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J Tsevat

Publications and source records attributed to J Tsevat.

At least 37 records · Page 2Linked to original sources

Outcomes of acute exacerbation of severe congestive heart failure: quality of life, resource use, and survival. SUPPORT Investigators. The Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: Congestive heart failure (CHF) is a common disease with high health care costs and high mortality rates. Knowledge of the health-related quality of life outcomes of CHF may guide decision making and be useful in assessing new therapies for this population. METHODS: A prospective cohort study was conducted involving 1390 adult patients hospitalized with an acute exacerbation of severe CHF (New York Heart Association class III-IV). Demographic data and health-related quality of life were determined by interview; physiologic status and cost and intensity of care were determined from hospital charts. RESULTS: The median (25th, 75th percentiles) age of patients was 68.0 (58.2, 76.9) years; 61.7% were male. Survival was 93.4% at discharge from the index hospitalization, 72.9% at 180 days, and 61.5% at 1 year. Of patients interviewed at 180 days, the median health rating on a scale of 0 to 100 (0 indicates death; 100, excellent health) was 60 (interquartile range, 50-80), and 59.7% were independent in their activities of daily living. Overall quality of life was reported to be good, very good, or excellent in 58.2% at 180 days. Patients with worse functional capacity were more likely to die. Health perceptions among the patients with available interview data improved at 60 and 180 days after acute exacerbation of severe CHF. CONCLUSIONS: Patients hospitalized for acute exacerbation of severe CHF have a generally poor 6-month survival, but survivors retain relatively good functional status and have good health perceptions. Furthermore, health perceptions improve after the acute exacerbation.

Acute Disease↗

Depressed mood and survival in seriously ill hospitalized adults. The SUPPORT Investigators.

OBJECTIVES: To assess the relationship among depressed mood, physical functioning, and severity of illness and to determine the relationship between depressed mood and survival time, controlling for severity of illness, baseline functioning, and characteristics of patients. METHODS: Prospective cohort study of data for 3529 seriously ill hospitalized adults who received care at 5 tertiary care teaching hospitals and who completed a depressed mood assessment 7 to 11 days after admission to the study. The Profile of Mood States depression subscale was used to assess depressed mood. A stratified Cox proportional hazards model was used to assess the independent effect of depressed mood on survival time, adjusting for demographic characteristics of patients and health status. RESULTS: Greater magnitudes of depressed mood were associated with worse levels of physical functioning (r = 0.151; P < .001) and more severity of illness. Depressed mood was associated with reduced survival time after adjusting for patient demographics and health status (hazards ratio, 1.134; 95% confidence interval, 1.071-1.200; P < or = .001). CONCLUSION: Seriously ill patients should be assessed for the presence of depressed mood even if they have not been given a diagnosis of depression. Further study is needed to determine whether interventions aimed at relieving depressed mood may improve prognosis.

Affect↗

Health values of hospitalized patients 80 years or older. HELP Investigators. Hospitalized Elderly Longitudinal Project.

CONTEXT: Health values (utilities or preferences for health states) are often incorporated into clinical decisions and health care policy when issues of quality vs length of life arise, but little is known about health values of the very old. OBJECTIVE: To assess health values of older hospitalized patients, compare their values with those of their surrogate decision makers, investigate possible determinants of health values, and determine whether health values change over time. DESIGN: A prospective, longitudinal, multicenter cohort study. SETTING: Four academic medical centers. PARTICIPANTS: Four hundred fourteen hospitalized patients aged 80 years or older and their surrogate decision makers who were interviewed and understood the task. MAIN OUTCOME MEASURES: Time-trade-off utilities, reflecting preferences for current health relative to a shorter but healthy life. RESULTS: On average, patients equated living 1 year in their current state of health with living 9.7 months in excellent health (mean [SD] utility, 0.81 [0.28]). Although only 126 patients (30.7%) rated their current quality of life as excellent or very good, 284 (68.6%) were willing to give up at most 1 month of 12 in exchange for excellent health (utility > or =0.92). At the other extreme, 25 (6.0%) were willing to live 2 weeks or less in excellent health rather than 1 year in their current state of health (utility < or =0.04). Patients were willing to trade significantly less time for a healthy life than their surrogates assumed they would (mean difference, 0.05; P=.007); 61 surrogates (20.3%) underestimated the patient's time-trade-off score by 0.25 (3 months of 12) or more. Patients willing to trade less time for better health were more likely to want resuscitation and other measures to extend life. Time-trade-off score correlated only modestly with quality-of-life rating (r=0.28) and inversely with depression score (r=-0.27), but there were few other clinical or demographic predictors of health values. When patients who survived were asked the time-trade-off question again at 1 year, they were willing to trade less time for better health than at baseline (mean difference, 0.04; P=.04). CONCLUSION: Very old hospitalized patients who could be interviewed were able, in most cases, to have their health values assessed using the time-trade-off technique. Most patients were unwilling to trade much time for excellent health, but preferences varied greatly. Because proxies and multivariable analyses cannot gauge health values of elderly hospitalized patients accurately, health values of the very old should be elicited directly from the patient.

Advance Directives↗

Heterogeneity in the relationship between the time tradeoff and Short Form-36 for HIV-infected and primary care patients.

OBJECTIVES: Evidence in the literature suggests that the overall correlation between descriptive and valuational measures of health are weak to moderate. In this study, the relationship between descriptive health status measures, obtained using the Short-Form 36, and health values, measured with the time tradeoff, was explored. METHODS: Two groups of patients matched for age and gender were interviewed. One group comprised 139 human immunodeficiency virus (HIV)-infected patients; the other group comprised 124 primary care patients. The relationship between the SF-36 and the time tradeoff was estimated, assuming homogeneity across patients, using multiple regression analysis. Subsequently, the relationship was examined assuming heterogeneity across patients and using the expectation maximization algorithm in a maximum likelihood context (latent class analysis). RESULTS: Four classes, representing 47%, 13%, 8%, and 32% of the population, respectively, were found. The overall percentage of variation explained under the assumption of a homogeneous relationship was only 33% as compared with 85% when heterogeneity was accounted for. Only three characteristics (educational level, employment status, and the SF-36 social functioning score) sufficed to generate a nearly perfect classification of the patients. CONCLUSIONS: Heterogeneity across subjects should be taken into account in describing the relationship between health values and health status dimensions.

Attitude to Health↗

Outcomes and cost-effectiveness of initiating dialysis and continuing aggressive care in seriously ill hospitalized adults. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: Renal failure requiring dialysis in the setting of hospitalization for serious illness is a poor prognostic sign, and dialysis and aggressive care are sometimes withheld. OBJECTIVE: To evaluate the clinical outcomes and cost-effectiveness of initiating dialysis and continuing aggressive care for seriously ill hospitalized patients. DESIGN: Prospective cohort study and cost-effectiveness analysis. SETTING: Five geographically diverse teaching hospitals. PATIENTS: 490 patients (median age, 61 years; 58% women) enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) in whom dialysis was initiated. MEASUREMENTS: Survival, functional status, quality of life, and health care costs. Life expectancy was estimated by extrapolating survival data (up to 4.4 years of follow-up) using a declining exponential function. Utilities (quality-of-life weights) were estimated by using time-tradeoff questions. Costs were based on data from SUPPORT and published Medicare data. RESULTS: Median duration of survival was 32 days, and only 27% of patients were alive after 5 months. Survivors reported a median of one dependency in activities of daily living, and 62% rated their quality of life as "good" or better. Overall, the estimated cost per quality-adjusted life-year saved by initiating dialysis and continuing aggressive care rather than withholding dialysis and allowing death to occur was $128,200. For the 103 patients in the worst prognostic category, the estimated cost per quality-adjusted life-year was $274,100; for the 94 patients in the best prognostic category, the cost per quality-adjusted life-year was $61,900. CONCLUSIONS: For the few patients who survived, clinical outcomes were fairly good. With the exception of patients with the best prognoses, however, the cost-effectiveness of initiating dialysis and continuing aggressive care far exceeded $50,000 per quality-adjusted life-year, a commonly cited threshold for cost-effective care.

Aged↗

The recent decline in mortality from coronary heart disease, 1980-1990. The effect of secular trends in risk factors and treatment.

OBJECTIVE: To examine whether secular trends in risk factor levels and improvements in treatment can account for the observed decline in coronary heart disease mortality in the United States from 1980 to 1990 and to analyze the proportional contribution of these changes. DATA SOURCES: Literature review, US statistics, health surveys, and ongoing clinical trials. STUDY SELECTION: Data representative of the US situation nationwide reported in adequate detail. DATA EXTRACTION: A computer-simulation state-transition model of the US population between the ages of 35 and 84 years was developed to forecast coronary mortality. The input variables were estimated such that the combination of values led to an adequate agreement with reported coronary mortality figures. Subsequently, secular trends were modeled. DATA SYNTHESIS: Actual coronary mortality in 1990 was 34% (127,000 deaths) lower than would be predicted if risk factor levels, case-fatality rates, and event rates in those with and without coronary disease remained the same as in 1980. When secular changes in these factors were included in the model, predicted coronary mortality in 1990 was within 3% (10,000 deaths) of the observed mortality and explained 92% of the decline; only 25% of the decline was explained by primary prevention, while 29% was explained by secondary reduction in risk factors in patients with coronary disease and 43% by other improvements in treatment in patients with coronary disease. CONCLUSIONS: These results suggest that primary and secondary risk factor reductions explain about 50% of the striking decline in coronary mortality in the United States between 1980 and 1990 but that more than 70% of the overall decline in mortality has occurred among patients with coronary disease.

Adult↗

Cost-effectiveness of transesophageal echocardiographic-guided cardioversion: a decision analytic model for patients admitted to the hospital with atrial fibrillation.

OBJECTIVES: Using a decision-analytic model, we sought to examine the cost-effectiveness of three strategies for cardioversion of patients admitted to the hospital with atrial fibrillation. BACKGROUND: Transesophageal echocardiographic (TEE)-guided cardioversion has been proposed as a method for early cardioversion of patients with atrial fibrillation. The cost-effectiveness of this approach, relative to conventional therapy, has not been studied. METHODS: We ascertained the cost per quality-adjusted life-year (QALY) of three strategies: 1) conventional therapy--transthoracic echocardiography (TTE) and warfarin therapy for 1 month before cardioversion; 2) initial TTE, followed by TEE and early cardioversion if no thrombus is detected; 3) initial TEE, with early cardioversion if no thrombus is detected. With strategies 2 and 3, if a thrombus is seen, follow-up TEE is performed. If no thrombus is seen, cardioversion is then performed. All strategies utilized anticoagulation before and extending for 1 month after cardioversion. Life expectancy, utilities (quality-of-life weights) and event probabilities were ascertained from published reports. Cost estimates were based on published data and hospital accounting information. RESULTS: Transesophageal echocardiographic-guided early cardioversion (strategy 3: cost $2,774, QALY 8.49) dominates TTE/TEE-guided cardioversion (strategy 2: cost $3,106, QALY 8.48) and conventional therapy (strategy 1: cost $3,070, QALY 8.48) because it is the least costly with similar effectiveness. Sensitivity analyses demonstrated that TEE-guided cardioversion (strategy 3) dominates conventional therapy if the risk of stroke after TEE negative for atrial thrombus is slightly less than that after conventional therapy (baseline estimate 0.8%). The results also depend on the risk of major hemorrhage but are less sensitive to baseline estimates of morbidity from TEE, cost of TTE, cost of hospital admission for cardioversion and utilities for health states. CONCLUSIONS: On the basis of a decision-analytic model, TEE-guided early cardioversion, without TTE, is a reasonable cost-saving alternative to conventional therapy for patients admitted to the hospital with atrial fibrillation. Such a strategy appears particularly beneficial for patients with an increased risk of hemorrhagic complications. Future clinical studies examining the TEE strategy should consider eliminating initial TTE and carefully assess both the thromboembolic and hemorrhagic risk.

Aged↗

Cost-effectiveness of routine coronary angiography after acute myocardial infarction.

BACKGROUND: Coronary angiography is indicated for many patients after acute myocardial infarction (AMI). There are a number of subgroups of AMI patients, however, for whom the indication for coronary angiography is not well established. METHODS AND RESULTS: We developed a decision-analytic model for AMI in representative patient subgroups based on relevant clinical characteristics. The model estimates quality-adjusted life expectancy and direct lifetime costs for two strategies: coronary angiography and treatment guided by its results versus initial medical therapy without angiography. Decision tree chance node probabilities were estimated with the use of pooled data from randomized clinical trials and other relevant literature, costs were estimated with the use of the Medicare Part A database, and quality of life adjustments were derived from a survey of 1051 patients who had had a recent AMI. In our analysis, incremental cost-effectiveness ratios for coronary angiography and treatment guided by its result, compared with initial medical therapy without angiography, ranged between $17,000 and > $1 million per quality-adjusted year of life gained. Patient subgroups with severe postinfarction angina or a strongly positive exercise tolerance test (ETT) typically had cost-effectiveness ratios of < $50,000 per quality-adjusted year of life gained. In addition, most patient subgroups with a prior AMI had cost-effectiveness ratios of < $50,000 per quality-adjusted year of life gained, even with a negative ETT result. CONCLUSIONS: In many patient subgroups after AMI, the cost-effectiveness of routine coronary angiography and treatment guided by its results compares favorably with other treatment strategies for coronary heart disease.

Adult↗

Health values of patients infected with human immunodeficiency virus. Relationship to mental health and physical functioning.

To assess the health values of patients infected with human immunodeficiency virus (HIV) and examine the relationships between their health values and health status at two points in time, the authors sought to determine whether patients' physical and mental health statuses were good predictors of how they valued their current state of health. One hundred thirty-nine patients with various stages of HIV infection were interviewed in a prospective cohort study based in a primary care practice of a community-based teaching hospital. Patients were interviewed twice at 6-month intervals using three health value measures--the time trade off, rating scale, and Quality of Well-being Scale--and three health status measures: the 18-item Mental Health Inventory, the Dyspnea-Fatigue Index, and the Medical Outcomes Study SF-36 Health Survey. The health status of HIV-infected patients was compromised and, with the exception of mental health, generally was worse among patients with more advanced HIV-infection. Rating scale and Quality of Well-being Scale scores were related inversely to disease stage, but time-trade off scores generally were higher regardless of disease stage. Health value measures showed moderate relationships with measures of physical functioning (r = 0.34-0.68) but only a fair relationship with mental health (r = 0.00-0.48). The health status of HIV-infected patients who remained asymptomatic or remained symptomatic but without developing acquired immunodeficiency syndrome (AIDS) changed little over 6 months, whereas the health status of patients with AIDS and of patients manifesting progression of HIV-infection deteriorated over time. In contrast, health values, particularly time-tradeoff scores, remained stable even in the face of changes in health status and disease progression. With the exception of mental health, the impact of HIV infection on health status tends to parallel the clinical stage of disease. Health values of HIV-infected patients, however, generally are high and correlate better with physical functioning than with mental health.

Activities of Daily Living↗

Health values of the seriously ill. SUPPORT investigators.

OBJECTIVE: To assess 1) the health values and health ratings of seriously ill hospitalized patients, their surrogate decision makers, and their physicians; 2) the determinants of health values; and 3) whether health values change over time. DESIGN: Prospective, longitudinal, multicenter study. SETTING: 5 academic medical centers. PARTICIPANTS: 1438 seriously ill patients with at least one of nine diseases who had a projected overall 6-month mortality rate of 50%; their surrogates; and their physicians. MEASUREMENTS: Time-tradeoff utilities (reflecting preferences for a shorter but healthy life) and health ratings. RESULTS: At study day 3, patients had a mean time-tradeoff utility of 0.73 +/- 0.32 (median [25th, 75th percentile], 0.92 [0.63, 1.0]), indicating that they equated living 1 year in their current state of health with living 8.8 months in excellent health. However, scores varied widely; 34.8% of patients were unwilling to exchange any time in their current state of health for a shorter life in excellent health (utility, 1.0), and 9.0% were willing to live 2 weeks or less in excellent health rather than 1 year in their current state of health (utility, 0.04). Health rating scores averaged 57.8 +/- 24.0 (median [25th percentile, 75th percentile], 60 [50, 75]) on a scale of 0 (death) to 100 (perfect health). The patients' mean time-tradeoff score exceeded that of their paired surrogates (n = 1041) by 0.08 (P < 0.0001). Time-tradeoff scores were related to psychosocial well-being; health ratings; desire for resuscitation and extension of life rather than relief of pain and discomfort; degree of willingness to live with constant pain; and perceived prognosis for survival and independent functioning. Scores of surviving patients increased by an average of 0.06 after 2 months (P < 0.0001) and 0.08 after 6 months (P < 0.0001). CONCLUSIONS: Health values of seriously ill patients vary widely, are higher than patients' surrogates believe, are related to few other preference and health status measures, and increase over time.

Aged↗

Predicting future functional status for seriously ill hospitalized adults. The SUPPORT prognostic model.

OBJECTIVE: To develop a model estimating the probability of an adult patient having severe functional limitations 2 months after being hospitalized with one of nine serious illnesses. DESIGN: Prospective cohort study. SETTING: Five teaching hospitals in the United States. PARTICIPANTS: 1746 patients (model development) who survived 2 months and completed an interview, selected from 4301 patients in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT); independent validation sample of 2478 patients. MEASUREMENTS AND MAIN OUTCOMES: Patient function 2 months after admission categorized as absence or presence of severe functional limitations (defined as Sickness Impact Profile scores > or = 30 or as activities of daily living scores > or = 4 [levels that require near-constant personal assistance]). A logistic regression model was constructed to predict severe functional limitation. RESULTS: One third (n = 590) of patients who were interviewed at 2 months had severe functional limitations. Changes in functional status were common: Of those with no baseline dependencies (not dependent on personal assistance), 21% were severely limited at 2 months; of those with 4 or more baseline limitations, 30% had improved. The patient's ability to do activities of daily living was the most important predictor of functional status. Physiologic abnormalities, diagnosis, days in hospital, age, quality of life, and previous exercise capacity also contributed substantially. Model performance, assessed using receiver-operating characteristic curves, was 0.79 for the development sample and 0.75 for the validation sample. The model was well calibrated for the entire risk range. CONCLUSIONS: Functional outcome varied substantially after hospitalization for a serious illness. A small amount of readily available clinical information can estimate the probability of severe functional limitations.

Activities of Daily Living↗

Cost-effectiveness of captopril therapy after myocardial infarction.

OBJECTIVES: This study sought to assess the cost-effectiveness of captopril therapy for survivors of myocardial infarction. BACKGROUND: The recent randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed that captopril therapy improves survival in survivors of myocardial infarction with an ejection fraction < or = 40%. The present ancillary study was designed to determine how the costs required to achieve this increase in survival compared with those of other medical interventions. METHODS: We developed a decision-analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80-year old survivors of myocardial infarction with an ejection fraction < or = 40%. Data on costs, utilities (health-related quality of life weights) and 4-year survival were obtained directly from the SAVE trial, and long-term survival was estimated using a Markov model. In one set of analyses, we assumed that the survival benefit associated with captopril therapy would persist beyond 4 years (persistent-benefit analyses), whereas in another set we assumed that captopril therapy incurred costs but no survival benefit beyond 4 years (limited-benefit analyses). RESULTS: In the limited-benefit analyses, the incremental cost-effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old patients. In the persistent-benefit analyses, incremental cost-effectiveness ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on age. The outcome was generally not sensitive to changes in estimates of variables when they were varied individually over wide ranges. In a "worst-case" analysis, incremental cost-effectiveness ratios for captopril therapy remained favorable ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients but were higher ($217,600/quality-adjusted life-year) for 50-year old patients. CONCLUSIONS: We conclude that the cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of myocardial infarction.

Aged↗

Toward a peer review process for medical decision analysis models.

This paper presents a framework for a peer review process for medical decision analysis models. This framework is based on the collective experience of the members of the Inter-PORT Decision Modeling work group, a team of decision analysis experts comprising members from each of the Patient Outcomes Research Teams (PORTs), sponsored by the Agency for Health Care Policy and Research. Important general principles of correct model structure include choice of model type, perspective of the analysis, choice of utility scheme and identification of strategies that should be included and events that should be modeled. In addition, a set of rules for correct decision model structure may help to identify common errors. Although not necessarily exhaustive, this scheme provides an approach by which a reviewer may judge the adequacy of a decision model presented for publication or as the basis for a health policy.

Decision Support Techniques↗

Cost-effectiveness of a smoking cessation program after myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of a smoking cessation program initiated after acute myocardial infarction. BACKGROUND: The value of allocating health care resources to smoking cessation programs after myocardial infarction has not been compared with the value of other currently accepted interventions. METHODS: A model was developed to examine the cost-effectiveness of a recently reported smoking cessation program after an acute myocardial infarction. The cost was estimated by considering the resources necessary to implement the program, and the effectiveness was expressed as discounted years of life saved. Years of life saved were estimated by modeling life expectancy using a single declining exponential approximation of life expectancy based on data from published reports. RESULTS: The cost-effectiveness of the nurse-managed smoking cessation program was estimated to be $220/year of life saved. In a one-way sensitivity analysis, the cost-effectiveness of the program remained < $20,000/year of life saved if the program decreased the smoking rate by only 3/1,000 smokers (baseline assumption 26/100 smokers), or if the program cost as much as $8,840/smoker (baseline assumption $100). In a two-way sensitivity analysis, even if the cost of the program were as high as $2,000/participant, the cost-effectiveness of the program would be < $10,000/year of life saved so long as the program helped an additional 12 smokers quit for every 100 enrolled. CONCLUSIONS: Over a wide range of estimates of costs and effectiveness, a nurse-managed smoking cessation program after acute myocardial infarction is an extremely cost-effective intervention. This program is more cost-effective than beta-adrenergic antagonist therapy after myocardial infarction.

Analysis of Variance↗

Impact and cost-effectiveness of smoking interventions.

Cigarette smoking is the foremost preventable cause of death in the United States. Along with being a major contributor to lung cancer, chronic obstructive pulmonary disease, and cerebrovascular disease, smoking is one of several modifiable risk factors for coronary artery disease (CAD). The Coronary Heart Disease Policy Model is a computer simulation model of CAD in the United States. Using the model, one can project CAD incidence, prevalence, events, mortality, cost, cost-effectiveness, and gains in life expectancy from various risk factor modifications, including smoking interventions. The model projects that reducing the number of cigarettes smoked by 50% would increase the population-wide life expectancy of 35-year-old U.S. citizens by 0.4 year. Eliminating smoking would yield population-wide gains of 0.8 year for 35-year-old males and 0.7 year for 35-year-old females. These gains are comparable to those achieved with strict control of cholesterol levels, diastolic blood pressure, or weight. Gains for the smokers themselves would be much greater. On average, 35-year-old male smokers would live 1.2 years longer if they reduced the number of cigarettes smoked by 50%, and 2.3 years longer if they quit smoking. Females 35 years of age would live 1.5 years longer by cutting back by 50% and 2.8 years longer by quitting. These gains are equal to or greater than gains that individuals would realize by reducing serum cholesterol levels of 240-299 mg/dL to 200 mg/dL; controlling mild hypertension; or reducing weight from greater than or equal to 130% ideal body weight to ideal body weight. Gains projected by the Coronary Heart Disease Policy Model are comparable to those forecast by others, who have projected that young adults would gain approximately 0.2-8.7 years by quitting smoking, depending on their smoking history. Two studies have examined the cost-effectiveness of smoking interventions. One found that counseling smokers to quit would cost only $705-988 per year of life saved for males and $1,204-2,058 per year of life saved for females. The second study found that prescribing nicotine gum as an adjunct to counseling would cost only $4,113-6,465 per year of life saved for males and $6,880-9,473 per year of life saved for females. These cost-effectiveness ratios are more favorable than those of most other current healthcare interventions. Smoking cessation would increase population-wide life expectancy by about a year and the life expectancy of a smoker by several years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗