47.6%)
—
—
18 weeks
44.6 weeks
56
13
43
57
25
52.4
(24.1-70.4)
CI = confidence interval; KPS = Karnofsky performance score; OS = overall survival; PFS = progression-free survival; (—) = none described.
69
REVIEW article
continuing the cycle.24 Both the density
of the microvasculature and the level of
VEGF secretion in glial tumors have been
associated with tumor grade and clinical
outcomes, with low overall survival scores
for patients who expressed high levels of
messenger RNA secretion.18,25-27 Therefore,
the development of an antiangiogenic
biologic therapy targeting VEGF-A for
highly vascular tumors such as glioblastoma gained popularity.28 It is postulated
that anti-VEGF-A immunoglobulin G
acts by sequestering VEGF and therefore
preventing the protein from initiating
the signaling cascade, which will lead
to recruitment of endothelial cells and
proliferation of blood vessels (Figure 2).
In glioma models the preclinical data
for the use of bevacizumab showed that
the tumors exhibited microvascular regression, normalization of mature blood
vessels, and inhibition of new vessel
growth.29 Clinical trials demonstrated
efficacy of bevacizumab and led to FDA
approval for use in malignant colorectal
cancer in 2004 and recurrent glioblastoma
in 2009.22 Two independent, randomized,
prospective trials of bevacizumab for
recurrent GBM demonstrated an increase
in progression-free survival (PFS) of 3.9
to 4.2 months in patients with recurrent
disease already treated with prior surgery,
radiotherapy, and temozolomide.19 Bevacizumab received accelerated approval as
single-agent therapy for recurrent GBM
refractory to surgical treatment, chemotherapy, and radiotherapy.19
Figure 1. Treatment algorithm for glioblastoma
multiforme (GBM).
70
Bevacizumab Use in
Glioblastoma
Most investigations into bevacizumab
therapy for GBM have consisted of Phase
2 trials to determine safety and efficacy
of the biologic agent in patients who
have recurrence of GBM after attempting
first-line surgical resection followed by
adjuvant radiotherapy and temozolomide
chemotherapy. The primary endpoint
for these studies was 6-month PFS30; the
North American Brain Tumor Consortium
uses 6-month PFS as the efficacy endpoint
of therapeutic trials for adult patients with
recurrent high-grade gliomas.31 Historic
evidence suggests that 6-month PFS in
absence of treatment of recurrent GBM
ranges from 9%30 to 16%.31 These findings are based on retrospective data from
pooled trials of nonefficacious therapies;
most investigators usually tailor their studies to demonstrate the presence or lack of
a significant difference from this baseline.
Patient populations are typically selected on the basis of performance status,
failure of first-line therapy with radiologic
proof of disease progression, and lack of
major comorbidities in light of a histologic
diagnosis of Grade 4 glioma. Exclusion
criteria generally include previous treatment with carmustine wafer or anti-VEGF
agents; history of bleeding diathesis,
intracranial hemorrhage, or coagulopathy; clinically significant cardiovascular
disease; recent arterial thromboembolism;
uncontrolled hypertension; and Karnofsky
performance score less than 70.19,32,33
Efficacy
In the first prospective Phase 2 trial
of bevacizumab, Vredenburgh et al 34
administered irinotecan, a topoisomerase
inhibitor, as conjunctive adjuvant therapy
because of the combination’s history of
success in colorectal cancer. They observed partial or complete response in 20
(57%) of 35 patients, with a 6-month PFS
rate of 46% (n = 16; 95% confidence interval [CI], 32%-66%),34 in excess of the baseline 6-month PFS rate of 9% to 16% in 345
untreated patients with recurrent GBM.30,31
A study sponsored by Genentech demonstrated similar findings, noting a 6-month
PFS rate of 36.0% (n = 31; CI, 25.0%47.0%) in a Phase 2 trial of bevacizumab
and irinotecan in 85 patients.19 Since that
time, multiple authors have documented
6-month PFS rates for bevacizumab and
irinotecan combination therapy between
25% and 40% (Table 1).35-38 Friedman et
al32 performed a large trial both with and
without combination irinotecan therapy.
They found a 6-month PFS rate of 42.6%
(CI, 29.6%-55.5%) in patients receiving
combination irinotecan-bevacizumab
therapy and a 6-month PFS rate of 50.3%
(CI, 36.8%-63.9%) in those receiving
single-agent bevacizumab, with no significant difference in 6-month PFS or median
PFS between the 2 arms. Investigation into
bevacizumab monotherapy has yielded
similar results. Kreisl et al39 recorded a
6-month PFS rate of 29% (n = 14; CI,
18%-48%) in a Phase 2 trial of 48 patients,
and Chamberlain and Johnston40 found
a 6-month PFS rate of 42% (n = 21) in a
retrospective review of 50 patients using
bevacizumab monotherapy. Overall, the
results between single-agent bevacizumab
and combination therapy with cytotoxic
agents, specifically irinotecan, have been
similar to date, with no clear superiority
among either regimen.
New combination therapies are currently under clinical investigation as well.
Hasselbalch et al33 combined adjuvant
bevacizumab therapy with irinotecan and
cetuximab, a monoclonal anti-epidermal
growth factor antibody also used in
colorectal cancer, and reported a 6-month
PFS of 33% (n = 14; CI 19%-48%) among
43 patients. Gutin et al41 administered hypofractionated stereotactic radiotherapy in
combination with bevacizumab for treatment of recurrent GBM in 20 patients and
reported a 65% (n = 13; CI unreported)
6-month PFS. Additionally, Sathornsumetee et al42 combined bevacizumab with
erlotinib, an epidermal growth factor
receptor tyrosine kinase inhibitor, in 25
patients with recurrent GBM and found a
6-month PFS rate of 29.2% (n = 7).
These studies are noncomparative,
Phase 2 safety studies, and there is no statistically significant evidence to indicate the
comparative effectiveness of bevacizumab
in single-agent or combination therapy for
recurrent GBM. However, all studies in our
literature search, regardless of combination
therapy, reported 6-month PFS rates in excess of 25% (Table 1), suggesting that there
may be benefit to bevacizumab therapy in
delaying disease progression.
Review article
Artwork by Daniela Alexandru, MD.
Figure 2. Artist’s depiction of mechanism of action of bevacizumab. Tumor secretes
vascular endothelial growth factor (VEGF) to promote proliferation of blood vessels
(top). Bevacizumab sequesters VEGF, leading to decreased vascular proliferation and
decreased tumor size (bottom).
Safety
Bevacizumab is typically well tolerated
by patients, and its side effect profile
in those with GBM is equivalent to the
adverse events encountered in patients
receiving bevacizumab therapy for malignant colorectal cancer, non-small-cell lung
cancer, and metastatic breast cancer.43 In
trials of bevacizumab for recurrent GBM,
the most commonly encountered Grade
3 or 4 adverse events (graded according
to the National Cancer Institute Common
Terminology Criteria for Adverse Events,
version 3.0) 44 include hypertension,
hemorrhage (eg, epistaxis, intracranial),
thromboembolic complications, and
convulsions. 32 Other serious adverse
events reported in the literature include
proteinuria, gastrointestinal tract perforation, wound healing complications,
reversible posterior leukoencephalopathic
syndrome, intractable convulsion, and
neutropenia,32 but the frequency of such
outcomes is generally very low (< 4% in
large studies).19,32
The overall rate of Grade 3 or greater
adverse events in studies of bevacizumab
to date has ranged from 12% to 66%32,35
(Table 2). These events are hypothesized
to be caused by the incidental effect of
anti-VEGF blockade on the vasculature
of normal healthy tissues or caused by
postoperative wound healing complications presumably caused by inhibition
of neovascularization of wound tissue in
neurosurgical patients.18 Although there
are no formal recommendations for the
interval between surgery and initiation
of bevacizumab therapy in patients after
repeated surgical resection of GBM, most
Table 2. Adverse outcomes in bevacizumab trials
Vredenburgh,34 2007
Bokstein,35 2007
Kreisl,39 2009
Cohen,19 2009
Combination
therapy
Irinotecan
None
Irinotecan
Irinotecan
None
Irinotecan
Ali,37 2008
Hasselbalch,33 2010
Chamberlain,40 2010
Gilbert,38 2009
Irinotecan
Irinotecan, cetuximab
None
Irinotecan
Author
Friedman,32 2009 Grade ≥ 3 adverse
events, percentage
65.8
46.4
22.9
11.8
27.1
46.4
Grade 5 adverse
events, percentage
1.3
2.5
0.0
0.0
0.0
3.6
23.1
58.0
24.0
49.0
0.0
0.0
0.0
2.0
Description of Grade 5
adverse events
Convulsion
Neutropenia/infection, pulmonary embolism
—
—
—
Neutropenia/infection, pulmonary embolism,
operative complications
—
—
—
Intracranial hemorrhage
(—) = none described.
71
REVIEW article
studies in the literature cite 3 to 4 weeks
as an appropriately safe interval.41,45
Neurosurgeons and neuro-oncologists
should be wary of the potential for adverse outcomes with premature repeated
operation in patients using bevacizumab
who require additional resection of tumor
after initiation of adjuvant chemotherapy.
Grade 5 events (ie, those
leading to death) are rare,
Although
occurring in less than 3.6%
it has little
of patients (Table 2). Causes
effect on
of mortality in clinical studoverall
ies thus far include infection
secondary to drug-induced
survival,
neutropenia, pulmonary embevacizumab
bolism, and intracranial hemortherapy
rhage.19,32,38 Even in studies in
maintains
which fatal intracranial hemorthe patient’s
rhage occurred,38 the rate of
Karnofsky
hemorrhage approaches the
performance
expected incidence of intrascore by
cranial hemorrhage in patients
increasing
with intracranial malignancy in
the PFS and
the absence of treatment (apconsequently
proximately 2.5%).46
There is some evidence that
increasing the
single-agent
bevacizumab is
quality of life.
associated with lower rates
of Grade 3 or higher adverse
events than combination therapy with
irinotecan.18,38,40 Chamberlain et al40 and
Kreisl et al38 noted Grade 3 or greater
adverse events in only 24.0% to 27.1% of
enrolled patients receiving single-agent
bevacizumab therapy, whereas benchmark studies for combined bevacizumab
and irinotecan treatment, such as by
Friedman et al,32 found rates of Grade
3 or greater adverse events as high as
65.8%. Regardless, these data are limited
to cross-trial comparisons of different
study populations. Friedman and colleagues’ own single-agent bevacizumab
arm had Grade 3 or greater adverse events
in 46.4% of patients, and any differences
in the safety profile of single-agent or
combined therapies of bevacizumab are
still speculative at this time.
Prospects for Future Use
More recent investigations have led
to the experimental use of bevacizumab
as combination therapy with first-line
adjuvant radiotherapy and temozolomide
after surgical resection of new-onset
GBM. Vredenburgh et al47 treated 125
72
patients with bevacizumab, radiotherapy,
and temozolomide beginning 4 weeks
after surgical resection and found no
increase in patient dropout compared
with similar trials of radiotherapy and
temozolomide in the absence of bevacizumab. They found that 93% of patients
were able to tolerate combined adjuvant
therapy of irradiation, temozolomide,
and bevacizumab compared with an
83% completion rate in similar trials of
temozolomide and irradiation alone.47
Importantly, less than 2% of patients
enrolled experienced clinically significant
intracranial hemorrhage or craniotomy
wound dehiscence despite theoretical
concerns of increased risks of wound
healing complications.47 Furthermore,
the median PFS was measured at 13.8
months, which compared favorably with
the median PFS of 6.9 months in similar
temozolomide and radiotherapy trials.14
Lai et al45 also treated 70 patients with
adjuvant bevacizumab, temozolomide,
and radiotherapy in new-onset GBM
and recorded a statistically significant
increase in 6-month PFS (range, 7.6
months to 13.6 months) without change
in median overall survival compared
with accumulated data of radiotherapy
plus temozolomide without bevacizumab
given at their institution.
These were noncomparative trials
to determine the efficacy and safety of
bevacizumab in combination with radiotherapy and temozolomide. Bevacizumab
is currently labeled for use only in patients
with recurrent GBM with progression
after the options of surgical resection,
radiotherapy, and temozolomide chemotherapy have been exhausted. Phase
2 studies of temozolomide have shown
a 6-month PFS of 13% to 29% (95% CI)
in temozolomide-treated patients48; these
studies suggest that bevacizumab may
provide clinical benefit above this benchmark. The potential safety of bevacizumab
after a sufficient postoperative interval is
theorized to increase the clinical benefit
of angiogenic inhibition and to improve
the clinical effect of bevacizumab.47
Discussion
Glioblastoma multiforme is a highly
aggressive and deadly class of malignancy. Patients receiving this diagnosis
have on average less than a year to live,
and even those who respond to first-line
therapy will likely face most of that time
neurologically impaired or debilitated.
Furthermore, the financial expense of
bevacizumab is daunting. One study
estimated the cost per quality-adjusted
life year for use in colorectal and breast
cancer at approximately $300,000.49 Even
for these neurologically intact patients,
only 25% of surveyed oncologists believed
that bevacizumab offered “good value.”49
However, most surveyed oncologists
believe that patients should have access
to high-quality care despite the financial
costs of treatment, as it is difficult to place
a price tag on extending life.49
Options for patients with GBM are
limited at tumor recurrence. Often, repeated irradiation and repeated surgery
are not suitable options, and the tumors
have already demonstrated resistance
to first-line cytotoxic alkylating therapy
with temozolomide.18 Despite the data
supporting the safety and efficacy of
bevacizumab (measured by increased
6-month PFS) in patients with recurrent
GBM (Tables 1 and 2), some studies
show only a very modest increase in
median overall survival.36 Lai et al,45 in
their study of bevacizumab in combination with adjuvant radiotherapy and
temozolomide in new-onset GBM, also
found a statistically significant difference
in 6-month PFS among patients receiving bevacizumab compared with historic
institutional data without corresponding
change in median overall survival. This
suggests that the use of bevacizumab
delays progression. Although it has little
effect on overall survival, bevacizumab
therapy maintains the patient’s Karnofsky performance score by increasing
the PFS and consequently increasing
the quality of life.
However, there exist no reliable a priori
evaluations to determine whether a patient is suitable for bevacizumab therapy,
or in which patients bevacizumab will
provide optimal benefit.18 Increased age
(> 55 years) and lower performance (Karnofsky performance score < 80) has been
associated with greater benefit from bevacizumab, possibly because of the higher
VEGF expression in these patients. 50
Furthermore, patients treated with bevacizumab are able to maintain functional
status longer than patients historically not
Review article
treated with bevacizumab.50 Age at time of
diagnosis is still the strongest prognostic
indicator for survival in GBM, with median
survival as low as 2 months in patients
older than age 80 years.51 Although overall survival for patients with GBM has
increased since the 1990s, the youngest
(aged 20 to 44 years) and most functional
patients have received the greatest benefit,
achieving 2-year survival rates as high as
39%; the most elderly patients (aged > 80
years) have experienced minimal benefit
and have achieved a disappointing 2-year
survival rate of 1%.4
Recent studies of bevacizumab threaten
to change this trend by increasing the
median PFS and prolonging the functional status of patients whose disease
was previously resistant to traditional
radiotherapy and cytotoxic adjuvant
therapies. Furthermore, recent studies
have begun experimental investigation
into the use of bevacizumab as adjuvant
therapy for new-onset GBM.45,47 Given
the antiangiogenic mechanism of bevacizumab, it is widely theorized that
early administration of VEGF inhibitors
will prevent wound healing and increase
operative complications.52 These studies suggest not only that postoperative
administration of bevacizumab (after an
appropriate time window) is safe, it may
actually be efficacious in prolonging median PFS and increasing six-month PFS.45,47
Preliminary results from the AVAglio study,
the first prospective Phase 3 trial for the
use of bevacizumab (Avastin) in recurrent
glioma, were recently announced at the
2013 American Society of Clinical Oncology meeting. The study found that the
addition of bevacizumab to treatment of
newly diagnosed GBM did not improve
overall survival, although it did improve
the PFS but not to a significant statistical
criterion.53 The study also found that the
MGMT methylation profile did not identify
to be a selective benefit, but instead was
a risk subset. To date, the results of this
study suggest that bevacizumab should
not be used as first-line therapy for the
treatment of GBM.
Bevacizumab has been shown to be
safe in new-onset and recurrent disease.
This is especially important for older
patients (age > 55 years) for whom the
prognosis is worse and the benefits of
bevacizumab more promising. More pro-
spective Phase 3 trials are needed to determine the appropriate patient population
for bevacizumab therapy, the appropriate
combination therapy, and the appropriate
timing of therapy (adjuvant for new-onset
vs recurrent disease). Although the effect
on overall survival and the appropriate
patient population is still unclear for bevacizumab, its ability to increase the number
of patients who survive for 6 months
without impairment should be cause for
further investigation and clinical use. v
to disclose.
Acknowledgment
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org/10.1002/cncr.23401
36. Norden AD, Drappatz J, Muzikansky A, et al.
An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma.
J Neurooncol 2009 Apr;92(2):149-55. DOI:
http://dx.doi.org/10.1007/s11060-008-9745-8
37. Ali SA, McHayleh WM, Ahmad A, et al. Bevacizumab and irinotecan therapy in glioblastoma
multiforme: a series of 13 cases. J Neurosurg
org/10.3171/JNS/2008/109/8/0268
38. Gilbert MR, Wang M, Aldape K, et al. RTOG
0625: a phase II study of bevacizumab with
irinotecan in recurrent glioblastoma (GBM).
J Clin Oncol (Meeting Abstracts) 2009
May;27(15S):2011.
39. Kreisl TN, Kim L, Moore K, et al. Phase II trial
of single-agent bevacizumab followed by
bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol
2009 Feb 10;27(5):740-5. DOI: http://dx.doi.
org/10.1200/JCO.2008.16.3055
40. Chamberlain MC, Johnston SK. Salvage
therapy with single agent bevacizumab
for recurrent glioblastoma. J Neurooncol
org/10.1007/s11060-009-9957-6
41. Gutin PH, Iwamoto FM, Beal K, et al. Safety
and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent
malignant gliomas. Int J Radiat Oncol Biol Phys
2009 Sep 1;75(1):156-63. DOI: http://dx.doi.
org/10.1016/j.ijrobp.2008.10.043
42. Sathornsumetee S, Desjardins A, Vredenburgh
JJ, et al. Phase II trial of bevacizumab and
erlotinib in patients with recurrent malignant
glioma. Neuro Oncol 2010 Dec;12(12):1300-10.
DOI: http://dx.doi.org/10.1093/neuonc/noq099
43. Hurwitz H, Saini S. Bevacizumab in the treatment of metastatic colorectal cancer: safety
profile and management of adverse events.
Semin Oncol 2006 Oct;33(5 Suppl 10):S26-34.
DOI: http://dx.doi.org/10.1053/j.seminoncol.2006.08.001
44. Trotti A, Colevas AD, Setser A, et al. CTCAE
v3.0: development of a comprehensive grading
system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003 Jul;13(3)17681. DOI: http://dx.doi.org/10.1016/S10534296(03)00031-6
45. Lai A, Tran A, Nghiemphu PL, et al. Phase II
study of bevacizumab plus temozolomide
during and after radiation therapy for patients
with newly diagnosed glioblastoma multiforme.
J Clin Oncol 2011 Jan 10;29(2):142-8. DOI:
http://dx.doi.org/10.1200/JCO.2010.30.2729
46. Schrader B, Barth H, Lang EW, et al.
Spontaneous intracranial haematomas
caused by neoplasms. Acta Neurochir (Wien)
2000;142(9):979-85. DOI: http://dx.doi.
org/10.1007/s007010070052
47. Vredenburgh JJ, Desjardins A, Kirkpatrick JP, et
al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed
glioblastoma multiforme. Int J Radiat Oncol
Biol Phys 2012 Jan 1;82(1):58-66. DOI: http://
dx.doi.org/10.1016/j.ijrobp.2010.08.058
48. Yung WK, Albright RE, Olson J, et al. A phase
II study of temozolomide vs procarbazine in
patients with glioblastoma multiforme at first
relapse. Br J Cancer 2000 Sep;83(5):588-93.
DOI: http://dx.doi.org/10.1054/bjoc.2000.1316
49. Nadler E, Eckert B, Neumann PJ. Do oncologists
believe new cancer drugs offer good value?
Oncologist 2006 Feb;11(2):90-5. DOI: http://
dx.doi.org/10.1634/theoncologist.11-2-90
50. Nghiemphu PL, Liu W, Lee Y, et al. Bevacizumab and chemotherapy for recurrent glioblastoma: a single-institution experience. Neurology
2009 Apr 7;72(14):1217-22. DOI: http://dx.doi.
org/10.1212/01.wnl.0000345668.03039.90
51. Ohgaki H, Kleihues P. Epidemiology and
etiology of gliomas. Acta Neuropathol
org/10.1007/s00401-005-0991-y
52. Clark AJ, Butowski NA, Chang SM, et al.
Impact of bevacizumab chemotherapy on
craniotomy wound healing. J Neurosurg
org/10.3171/2010.10.JNS101042
53. Chinot OL, de La Motte Rouge T, Moore N,
et al. AVAglio: phase 3 trial of bevacizumab
plus temozolomide and radiotherapy in newly
diagnosed glioblastoma multiforme. Adv Ther
org/10.1007/s12325-011-0007-3
Mystery
As long as our brain is a mystery, the universe, the reflection of the structure of the brain, will also be a mystery.
— Santiago Ramón y Cajal, 1852-1934, Spanish pathologist, histologist, neuroscientist, and 1906 Nobel Laureate for Physiology or Medicine
74
Commentary
Choosing Wisely and Beyond: Shared Decision Making and Chronic Kidney Disease
Phillip Tuso, MD
Perm J 2013 Fall;17(4):75-78
Abstract
In 2012, the Kaiser Permanente Area Medical Directors of
Quality decided to sponsor analytic activities to improve shared
decision making for patients with chronic kidney disease. The
objective was to move shared decision making for renal replacement therapy or maximal conservative management upstream
rather than waiting until the patient presented to the emergency
room requiring acute dialysis. Nephrologists have multiple opportunities to discuss treatment options with patients throughout
the course of their disease. However, despite these opportunities
most patients beginning dialysis have not experienced shared
decision making with their physicians. The shared-decisionmaking process may help patients understand the importance
of being prepared to start dialysis and the benefits of maximal
conservative management.
By having these discussions upstream we may be able to
improve survival (save lives), slow down renal disease progression (save kidneys), preserve central veins for future vascular
access (save veins), and be better stewards of finite resources
needed to care for patients with end-stage kidney disease
(save resources).
Introduction
In 2012, the American Society of Nephrology joined the
American Board of Internal Medicine Foundation and Consumer
Reports in the Choosing Wisely campaign. The purpose of this
multiple-year campaign is to help physicians be better stewards
of finite health care resources.1 The campaign strongly reflects
a focus on high-quality and affordable care for all patients with
chronic kidney disease (CKD). The campaign was designed to
encourage shared decision making between patients and their
physicians. Internal medicine specialists were asked to come up
with five things physicians and patients should question. One
of these questions from nephrologists was, “Should we initiate
chronic dialysis without ensuring a shared-decision-making
process between patients, their families, and their physicians?” In
2010, the Renal Physician Association published clinical practice
guidelines on shared decision making for chronic kidney disease.2 They outlined three approaches to care for patients with
end-stage kidney disease (ESKD) at the time of initiation of renal
replacement therapy: 1) dialysis therapy without limitations on
other treatments, 2) dialysis therapy without cardiopulmonary
resuscitation, and 3) no dialysis therapy.
Because most nephrologists have been trained to use all
therapies necessary to prolong life of patients with ESKD, they
may hesitate to have an end-of-life discussion with patients who
are preparing to start dialysis. Most patients will continue dialysis
therapy until death, unless there is a paradigm shift regarding
end-of-life care for patients with CKD. Recent surveys suggest
that not all patients with ESKD want to preserve life by any
means necessary.3 In addition, a study from the United Kingdom
suggests dialysis may offer no survival advantage over 75 years
for patients with stage 5 CKD (CKD5) and multiple comorbidities compared to CKD5 patients without multiple comorbidities.4
These studies suggest we have an opportunity to improve the
process of shared decision making with CKD patients.5
Shared Decision-Making Process and Chronic
Kidney Disease
Because renal function of patients with kidney disease usually
declines gradually, nephrologists have multiple opportunities to
discuss options for renal replacement therapy and end-of-life
care. However, despite multiple visits to a nephrologist before
starting dialysis therapy, less than 10% of ESKD patients reported
a discussion about end-of-life care with their nephrologists in
the last 12 months.3 There are at least 3 times when shared decision making with a CKD patient is critical: when the patient
enters stage 4 (estimated glomerular filtration rate [eGFR] <
30 mL·min-1·1.73 m-2), when the patient is about to start renal
replacement therapy (eGFR < 15 mL·min-1·1.73 m-2), or when
the there is no evidence that further therapy will prolong life
(eGFR < 5 mL·min-1·1.73 m-2, or age > 75 years and multiple
comorbidities). In addition to these 3 key times, progression to
each substage of stage 4 CKD (CKD4) and CKD5 may prompt
a nephrologist to discuss options for renal replacement therapy
with the patient (Figure 1).
The new paradigm suggests that chronic disease is a journey
of many months or years. During this journey the nephrologist
and patient are in constant communication about prognosis and
treatment options.6
The Optimal Start Initiative
In 2012, the Kaiser Permanente Associate Medical Directors
of Quality decided to sponsor analytic activities to improve
shared decision making with CKD patients. The goal was to
move shared decision making about renal replacement therapy
or maximal conservative management upstream, rather than
waiting until the patient presented to the emergency room
requiring acute dialysis. As outlined above, nephrologists
have multiple opportunities to discuss treatment options with
patients throughout the course of their disease. However,
Phillip Tuso, MD, is the Care Management Institute Physician Lead for Total Health. E-mail: phillip.j.tuso@kp.org.
75
Commentary
Figure 1. The top of the figure illustrates how the topic of life-sustaining treatment and the topic of palliative care can be integrated
in discussions with the patient as the disease progresses. This approach is in contrast to management of end-stage kidney disease
with dialysis until the very end of life, which leaves the patient
unprepared for death and dying. The bottom of the figure relates
stage of kidney disease and estimated glomerular filtration rate
(eGFR). Patients enter stage 4 chronic kidney disease (CKD) when
their eGFR decreases below 30 mL·min-1·1.73 m-2. Each additional
decrease of approximately 5 mL·min-1·1.73 m-2 corresponds to the
following substage. The arrows indicate 3 stages when shared
decision making is critical.
despite these opportunities, most patients do not have an
optimal start to renal replacement therapy.
An optimal start of dialysis means that the patient begins
dialysis without a vascular catheter. Vascular catheters are associated with increased infectious complications, central vein
stenosis, mortality, and greater cost compared with arteriovenous
fistula.7 For this reason, CKD patients are encouraged to start
renal replacement therapy with a preemptive transplant, arteriovenous fistula, peritoneal dialysis, or maximal conservative
management. Despite our best efforts to reduce the number of
patients who start dialysis with a vascular catheter, only 27% of
ESKD patients in the US start dialysis without a vascular catheter.7 This represents a significant opportunity for improvement.
To improve outcomes, we should consider intervening earlier
and have upstream discussions with our patients about risks of
nonoptimal start of renal replacement therapy. We should be
able to decrease the risk of nonoptimal start by initiating life-plan
conversations when CKD patients first present to the renal clinic.
We would also like our patients to have an optimal start on
their journey toward end-of-life care. Two recent studies suggest
we may not be accomplishing this effectively. In 2012, Wong et
al8 reported that 76% of dialysis patients were hospitalized in
their final month of life. On average, these patients were in the
hospital for 9.8 days. Forty-eight percent were admitted to the
intensive care unit, and 29% had an intensive procedure performed during the hospital stay. Only 20% were admitted to a
hospice. Forty-four percent of these patients died in the hospital.
In comparison, 39% of cancer patients and 55% of heart failure
patients were admitted to a hospice. Only 35% of cancer patients
and 29% of heart failure patients died in the hospital during
their last month of life. Davison3 surveyed a total of 584 CKD4
and CKD5 patients as they presented to dialysis, transplantation, or predialysis clinics in Canada. Participants reported poor
knowledge of palliative care options and their illness trajectory.
76
Sixty-one percent of patients regretted their decision to start
dialysis. More patients wanted to die at home (36.1%) or in a
hospice (28.8%) compared with a hospital (27.4%).
The latter studies suggest that we are not having effective
conversations with our patients about end-of-life care until
their death is very near. Our current paradigm for care needs to
be questioned. We propose a new paradigm that encourages
shared decision making and development of life-care plans.
In this paradigm, conversation with CKD patients would shift
from planning short-term goals to charting a course to deliver
what is best for patients by reducing risk and maximizing the
potential for effective, proactive care. These conversations can
focus on survival and action plans to improve the health of the
CKD patient’s mind, body, and spirituality.
Stage 4 Chronic Kidney Disease
The optimal time to begin the “life with kidney disease”
discussion is when a patient presents to the renal clinic with
CKD4.9 These initial discussions should include 1) major causes
of kidney disease, 2) stages of kidney disease, and 3) treatment
of kidney disease. It may be appropriate to discuss 5-year survival rates for CKD4 and the risk of starting dialysis in the next
5 years. In 2004, Keith et al published a longitudinal follow-up
and outcomes study of patients with CKD in a large managedcare organization.10 The study reported the percentage of patients
who started renal replacement therapy or died before starting
dialysis or transplantation. The risk of starting dialysis over a
5-year period was 1.1%, 1.3%, and 19.9% for CKD2, CKD3, and
CKD4 patients, respectively. The study also reported that the
risk of death over a 5-year period was 19.5%, 24.3%, and 45.7%
for CKD2, CKD3, and CKD4 patients, respectively. This information may help patients with CKD understand their prognosis.
These data can be integrated into their life plan to help them
develop a strategy with their nephrologist that will decrease
their risk of dialysis and death.11 Nephrologists can initiate these
discussions, and educational shared-decision-making classes
can reinforce them.
End-Stage Kidney Disease
Shared decision making should occur between patients and
their families and physicians before chronic dialysis begins.
The discussions should focus on 4 goals: 1) save lives, 2) save
kidneys, 3) save veins, and 4) save resources (Table 1). The US
Renal Data System 2012 reported that there were no significant
differences between 5-year survival rates for patients treated with
peritoneal dialysis and those treated with hemodialysis.7 Transplantation, however, has a significant survival benefit compared
with dialysis and should be the preferred form of renal replacement therapy. The main problem with renal transplantation is
the risk of death while waiting for a renal transplant. Data from
the US Renal Data System 2012 showed that there are currently
about 86,000 ESKD patients on the waiting list, and we only
perform about 17,000 renal transplantations per year in the US.
The median time patients spend on a waiting list for a renal
transplant is 2.6 years. The proportion of patients who die after
1, 3, and 5 years waiting for a renal transplant is 1.7%, 9.6%,
and 20.3%, respectively.
Commentary
The next important goal of ESKD management is to preserve
existing renal function.12 Wang and Lai reviewed the importance
of saving kidney function during dialysis.13 Preserving residual
renal function has always been the primary clinical goal of
nephrology, and there is no reason why this goal should not
extend to patients on dialysis. Since we do not routinely report
survival outcomes of patients on dialysis by eGFR or CKD5 substage, there is no clear evidence that preserving residual renal
function remains important after dialysis therapy commences.
However, residual renal function contributes significantly to the
overall health of dialysis patients. A patient with an eGFR of 10
mL·min-1·1.73 m-2 is better off than a patient with an eGFR of 5
mL·min-1·1.73 m-2 in terms of maintaining fluid balance, phosphorus control, removal of uremic toxins, and prevention of
vascular calcifications. In addition, a decline in residual renal
function may contribute significantly to anemia and malnutrition
in patients on dialysis. We can prevent loss of residual renal
function with many of the treatments we use to prevent loss
of residual function during CKD4. These include angiotensinconverting enzyme inhibitors and avoidance of acute kidney
injury caused by dehydration, high doses of antibiotics, nonsteroidal anti-inflammatory agents, or contrast dye.
The third goal for patients starting dialysis is to save their veins.
Central veins are the lifeline for patients on hemodialysis. Creation of a successful arteriovenous fistula for dialysis depends on
the central veins being healthy. Use of central vein catheters may
increase the risk of central vein stenosis caused by scarring and
infection. Once the central vein is stenosed, creating a functioning arteriovenous fistula will be more difficult. Vascular catheters
should be avoided for dialysis. A good way to save the veins is
to start with peritoneal dialysis instead of hemodialysis with a
vascular catheter.14 The benefits of peritoneal dialysis have been
outlined by Chaudhary15 and include similar survival rate, lower
cost, and improved quality of life compared with hemodialysis.
The final goal is to save resources. In 2012, we spent almost
$30 billion treating ESKD. This is almost 8% of total Medicare
spending.7 Medicare spending per patient per year by type of
renal replacement therapy is $32,914 for renal transplantation,
$66,751 for peritoneal dialysis, and $87,561 for hemodialysis.
About a third of Medicare ESKD costs is for inpatient treatment,
a third is for dialysis therapy, and a third is for outpatient treatTable 1. Shared decision making during chronic
kidney disease
Stage
4
4a
eGFR
< 30
26-30
4b
4c
5
5a
5b
5c
21-25
16-20
< 15
10-15
5-9
<5
Plan
Shared decision making
Reduce risk of cardiovascular disease
Reduce risk of kidney disease progression
Upstream optimal start initiative
Preemptive renal transplantation
Optimal start
Peritoneal dialysis bridge therapy
Home dialysis bridge therapy
In-center hemodialysis
eGFR = estimated glomerular filtration rate, mL·min-1·1.73 m-2
ment. These data indicate an opportunity
to reduce costs by treating more patients
with peritoneal dialysis and transplantation. In addition, readmission rates for
dialysis patients significantly exceed those
for Medicare patients without ESKD.7 Reducing avoidable readmissions should be
associated with better proactive management of CKD.
… patients [with
chronic kidney
disease stage 5] who
choose conservative
therapy will
have extensive
health care needs,
including control of
symptoms, measures
to retard disease
progression, and
management of
complications of
renal disease.
Maximum Conservative
Management
The final critical time to have a shareddecision-making discussion with a patient
is when there may be no survival benefit
from renal replacement therapy. Murtagh
et al16 performed a retrospective analysis
of the survival of 129 CKD5 patients older
than 75 years; the patients attended a dedicated multidisciplinary
predialysis clinic. The dialysis group had 1- and 2-year survival
rates of 84% and 76%, respectively, compared with 68% and 47%
for the conservative management (no dialysis therapy) group.
However, this survival advantage was lost in those patients with
high comorbidity scores, especially when the comorbidity included ischemic heart disease. The authors conclude that CKD5
patients older than 75 years who receive specialist nephrology
care and follow a planned management pathway have a substantially reduced survival advantage on dialysis if they have multiple
comorbidities. These data suggest that comorbidity should be
a major consideration when advising elderly patients for or
against dialysis. Dialysis is prescribed for many patients who
may not have a survival advantage attributable to dialysis. This
is a good example of a situation where shared decision making
may help inform a patient of the risks and benefits of dialysis.
In patients older than 75 years with multiple comorbidities, the
risk of dialysis may outweigh the benefits. Why should patients
undergo surgery for arteriovenous fistula and go to therapy for
up to 12 hours per week if there is no good evidence that this
type of therapy will increase survival?
Maximal conservative management programs are developing around the country to help care for patients who choose
no dialysis therapy. These programs are in their infancy but
are projected to increase in size over time and may care for
an estimated 10% to 20% of the ESKD population.17 Models of
care are still developing, but they may follow 3 patterns: renal
palliative care programs run by nephrology teams trained in
palliative care; palliative care programs run by palliative care
physicians trained in CKD5 care; or a combined program where
patients are seen by both a nephrology team and a palliative
care team. These teams will work together to provide individualized, patient-focused care. They will have discussions that focus
on listening to and understanding the patient while providing
prognostic information. Important to these discussions will be
the balancing of expectations with anticipated complications
that are associated with disease progression. Synergy between
the nephrology team and the palliative care team will provide
the expertise needed to achieve these goals.
77
Commentary
Conclusion
Shared decision making is critical to the long-term outcome of
the patient with kidney disease. New information provided by
the leadership of the American Board of Internal Medicine and
the American Society of Nephrology has laid the groundwork
for the Choosing Wisely initiative. This initiative encourages
nephrologists to have shared-decision-making discussions with
their patients with kidney disease. If the physician and patient
work together as a team, they maximize the patient’s ability to
develop an effective life plan that improves survival and prepares
the patient for end-of-life care (Table 1).
Increasing numbers of cases of CKD5 may be managed without dialysis. Dialysis may offer no survival advantage to high-risk,
older patients with CKD5 and multiple comorbidities.16 CKD5
patients who choose conservative therapy will have extensive
health care needs, including control of symptoms, measures to
retard disease progression, and management of complications
of renal disease. Meeting the palliative care needs of CKD5
patients who choose conservative therapy will require both that
nephrologists learn about palliative care and that palliative care
physicians learn about nephrology.
A collaborative approach that includes the patient and physician can improve services for all patients with CKD, although
models of care implementing an upstream shared-decisionmaking process need further evaluation and development. These
therapy pathways are being developed to help nephrologists
develop effective service delivery programs for all CKD patients.
Future efforts in nephrology should implement a broad, patientcentered, upstream shared-decision-making process focused on
saving lives, saving kidneys, saving veins, and efficient use of
resources needed to care for all patients with kidney disease. Our
overall goal should be to treat the patient, not just the disease. v
Acknowledgment
References
1. Choosing wisely [Web site on the Internet]. Philadelphia, PA: ABIM Foundation; c2013 [cited 2012 Nov 26]. Available from: www.abimfoundation.org/
Initiatives/Choosing-Wisely.aspx.
2. Shared decision-making in the appropriate initiation of and withdrawal
from dialysis: clinical practice guideline. 2nd ed. Recommendations
summary [monograph on the Internet]. Rockville, MD: Renal Physicians Association; 2010 Oct [cited 2012 Nov 26]. Available from: www.renalmd.org/
catalogue-item.aspx?id=682.
3. Davison SN. End-of-life care preferences and needs: perceptions of patients
with chronic kidney disease. Clin J Am Soc Nephrol 2010 Feb;5(2):195-204.
DOI: http://dx.doi.org/10.2215/CJN.05960809
4. Murtagh FR, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS, Harris FR. Dialysis
or not? A comparative survival study of patients over 75 years with chronic
kidney disease stage 5. Nephrol Dial Transplant 2007 Jul;22(7):1955-62.
DOI: http://dx.doi.org/10.1093/ndt/gfm153
5. Williams AW, Dwyer AC, Eddy AA, et al; American Society of Nephrology
Quality, and Patient Safety Task Force. Critical and honest conversations:
the evidence behind the “Choosing Wisely” campaign recommendations
by the American Society of Nephrology. Clin J Am Soc Nephrol. 2012
Oct;7(10):1664-72. DOI: http://dx.doi.org/10.2215/CJN.04970512
6. Burns A, Davenport A. Maximum conservative management for patients
with chronic kidney disease stage 5. Hemodial Int 2010 Oct;14 Suppl
1:S32-7. DOI: http://dx.doi.org/10.1111/j.1542-4758.2010.00488.x
7. United States Renal Data System [homepage on the Internet]. Minneapolis,
MN: USRDS Coordinating Center; [cited 2012 Nov 26]. Available from:
www.usrds.org.
8. Wong SP, Kreuter W, O’Hare AM. Treatment intensity at the end of life
in older adults receiving long-term dialysis. Arch Intern Med 2012 Apr
23;172(8):661-4. DOI: http://dx.doi.org/10.1001/archinternmed.2012.268
9. Abboud H, Henrich WL. Clinical practice. Stage IV chronic kidney disease.
N Engl J Med 2010 Jan 7;362(1):56-65. DOI: http://dx.doi.org/10.1056/
NEJMcp0906797
10. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney
disease in a large managed care organization. Arch Intern Med 2004 Mar
22;164(6):659-63. DOI: http://dx.doi.org/10.1001/archinte.164.6.659
11. Obrador GT, Arora P, Kausz AT, Pereira BJ. Pre-end-stage renal disease care
in the United States: a state of disrepair. J Am Soc Nephrol 1998 Dec;9(12
Suppl):S44-54.
12. Perl J, Bargman JM. The importance of residual kidney function for patients
on dialysis: a critical review. Am J Kidney Dis 2009 Jun;53(6):1068-81. DOI:
http://dx.doi.org/10.1053/j.ajkd.2009.02.012
13. Wang AY, Lai KN. The importance of residual renal function in dialysis patients. Kidney Int 2006 May;69(10):1726-32. DOI: http://dx.doi.
org/10.1038/sj.ki.5000382
14. Ghaffari A. Urgent-start peritoneal dialysis: a quality improvement report.
Am J Kidney Dis 2012 Mar;59(3):400-8. DOI: http://dx.doi.org/10.1053/j.
ajkd.2011.08.034
15. Chaudhary K, Sangha H, Khanna R. Peritoneal dialysis first: rationale. Clin
J Am Soc Nephrol 2011 Feb;6(2):447-56. DOI: http://dx.doi.org/10.2215/
CJN.07920910
16. Murtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin N, Harris FE. Dialysis
or not? A comparative survival study of patients over 75 years with chronic
kidney disease stage 5. Nephrol Dial Transplant 2007 Jul;22(7):1955-62.
DOI: http://dx.doi.org/10.1093/ndt/gfm153
17. Swidler MA. Geriatric renal palliative care. J Gerontol A Biol Sci Med Sci
2012 Dec;67(12):1400-9. DOI: http://dx.doi.org/10.1093/gerona/gls202
Kidney Philosophy
Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself.
— Homer W Smith, 1895-1962, American physiologist and science advocate
78
SOUL OF THE HEALER
“Arctic Ice Pack”
photograph
Carol S Gee, MD
From the photographer: “This image was captured in the ice pack north of Svalbard, an archipelago in the
Arctic Ocean halfway between Norway and the North Pole. The polar bear was spotted slowly ambling towards
our ship and paused to check us out. It was an exciting privilege to see this magnificent animal in the wild.”
Dr Gee is a retired physician from West Los Angeles Medical Center.
She enjoys looking through the lens—meditating and breathing in nature’s beauty.
79
Editorial
Integrating Naturopathy: Can We Move Forward?
Charles R Elder, MD, MPH, FACP
Perm J 2013 Fall;17(4):80-83
Abstract
Although acupuncture and chiropractic care have achieved some measure of acceptance within mainstream medicine, the integrative role for naturopathy has yet to be
well specified. This essay provides a discussion of the potential benefits of naturopathic
medicine, as well as an overview of current obstacles to its integration. Action steps
toward improving communication between allopathic and naturopathic physicians
are suggested.
Introduction
The popularity of Complementary
and Alternative Medicine (CAM) has
been well documented, 1 and it is increasingly common for patients to ask
their primary care physicians for referrals for CAM care. Indeed, at Kaiser
Permanente (KP) Northwest (KPNW),
external referrals of chronic musculoskeletal pain patients for acupuncture
and chiropractic care increased approximately twofold between January
2007 and July 2010.2 However, although
acupuncture and chiropractic care have
achieved some measure of scientific validation3,4 and integration in the setting
of chronic pain, the integrative role for
naturopathy has yet to be well specified.
What is Naturopathy?
According to the House of Delegates
position paper from the American Association of Naturopathic Physicians,5
“Naturopathic medicine is a distinct
method of primary health care—an art,
science, philosophy and practice of
diagnosis, treatment, and prevention of
illness.” In stark contrast to a narrowly
interpreted biomedical model, where
pharmaceuticals are administered to
battle disease, “Naturopathic physicians
seek to restore and maintain optimum
health in their patients by emphasizing
nature’s inherent self-healing process … .
This is accomplished through education
and the rational use of natural therapeutics.” The naturopathic physician thus
uses holistic approaches to enhance and
restore the body’s own innate healing
systems. Naturopaths undergo a 4-year
graduate-level course of study but are
generally not residency trained. The
American Association of Naturopathic
Medical Colleges includes 7 institutions
in North America, 3 of which are in the
Pacific Northwest. Currently, in the US,
licensing laws for naturopathic physicians exist in 16 states.
Naturopathy is most accurately viewed
as a “whole system” medical practice,6,7
representing not a distinct modality, but
rather a paradigm guiding the selection
and prescription of relatively complex,
individualized, multimodality treatment
regimens. In contrast to traditional
Chinese medicine, which the allopathic
community reduces to acupuncture, and
chiropracty, which the allopathic community reduces to spinal manipulation,
naturopathy has defied reduction to a
single modality. This has rendered naturopathy both difficult to study in randomized controlled trial (RCT) settings and
challenging to integrate into conventional
medical treatment algorithms.
Potential Benefits
Nevertheless, a range of factors,
including patient demand, work to
pressure health insurers to provide
limited coverage for naturopathy. State
law in Washington requires insurance
companies to provide coverage for any
category of licensed health care provider. In practice, because Washington
licenses naturopaths, KPNW and other
health insurers operating in the state
must, by law, provide coverage for
naturopathic care. In response, KPNW
has developed medical necessity criteria to define when naturopathic care
may be medically indicated. The usual
approach to the development of such
criteria would be a systematic evaluation of efficacy data from RCTs. Such
evidence reviews have been conducted
in the development of medical necessity criteria for both acupuncture and
chiropractic manipulation and are
regularly updated. However, because
naturopathy defines not a single modality but rather a paradigm, there is little
such RCT data in the literature, and the
evidence review toward defining medical necessity criteria for naturopathy
thus requires a modified, evidenceinformed approach. To accomplish
this, we queried leading naturopathic
physicians in our community to identify
those conditions they thought most
appropriate for naturopathic referral.
We then searched the literature across
each of these conditions for evidence
of efficacy for individual modalities
commonly prescribed in naturopathy,
such as diet, herbals, counseling, exercise, and stress reduction. The resulting
“evidence grid” provided a picture of
where naturopathic care could potentially be expected to be effective.
Currently, KPNW will refer patients
for naturopathic care who have failed
usual care for any of several conditions,
including osteoarthritis, menopausal
symptoms, irritable bowel, headache,
chronic fatigue, and eczema.
In addition, considerable anecdotal
evidence supports the claim that naturopathic care often benefits these
patients. Most primary care physicians
in our Medical Group will have had the
experience of a patient with a functional
or other ill-defined chronic disorder
Charles R Elder, MD, MPH, FACP, is Physician Lead for Integrative Medicine at Kaiser Permanente
Northwest; an Affiliate Investigator at the Center for Health Research in Portland, OR; and an
Associate Editor of The Permanente Journal. E-mail: charles.elder@kpchr.org.
80
EDITORIAL
who finally reports considerable improvement after seeing a naturopathic
physician. Some types of supplements
long prescribed by naturopaths have
now been studied and validated in
clinical trials.8 Other features of naturopathic care may also be helpful to or
resonate with patients. Naturopathic
physicians may spend more time with
their patients than their conventional
medicine primary care peers, and their
medical offices may provide for a less
sterile and more pleasant and healing
environment. Naturopaths will support
and reinforce the world view of the
patient who prefers dietary and herbal
modalities to drugs in ways that allopathic physicians may not.9 Naturopaths
will take time and effort to carefully
review dietary and lifestyle patterns and
may offer prescriptions in these areas
at a level of detail that exceeds what
is commonly provided by allopathic
primary care physicians. Naturopathic
physicians have training and expertise
in herbal medicines, which allopathic
physicians generally lack. Finally, in a
clinical trial performed at the Center
for Health Research in Portland, OR,
assessing the impact of whole system
naturopathy on patients with temporomandibular joint dysfunction multimodality naturopathic care provided for
improvements in both facial pain and
psychosocial interference compared
with conventional specialty temporomandibular joint dysfunction care.10
Conflicting Paradigms
It seems clear, then, that the care provided by naturopaths meets the needs
of many of our patients. Unfortunately,
a number of serious difficulties can be
encountered by internal medicine, family medicine, and pediatric physicians
who refer patients to, or attempt to
comanage patients with, naturopathic
physicians. A common dilemma arises
when the patient has insurance coverage for tests if ordered by allopathic, but
not naturopathic, physicians. To avoid
out-of-pocket expenses, such patients
frequently contact their internist requesting that s/he order tests recommended by
a naturopath. Yet because of differentials
in paradigm and/or clinical experience,
naturopaths commonly order labora-
tory tests that are either unrecognizable
or seem inappropriate to internists.
The most frequent example relates to
evaluation and management of thyroid
disorders. Naturopathic physicians
will commonly recommend multiple
hormone studies, including T3 and T4
levels, in settings where, from a primary
care internal medicine perspective, the
sensitive thyroid stimulating hormone
(TSH) test is the only appropriate test.
The patient is understandably confused,
having received contradictory advice
from the naturopath on the one side
and internist, or endocrinologist, on the
other. Whom to believe? Many patients
do not discriminate that endocrinologists, who are residency and fellowship
trained, have five more years of training than the naturopathic physician in
this area. Instead, some perceive the
conventional medical community to be
in complicity with “Big Pharm,” (not
entirely without justification)11,12 and may
take a militant stand.
The discrepancies can extend to
patient management as well. Naturopaths will typically advise patients to
supplement with combination T3-T4
preparations, such as desiccated thyroid.
This contradicts conventional endocrine
guidelines for Levothroid T4 supplementation in the setting of hypothyroidism.
Desiccated thyroid preparations may
provide inconsistent levels of thyroid
hormone from one batch to the next.
T3-containing preparations may also
provide for more fluctuation, and less
steady state, of thyroid hormone levels
because of the rapid gastrointestinal
absorption and the relatively short halflife of T3. In addition, blinded RCT data
have shown no benefit of combination
T3-T4 preparations over T4 in terms
of patients’ symptoms and quality of
life. 13 The naturopathic community’s
failure to clearly articulate responses to
these points severely aggravates negative perceptions of naturopathy within
mainstream medicine. Some naturopaths
will recommend thyroid supplementation
for patients who are biochemically euthryoid (normal TSH). A subset of these
patients will later present to the primary
care internist or endocrinologist on inappropriate doses of thyroid hormone,
with a suppressed TSH. In the worst-case
scenario, the patient rejects the internist’s
advice to change and reduce thyroid
supplementation, and assumes a hostile
stance to the internist’s refusal to order
T4 and T3 levels. Yet such inappropriate
thyroid supplementation will increase
the patient’s risk for atrial fibrillation,
osteoporosis, and other complications
of hyperthyroidism.
Beyond endocrine evaluation and
management, there are numerous other
sources of contention. Many patients with
fatigue and other nonspecific complaints
will be given the diagnosis of “systemic
candidiasis” by their naturopathic physician. This naturopathic diagnosis presumably suggests some imbalance or
irregularity of the indigenous microbial
flora. These patients sometimes present to
their internists for further evaluation and
management of this condition. However,
as the patients generally have no clinical
or laboratory evidence of candidemia, the
baffled internist cannot locate or reinforce
the diagnosis, leaving all parties frustrated.
Although most allopathic primary care
physicians welcome additional attention
and counseling for the patient toward
proper and healthy dietary habits, many
in the naturopathic community seem to
promote eating patterns that may appear
faddish to the internist. For example,
patients who visit naturopaths are almost universally advised to discontinue
consumption of wheat
and dairy products.
Although most
These foodstuffs, having
allopathic primary
served as dietary staples
care physicians
for millennia, suddenly
welcome additional
are contra-indicated for
attention and
everyone. Yet ample
counseling
for the
evidence supports the
patient toward
judicious inclusion of
proper and healthy
dairy products for a
healthy diet. The DASH
dietary habits, many
diet includes a strong
in the naturopathic
emphasis on low-fat
community seem
dairy products and has
to promote eating
been shown to facilipatterns that may
tate reductions in blood
appear faddish to
pressure.14,15 Even within
the internist.
CAM systems there is
strong support for the
proper use of dairy. According to Ayurveda, the indigenous system of Indian
medicine, which predates naturopathy
by thousands of years, dairy products,
81
EDITORIAL
properly prepared, are a “satvic” food, of
the highest order of nutritional value.16
Similarly, prescribing a strict gluten-free
diet in the absence of objective biopsy
or serologic evidence of celiac disease
imposes extremely severe restrictions
on the patient’s cuisine which may be
largely unnecessary.
Can We Move Forward?
Despite these frustrations, many internists and family medicine physicians
perceive a need for improved partnership with naturopathic physicians. With
so many of our patients presenting with
chronic pain, functional disorders, and
other difficult-to-manage chronic conditions, allopathic primary care physicians
clearly need more compelling options
for managing chronic disease. Indeed,
in the case of chronic pain, conventional
medical regimens, including nonsteroidal anti-inflammatories, skeletal muscle
relaxants, and narcotics, are also associated with the potential for serious toxicities.17,18 Chiropractic and acupuncture interventions have been shown efficacious
in the setting of pain management3,4 and
can be integrated into conventional care
systems in this context. However, allopathic practitioners likewise need a CAM
partner to optimize the integrative multidisciplinary care algorithms for other
types of complex chronic patients as
well, including those with mental health,
functional gastrointestinal, chronic cardiovascular, and other disorders. Naturopaths would seem ideally positioned
to fill this partnership role. Naturopathic
medicine owns a history of promoting
holistic, prevention-oriented care in
North America and has established infrastructure for the accredited training
and licensing of practitioners. Naturopathic physicians can offer the patient
and health care team unique expertise
in herbal medicine, diet and nutrition,
stress reduction, disease prevention, and
other areas to help optimize chronic
disease management.
As practiced today, however, naturopathy too often migrates from complementary to alternative care to pragmatically function in such a partnership role.
This is not intended as a criticism of
naturopathy, but rather as a statement
of fact. Inspection of KPNW operations
82
data reveals that of the funds spent on
referrals to CAM practitioners over the
first 8 months of 2012, 72% was paid to
acupuncturists, 23% to chiropractors, but
only 4% to naturopaths. The explanation
for the discrepancy is straightforward.
Acupuncturists and chiropractors provide
useful care to our musculoskeletal pain
patients without upsetting the apple cart.
Naturopathic visits, in contrast, despite
the many potential benefits, simply generate too many problems for the conventional delivery system: patient requests
for labs that to the internist seem unnecessary; patient ingestion of hormonal
supplements that to the endocrinologist
seem inappropriate; and friction within
the physician-patient relationship where
the patient is receiving advice from another medical professional that directly
contradicts the primary physician’s. Thus,
despite the need for an improved holistic
care model, and the fact that so many patients report benefiting from naturopathic
care, we avoid naturopathy referrals.
Improving Communication
Better communication can potentially
improve this situation and result in enhanced care for patients. Indeed, many
patients are seeing both allopathic and
naturopathic physicians concurrently,
yet dialogue between naturopathic
and allopathic physicians is virtually
nonexistent. This leaves the patient
with the unenviable task of delivering
information and messages between
two clinicians offering conflicting recommendations based upon disparate
assumptions and paradigms.
In the same way, naturopathic institutions could consider inviting internists
and family medicine physicians to their
CME events to improve dialogue and
awareness in this area. This could help
naturopaths better identify which naturopathic practices and approaches may
be most compatible with a collaborative
care model where allopathic institutions
and practitioners are involved.
As an excellent example, the Helfgott
Research Institute at the Natural College of
Natural Medicine sponsors an annual interdisciplinary research conference called
“SPARC” (Symposium for Portland Area
Research on Complementary and Alternative Medicine). The conference brings
together naturopathic physicians, allopathic physicians, and investigators from
multiple disciplines for peer-reviewed
presentations and discussion of scientific
projects relevant to CAM. SPARC provides
a forum for dialogue and networking that
can lead to future collaboration in both
research and clinical realms.
KPNW has implemented a laboratory
formulary specifying the range of tests
that are covered for payment by KP. The
document serves as a reference resource
for both allopathic and naturopathic
physicians and can be used as a tool for
establishing appropriate and informed
expectations for the patient.
Establishing and improving lines of
open, respectful, constructive communication will be a first step toward developing the type of collaboration between
allopathic and naturopathic physicians
that our patients deserve. v
References
What Steps Can Be Taken?
Coordination at the level of Continuing Medical Education (CME) can serve
as a pragmatic avenue for communication. KPNW and other conventional care
organizations can invite naturopathic
physicians to speak at CME events. In
particular, learning how naturopaths
manage specific chronic conditions can
be helpful for allopathic physicians in
understanding more about how naturopaths care for patients, in gaining skills in
herbal and other noninvasive modalities
for chronic disease management, and in
discerning when naturopathic consultation or collaboration may be helpful.
1. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults
and children: United States, 2007. Natl Health
Stat Report 2008 Dec 10;(12):1-23.
2. DeBar LL, Elder C, Ritenbaugh C, et al.
Acupuncture and chiropractic care for chronic
pain in an integrated health plan: a mixed
methods study. BMC Complement Altern
Med 2011 Nov 25;11:118. DOI: http://dx.doi.
org/10.1186/1472-6882-11-118
3. Bronfort G, Haas M, Evans R, Leininger B, Triano J. Effectiveness of manual therapies: the UK
evidence report. Chiropr Osteopat 2010 Feb
25;18:3. DOI: http://dx.doi.org/10.1186/17461340-18-3
4. Vickers AJ, Cronin AM, Maschino AC, et al;
Acupuncture Trialists’ Collaboration. Acupuncture for chronic pain: individual patient
data meta-analysis. Arch Intern Med 2012
EDITORIAL
5. House of delegates position paper: definition
of naturopathic medicine [monograph on the
Internet]. Washington, DC: American Association of Naturopathic Physicians; amended
2011 [cited 2013 Feb 14]. Available from:
www.naturopathic.org/files/Committees/HOD/
Position%20Paper%20Docs/Definition%20
Naturopathic%20Medicine.pdf.
6. Ritenbaugh C, Verhoef M, Fleishman S, Boon
H, Leis A. Whole systems research: a discipline
for studying complementary and alternative
medicine. Altern Ther Health Med 2003 JulAug;9(4):32-6.
7. Elder C, Aickin M, Bell IR, et al. Methodological challenges in whole systems research. J
Altern Complement Med 2006 Nov;12(9):84350. DOI: http://dx.doi.org/10.1089/
acm.2006.12.843
8. Johnston BC, Ma SS, Goldenberg JZ, et al.
Probiotics for the prevention of Clostridium
difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med 2012
Dec 18;157(12):878-88. DOI: http://dx.doi.
org/10.7326/0003-4819-157-12-20121218000563
9. Elder C, Ritenbaugh CK. Transforming medicines. Perm J 2007 Summer;11(3):79-82. DOI:
10. Ritenbaugh C, Hammerschlag R, Calabrese
C, et al. A pilot whole systems clinical trial of
traditional Chinese medicine and naturopathic
medicine for the treatment of temporomandibular disorders. J Altern Complement Med
org/10.1089/acm.2007.0738
11. Kassirer JP. On the take: how medicine’s
complicity with big business can endanger your
health. New York, NY: Oxford University Press;
2005.
12. Angell M. The truth about the drug comapanies: how they deceive us and what to do
about it. New York, NY: Random House Trade
Paperbacks; 2005.
13. Grozinsky-Glasberg S, Fraser A, Nahshoni E,
Weizman A, Leibovici L. Thyroxine-triiodothyronine combination therapy versus thyroxine
monotherapy for clinical hypothyroidism:
meta-analysis of randomized controlled trials. J
Clin Endocrinol Metab 2006 Jul;91(7):2592-9.
DOI: http://dx.doi.org/10.1210/jc.2006-0448
14. Elmer PJ, Obarzanek E, Vollmer WM, et al;
PREMIER Collaborative Research Group. Effects
of comprehensive lifestyle modification on diet,
weight, physical fitness, and blood pressure
control: 18-month results of a randomized
trial. Ann Intern Med 2006 Apr 4;144(7):485-
15.
16.
17.
18.
95. DOI: http://dx.doi.org/10.7326/0003-4819144-7-200604040-00007
Appel LJ, Champagne CM, Harsha DW, et al;
Writing Group of the PREMIER Collaborative
Research Group. Effects of comprehensive lifestyle modification on blood pressure control:
main results of the PREMIER clinical trial. JAMA
2003 Apr 23-30;289(16):2083-93. DOI: http://
dx.doi.org/10.1001/jama.289.16.2083
Sharma H, Clark C. Contemporary Ayurveda:
medicine and research in Maharishi Ayur-Veda.
1st ed. Philadelphia, PA: Churchill Livingstone;
1997 Dec 2.
Beebe FA, Barkin RL, Barkin S. A clinical and
pharmacologic review of skeletal muscle relaxants for musculoskeletal conditions. Am J Ther
2005 Mar-Apr;12(2):151-71. DOI: http://dx.doi.
org/10.1097/01.mjt.0000134786.50087.d8
Von Korff M, Kolodny A, Deyo RA, Chou R.
Long-term opioid therapy reconsidered. Ann
Intern Med 2011 Sep 6;155(5):325-8. DOI:
http://dx.doi.org/10.7326/0003-4819-155-5201109060-00011
Verbis, Herbis, et Lapidibus
The greatest secrets, forces, and effects are
hidden in verbis, herbis et lapidibus.
— Johan Wolfgang von Goethe, 1749-1832, German author and politician
83
Narrative medicine
The Power of Reflective Writing: Narrative Medicine and Medical Education
Samir Johna, MD; Ahmed Dehal, MD
Perm J 2013 Fall;17(4):84-85
It was a good reminder that as physicians, we may not
always be able to fix patient problems, but we can certainly
be loving and supportive. It reminded me that good medicine
takes into account the whole person including body, mind,
and spirit and not just the sum of its parts.
— A third-year medical student
There is no doubt that medicine is an art and a science.
Today, practicing medicine as science is probably much easier
than practicing medicine as art, in light of the dazzling advances
in medical technology and informatics. Even before technology
gained the upper hand, patients were healed by physicians
when most of the remedies were useless if not harmful, and
when remedies were driven by theories that did not stand the
test of time.1 To some extent, the art of fostering the sacred
physician-patient relationship might have played a major role
in the dramatic healing process.2
The physician-patient relationship is not limited to a comprehensive history and physical examination, a diagnostic workup,
and the final discussion about a plan for action. Medicine requires
that the physician establish deep connections by which s/he
can dive deep into the crying soul of the patient. Healing an
ailment is a complex process that must address two domains:
disease, which is the alteration in the biologic structure and/
or function of the body; and illness, which is the psychological and social aspect of the ailment.3 Proper healing starts with
open communication between physicians and patients. Patients
draw on physicians’ attributes of honesty, integrity, empathy,
and compassion to share their stories as they strive to heal.4
Narrative medicine offers a unique framework to explore and
manage the complexity of healing. Its impact extends beyond the
physician-patient relationship and into the relationships between
physician and self, physician and colleagues, and physician and
society. It is no wonder that many medical schools and residency
programs have incorporated narrative medicine in the form of
reflective writing into their curricula.4
Our learners, students and residents, are encouraged to be
engaged in reflective writing as they search to understand what
medical practice means to them, their patients, their colleagues,
and society at large. Learners meet with the first author (SJ) on
a regular basis to discuss and analyze their short, open-ended
narratives. They are frequently asked to reflect on events of their
choice that had a lasting impact on them, negative or positive, at
any institution where they rotated. We (SJ and AD) are mesmer-
ized by the insight of the learners and depth of their reflective
capacity in their quest for self-identity, ideals, and values as they
enter the complex environment of medical practice.
It is only fitting to share some excerpts from learners’ narratives about valuable lessons from rich experiences in which
they found themselves deeply immersed.
One learner ruminated over the discrepancy between what we
preach and how we act. He described his negative experience
tagging along with his attending physician in a busy outpatient
clinic. He wrote:
I saw a 45-year-old patient with an advanced hepatocellular
carcinoma. He came with his wife to learn about the results of his
liver biopsy performed with [computed-tomography] guidance. He
had no clue what was wrong with him, much less his prognosis.
He was smiling and engaged in a conversation with his wife as
I walked into the room. I asked him how much he knew about
his condition. “They told me I might have a tumor, but I was told
that you will be telling me more.” I was in my second month of
training and did not feel comfortable breaking the bad news to
him. I decided to leave it to my attending. A few minutes later,
my attending and I went into the room. After introducing himself
to the patient, the attending asked me to bring the ultrasound
machine because he wanted to examine the patient for ascites.
After he was done, he told the patient that there was no fluid and
all this abdominal distension was probably due to an enlarged
liver and suggested that the patient [go] to radiology for palliative
chemo-embolization. While he was standing next to the door that
was half open, the attending asked the patient “So, do you know
what is going on with you?” The patient did not say anything
but his [facial] expressions were enough for us to tell that he was
not aware of how serious his condition was. “You have a very
bad cancer and you will die in six months,” the attending said.
Surprisingly, just [a] few days before that, the same attending
gave us a lecture for an hour about palliative therapy of terminal
cancer [patients]. The whole lecture was centered around dealing
with terminal cancer patients and breaking bad news. He talked
about some personal experiences as well as some skills and strategies of how to build a relationship with your patient[s] and how
to earn their trust. “Touching the patient, sitting close to them,
smiling, and some other simple things make all the difference in
the world for them,” the attending had said.
After we left the room, I was thinking of how shocking and
overwhelming that was to the patient. I was wondering if being
busy can be an acceptable excuse for not showing empathy and
Samir Johna, MD, is the Residency Program Director at Arrowhead Regional/Kaiser Fontana Medical
Centers in CA. E-mail: samir.d.johna@kp.org. Ahmed Dehal, MD, is a Resident in General Surgery at
Arrowhead Regional/Kaiser Fontana Medical Centers in CA. E-mail: ahmed.n.dehal@kp.org.
84
Narrative medicine
The Power of Reflective Writing: Narrative Medicine and Medical Education
respect when talking to patients about their serious illnesses … I
now realize how much contradiction and incongruity there is
between what we have been taught and what actually happens
in real life.
In this narrative, the learner struggles as he tries to reconcile
what he was taught in the classroom with what he saw in the
examination room. He eloquently describes the dilemma of a
hidden curriculum: teachers who do not walk their talk!
A second learner described her positive experience shadowing a busy practitioner:
I was shadowing a family practitioner over summer break. His
first patient was an 81-year-old female he saw for a follow-up.
She had a long list of chronic comorbidities including diabetes,
HTN [hypertension], CAD [coronary artery disease], osteoporosis,
arthritis, and depression. Upon entering the exam room, it was
apparent that walking caused her pain. She walked slowly into
the exam room and seemed relieved to sit down. She initially was
quiet and told the doctor that everything was fine and [she] only
needed her prescriptions refilled. The [doctor] asked her basic
questions followed by a physical examination.
Just when I thought the appointment was about to come to an
end, the doctor started conversing and joking with her. She was
initially passive but finally cracked a smile, looked over at me
and said, “This is why I don’t change doctors. I have to take two
buses to see him, but I won’t change him.” What seemed to be
an uneventful doctor’s appointment left a lasting impression on
me. Those extra fifteen minutes the doctor dedicated to her made
her day and she probably forgot about her pain for a moment.
It was a good reminder that as physicians, we may not always
be able to fix patient problems, but we can certainly be loving
and supportive. It reminded me that good medicine takes into
account the whole person including body, mind, and spirit and
not just the sum of its parts.
Every teacher’s dream is to be an ideal role model. A positive
role model can drive the point home and leave an everlasting
impression on learners as they try to discover, to self-identify,
and to develop professional attributes.
A third learner shared an inspirational story about shadowing
a young and promising surgical resident who practiced empathy
at its best. She wrote:
One of the most memorable and useful things that I’ve observed
during medical school is the art of empathy. It is something that
our curriculum has touched on several times throughout our
classroom years. While it is one thing to read about it in class, it
is a completely different thing to observe it in practice.
While on my plastic surgery rotation, I met a 70-year-old
trauma patient who had to have her arm amputated. At the end of
our consult with this woman, it was decided that this case would
be referred back to orthopedic surgery. The resident with me could
have easily just left it at that, since she was no longer to be our
patient. However, the resident then sat on the patient’s bed and
reassured her that her life was still going to be full, despite the loss
of her arm. She proceeded to tell the patient about her own best
friend, who lost her arm in a boating accident at the age of 19.
She still went on to go to college, got married, and
We spend so
now has beautiful kids. She even travels around
much of our
the country as an inspirational speaker. The patient
time studying
kept thanking the resident, and assuring her that
the science of
she was not going to let the loss of her arm stop her
from living a full life.
medicine …
This encounter really impressed me. It would
However, part
have been way too easy to just write this patient off
of being a good
as an older lady, who would not be as affected as
doctor is also
a younger person who had their whole life ahead
mastering the
of them. She wasn’t even going to be [the resident’s]
art of patient
patient anymore, and [her] responsibilities were
care and
technically done. However, the resident went the
learning
how
extra mile, and it only took a few minutes of her
to interact with
time. The manner in which she did it was also
others.
something that impressed me. The resident was so
genuine in her conversation. There was never a
hint that she looked down on this patient, or felt
sorry for her.
As a medical student, I really hope to find that subtlety and
master it. Of course every medical student wants to be the best
doctor they can be. We spend so much of our time studying the
science of medicine in order to achieve that goal. However, part
of being a good doctor is also mastering the art of patient care
and learning how to interact with others.
We believe that narrative medicine is an invaluable tool and
an excellent opportunity for learners to delve into their own
consciousness as they react and interact within their learning
environment.4,5 We hope that they view negative role models
as an impetus to improve their own behavior as they stand by
their resolve to become responsible, caring, and compassionate
physicians.6,7 For educators, such experiences become food for
thought. We should not be afraid of our failures, for success is
nothing but failure turned inside out! v
Acknowledgment
References
1. Novack DH, Epstein RM, Paulsen RH. Toward creating physician-healers: fostering medical students’ self-awareness, personal growth, and well-being.
Acad Med 1999 May;74(5):516-20.
2. Novack DH. Therapeutic aspects of the clinical encounter. J Gen Intern Med
1987 Sep-Oct;2(5):346-55. DOI: http://dx.doi.org/10.1007/BF02596174
3. Kleinman A. The illness narratives: suffering, healing, and the human condition. New York: Basic Books; 1988. p 3.
4. Charon R. The patient-physician relationship. Narrative medicine: a
model for empathy, reflection, profession, and trust. JAMA 2001 Oct
17;286(15):1897-902. DOI: http://dx.doi.org/10.1001/jama.286.15.1897
5. Branch W, Pels RJ, Lawrence RS, Arky R. Becoming a doctor. Criticalincident reports from third-year medical students. N Engl J Med 1993 Oct
7;329(15):1130-2. DOI: http://dx.doi.org/10.1056/NEJM199310073291518
6. Arjmand S. The use of narrative in medical education. Journal for
Learning through the Arts [serial on the Internet]. 2012 [cited 2013
Mar 7];8(1):[about 8 p]. Available from: www.escholarship.org/uc/
item/1b95d8vv.
7. Johna S, Rahman S. Humanity before science: narrative medicine, clinical
practice, and medical education. Perm J 2011 Fall;15(4):92-4. DOI: http://
dx.doi.org/10.7812/TPP/11-111
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Boatbuilding On The Aspetuck: An Artist’s Thoughts About Art, Aging, and Anxiety
Phillip LaBorie
Perm J 2013 Fall;17(4):86-88
Editor’s note: Mr LaBorie’s artwork “Boatbuilding on the Aspetuck” may be seen on page 89.
For the readers of this learned journal, please note: I’m not a practicing
psychologist; I don’t have a degree in
psychiatry; and I’m not an expert in
gerontology; but having been up the
creek without a paddle a few times, I
can draw some conclusions about art,
aging, anxiety, and how the Aspetuck
figures into this mélange.
Let’s start at the start, as my Aunt
Minnie used to say.
The Aspetuck River wends its way
south through Fairfield County in Connecticut. Although it isn’t a mighty
river in its own right—the reputations
of the Mississippi and the Amazon are
hardly at risk—it is a stream with some
significance for local residents and for
me in particular.
I doubt if there was ever any serious
ship or even boatbuilding efforts on the
Aspetuck itself but, when it joins the Saugatuck River in Westport, the combined
waters marked the scene of very active
river commerce during the 19th century.
So much for the facts.
Occasionally the Aspetuck overflows
its banks, like some small child acting
out. In general, however, it simply
goes about its mission, minding its
own business and steadily working its
way to the sea. It always operates in
the present moment, and best of all,
it’s inventive: it accepts obstacles on its
way downstream, works around them
when it can, has the innate wisdom
to understand the difference, and just
keeps on keeping on. In short, it’s a
good example of growing older with
grace and dignity—an art form we can
all practice and learn from.
Art does not reproduce what we see;
rather, it makes us see.
—Paul Klee1
I love Paul Klee’s thought, because
it seems to me that learning to really
see the world around us and for me,
the Aspetuck in particular, and then to
translate our vision into an expressive
art form, is a lifelong adventure that can
have considerable therapeutic value.
I began attempting to see inside the
temporal world when I was about six
years old. I was bed-ridden with rheumatic fever for more than six months.
World War II had just ended, and the
long nights of blackout curtains, hooded
car headlights, ration books, air raid
drills, and dreams about sinister Nazis
(always in uniform) sneaking through
our backyard with dark intentions
were over.
Nothing Much To Do
With nothing much to do and too
weak to hold a book, I listened to the
radio for hours on end. I tuned in to
Franklin Delano Roosevelt’s funeral,
heard the clip-clopping of the horses’
hooves as they pulled the president’s
flag-draped casket down Pennsylvania
Avenue, the muffled drums rolling in
the background, and the announcer’s
hushed tones as he breathed into the microphone—the solemnity of the occasion
made a deep and lasting impression on
me. An era was over, but it is still quite
alive in my memory and imagination.
While I lay in bed, I started to visualize
wartime activity in the cracks and crevices of the wooden headboard. I imagined
lines of soldiers following mountain trails
along the cracks, important crossroads
complete with military vehicles appeared
where the cracks converged. There were
rivers to be forded, machine gun nests to
be dealt with, small villages came into being in knotholes. In short, an entire world
opened up to me, right in my bedroom.
It was all in my head, but that dream
world stirred my imagination and has
stuck with me to this day. However,
because of my illness, I failed first grade
and had to sit quietly at home all summer long, while my few friends went
off on vacation.
By the time I reached high school I
had won an award for a watercolor I’d
created, but I was still a tall, skinny kid
who was supposed to wear his glasses
all the time. In my mind, I was inferior
to my peers. I didn’t fit in.
In a Drawing Class
Now fast forward to college. I’m in a
drawing class; well, barely in a drawing
class, since I had a “D” average. How
was that possible for someone who liked
making art? Perhaps because I didn’t
draw what the professor asked me to
draw? Good possibility.
My instructor was thoroughly frustrated and annoyed by my failure to
pay attention, follow instructions,
and in general, be part of his class. In
hindsight, those seem like reasonable
enough requests. Finally, faced with
the distinct possibility of flunking the
course, I tried following his directives.
Eureka! It worked! I could actually put
on paper what my eye saw rather than
just what my imagination created! It was
an exciting discovery, and I got reasonably good at it. Of course, I failed to
do anything further with my newfound
ability. What is it about youth?
After college graduation, I eventually
got a position as a copywriter in an ad-
Phillip LaBorie is an Artist and Writer in Murrells Inlet, SC. E-mail: plaborie@voxinc.net.
86
Narrative medicine
vertising agency in Philadelphia (I was
actually an English major). A few years
later, I was offered another copywriting
job at an agency in San Francisco and
moved to the West Coast. Then, at the
suggestion of a photographer friend of
mine, I dropped out of the ad biz and enrolled in The San Francisco Art Institute.
It was the mid-1960s, and undergraduate work at the Institute was an
amazing experience. Our instructors
were some of the best-known artists
on the West Coast, at the time and I
came away from that experience with
some sound advice that my mentors had
drilled into my thick head: don’t give
up, look harder, think more, keep your
mouth shut, and don’t, for any reason,
settle for “It’s good enough.”
Now that I’m 73
I try to keep their advice in mind. I
find that it’s easy enough to settle for
work that has visual appeal, at least for
some people, but doesn’t press the envelope hard enough. I’m a big fan of a
quote that I heard from Philip Glass. On
his 75th birthday he said, “… our brains
are constantly evolving. Our brains are
very plastic; they continue to grow.”2
I think we should all feel that way; the
older we get, with any luck, the more we
can learn, execute, and pass on to others.
But it’s a tough lesson to put into action, even though so many elders have so
much to contribute to our understanding
of what life and art are all about.
Think about the wonderful work
that aging artists have produced over
the years—some famous, some not so
famous: Rembrandt, with his marvelous
self-portrait in old age; Monet, painting
well into his 80s, even though he suffered
from cataracts; Matisse, carefully arranging
bold, colored shapes on his deathbed;
Georgia O’Keefe and the intimate flower
series she created in her later years; and
the efforts by one of my favorite contemporary painters, the late Estaban Vicente.
Age Didn’t Restrict
Their Insights
In each case, age didn’t restrict their
insights. Their visions became that much
more acute as well as their ability to
continually expand their thinking and
beliefs as they grew older. Today, I’ve
challenged myself to finally take the
bull by the horns and expose my inner feelings to the public at large. I’m
painting for myself, and if anyone else
is interested, that’s great; if not, not.
Will I be another Matisse or Vicente?
Highly doubtful. Am I finding satisfaction in what I’m creating? Certainly.
Does creating works of art ensure some
measure of confidence in a time of crisis? In my case, it certainly appears to
be that way.
The present moment is where life can
be found, and if you don’t arrive there,
you miss your appointment with life.
—Thich Nhat Hanh3
By living in the present (just the way
any river does)—not worrying about the
past, but learning from it—not by anticipating what the next wave of events
will bring, or when it will happen, we
create an opportunity to practice the art
of living life to its fullest.
And, after all, when you think about
it, why not? The future hasn’t arrived
yet, and it will be what you make of it,
and the past is the past—it was what
you made of it.
By being fully aware of just what
you’re doing, how you feel, and what
you see, you can turn what might just
be ordinary, even mundane events into
what Lodro Rinzler terms “… seeing the
world as sacred, and appreciating the
magic of ordinary moments.”4
For instance, it’s a no brainer that
anxiety will affect most of us at some
point or another. You know, the worries
many of us encounter about paying the
bills, losing our income, screwing up
on the job or with the kids—and all
the turmoil and self-doubt these events
can create.
Creating Stuff
It turns out that a good antidote for
dealing with anxiety is creating “stuff.”
The more positive mental stimulation
a person experiences, the better their
mental health becomes—apparently
the brain responds favorably to the
right stimulation. The trick is to find
the proper stimulation—not all that easy
sometimes.
In my case, anxiety reared its head
when job loss and illness created a fi-
nancial and emotional crisis.
Most of all,
How were we going to pay
I feel that
the mortgage, for starters?
my artistic
If that wasn’t enough,
efforts will
our advertising business,
which had been quite succontinue to pay
cessful for more than ten
dividends—if
years, simply disintegrated.
not in monetary
Long-time clients disapreturns, at
peared, no new clients apleast in real
peared, income dropped to
satisfaction
zero—in fact, at one point,
and a sense of
we were living on social seaccomplishment.
curity and unemployment
benefits—period.
Anxious times, indeed, but, with my
family’s support, I continued to make
art, even though there were times when
I wasn’t sure where the money was going to come from to pay for the supplies.
So, given all that was happening to
our family—conventional thinking says
we should have felt overwhelmed and
discouraged. But, during all those trials,
I felt just the opposite.
Certainly, we were and still are facing considerable challenges, but we
will survive. Although I’m hopeful that
our financial situation will eventually
change for the better, perhaps scrambling for money to pay the bills will be
our new “normal,” and we’ll just have
to adjust to it.
Artistic Efforts
Pay Dividends
Most of all, I feel that my artistic efforts
will continue to pay dividends—if not in
monetary returns, at least in real satisfaction and a sense of accomplishment.
All of this is just an aspect of conscious aging in action. Embracing the future instead of retreating. Opening your
mind to new possibilities rather than
settling for the status quo. And, above
all, enjoying the questions—regardless
of your age, regardless of your domestic
or financial situation, and regardless of
what others think about what you’re
doing—as long as it isn’t detrimental to
those around you, let it loose!
Does it matter if anyone likes whatever art you make, or even buys a piece?
Not really, be nice if it happens, but
the real benefit comes from just doing
it. Is it going to hang in the Museum of
Modern Art or on your Aunt Minnie’s
87
Narrative medicine
wall? Who cares? Will you be the next
Grandma Moses? Who knows? As far as
I’m concerned, you just have to keep
on keeping on.
Everything will be all right in the end.
So if it is not all right, then it is not yet
the end.5
Aspetuck
Which brings us back to the Aspetuck.
I don’t know that splashing about in a
clean river automatically ensures one
will live a more productive life but,
looking back, the ideas of honest self
appraisal, being in the moment, and
creativity first came together many years
ago when my seven-year-old twin sons
from a previous marriage came to visit.
I had constructed two small river craft
for them to play with in the Aspetuck.
The boats were made of old barn wood,
assorted bits of plastic, and one vessel
was crowned with a sleek upper deck
made from a metal coat hanger—artistic
inventiveness at its best!
Unfortunately, the boats promptly
capsized when they were launched
and their maiden voyage was marked
by numerous attempts to get them to
float upright—all to no avail—an honest
appraisal of my efforts would conclude
that Dad’s model boatbuilding ability
wasn’t worth a plug nickel!
But, the boys didn’t seem to mind
at all as they happily splashed in the
somewhat chilly water and directed
their ships to unknown shores. All in
all, it was a fabulous way to spend a
summer afternoon: two young boys and
their part-time dad. Talk about being in
the moment!
So, in my experience, when the
world is too much for you, as an
antidote I recommend pausing for a
few minutes to admire a river. They
are natural philosophers, and there
is virtually no end to the constructive
things they can teach us about honest
self-examination of our motives and
aspirations, positive thinking, and creativity. All we need to do is take the
time to stop, look, and listen. v
References
1. Klee P; Klee F, editor. The Diaries of Paul Klee,
1898-1918. Berkeley, CA: University of California Press; 1968.
2. Woolfe Z. Whatever we do together will make
us different. The New York Times. 2012 Oct
7;Sect MM:40.
3. Hanh TN, Oda M. Present moment, wonderful
moment: mindfulness verses for daily living.
Berkeley, CA: Parallax Press; 1990.
4. Rinzler L. The Buddha walks into a bar: a guide
to life for a new generation. Boston, MA:
Shambhala Publications; 2012.
5. Parker O, Moggach D. The best exotic marigold hotel. London, UK: Blueprint Pictures;
2012.
Alchemy
There is an alchemy in sorrow. It can be transmuted into
wisdom, which, if does not bring joy, can yet bring happiness.
— Pearl S Buck, 1892-1973, American writer and novelist, 1938 Nobel Laureate for Literature
88
SOUL OF THE HEALER
“Boatbuilding On The Aspetuck”
18” x 24”
mixed media
Phillip LaBorie
The original artwork to accompany “Boatbuilding On The Aspetuck: An Artist’s Thoughts
About Art, Aging, and Anxiety” (page 86). It is composed of watercolor and acrylic paints,
colored pencil highlights, scraps of paper, and natural and manufactured items.
The artwork was three-dimensionally scanned and prepared for accurate
reproduction by Photographic Solutions of Norwalk, CT.
Mr LaBorie is an Artist and Writer in Murrells Inlet, SC. E-mail: plaborie@voxinc.net.
89
Narrative medicine
Illness and Death in the Universe
Carlos Franco-Paredes, MD, MPH
Perm J 2013 Fall;17(4):90-91
The morgue attendant guided me to
my mother’s lifeless body residing inside
a black bag at the hospital where she
was pronounced dead. The coldness of
the morgue was not only measurable in
degrees of temperature but also felt with
the heaviness of unsaid words during
farewells. I glanced around the room
to discover that in the seemingly perennial emptiness and intolerable silence,
there were many more bags being filled
with someone else’s parents, children,
or grandparents. The unyielding grip of
death annihilated the possibility that this
was part of a movie scene or the bewilderment of waking up from a bad dream. To
make things worse, a fly landed on my
mother’s forehead while the staff member unzipped the bag. I felt trivial and
lonely. Watching the fly moving across my
mother’s face only amplified the gloom.
The only certainty of that moment: my
life and my view of the essence of life
would never be the same. The emotional
resilience and spirituality hardwired into
my neuronal circuits and pruned during
my lifetime struggles were immediately
depleted by grief.
Why Illness and Death
in the Universe?
My mother’s unexpected death unmercifully uncovered the landscape of our
human frailties in the cosmic immensity
and eliminated my Machiavellian stand
in this complex world. Sadness eventually transitioned into the rationalization
that our predicament of life and death
deserves to be viewed through the lens
of our biologic heritage in a larger and
highly dynamic natural scene.
Our human history is a history of
spaces, where geography has shaped our
destiny. Our planet came to rest at the
right distance from the sun and the stage
was set for the occurrence of life in the
Milky Way.1 We are a collection of many
atoms that have become organized to be
self-aware of our existence. The forces of
evolution by natural selection underlie the
adaptation, complexity, and diversity of life
on the earth.2 Humanity represents a small
branch in an enormous and dynamic tree
of life that emerged millions of years ago.1,2
Our “unique” human identity is blurred
when we look through a historic mirror.
Human genomes are not really human:
we are hybrids of viruses, plants, animals,
and extinct organisms.3 The anatomically
modern human body harbors a collection
of different types of some 10 trillion cells
under the direct control of 23,000 genes.4
Similar to other members of the animal
kingdom, our development involves a few
fundamental processes: fertilization, cleavage, gastrulation, organogenesis, postnatal
development, and gametogenesis.5 In our
mammalian development, we also share
the fact that every adult human organism
eventually undergoes senescence and dies.
Throughout all these stages, the microbial
community living in the human gut, skin,
and respiratory tract play a crucial role in
modulating health and disease by combining genomes (microbiome).6,7 Therefore,
from an evolutionary perspective, our human nature is that of an ecosystem where
the interests of the human body and the
commensal microbiota are aligned.7
Suffering diseases and dying have
governed the history of humankind.8 The
mystery and tragedy of human illness
during our life trajectories relies upon the
narrative accounts of our ancestral DNA.3
Our biologic fortune has been sculpted
through ancient molecular battles, biochemical compromises, and trade-offs.9,10 A
dynamic interplay among mutations, environmental factors, and epigenetic changes
may alter cell behavior. In this sense, genes
that make human bodies having superior
reproductive success will become more
common, even if they compromise the
individual’s health in the end.10
Humanity’s transformation of the environmental framework of the earth has an
important influence on human health.11
The emergence of the cognition has
paradoxically affected the same essential
forces that have led to its existence in the
first place.1,2 Vladmir Vernadsky, a Russian
scientist, and the French philosopher
Pierre Teilhard de Chardin developed
the concept of a thinking layer or sphere
of the earth or noosphere constituted
by the interaction of human minds.12 As
predicted by them, the human brain has
fundamentally transformed all spheres
of earth’s development including the
geosphere, the biosphere, and ultimately
the noosphere.11 Contemporary human
activity has accelerated this process by
increased international connectivity in
the form of information flow, trading
patterns, human mobility, capital flow,
cultural diffusion, and other large-scale
forces. These global forces converge to
bear on patterns of human health by
historically unprecedented environmental
and social transformations.13,14 Thus, in
many ways, modern human history has
provided important health benefits and
increased longevity in our lifespan, but
in many other ways, it has exacerbated a
clash between our biologic ancestry and
our surroundings, leading to new health
challenges.14 My mother was one of those
casualties trapped in an epidemiologic
transition dominated by increasing rates
of chronic diseases such as cancer and
cardiovascular disease.
Incorporating Modern Science
Literacy into Clinical Care
In the history of mankind, conceptions of
life and death have traditionally pertained
to the realm of philosophy and religion.
However, at this point in time, our views
of life and death must also be critically
assessed through the knowledge acquired
by the scientific revolution of the history
Carlos Franco-Paredes MD, MPH, is an Infectious Disease and Travel Medicine Physician
at Phoebe Putney Memorial Hospital in Albany, GA. E-mail: cfranco@ppmh.org.
90
Narrative medicine
Illness and Death in the Universe
of the universe. Indeed, science literacy
matters as much as other forms of culture
and knowledge in modern human societies.
In the modern history of mankind,
prominent scientists including Galileo,
Newton, Darwin, and others employed
logic and observation to develop a rational view of the universe and humanity’s
place in it. Galileo, considered by many
to be the founder of modern science,
confirmed the Copernican notion that the
earth orbits around the sun rather than
vice versa, which was considered heretical
by the Roman Catholic Inquisition. Yet,
Galileo’s scientific observations conclusively transformed our understanding of
the role of humanity in the cosmos. With
modern clarity, a plethora of scientific
facts and ideas that range from the origins
of diversity of life on earth to the discoveries of billions of galaxies in the universe
strongly suggest that the cosmos was not
created only for the purpose and destiny
of the life cycle of the human species.
Today, with the growing number
of available technologies and human
development, the number of scientific
discoveries will only continue to disenthrall
previously accepted misconceptions of the
position of humanity in the cosmos. As
an example, on April 18, 2013, the Kepler
Project at NASA announced that among
many planet candidates orbiting stars, there
are at least 2 planets (Kepler 62 and Kepler
69) with similar habitable features to Planet
Earth.15 These findings suggest that life,
in some form, may currently exist, may
have existed, or may potentially emerge
elsewhere in the universe in the future.
Modern medical knowledge requires
scientific literacy. Knowing clinical
medicine without a more conscious approach of critical thinking of our ancestral
biologic heritage and of our stand in the
natural word is incomplete. We must
learn continuously the scientific revolution in physics, cosmology, evolutionary
biology, paleoanthropology, and other
disciplines to widen our understanding of
the phenomena of life and death in the
wider natural scene. Caring for the sick
with the utmost compassion, respect for
their belief system, and empathy, coupled
with a competency in understanding our
organic reality, may assist us in optimiz-
ing the patient-physician relationship.
Moreover, these facts must be shared
and discussed with ill patients and their
families, particularly when assessing
end-of-life interventions. This approach
is not a departure from faith-based systems, cultures, and traditions. The noble
Hippocratic aspiration of curing diseases
and alleviating suffering requires a concomitant view where death is not seen as
a medical failure. We must demedicalize
death: it is a personal human event.
The death of a loving family member
perhaps is measured in a different emotional and spiritual scale compared to the
end of life of one of our patients. Yet,
we must accept death as an inevitable
part of our biologic animal life cycle; and
ironically, it is an event that shapes and
brings cohesion to many levels of life. In
this sense, the fly and I understood each
other’s role in this natural world: there is
no decay or disorder. We exist as part of a
continuum process of biologic renovation
under unswerving DNA control: there is
no death, only transformation. Accepting this reality may be the highest form
of spirituality.
In the personal realm, and as practicing
clinicians, we must understand death and
our infirmity with humility. A sense of cosmic humility stems from an understanding
that we are made from the same materials and forces that make up galaxies.
Realizing the shared biologic kinship and
biologic antiquity with other forms of life
and the mechanisms employed by nature
assisted me in overcoming my despair and
allowed me to mourn my mother’s death
with dignity. As Octavio Paz, 1990 Nobel
Prize for Literature recipient, wrote in
The Broken Water Jug published in 1955:
“… life and death are not opposite worlds,
we are part of a stem with twin flowers … .”16
Before my mother was buried, I kissed
her for the last time. The history of life
continues even after my mother’s coffin
was covered with dirt. Although our
biologic heritage can be measured in
the scientific timescale of a molecular
clock,17 the memory of my mother, the
honor of caring for the dying sick, and
the empathy towards other individuals
inside black bags at the morgue and their
families, is timeless. v
References
1. Wilson EO. The social conquest of earth. New
York, NY: Liveright Publishing Corporation;
2012.
2. Walter C. Last ape standing: the seven-millionyear story of how and why we survived. New
York, NY: Walker Publishing Company, Inc;
2013.
3. Zimmer C. A planet of viruses. Chicago, IL: The
University of Chicago Press; 2011.
4. Wolpert L. DNA and its message. Lancet 1984
org/10.1016/S0140-6736(84)90885-7
5. Wolpert L. Developmental biology: a very short
introduction. 1st ed. Oxford, England: Oxford
University Press; 2011.
6. Human Microbiome Project Consortium.
Structure, function, and diversity of the
healthy human microbiome. Nature 2012
org/10.1038/nature11234
7. Sommer F, Bäckhed F. The gut microbiota—
masters of host development and physiology.
Nat Rev Microbiol 2013 Apr;11(4):227-38.
DOI: http://dx.doi.org/10.1038/nrmicro2974
8. Franco-Paredes C, Santos-Preciado JI. Freedom,
justice, and neglected tropical diseases.
PLoS Negl Trop Dis 2011 Aug;5(8):e1235.
DOI: http://dx.doi.org/10.1371/journal.
pntd.0001235
9. Zimmer C. Evolved for cancer? Sci Am 2007
Jan;296(1):68-74, 74A. DOI: http://dx.doi.
org/10.1038/scientificamerican0107-68
10. Stearns SC, Nesse RM, Govindaraju DR, Ellison
PT. Evolution in health and medicine Sackler
colloquium: evolutionary perspectives on
health and medicine. Proc Natl Acad Sci U S A
2010 Jan 26;107 Suppl 1:1691-5. DOI: http://
dx.doi.org/10.1073/pnas.0914475107
11. Revkin AC. Managing planet earth: forget
nature. Even Eden is engineered. The
New York Times [serial on the Internet].
2002 Aug 20 [cited 2013 Aug 29]:[about
8 p]. Available from: www.nytimes.
com/2002/08/20/science/managing-planetearth-forget-nature-even-eden-is-engineered.
html?pagewanted=all&src=pm.
12. Lapo AV. Vladmir I. Vernadsky (1863-1945),
founder of the biosphere concept. Int Microbiol 2001 Mar;4(1):47-9. DOI: http://dx.doi.
org/10.1007/s101230100008
13. McMichael AJ. Globalization, climate change,
and human health. N Engl J Med 2013
org/10.1056/NEJMra1109341
14. Labonté R, Mohindra K, Schrecker T.
The growing impact of globalization for
health and public health practice. Annu
Rev Public Health 2011;32:263-83. DOI:
http://dx.doi.org/10.1146/annurev-publhealth-031210-101225
15. Kepler: a search for habitable planets
[homepage on the Internet]. Moffett Field,
CA: NASA Ames Research Center; updated
2013 Aug 21 [cited 2013 August 30, 2013].
Available from: http://kepler.nasa.gov/.
16. Paz O. El cántaro roto. Revista Mexicana de
Literatura 1955 noviembre-diciembre;(1):259.
17. Zuckerkandl E, Pauling L. Molecules as documents of evolutionary history. J Theor Biol
org/10.1016/0022-5193(65)90083-4
91
SOUL OF THE HEALER
“(858) 457-137”
from Alone/Together: Meditations on Alienation
18” x 12”, 572 mm x 871 mm
Acrylic and polylith photograph on birchboard
Eric Blau, MD and Li Huai
This piece, which is part of a larger body of work, explores how our cultures both influence and alienate us.
Artists Eric Blau, MD, of the Southern California Permanente Medical Group, and Li Huai
have been friends since Huai arrived in the United States from China. The two have often talked
about collaborating on a project. Their collaboration has resulted in the remarkable Alone/Together:
Meditations on Alienation series, more of which can be viewed at www.ericblauphotography.com.
92
Letters
Plant-Based Diets Are Not Nutritionally Deficient
Re: Tuso PJ, Ismail MH, Ha BP, Bartolotto C.
Nutritional update for physicians: plant-based
diets. Perm J 2013 Spring;17(2):61-66. DOI: http://dx.doi.org/10.7812/TPP/12-085
Dear Editor,
We would like to thank Philip Tuso, MD,
and associates for their comprehensive review
of the evidence supporting the value of plantbased diets for preventing and curing the
epidemic of diseases caused by overnutrition
that are sickening millions of people in the US
and crippling our nation’s economy. However,
counterproductive to the authors’ goal that
“physicians should consider recommending a
plant-based diet to all of their patients” is the
authors’ dedication of a substantial portion
of their article to the possibility of deficiencies of selected nutrients. In our experience
of treating more than 5000 patients with a
low-fat, whole foods, plant-based (vegan)
diet, with follow-up lasting as long as 28
years, we have not seen any deficiencies of
protein, iron, calcium, or essential fatty acids.
(We do recommend to our patients a vitamin
B12 supplement and adequate sunshine for
vitamin D.)
Tuso et al characterize the risk of these deficiencies as low, but deserving of monitoring.
The risks are so low that illnesses because of
the lack of any of these essential nutrients,
including protein,1 have not been reported to
occur on any natural human diet (as long as
calorie intake is sufficient). Dietary manipulation or supplementation to improve the overall
quality, or to increase the absolute quantity,
of protein, iron, calcium, or fatty acids has not
been found to be beneficial. To the contrary,
excess protein is a major contributor to bone
loss,2 kidney stones, and kidney failure.3 Although iron stores may be lower in vegetarians, there is no reported increase in incidence
of iron deficiency anemia.4 Data supporting
the benefits of calcium supplementation to
improve bone health is lacking, and adverse
effects, such as an increased risk of fracture5
and myocardial infarction6 from supplementation have been reported. Plasma levels of
essential fatty acids can be lower in vegetarians, but there has been no reported clinical
consequence of this laboratory finding.7 In
addition, randomized placebo controlled
trials for the primary8 and secondary9 prevention of cardiovascular disease with omega-3
supplements have been disappointing as of
late. Furthermore, there is concern that these
“good fats” may increase the risk of common
cancers, including prostate cancer.10
More than a half-century of creative marketing by the meat, dairy, egg, and fish industries
has produced fears surrounding nonexistent
deficiencies, which in clinical practice need
no patient monitoring by physicians and dietitians. Hopefully our concerns for overemphasizing the importance of largely theoretical
risk will remove an unnecessary hindrance to
the acceptance and practice of scientifically
sound plant-based diets as recommended by
Tuso and associates. v
Craig McDougall, MD
Northwest Permanente, Portland, OR
John McDougall, MD
The McDougall Program, Santa Rosa, CA
References
3. Adeva MM, Souto G. Diet-induced metabolic acidosis.
Clin Nutr 2011 Aug;30(4):416-21. DOI: http://dx.doi.
org/10.1016/j.clnu.2011.03.008
4. Hunt JR. Bioavailability of iron, zinc, and other trace
minerals from vegetarian diets. Am J Clin Nutr 2003
Sep;78(3 Suppl):633S-639S.
5. Seeman E. Evidence that calcium supplements reduce
fracture risk is lacking. Clin J Am Soc Nephrol 2010
Jan;5 Suppl 1:S3-11. DOI: http://dx.doi.org/10.2215/
CJN.06160809
6. Bolland MJ, Avenell A, Baron JA, et al. Effect of
calcium supplements on risk of myocardial infarction
and cardiovascular events: meta-analysis. BMJ 2010
Jul 29;341:c3691. DOI: http://dx.doi.org/10.1136/bmj.
c3691
7. Sanders TA. DHA status of vegetarians. Prostaglandins Leukot Essent Fatty Acids 2009 AugSep;81(2-3):137-41. DOI: http://dx.doi.org/10.1016/j.
plefa.2009.05.013
8. Risk and Prevention Study Collaborative Group; Roncaglioni MC, Tombesi M, Avanzini F, et al. n-3 fatty acids
in patients with multiple cardiovascular risk factors. N
Engl J Med 2013 May 9;368(19):1800-8. DOI: http://
dx.doi.org/10.1056/NEJMoa1205409
9. Galan P, Kesse-Guyot E, Czernichow S, Briancon S,
Blacher J, Hercberg S; SU.FOL.OM3 Collaborative
Group. Effect of B vitamins and omega 3 fatty acids
on cardiovascular diseases: a randomised placebo controlled trial. BMJ 2010 Nov 29;341:c6273. DOI: http://
dx.doi.org/10.1136/bmj.c6273
10. Brasky TM, Darke AK, Song X, et al. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT
trial. J Natl Cancer Inst 2013 Aug 7;105(15):1132-41.
DOI: http://dx.doi.org/10.1093/jnci/djt174
1. Millward DJ. Meat or wheat for the next millennium?
Plenary lecture. The nutritional value of plant-based
diets in relation to human amino acid and protein requirements. Proceedings of the Nutrition Society 1999
May;58(2):249-60. DOI: http://dx.doi.org/10.1017/
S0029665199000348
2. Frassetto LA, Sebastian A. Commentary to accompany
the paper entitled ‘Nutritional disturbance in acid-base
balance and osteoporosis: a hypothesis that disregards
the essential homeostatic role of the kidney’, by
Jean-Philippe Bonjour. Br J Nutr 2013 Jun 17:1-3. DOI:
http://dx.doi.org/10.1017/S0007114513001499
Response to Drs Craig and John McDougall
We thank Drs John and Craig McDougall for their interest in our article. Although
we understand their point of view, from a clinical perspective, we are obligated to
inform physicians of potential concerns, even if the risk for harm is low.
It may be true that eating a healthy, plant-based diet can offer the optimal amount
of most nutrients needed to support health. Not every person however, will follow
a quality diet, so it is important for physicians to understand what these potential
concerns might be. v
Phillip Tuso, MD
Mohamed Ismail, MD
Benjamin Ha, MD
Carole Bartolotto, MA, RD
93
LETTERS
Letters to the Editor
Disclosing Medical Mistakes:
A Communication Management
Plan for Physicians
Re: Petronio S, Torke A, Bosslet G, Isenberg S,
Wocial L, Helft PR. Disclosing medical mistakes: a communication management plan for physicians. Perm J 2013 Spring;17(2):73-79. DOI: http://dx.doi.org/10.7812/TPP/12-106
Dear Editor,
I was appalled to read the first words of this
abstract: “There is a growing consensus that
disclosure of medical mistakes is ethically and
legally appropriate …”
It has always been appropriate to acknowledge ones’ mistakes as soon as discovered, even
if the patient is unaware. Forget “the plan” and
do not weigh the consequences, but simply
say to all in the room: “It’s my fault”; “I made
a mistake”; “I caused the problem”; “I’m sorry,
but let’s see if we can fix it.” The patient will
appreciate your honesty, realizing that we all
make mistakes. To balk, question, or deny the
mistake is not only wrong but greatly increases
the likelihood of legal action.
The first half of my 40-year otolaryngology
career was spent in private practice, and the
last half at the Kaiser Permanente Santa Clara
Medical Center. I certainly made my share of
mistakes, but by following this path, not once
was I threatened with legal action. v
J Richard Gaskill, MD
Retired Otolarygologist
Santa Clara Medical Center
Santa Clara, CA
Response to Dr Gaskill
Thank you for your response. We agree
with Dr Gaskill that disclosure of medical
mistakes has always been—and remains—
the most ethically acceptable strategy.
However, it has not always been the case
that practitioners, risk managers, and health
care administrators have been in favor of
full and immediate disclosure. We appreciate Dr Gaskill’s passionate advocacy of
the ethical position of disclosure and for
offering his opinion. v
What Does Professionalism Mean to the Physician?
Re: Kanter MH, Nguyen M, Klau MH, Spiegel NH, Ambrosini VL. What does professionalism mean
to the physician? Perm J 2013 Summer;17(3):87-90. DOI: http://dx.doi.org/10.7812/TPP/12-120
Dear Editor,
Thank you for publishing the commentary “What Does Professionalism Mean to the
Physician?” in the Summer 2013 issue of The Permanente Journal. I agree that the core
principles of professionalism include excellence, accountability, altruism, humanitarianism,
respect for others, honor, and integrity. I would like to suggest that “duty” be considered
as an additional core principle of professionalism. One could argue that duty is already
incorporated into the existing core principles of professionalism. However, as a separate
core principle, duty would weave a deontologic thread into the fabric of professionalism.
According to Merriam-Webster’s Collegiate Dictionary, deontology is “the theory or study
of moral obligation.”1 The root of the word, deon, is Greek, which means “duty,” according
to Stanford Encyclopedia of Philosophy.2 By including a deontologic thread into the fabric
of professionalism, it acknowledges that physicians are driven by a sense of duty to their
patients, their organization, and their communities. In fact, when other core principles of
professionalism have failed, it is often the principle of duty that the physician must depend
upon in order to continue her or his work.
Once again, thank you for the excellent commentary. v
Tim Ho, MD
Physician Co-Lead, Complete Care
Irvine Medical Office
Irvine, CA
References
1. Merriam-Webster’s Collegiate Dictionary, Tenth edition. Springfield, MA: Merriam-Webster, Inc; 2000.
2. Zalta EN, editor. Stanford Encyclopedia of Philosophy. Stanford, CA: The Metaphysics Research Lab of Stanford
University; 2012.
Response to Dr Ho
Dear Dr Ho,
We are pleased that you found our article an important commentary on professionalism.
Our main purpose was to have physicians incorporate the ideals of professionalism into
their daily work. There are other principles that could be listed under professionalism.
“Duty” as it applies to caring for our patients is certainly an important concept and
could be considered as a separate principle. We believe that it is part of accountability
and altruism. Ultimately, our goal was to continue the dialogue on this topic. You have
added insights to this important work. Thank you for your contribution. v
Michael H Kanter, MD
Miki Nguyen, MPH
Marc H Klau, MD; MBA
Nancy H Spiegel, MS
Virginia L Ambrosini, MD
Sandra Petronia, PhD
Alexia Torke, MD, MS
Gabriel Bosslet, MD, MA
Steven Isenberg, MD
Lucia Wocial, RN, PhD
Paul R Helft, MD
94
Book review
WHOLE—Rethinking the Science of Nutrition by T Colin Campbell, PhD with Howard Jacobson, PhD
Review by Herbert J Sorensen, MD
Perm J 2013 Fall;17(4):95
In the Fall 2006 issue of The Permanente Journal, The China
Study by T Colin Campbell and his son Thomas was reviewed.
Now, in 2013, we have WHOLE—Rethinking the Science of
Nutrition, as a sequel. Why did the author decide to bring this
book to print? The China Study focused on the evidence that
tells us that a whole food, plant-based diet is the healthiest
human diet. WHOLE focuses on why it’s been so hard to bring
that evidence to light and on what still needs to happen for
real change to take place. In this book, the word “whole” is
a reference to a whole food, plant-based diet, but imbedded
in the chapters is a much wider application—the whole story
and the whole truth about the conflict between two competing
world views of health. The narrative of the two contrasting
paradigms provides the most comprehensive compendium that
I have ever encountered in a single volume of facts regarding
these two world views. It’s an eye opener!
What are these two world views of health? First, it’s necessary
to define reductionism—a paradigm that looks for truth only
in the smallest details, while ignoring the big picture. Table 1
is a summary of the two contrasting paradigms.
By functioning within the reductionist model, medicine
focuses on the individual symptoms and calls each of them a
disease. For each disease, an identified biochemical element is
used in a linear fashion to address the target symptom. Having
authored some 350+ publications on nutrition, having written
The China Study, and having served on multiple expert and
grant review panels, the author has unique insights into how
government, drug companies, the medical system, patient
advocacy groups, and lobbies work exclusively within the
reductionist model. He details how these entities are interconnected, functioning for profit, to the detriment of the health
of individuals, the nation, and our environment. The use of a
Table 1. Summary of two contrasting paradigms
Disease management
(reductionist)
Reactive
Looks at symptoms
Prefers isolated treatments
Magical
Instant/easy
Pursuit of profit/patents
Nutrition
(wholistic)
Preventive
Looks at underlying causes
Prefers systemic treatments
Realistic
Takes time/requires effort
Human health/no patents
whole food, plant-based diet continues to provide the most
effective approach to being healthy, but the forces aligned
against it are huge and often hidden.
What, then, are the authors’ take home messages of WHOLE?
“We must recognize nutrition as a cornerstone of our healthcare system, not a footnote.”1:285 “It’s time for us to begin a
real revolution—one that begins by challenging our individual
beliefs and changing our diets, and ends with the transformation
of our society as a whole.”1:290 “The crucial shift in the way we
think about our health will happen, one person at a time.”1:289
“The most important step is to change the way you eat.”1:289
The clinical insights and relevance of WHOLE are important
and often unexpected. I hope some of you reading this review
will decide to delve deeper into this subject by reading and
profiting from WHOLE. The choice is yours—one at a time! v
Reference
1. Campbell TC. Whole—Rethinking the science of nutrition. Dallas, TX:
BenBella Books; 2013.
Herbert J Sorensen, MD, is a retired Obstetrician-Gynecologist and past Medical Director
at the San Diego Medical Center in CA. E-mail: heandre@cox.net.
95
Physicians may earn up to 1 AMA PRA Category 1 Credit™ per article for reading and analyzing the designated CME
articles published in each edition of TPJ. Each edition has four articles available for review. Other clinicians for whom CME is
acceptable in meeting educational requirements may report up to four hours of participation. Please return (fax or mail to the
address listed on the bottom of this form) to The Permanente Journal by December 30, 2013. Forms may also be completed
and submitted online at: www.thepermanentejournal.org. You must complete all sections to receive credit. (Completed forms
will be accepted until September 2014. Acknowledgment will be mailed within 2 months after receipt of form.)
To earn CME for reading each article designated for AMA PRA Category 1 Credit, you must:
• Score at least 50% in the post-test
• Complete the evaluation and provide your contact information
This form is also available online: www.thepermanentejournal.org
CME Evaluation Program
Section A.
Article 1. (page 32) Making Hospitals Safer for Older Adults: Updating Quality Metrics
by Understanding Hospital-Acquired Delirium and Its Link to Falls
Article 3. (page 47) Deep Brain Stimulation for the Treatment of Severe, Medically Refractory
Obsessive-Compulsive Disorder
What is incorrect about the characterization of delirium in hospitalized older patients?
a. it may be a risk factor for dementia
b. it is not preventable
c. 4% of patients will have all symptoms of delirium resolved upon hospital discharge
d. 18% have all symptoms of delirium resolved 6 months after hospital discharge
Deep brain stimulation for psychiatric conditions is:
a. not currently approved, available only under institutional review board-approved research protocols
b. Federal Drug Administration approved under a humanitarian device exemption for treatmentrefractory obsessive-compulsive disorder and depression
c. Federal Drug Administration approved for treatment refractory obsessive-compulsive disorder
and posttraumatic stress disorder
d. Federal Drug Administration approved under a humanitarian device exemption for treatmentrefractory obsessive-compulsive disorder only
What are possible indications for continued use of a proton pump inhibitor in hospitalized
older adults?
a. history of a peptic ulcer disease from 5 years ago
b. Barrett esophagitis
c. suspected upper gastrointestinal bleeding
d. use of nonsteroidal anti-inflammatory drugs
Which of the following is currently not used as an approved surgical treatment for
obsessive-compulsive disorder?
a. cingulotomy
b. subcaudate tractotomy
c. deep brain stimulation
d. orbitofrontal leucotomy
e. capsulotomy
Article 2. (page 37) Preventing Falls in the Geriatric Population
What is the most important first step in fall prevention?
a. vision screen every year
b. removing or reducing psychoactive medications
c. Timed Up and Go Test in the office
d. ask about a history of falls or balance problems
e. home safety assessment
Article 4. (page 75) Choosing Wisely and Beyond: Shared Decision Making
and Chronic Kidney Disease
In 2010, the Renal Physician Association published clinical practice guidelines on shared decision making
for chronic kidney disease. The outlined approaches to caring for patients with end-stage kidney disease
at the time of initiation of renal replacement therapy include all of the following except:
a. dialysis therapy without limitations on other treatments
b. dialysis therapy without cardiopulmonary resuscitation
c. no dialysis therapy
d. dialysis therapy without a discussion about end-of-life decisions
What does not qualify as one of the top five risk factors for falls?
a. previous falls
b. decreased strength
c. gait/balance impairments
d. use of psychoactive medications
e. fear of falling
An optimal start of dialysis means that a patient starts therapy with all of the following except:
a. vascular catheter
b. peritoneal dialysis catheter
c. arteriovenous fistula
d. maximal conservative management
Please return completed form by December 30, 2013
Section C.
Section B.
Referring to the CME articles, how likely is it that you will implement this learning to improve your practice
within the next 3 months?
Objective 1
Key
5 = highly likely
4 = likely
3 = unsure
2 = unlikely
1 = highly unlikely
0 = I already did this
Integrate learned
knowledge and
increase competence/
confidence to support
improvement and
change in specific
practices, behaviors,
and performance.
Objective 2
Lead in further developing “PatientCentered Care” activities by acquiring
new skills and methods to overcome
barriers, improve physician/patient
relationships, better identify diagnosis
and treatment of clinical conditions,
as well as, efficiently stratify health
needs of varying patient populations.
Objective 3
Implement changes and
apply updates in services and
practice/policy guidelines,
incorporate systems and
quality improvements, and
effectively utilize evidencebased medicine to produce
better patient outcomes.
____________________________________________________________
____________________________________________________________
____________________________________________________________
Section D. (Please print)
Name __________________________________________________
Article 1
5
4
3
2
1
0
5
4
3
2
1
0
5
4
3
2
1
0
Article 2
5
4
3
2
1
0
5
4
3
2
1
0
5
4
3
2
1
0
Title __________________________________________________
Article 3
5
4
3
2
1
0
5
4
3
2
1
0
5
4
3
2
1
0
E-mail __________________________________________________
Article 4
5
4
3
2
1
0
5
4
3
2
1
0
5
4
3
2
1
0
Address __________________________________________________
__________________________________________________
The Kaiser Permanente National CME Program is accredited by the
Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing medical education for physicians.
The Kaiser Permanente National CME Program designates this journal-based
CME activity for 4 AMA PRA Category 1 Credits™. Physicians should claim
only the credit commensurate with the extent of their participation in the activity.
96
What other changes, if any, do you plan to make in your practice as
a result of reading these articles?
Mail or fax completed form to:
Phone: 503-813-3286
Fax: 503-813-2348
Physician
Non-Physician Signature __________________________________________________
Date __________________________________________________

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