Doi:10.1016/s0002-9343(03)00666-
The End of the Disease EraMary E. Tinetti, MD, Terri Fried, MD 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the diagnosis and treatment of individualized approach range from concerns about medical- individual diseases at best out of date and at worst harmful.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 overtreatment, or mistreatment.
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 tributing factors.
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, [email protected].
nomic, psychological, and environmental factors, as well 2004 by Excerpta Medica Inc.
0002-9343/04/$–see front matter All rights reserved.
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- health outcomes.
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 ical practice.
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 focus on individual diseases 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威 Volume 116 The End of the Disease Era/Tinetti and Fried Table 1. Characteristics of Two Models of Medical Care
Disease-Oriented Model Integrated, Individually Tailored Model 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.
and other factors.
Treatment is targeted at the pathophysiologic mechanisms Treatment is targeted at the modifiable factors contributing to thought to cause the disease(s).
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 patient preference.
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, at present, the end goal itself.
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 health care and policy groups.
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 tailored model.
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威 Volume 116 181
The End of the Disease Era/Tinetti and Fried Table 2. Clinical Decision Making with the Disease-Oriented and Integrated, Individually Tailored Models for a 44-Year-Old Obese
Man Reporting Decreased Activity Tolerance
Disease-Oriented Model Integrated, Individually Tailored Model Collect clinical data Collect patient-specific data 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 cardiac examination) 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, stroke to avoid these problems now) 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, tobacco and alcohol abuse 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 ⫹/⫺ angiotensin-converting enzyme inhibitor) activities rather than exercise Treat cholesterol (e.g., statin) 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) Blood pressure level Physical activity level and sexual functioning Cholesterol level Maintain employment Myocardial infarction, stroke, heart failure, survival Survival, myocardial infarction 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 the health care system.
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威 Volume 116 The End of the Disease Era/Tinetti and Fried Table 3. Clinical Decision Making with the Disease-Oriented and Integrated, Individually Tailored Models for a 76-Year-Old
Woman with Fatigue and Weight Loss
Disease-Oriented Model Integrated, Individually Tailored Model Collect clinical data Collect patient-specific data 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, fibrillation, heart failure, depression) 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) are doing her more harm than good) 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 unremarkable cardiovascular, pulmonary, be more physically and socially functional now, but is neurological, and abdominal examinations; fingerstick afraid of experiencing an exacerbation of heart glucose 112 mg/dL) 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 depression; rule out occult cancer 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 occult blood testing) reducing fluid and salt restriction and canceling Medications (e.g., continue current doses of all diabetic and cardiac diets 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 reassurance of low likelihood of cancer arrangements with daughter to better meet needs ofthe family members Encourage participation in senior center for meals, exercise programs, and social activities Change antidepressant if inadequate response to these interventions 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 Psychological functioning 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威 Volume 116 183
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Hamilton o. smith - nobel lecture
NUCLEOTIDE SEQUENCE SPECIFICITY OF RESTRICTION ENDONUCLEASESNobel Lecture, 8 December, 1978 HAMILTON O. SMITHDepartment of Microbiology, The Johns Hopkins University School ofMedicine Baltimore, Maryland, U. S. A. In the past seven to eight years we have witnessed the development of anew DNA technology that has fundamentally altered our approach tomodern genetics. The basic ingredients of this new technology are the
Mmrf march 07 book.qxd
MMRF March 07 Book.qxd 4/16/07 8:33 AM Page 1 Clinical Medicine & ResearchVolume 5, Number 1: 1-7©2007 Marshfield Clinic http://www.clinmedres.org Original Research Use of an Electronic Medical Record for the Identification of Research Subjects with Diabetes Mellitus Russell A. Wilke, MD, PhD; Richard L. Berg, MS; Peggy Peissig, MBA; Terrie Kitchner;