SPECIAL ARTICLES The End of the Disease Era
The time has come to abandon disease as the focus of medical
individual goals and the identification and treatment of all
care. The changed spectrum of health, the complex interplay
modifiable biological and nonbiological factors, rather than
of biological and nonbiological factors, the aging population,
solely on the diagnosis, treatment, or prevention of individual
and the interindividual variability in health priorities render
diseases. Anticipated arguments against a more integrated and
medical care that is centered on the diagnosis and treatment of
individualized approach range from concerns about medical-
individual diseases at best out of date and at worst harmful. A
ization of life problems to "this is nothing new" and "resources
primary focus on disease may inadvertently lead to undertreat-
would be better spent determining the underlying biological
ment, overtreatment, or mistreatment. The numerous strate-
mechanisms." The perception that the disease model is "truth"
gies that have evolved to address the limitations of the disease
rather than a previously useful model will be a barrier as well.
model, although laudable, are offered only to a select subset of
Notwithstanding these barriers, medical care must evolve to
persons and often further fragment care. Clinical decision mak-
meet the health care needs of patients in the 21st century. Am J
ing for all patients should be predicated on the attainment of
Med. 2004;116:179 -185. 2004 by Excerpta Medica Inc. THE PROBLEM
ful. A primary focus on disease, given the changed healthneeds of patients, inadvertently leads to undertreatment,
Chronic dizziness remains unrelieved; psychological
contributors to cardiovascular disease are ignored; 75-year-old patients consume an average of 15 medication
doses each day; patients leave the hospital with their
One cause of undertreatment is a reluctance to treat
pneumonia cured but their cognitive and physical func-
symptomatic patients who do not meet currently ac-
tioning irreversibly impaired. The diagnosis in each of
cepted diagnostic criteria. For example, clinicians are
these cases is a primary focus of medical care on disease.
hesitant to treat depressive symptoms if the patient does
The time has come to abandon disease as the primary
not meet Diagnostic Statistical Manual criteria, despite
focus of medical care. When disease became the focus of
evidence that depressive symptoms are responsive to in-
Western medicine in the 19th and early 20th century, the
tervention Many symptoms or impairments cannot
average life expectancy was 47 years and most clinical
be ascribed to a single disease even after exhaustive diag-
encounters were for acute illnesses Today, the aver-
nostic evaluations Chronic dizziness and noncan-
age life expectancy in developed countries is 74 years and
cer pain are two common symptoms, known to result
increasing, and most clinical encounters are for chronic
from the interplay among treatable physical and psycho-
illnesses or nondisease-specific complaints Com-
logical factors which often are left unalleviated
pared with acute diseases, chronic diseases have a broader
when the diagnostic workup fails to reveal a "causative"
spectrum of clinical manifestations and a poorer correla-
disease. The designation, however, of what is a symptom
tion between clinical manifestations and underlying pa-
(e.g., dizziness), an impairment (e.g., hearing loss), or a
thology. The changed spectrum of health conditions, the
disease (e.g., pneumonia) is partly an artifact of the dis-
complex interplay of biological and nonbiological fac-
ease model. The existing disease-oriented categorization
tors, the aging population, and the interindividual vari-
of clinical entities classifies symptoms and impairments
ability in health priorities render medical care that is cen-
as the subjective and objective presentations of underly-
tered primarily on the diagnosis and treatment of
ing diseases, whereas diseases are considered manifesta-
individual diseases at best out of date and at worst harm-
tions of discrete pathology. If the structure imposed bythe disease model is stripped away, however, each can beviewed as a health condition causing discomfort, having
From the Departments of Internal Medicine (MET, TF) and Epidemi-
adverse consequences, and resulting from multiple con-
ology and Public Health (MET), Yale School of Medicine, and Clinical
Epidemiology Unit (TF), VA Connecticut Healthcare System, New Ha-ven, Connecticut.
Undertreatment also occurs in "traditional" disease
Requests for reprints should be addressed to Mary E. Tinetti, MD,
categories such as coronary artery disease. A wealth of
Department of Internal Medicine, Yale School of Medicine, P.O. Box
data links adverse cardiovascular outcomes to socioeco-
208025, 333 Cedar Street, New Haven, Connecticut 06520-8025, ormary.tinetti@yale.edu.
nomic, psychological, and environmental factors, as well
The End of the Disease Era/Tinetti and Fried
as to biological determinants Despite compel-
up-to-date technology but whose physical, cognitive, and
ling evidence of the effectiveness of interventions such as
psychological functioning deteriorated.
antidepressants or counseling clinical attention
Numerous strategies have evolved to address the limi-
remains primarily targeted on the use of beta-blockers,
tations of disease-oriented care. These disparate efforts by
lipid-lowering drugs, and other such treatments
select groups of practitioners for select subsets of health
Treating only the biological mechanisms-an offshoot of
conditions and patients, although laudable, unfortu-
the focus on disease-rather than addressing all contrib-
nately fragment care and reinforce the view that these
uting factors results in lost opportunities to maximize
approaches are worthwhile only when the dominant dis-
ease-oriented approach fails. Multidisciplinary team
care, for example, is available in a limited number of set-tings to manage the physical, medical, psychological, en-
At the other end of the spectrum, the emphasis on pre-
vironmental, and other factors that contribute to the
venting and treating individual diseases leads to over-
health problems of typically older, or chronically ill, per-
treatment, often with serious consequences. It is tempt-
sons The concept of the geriatric syndrome was de-
ing to focus on egregious examples such as the 90-year-
veloped to explain common multifactorial health condi-
old patient with dementia and several comorbid
tions, such as falls, which are otherwise ignored under the
conditions who experiences severe postural hypotension
disease paradigm But are not most health condi-
from aggressive antihypertensive therapy or the 85-year-
tions multifactorial? Inadequate attention to symptom
old patient with lung cancer who has recurrent episodes
relief led to the emergence of palliative care Al-
of hypoglycemia from attempts at "tight" glycemic con-
though designed to address symptom relief in all patients
trol. More common but less acknowledged, however, are
with chronic illnesses, in practice access is often limited to
the consequences of medical care focused primarily on
those with terminal illnesses. The biopsychosocial model,
disease in the "typical" 70-year-old patient who suffers
which was introduced by Engel more than 30 years ago
from an average of four chronic diseases in addition to
is widely accepted and taught, but is employed clin-
nondisease-specific health conditions such as pain, im-
ically in a rather limited spectrum of entities The
paired mobility, and disordered sleep The emphasis
multiplicity of potential outcomes in the treatment of
on diagnosing and treating individual diseases has led to a
chronic diseases and the increased recognition that treat-
plethora of disease management guidelines For
ment decisions require trade-offs have led to the creation
example, for a patient with the not uncommon combina-
of sophisticated methods for eliciting patient preferences
tion of diabetes, heart failure, myocardial infarction, hy-
or goals, and involving patients in decision making
pertension, and osteoporosis to comply with existing
To date, however, these methods have been used pri-
guidelines, a physician must prescribe up to 15 medica-
marily for research or in a narrow spectrum of clinical
settings, and have not been widely incorporated into clin-
Excess medication is an unintended consequence of
attempts to prevent or treat individual diseases. Multiplemedication use increases costs, compromises adherenceand augments the risk of adverse drug eventsAlthough adverse drug events are the targets of sci-
A SOLUTION
entific and public scrutiny the role of the number of
The obvious solution is to better align medical care with
medications as a leading risk factor has largely been ig-
health needs by integrating existing knowledge and effec-
nored The increased use of medications, with their
tive strategies. Rather than waiting until the disease
adverse as well as beneficial effects, is inherent in the
model fails to invoke alternative strategies, the integra-
present medical paradigm mandating the prevention or
tion and coordination of such strategies should constitute
treatment of individual disease processes. The paired
the standard of care for all patients. Clinical decision
problems of polypharmacy and adverse drug events will
making should be predicated on the attainment of patient
not be solved easily while clinical decision making re-
goals and on the identification and treatment of modifi-
mains focused on the management of individual diseases.
able biological and nonbiological factors, rather than on
the diagnosis, treatment, or prevention of individual dis-
Mistreatment may result, albeit unintentionally, when
eases. This principle imposes on medical care certain
clinical decision making is based on disease-specific out-
characteristics that are distinct from care governed by a
comes rather than on patient preferences. Patients vary in
the importance they place on survival, comfort, and func-
The concept of individual disease should not be aban-
tioning, and in the choices they make when faced with
doned, but should be better integrated into individually
difficult trade-offs Hospitals are filled with pa-
tailored care. When treatable acute or chronic diseases
tients whose infection or organ failure "responded" to
impede the health goals of patients, disease diagnosis and
THE AMERICAN JOURNAL OF MEDICINE Volume 116
The End of the Disease Era/Tinetti and FriedTable 1. Characteristics of Two Models of Medical Care
Clinical decision making is focused primarily on the
Clinical decision making is focused primarily on the priorities
diagnosis, prevention, and treatment of individual diseases.
and preferences of individual patients.
Discrete pathology is believed to cause disease; psychological,
Health conditions are believed to result from the complex
social, cultural, environmental and other factors are
interplay of genetic, environmental, psychological, social,
secondary factors, not primary determinants of disease.
Treatment is targeted at the pathophysiologic mechanisms
Treatment is targeted at the modifiable factors contributing to
the health conditions impeding the patient's health goals.
Symptoms and impairments are best addressed by diagnosing
Symptoms and impairments are the primary foci of treatment
and treating "causative" disease(s).
even if they cannot be ascribed to a discrete disease.
Relevant clinical outcomes are determined by the disease(s).
Relevant clinical outcomes are determined by individual
Survival is the usual primary focus of disease prevention and
Survival is one of several competing goals.
treatment remain integral parts of the overall clinical de-
mended behaviors (e.g., smoking cessation, safe sex, in-
cision-making process. Disease management becomes
creased physical activity, and decreased alcohol intake);
one of several means towards the end goal, rather than, as
preventive services (e.g., mammography, colonoscopy,
regular dental care, bone mineral density measurement,
For the integrated, individually tailored model to take
immunization); and, depending on age, sex, genetic pre-
hold, marked changes must occur in the process of clini-
disposition, and screening results, daily use of medica-
cal decision making. In the disease model, the patient's
tions such as aspirin, statins, calcium, vitamin D, and
"chief complaint" leads to the creation of a differential
bisphosphonates, which are all predicated on preventing
diagnosis. Further history, physical examination, and an-
specific diseases. Under a more individually tailored
cillary tests help to determine which diseases most likely
model, preventive decision making is based on a patient's
explain the patient's symptoms or complaints. Treatment
articulation of preferred trade-offs between long-term
then is aimed at this underlying disease. In the integrated,
outcomes such as survival or functioning and short-term
individually tailored model, the patient's complaints ini-
acceptance of testing burden, lifestyle changes, and the
tiate three sets of questions. The first set asks in what ways
inconvenience, costs, and side effects of daily medica-
the complaints are bothersome-what is the effect on the
tions. The details of how clinical encounters will be struc-
patient's physical, psychological, and social functioning?
tured under this more complex and individualized ap-
The second set elicits what the patient hopes to achieve
proach will require the combined efforts of patients and
from medical treatment. What domain of outcomes is
most important? What trade-offs are the patient willing
The need to ascertain and incorporate individual pri-
to make? In the case of prevention, does the patient value
orities, to address multiple contributing factors simulta-
"down the road" benefits more or does the patient have
neously, and to prescribe and monitor multifaceted in-
more immediate concerns about the side effects of daily
terventions will make clinical decision making more
medications? The third set of questions explores the non-
iterative, interactive, individualized, and complex. Cre-
biological determinants of health. For example, are psy-
ative use of information technologies should facilitate the
chological or social factors further impeding health and
organization, presentation, and integration of this infor-
functioning? The answers to these questions are integral
mation to arrive at individualized yet systematic clinical
to constructing the treatment plan. Examples of clinical
decision making predicated on individual patient priori-
decision making under these contrasting models are
shown in for a 44-year-old man with a singlehealth condition but many contributing factors, and infor an elderly woman with several conditions. CHALLENGES AND BARRIERS
Disease diagnosis and management, which is the focus ofthe disease model, is incorporated into, but does not
Attempts to develop a more integrated and individual-
dominate, decision making in the integrated, individually
ized model will be met with structural and philosophical
barriers. To accomplish its goals, health care must be-
The integrated, individually tailored approach also ap-
come more interdisciplinary. The lack of coordination,
plies to prevention. Decision making for relatively
or even communication, among relevant disciplines
healthy adults is governed at present by a litany of recom-
could worsen the already egregious fragmentation of
THE AMERICAN JOURNAL OF MEDICINE Volume 116 181 The End of the Disease Era/Tinetti and FriedTable 2. Clinical Decision Making with the Disease-Oriented and Integrated, Individually Tailored Models for a 44-Year-Old Obese Man Reporting Decreased Activity Tolerance
● History (e.g., heavy tobacco and alcohol intake, occasional
● Patient concerns (e.g., worried about losing job which
exercise-induced chest pain, family history of coronary artery
involves heavy lifting, worried about having a myocardial
infarction and dying before age 50 years like his father)
● Physical examination (e.g., blood pressure 158/94 mm Hg,
● Patient priorities (e.g., wants to live as long as possible but
body mass index 31.2 kg/m2, trace peripheral edema, S on
does not want to take medications if they interfere with
sexual functioning, energy level, or alertness; willing to
● Laboratory and ancillary testing (e.g., blood chemistries,
trade off some increased risk of myocardial infarction or
complete blood count, chest radiograph, electrocardiogram,
echocardiogram, pulmonary function tests, exercise stress
● Nonbiological determinants: increased smoking and
alcohol and decreased physical activity after his son diedin an accident; religion is a source of support
Contributing factors impeding goals
● Coronary artery disease, hypertension, hypercholesterolemia,
● Coronary artery disease, bereavement, tobacco, alcohol,
depressive symptoms, employment opportunities limitedby education
Management (based on patient's priorities)
● Risk factor modification (e.g., counsel to stop smoking,
● Bereavement counseling through church
reduce or eliminate alcohol, lose weight, begin exercise
● Patient selects risk factor(s) that he is willing to address
(e.g., Alcoholics Anonymous meeting at church)
● Treat blood pressure (e.g., thiazide diuretic, beta-blocker,
● Encourage increased physical activity during daily
ϩ/Ϫ angiotensin-converting enzyme inhibitor)
● Patient willing to start with thiazide diuretic and aspirin;
● Refer to cardiologist for further diagnosis and management
later agrees to a low-dose beta-blocker because a higherdose makes him tired; declines antidepressant but willingto undergo counseling
Outcomes (in order of patient's priorities)
● Physical activity level and sexual functioning
● Myocardial infarction, stroke, heart failure, survival
health care. The increased emphasis on psychological, so-
will be needed in the training of other health profession-
cial, environmental, and other factors will raise concerns
about the "medicalization" of life problems Al-
Research, along with clinical care, has shaped the de-
though necessitating a delineation of the components of
partmental structure of medical schools, which in turn
health, the debate should revolve not around medicaliza-
has influenced the organization of clinical practice. Re-
tion or interdisciplinary "boundaries," but around efforts
search is, however, already restructuring along method-
to coordinate and pay for efficient and effective interdis-
ological and technological lines, and away from an organ-
ciplinary care, whether it is provided within or outside
and specialty-based configuration. Basic research, aimed
at elucidating underlying pathophysiologic mechanisms,
The transition to this new model will require a major
will increasingly be organized with a structure distinct
reorganization of health care from education through de-
from clinical care. The organization of clinical services
livery systems. Medical education, for example, which
can thus evolve unencumbered by the need to artificially
has been organized around pathophysiologic mecha-
fit into a research-driven paradigm.
nisms or organ systems, is already moving toward a more
Reimbursement will be another challenge. In theory,
integrated curriculum. These changes are primarily in re-
coverage and payment decisions should follow logically
sponse to time constraints and information overload and
from a clear articulation of the goals and structure of care.
not to any acknowledged limitation of the disease-ori-
Indeed, the evolution of a new model offers the opportu-
ented approach. Nevertheless, it is worth taking advan-
nity, perhaps for the first time, to articulate coverage de-
tage of this transition to train the next generation of phy-
cisions based on evidence of effectiveness and on trans-
sicians, who are not yet wedded to the disease model, in a
parent societal and personal priorities. In practice,
more appropriate model of medical care. Parallel changes
however, restructuring reimbursement to better match
THE AMERICAN JOURNAL OF MEDICINE Volume 116
The End of the Disease Era/Tinetti and FriedTable 3. Clinical Decision Making with the Disease-Oriented and Integrated, Individually Tailored Models for a 76-Year-Old Woman with Fatigue and Weight Loss
● History (e.g., poor appetite; denies other
● Patient concerns (e.g., fatigue has caused her to cut
gastrointestinal complaints; tired all day; denies chest
back on activities, including caring for her
pain, dyspnea, or other cardiac or pulmonary
grandchildren; believes that the decreased appetite
complaints; known history of diabetes mellitus, atrial
and fatigue are caused partly by her medications,
although she knows several of her chronic illnesses
● Medications (e.g., coumadin, angiotensin-converting
can contribute as well; understands the benefits of the
enzyme inhibitor, furosemide, statin, sulfonylurea,
individual medications, but thinks that overall they
thiazolidinedione, beta-blocker, aspirin, mirtazapine)
● Physical examination (e.g., blood pressure 146/88 mm
● Physical examination (as in disease-oriented model)
Hg; heart rate 52 beats per minute and irregular;
● Patient priorities (e.g., willing to trade off an
weight 106 lbs, down from 121 pounds 1 year ago;
increased risk of stroke and myocardial infarction to
be more physically and socially functional now, but is
neurological, and abdominal examinations; fingerstick
afraid of experiencing an exacerbation of heart
● Nonbiological determinants (e.g., lives alone; does
not like eating alone; has difficulty paying for foodand medications; does not like taste of low-salt, low-fat diet; divorced daughter depending on her for childcare; exacerbation of depression when husband died)
Contributing factors impeding goals
● Heart failure and diabetes stable; hypertension not
● Several chronic conditions that can cause fatigue and
well controlled; atrial fibrillation; worsening
compromise appetite; living alone; several life
stressors; multiple medications that, in combination,may affect fatigue, muscle strength, affect, taste, andappetite
Management (based on patient's priorities)
● Laboratory and ancillary (e.g., complete blood count;
● Discontinue statin and reduce beta-blocker and
blood chemistries; thyroid function tests;
international normalized ratio; chest radiograph; fecal
● Encourage increased fluid and food intake by
reducing fluid and salt restriction and canceling
● Medications (e.g., continue current doses of all
● Monitor heart rate, signs of heart failure, and diabetic
● Refer to psychiatrist to adjust or switch antidepressant
● Consider referral to gastroenterologist or provide
● Encourage patient to discuss living and childcare
arrangements with daughter to better meet needs ofthe family members
● Encourage participation in senior center for meals,
● Change antidepressant if inadequate response to
Outcomes (in order of patient's priorities)
● Blood pressure, glucose, and heart rate level
● Absence of fatigue and return of appetite
● Stroke, cancer, heart failure, survival
effectiveness and priorities- under any payment sys-
this," and that "resources would be better spent investi-
tem-will require the courage and persistence of medical
gating and treating the underlying mechanisms through
and political leaders. Determining the boundaries of
which both biologic and nonbiologic factors operate." In
health care, given the broader definition of health implied
response to the first argument, although some clinicians
in this model, will present further reimbursement chal-
may practice in this fashion with some of their patients
some of the time, the majority do not. The organization,
Paradoxically, two anticipated arguments against
payment, and quality assessment of medical care remain
change will be that "this is nothing new, we already do
firmly entrenched in disease-specific, episodic care. To
THE AMERICAN JOURNAL OF MEDICINE Volume 116 183 The End of the Disease Era/Tinetti and Fried
address the second argument, although no one can deny
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FACULTY OF HISTORY Problems in the History of Science and Technology Michaelmas Term 2005 The following seminars will be held on Wednesday at 5 p.m. (except in Week 6, when the seminar will begin at 4pm) in the History of Science and Technology Seminar Room, Modern History Faculty. They will be preceded by tea in the Faculty Common Room at 4.40 p.m. (except in Week 6, when the se
Publikationsverzeichnis Prof. Dr. med. Anita Rauch A) Originalarbeiten 108. Göhring I, Tagariello A, Endele S, Stolt CC, Ghassibé M, Fisher M, Thiel CT, Trautmann U, Vikkula M, Winterpacht A, FitzPatrick DR, Rauch A (2009) Disruption of ST5 is associated with mental-retardation and multiple congenital anomalies. J Med Genet, in press 107. Segel R, Levy-Lahad E, Pasutto F, Picard