Showing papers in "JAMA Internal Medicine in 1996"

Dietary Flavonoids, Antioxidant Vitamins, and Incidence of Stroke: The Zutphen Study

Abstract: Background: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. Methods: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from crosscheck dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. Results: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake (≥28.6 mg/d vs Conclusions: The habitual intake of flavonoids and their major source (tea) may protect against stroke. (Arch Intern Med. 1996;154:637-642)

What role do patients wish to play in treatment decision making

Abstract: Background: Although current ideology suggests patients should be active participants in decision making about their care, the literature suggests that patients wish to be informed but not involved. Objective: To test the hypothesis that most patients want their physicians to take the responsibility for problem solving (PS, identifying the one right answer), but that many want to be involved in decision-making (DM, selecting the most desired bundle of outcomes) tasks. Methods: Survey responses from 300 patients undergoing angiogram at a Toronto, Ontario, hospital were analyzed (response rate, 72%). Survey items included scales to measure desire for information and participation, including Autonomy Preference Index, the Krantz Health Opinion Survey, and the Deber-Kraetschmer Problem-Solving Decision-Making Scale measured on a scale from 1 (doctor only) to 5 (patient only). Results: Patients had a relatively high desire for information. On the Problem-Solving Decision-Making Scale, they overwhelmingly wished the PS tasks to be performed by or shared with the physician (98.4% of the 12 PS scores are between 1 and 3), but wanted to be involved in DM (78% of the 6 DM scores are between 3 and 5). Preference for handing over control to the physician was significantly greater for the vignette involving potential mortality (chest pain) than for the vignettes involving mainly morbidity (urinary problems) or quality of life (fertility). Conclusions: Although patients do not wish to be involved in PS tasks, few wish to hand over DM control to their physician. These findings suggest 2 major roles for clinicians—assisting patients in PS to structure choices and supporting them in making often difficult decisions. Arch Intern Med. 1996;156:1414-1420

Functional Outcomes of Acute Medical Illness and Hospitalization in Older Persons

Abstract: Background: Short-stay hospitalization in older patients is frequently associated with a loss of function, which can lead to a need for postdischarge assistance and longer-term institutionalization. Because little is known about this adverse outcome of hospitalization, this study was conducted to (1) determine the discharge and 3-month postdischarge functional outcomes for a large cohort of older persons hospitalized for medical illness, (2) determine the extent to which patients were able to recover to preadmission levels of functioning after hospital discharge, and (3) identify the patient factors associated with an increased risk of developing disability associated with acute illness and hospitalization. Methods: A total of 1279 community-dwelling patients, aged 70 years and older, hospitalized for acute medical illness were enrolled in this multicenter, prospective cohort study. Functional measurements obtained at discharge (Activities of Daily Living) and at 3 months after discharge (Activities of Daily Living and Instrumental Activities of Daily Living) were compared with a preadmission baseline level of functioning to document loss and recovery of functioning. Results: At discharge, 59% of the study population reported no change, 10% improved, and 31% declined in Activities of Daily Living when compared with the preadmission baseline. At the 3-month follow-up, 51% of the original study population, for whom postdischarge data were available (n=1206), were found to have died (11%) or to report new Activities of Daily Living and/or Instrumental Activities of Daily Living disabilities (40%) when compared with the preadmission baseline. Among survivors, 19% reported a new Activities of Daily Living and 40% reported a new Instrumental Activities of Daily Living disability at follow-up. The 3-month outcomes were the result of the loss of function during the index hospitalization, the failure of many patients to recover after discharge, and the development of new postdischarge disabilities. Patients at greatest risk of adverse functional outcomes at follow-up were older, had preadmission Instrumental Activities of Daily Living disabilities and lower mental status scores on admission, and had been rehospitalized. Conclusions: This study documents a high incidence of functional decline after hospitalization for acute medical illness. Although there are several potential explanations for these findings, this study suggests a need to reexamine current inpatient and postdischarge practices that might influence the functioning of older patients. (Arch Intern Med. 1996;156:645-652)

Leisure-time physical activity among US adults. Results from the Third National Health and Nutrition Examination Survey.

Abstract: Background: The prevalence of no leisure-time physical activity (LTPA) among US adults is estimated to be between 24% and 30%. Such information, however, usually does not include prevalence estimates for non-Hispanic blacks, Mexican Americans, and the elderly. Objective: To assess the prevalence of participation in leisure-time physical activity among US adults. Methods: Between 1988 and 1991, 9488 adults aged 20 years and older were interviewed in their home as part of the third National Health and Nutrition Examination Survey. A clinic examination in a mobile center was also included. Mexican Americans, non-Hispanic blacks, and the elderly were oversampled to produce reliable estimates for these groups. Questions were asked about the type and frequency of physically active hobbies, sports, and exercises. Results: The prevalence of no LTPA for US adults aged 20 years or older from 1988 through 1991 was 22%. The rate was higher in women (27%) than in men (17%). Mexican-American men (33%) and women (46%) and non-Hispanic black women (40%) had the highest rates of no LTPA. Participation in moderate to vigorous LTPA five or more times per week decreased with age, with the largest decreases observed among non-Hispanic black men and women. In almost all subpopulations, gardening and/or yard work and walking were stated as the two top LTPAs of choice. Conclusions: Many Americans are inactive or irregularly active during their leisure time. Rates of inactivity are greater for women, older persons, non-Hispanic blacks, and Mexican Americans. Intervention strategies meant to promote lifetime physical activities among all Americans represents a major health priority. (Arch Intern Med. 1996;156:93-98)

Psychosocial interventions for patients with coronary artery disease: a meta-analysis.

Abstract: Background: Narrative review strategies and meta-analyses have shown that drug treatment and exercise rehabilitation regimens can reduce psychological distress and postmyocardial infarction mortality and recurrence. Objective: To question whether the addition of psychosocial interventions improves the outcome of a standard rehabilitation regimen for patients with coronary artery disease. Methods: We performed a statistical meta-analysis of 23 randomized controlled trials that evaluated the additional impact of psychosocial treatment of rehabilitation from documented coronary artery disease. Anxiety, depression, biological risk factors, mortality, and recurrence of cardiac events were the clinical end points that were studied. Mortality data were available from 12 studies, and recurrence data were available from 10 of the 23 studies. Results: The studies had evaluated 2024 patients who received psychosocial treatment vs 1156 control subjects. The psychosocially treated patients showed greater reductions in psychological distress, systolic blood pressure, heart rate, and cholesterol level (with effect size differences of 0.34, -0.24, -0.38, and -1.54, respectively). Patients who did not receive psychosocial treatment showed greater mortality and cardiac recurrence rates during the first 2 years of follow-up with log-adjusted odds ratios of 1.70 for mortality (95% confidence interval [CI], 1.09 to 2.64) and 1.84 for recurrence (CI, 1.12 to 2.99). Conclusions: The addition of psychosocial treatments to standard cardiac rehabilitation regimens reduces mortality and morbidity, psychological distress, and some biological risk factors. The benefits were clearly evident during the first 2 years and were weaker thereafter. At the clinical level, it is recommended to include routinely psychosocial treatment components in cardiac rehabilitation. The findings also suggest an urgent need to identify the specific, most effective types of psychosocial interventions via controlled research. (Arch Intern Med. 1996;156:745-752)

Estrogen replacement therapy and risk of Alzheimer disease.

Abstract: Background: With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. Objective: To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. Study Design and Methods: A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (±1 year). Results: The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (ie, injections and/or creams) routes of administration. The risk decreased significantly with both increasing dosages (P=.01) and increasing duration (P=.01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). Conclusion: This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women. Arch Intern Med. 1996;156:2213-2217

Long-term Renoprotective Effect of Angiotensin-converting Enzyme Inhibition in Non—insulin-dependent Diabetes Mellitus: A 7-Year Follow-up Study

Abstract: Background: Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. Duration of diabetes, blood pressure values, and metabolic status are the major determinants of the course of nephropathy, and microalbuminuria is the hallmark of its onset. Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non—insulin-dependent diabetes mellitus. Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy. Methods: Double-blinded (first phase) and open (second phase) randomized controlled study of 7 years. Ninety-four normotensive patients with non—insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 μmol/L (1.4 mg/dL) and who had microalbuminuria (30 to 300 mg/24 h) were given enalapril maleate, 10 mg/d, or placebo, for 5 years. For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment. Results: In the enalapril-treated patients, albuminuria remained stable for 7 years. An increase from (mean±SD) 123±58 to 310± 167 mg/24 h occurred in the untreated group after 5 years, and a further increase to (mean±SD) 393± 223 mg/24 h occurred after 7 years. Reciprocal creatinine was unchanged in treated patients for 7 years; in the untreated patients, the mean decline was 13% at 5 years and 16% at 7 years. Treatment with enalapril resulted in an absolute risk reduction of 42% for nephropathy to develop during 7 years (95% confidence interval, 15% to 69%; P Conclusions: Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with non— insulin-dependent diabetes mellitus who have microalbuminuria, and it stabilizes renal function in previously untreated patients with impaired renal function. Discontinuation of treatment results in renewed progression of nephropathy. Arch Intern Med. 1996;156:286-289)

Overweight, underweight, and mortality. A prospective study of 48,287 men and women

Abstract: Background: The relative contributions of a low and high body mass index (BMI [weight in kilograms divided by height in meters squared]) to all-cause and cause-specific mortality are still controversial. Objective: To examine mortality rates in relation to BMI in a prospective cohort study of 48 287 Dutch men and women aged 30 to 54 years at baseline from 1974 to 1980. Methods: During an average 12-year follow-up, 1319 deaths occurred. Relative risks (RRs) were calculated from the Cox proportional hazard model by using a BMI between 18.5 and 24.9 kg/m2as the reference category. Results: All-cause mortality was significantly increased in obese men (BMI, ≥30 kg/m2; RR, 1.5; 95% confidence interval [CI], 1.1-2.0) and in underweight men (BMI, Conclusions: Total mortality was increased in obese and underweight men but not in women. The increased mortality in overweight men was mainly attributable to CHD and, in underweight men, to early mortality and especially lung cancer mortality among smokers. (Arch Intern Med. 1996;156:958-963)

Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer

Abstract: A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an 11-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association.

Gastrointestinal Tract Complications of Nonsteroidal Anti-inflammatory Drug Treatment in Rheumatoid Arthritis: A Prospective Observational Cohort Study

Abstract: Background: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal antiinflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2receptor antagonists. Methods: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. Results: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5-year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14; 95% confidence interval, 1.06-4.32). Conclusions: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications. Arch Intern Med. 1996;156:1530-1536

Bleeding during antithrombotic therapy in patients with atrial fibrillation

Abstract: BACKGROUND The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation. Bleeding complications importantly detracted from warfarin's net effectiveness, particularly among older patients. OBJECTIVES To analyze bleeding complications according to assigned therapy. To identify risk factors for bleeding during anticoagulation. METHODS Eleven hundred patients (mean age, 70 years) were randomized to 325 mg of aspirin daily (enteric coated) vs warfarin (target prothrombin time ratio, 1.3 to 1.8; approximate international normalized ratio, 2.0 to 4.5). Major hemorrhages were defined prospectively. RESULTS The rate of major bleeding while receiving warfarin was 2.3% per year (95% confidence interval [CI], 1.7 to 3.2) vs 1.1% per year (95% CI, 0.7 to 1.8) while receiving aspirin (relative risk, 2.1; 95% CI, 1.1 to 3.1; P = .02). Intracranial hemorrhage occurred at 0.9% per year (95% CI, 0.5 to 1.5) with warfarin and 0.3% per year (95% CI, 0.1 to 0.8) with aspirin (relative risk, 2.4; P = .08). Age (P = .006), increasing number of prescribed medications (P = .007), and intensity of anticoagulation (P = .02) were independent risks for bleeding at any site during anticoagulation. The rate of major hemorrhage was 1.7% per year in patients aged 75 years or younger who received anticoagulation vs 4.2% per year in older patients (relative risk, 2.6, P = .009); rates by age for intracranial bleeding were 0.6% per year and 1.8% per year, respectively (P = .05). CONCLUSION Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention.

The Effect of Stroke and Stroke Prophylaxis With Aspirin or Warfarin on Quality of Life

Abstract: Background: Because most strokes cause neurological impairment rather than death, stroke prophylaxis may improve quality of life more than length of life. Thus, an understanding of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients. Methods: We elicited quality-of-life estimates, known as utilities, for 3 degrees of severity of anticipated stroke— mild, moderate, and major—and for stroke prophylaxis with either warfarin sodium or aspirin therapy. We used the time tradeoff and standard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation. Results: Seventy patients completed the interview successfully. Their utilities for stroke ranged from worse than death ( P Conclusion: Patients' utilities for stroke prophylaxis and anticipated stroke vary substantially. Many patients view the quality of life with major stroke as tantamount to or worse than death. These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis. Arch Intern Med. 1996;156:1829-1836

Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men.

Abstract: Background: Physical activity has been advocated as an important factor in the primary prevention of non-insulin-dependent diabetes mellitus (NIDDM), but information concerning the specific intensities and durations that are protective has been unavailable. Objective: To examine prospectively the association between self-reported levels of the intensity and duration of physical activities, and cardiorespiratory fitness (assessed by respiratory gas exchange) and incident cases of NIDDM (assessed by the oral glucose tolerance test) in a population-based sample of 897 middle-aged Finnish men. Results: After adjustment for age, baseline glucose values, body mass index, serum triglyceride levels, parental history of diabetes, and alcohol consumption, moderately intense physical activities (≥5.5 metabolic units) that were undertaken for at least a 40-minute duration per week were associated with a reduced risk of NIDDM (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.220.88). Activities with less than an intensity of 5.5 metabolic units, regardless of their duration, were not protective. Cardiorespiratory fitness levels greater than 31.0 mL of oxygen per kilogram per minute were protective against NIDDM (OR, 0.26; 95% CI, 0.08-0.82). A subgroup of men at high risk of NIDDM, because they were overweight and were hypertensive and had a positive parental history of NIDDM, who engaged in moderately intense physical activities above the 40-min/wk duration reduced their risk of NIDDM by 64% compared with men who did not participate in such activities. Conclusions: After adjustment for age, baseline glucose levels, and known risk factors, physical activities with an intensity of 5.5 metabolic units or greater and a duration of 40 minutes or greater per week protected against the development of NIDDM. These protective effects were even more pronounced in a subgroup of men who were at high risk for the development of the disease. (Arch Intern Med. 1996;156:1307-1314)

Testosterone therapy in glucocorticoid-treated men.

Abstract: Background: Treatment with glucocorticoid drugs is a valuable therapy, but the use of these drugs is associated with major side effects, including osteoporosis, muscle wasting, and obesity. In men who take glucocorticoids, circulating testosterone concentrations are reduced, and this might contribute to the changes in bone and soft-tissue mass. Objective: To assess the effect of testosterone replacement on these above-mentioned parameters in glucocorticoid-treated men. Methods: Fifteen asthmatic men who were receiving long-term glucocorticoid treatment were randomly allocated to receive therapy with testosterone esters (30 mg of proprionate, 60 mg of phenylprionate, 60 mg of isocaproate, and 100 mg of decanoate [Sustanon]) (250-mg/mo intramuscular depot injection) or to act as control subjects during 12 months. After a washout period for those men who were receiving testosterone, the groups were then crossed over and studied for a further 12 months. Bone density and body composition were assessed by dual-energy, x-ray absorptiometry. Paired or unpaired 2-tailed t tested were calculated. Unless otherwise stated, all values are given as mean±SEM. Results: Bone density in the lumbar spine increased 5.0%±1.4% (mean±SEM) ( P =.005) during testosterone supplementation, but it did not change during the control period (between-groups difference, P =.05). These changes were accompanied by a decrease in the indexes of bone turnover. There was a gain in body fat mass (2.1±0.06 kg, P =.01) and a loss of lean body mass (1.4±0.5 kg, P =.02) during the control period, with both changes being reversed by testosterone treatment ( P Conclusion: Testosterone treatment reverses the deleterious effects of glucocorticoid drugs on skeletal and soft tissues in men. (Arch Intern Med. 1996;156:1173-1177)

Variability in the interpretation of screening mammograms by US radiologists. Findings from a national sample.

Abstract: Objective: To evaluate the effectiveness of screening mammography by estimating the variability in radiologists' ability to detect breast cancer within the US population of radiologists at mammography centers accredited by the American College of Radiology. Methods: A two-way sample survey design was used as follows. Fifty mammography centers having an American College of Radiology—accredited unit were randomly sampled from across the United States. One hundred eight radiologists from these centers gave blinded interpretation to the same set of 79 randomly selected screening mammograms. The mammograms were from women who had been screened at a large screening center. Before their sampling, these women had been stratified by their breast disease status, established either by biopsy or by 2-year follow-up. Rates of biopsy recommendations were summarized by the mean, median, minimum, maximum, and range of sensitivity and specificity. Overall cancer detection ability was summarized by similar statistics for receiver operating characteristic curve areas. Ninety-five percent lower confidence bounds on the ranges in accuracy measures were established by bootstrapping. Results: There is a range of at least 40% among US radiologists in their screening sensitivity. There is a range of at least 45% in the rates at which women without breast cancer are recommended for biopsy. As indicated by receiver operating characteristic curve areas, the ability of radiologists to detect cancer mammograms varies by as much as 11%. Conclusions: Our findings indicate that there is wide variability in the accuracy of mammogram interpretation in the population of US radiologists. Current accreditation programs that certify the technical quality of radiographic equipment and images but not the accuracy of the interpretation given to mammograms may not be sufficient to help mammography fully realize its potential to reduce breast cancer mortality. (Arch Intern Med. 1996;156:209-213)

The importance of quality of primary studies in producing unbiased systematic reviews.

Abstract: Background: Traditional and largely qualitative reviews of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment. The latter approach is dependent on the quality of primary studies, which may introduce bias if they are of poor methodologic quality. Objective: To test the hypothesis that the inclusion of poor-quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect. Methods: An overview of randomized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis. Data sources included online searching of MEDLINE and Science Citation Index databases between 1966 and 1994, scanning the bibliography of known primary studies and review articles, and contacting experts in the field. After independent, blind assessment, nine of 149 originally identified studies met the inclusion criteria and were selected. We assessed study quality independently. Outcome data from each study were pooled and statistically summarized. Results: There was a marginal improvement in pregnancy rate with antiestrogen treatment (odds ratio, 1.6; 95% confidence interval, 0.9 to 2.6). Sensitivity analyses on the basis of methodologic quality demonstrated that poor-quality studies produced a positive effect with treatment, whereas no benefit was observed with high-quality studies. Conclusions: The results of a meta-analysis are influenced by the quality of the primary studies included. Methodologically, poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences. (Arch Intern Med. 1996;156:661-666)

A Prospective Study of Cigarette Smoking and the Risk of Pancreatic Cancer

Abstract: Objectives: To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer. Methods: We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118 339 women aged 30 to 55 years and 49 428 men aged 40 to 75 years who were without diagnosed cancer. During the 2116 229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants. Results: The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed ( P for trend=.004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smoking was 25%. Conclusions: Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smoking cessation could eliminate 25% of the 27 000 deaths from pancreatic cancer occurring annually in the United States. Arch Intern Med. 1996;156:2255-2260

Mortality Following Fractures in Older Women: The Study of Osteoporotic Fractures

Abstract: Background: Most investigators have hypothesized that the increase in mortality following osteoporotic fractures reflects poor underlying health status in addition to the acute effects of the fracture. Methods: We observed 9704 ambulatory women aged 65 years or older enrolled in the Study of Osteoporotic Fractures. We obtained reports of fractures and deaths every 4 months and reviewed death certificates and hospital discharge summaries. Multivariable proportional hazards models were used to determine the association between fractures and age-adjusted mortality. Results: During a mean follow-up of 5.9 years, 1737 women had nonspine fractures, with a postfracture mortality rate of 3 per 100 woman-years, compared with 1.8 per 100 woman-years in those who did not have fractures (P Conclusions: Mortality is increased following several types of fractures in older women. Most of the increase following hip and pelvic fractures is due to underlying conditions and probably would not be affected by reductions in the incidence of these fractures. Arch Intern Med. 1996;156:1521-1525

Change in Depression as a Precursor of Cardiovascular Events

Abstract: Objective: To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality. Design: Cohort analytic study of data from randomized placebo-controlled double-blind clinical trial of antihypertensive therapy. Depressive symptoms were assessed semiannually with the Center for Epidemiological Studies— Depression (CES-D) scale during an average follow-up of 4.5 years. Setting: Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program. Patients: Generally healthy men and women aged 60 years or older randomized to active antihypertensive drug therapy or placebo who were 79% white and 53% women and had follow-up CES-D scores and no outcome events during the first 6 months (N=4367). Main Outcome Measures: All-cause mortality, fatal or nonfatal stroke, or myocardial infarction. Results: Baseline depressive symptoms were not related to subsequent events; however, an increase in depression was prognostic. Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable, controlling for multiple covariates, indicated a 25% increased risk of death per 5-unit increase in the CES-D score (relative risk [RR], 1.25; 95% confidence interval [CI], 1.15 to 1.36). The RR for stroke or myocardial infarction was 1.18 (95% CI, 1.08 to 1.30). Increase in CES-D score was an independent predictor in both placebo and active drug groups, and it was strongest as a risk factor for stroke among women (RR, 1.29; 95% CI, 1.07 to 1.34). Conclusions: Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of causal pathways are needed before widespread screening for depression in clinical practice is to be recommended. (Arch Intern Med. 1996;156:553-561)

The gender bias in sleep apnea diagnosis : Are women missed because they have different symptoms ?

Abstract: Background: Population-based studies have shown that sleep apnea is underdiagnosed in women, relative to men. One hypothesis for this gender bias is that women with sleep apnea are missed because clinical guidelines for the evaluation and diagnosis of sleep apnea, established primarily on men, are not valid for women. In this investigation, data from the Wisconsin Sleep Cohort Study, a community-based study of the natural history of sleep apnea, were used to determine whether women with sleep apnea have unique symptoms or complaints. Methods: The sample comprised 551 men and 388 women, none of whom had ever been given a diagnosis of sleep apnea. Data on typical sleep apnea symptoms and other factors were obtained by interview and survey. Sleep apnea status was determined from the frequency of apneic and hypopneic events during sleep as recorded by in-laboratory, whole-night polysomnography. The sensitivity and relative predictive power of each symptom or factor for sleep apnea at different severity levels were calculated and compared by gender. Results: Regardless of severity level, women with sleep apnea did not report symptoms that differed significantly from those of men with the same level of sleep apnea. For men and women, snoring was the most sensitive and strongest predictor of sleep apnea. Conclusions: Current clinical indications for sleep apnea evaluation are as appropriate for women as they are for men. Other reasons for the gender disparity in sleep apnea diagnosis, including the possibility that health care providers disregard typical symptoms in women, should be pursued. Arch Intern Med. 1996;156:2445-2451

Adherence to National Guidelines for Drug Treatment of Suspected Acute Myocardial Infarction: Evidence for Undertreatment in Women and the Elderly

Abstract: Background: Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. Methods: Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, β-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. Results: Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for β-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received β-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6;β-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of β-blocker and thrombolytic use among eligible women. Conclusions: Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women. (Arch Intern Med. 1996;156:799-805)

Epidemiology and Outcome of Pseudomonas aeruginosa Bacteremia, With Special Emphasis on the Influence of Antibiotic Treatment Analysis of 189 Episodes

Abstract: Objective: To evaluate the trend in incidence of Pseudomonas aeruginosa bacteremia, underlying conditions of patients, mortality rate, and factors associated with poor outcome. Patients and Methods: Medical charts of 189 consecutive episodes of P aeruginosa bacteremia, detected between January 1, 1991, and December 31, 1994, were prospectively evaluated. Associated risk factors, treatment, and outcome were recorded. Results: Pseudomonas aeruginosa bacteremia represented 5.7% of the total number of bacteremias, 6.9% of nosocomial bacteremias, and 23.6% of nosocomial gram-negative bacteremias. There were 1.5 episodes per 1000 discharges. These numbers were slightly lower than those recorded at our hospital 10 years earlier. Human immunodeficiency virus infection was the most frequent underlying disease (28/189 [15%]). Overall mortality was 18% (34/189). The presence of fatal underlying disease ( P P =.001), pneumonia ( P =.02), and severe sepsis ( P P =.04) only when the subset of patients with intravenous catheter-associated bacteremia was excluded from the analysis. The survival rate was no greater in patients who received 2 or more antibiotics active in vitro against P aeruginosa than in those who received only 1. Neutropenia was not associated with increased mortality. The use of colony-stimulating factors did not affect the outcome of the neutropenic patients. Conclusions: The rate of P aeruginosa bacteremia is falling slightly at our hospital. The emergence of the human immunodeficiency virus epidemic has had a considerable impact on both epidemiology and mortality. The presence of severe underlying disease, surgery, pneumonia, and, especially, severe sepsis are associated with a poor outcome. With the exclusion of patients with intravenous catheter—associated P aeruginosa bacteremia, the administration of an appropriate antimicrobial therapy is essential to a good outcome. Treatment with 1 active antibiotic seems to be sufficient. Arch Intern Med. 1996;156:2121-2126

Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.

Abstract: Background: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. Methods: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). Results: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. Conclusion: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent. Arch Intern Med. 1996;156:2085-2092

How Do Patients Want Physicians to Handle Mistakes?: A Survey of Internal Medicine Patients in an Academic Setting

Abstract: Background: Mistakes are an inevitable part of the practice of medicine. While the frequency and severity of medical errors are documented, little is known about patients' attitudes toward physician mistakes. Objective: To examine patient attitudes about physician errors. Design: A survey instrument assessed attitudes to 3 levels of physician mistakes (minor, moderate, and severe) and 2 fundamental physician responses: disclosure or nondisclosure. One hundred forty-nine study subjects were randomly selected from an academic general internal medicine outpatient clinic. Results: Virtually all patients (98%) desired some acknowledgment of even minor errors. Patient's desire for referral to another physician ranged from 14% following a minor mistake to 65% following a severe mistake. For both moderate and severe mistakes, patients were significantly more likely to consider litigation if the physician did not disclose the error. In the moderate mistake scenario, 12% of patients would sue if informed by the physician vs 20% if the physician failed to disclose the error and they discovered it by some other means ( P Conclusions: Patients desire an acknowledgment from their physicians of even minor errors, and doing so may actually reduce the risk of punitive actions. These findings reinforce the importance of open communication between patients and physicians. Arch Intern Med. 1996;156:2565-2569

Chronic atrial fibrillation - Success of serial cardioversion therapy and safety of oral anticoagulation

Abstract: Background: Serial electrical cardioversion is often used for treatment of atrial fibrillation, but its long-term efficacy has not been determined prospectively. Objectives: To determine the long-term success rate of the serial electrical cardioversion approach in patients with chronic atrial fibrillation, to identify factors that predict its success, and to assess the efficacy and safety of oral anticoagulation in these patients. Methods: Patients with chronic (>24 hours) atrial fibrillation received anticoagulant therapy for at least 4 weeks prior to electrical cardioversion. No prophylactic antiarrhythmic agent was given after the first shock. Relapses were managed by using repeated cardioversions, after which serial antiarrhythmic drug therapy was started. Treatment with anticoagulants was withdrawn after 4 weeks of sinus rhythm. Results: Two hundred thirty-six patients were followed up for a mean±SD of 3.7±1.6 years. The actuarial cumulative percentages of patients who maintained sinus rhythm after serial cardioversion treatment was 42% and 27% after 1 and 4 years, respectively. Multivariate analysis showed that factors that were associated with failure of this approach included duration of atrial fibrillation that exceeded 36 months (risk ratio, 5.0;P Conclusions: Many patients with chronic atrial fibrillation failed to respond to the serial electrical cardioversion strategy. However, in younger patients with a fair exercise tolerance and a duration of atrial fibrillation shorter than 36 months, this approach may be worthwhile. In addition, thromboembolic events were infrequent in the patients who were subjected to this regimen. Arch Intern Med. 1996;156:2585-2592

Predictive Values of the Character, Timing, and Complications of Chronic Cough in Diagnosing Its Cause

Abstract: Background: It is not clear whether careful history taking with detailed questioning of the characteristics of cough is diagnostically useful. Objective: To determine if the character, timing, or complications of chronic cough were helpful in determining its cause. Methods: A prospective, descriptive study of consecutive, unselected, immunocompetent patients referred to our university outpatient clinic because of chronic cough. All patients were evaluated by a previously published and validated systematic diagnostic protocol, a self-administered questionnaire, and by observing the character of involuntary and voluntary coughs. The final diagnosis of the cause of cough required fulfillment of pre pretreatment criteria plus having cough disappear or substantially improve as a complaint with specific therapy. Results: Eighty-eight patients met inclusion criteria and were fully evaluated. The mean±SD age was 53.1 ± 16 years (range, 15-83 years) and 24 were males and 64 were females with a mean±SD history of cough for 6.6±9.8 years (range, 1 month-44 years). The cause of chronic cough was established in 86 (98%) of 88 patients. Eighty-one (92%) of 88 had cough disappear as a complaint. Cough was as a result of a single cause in 39% and multiple causes in 59%. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were the 3 most common causes of chronic cough and accounted for 90% % of diagnoses. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were again found to be the 3 most common causes of chronic cough irrespective of patient estimated quantity of daily sputum production. These 3 conditions caused chronic cough in 99.4% of patients with the following characteristics: (1) nonsmoker; (2) not receiving an angiotensin-converting enzyme inhibitor drug; and (3) normal or nearly normal and stable chest radiograph. With respect to the spectrum and frequency of diagnoses and their interrelationships with the character, timing, and complications of cough, multiple stepwise linear regression analysis showed that none of the variability of the character, timing, or complications of cough could be explained by any specific diagnosis. Conclusions: A carefully taken history with detailed questioning of the character, timing, and complications of chronic cough is not likely to be useful in diagnosing the cause of cough. The cause can be determined and successfully treated with specific therapy in the greatest majority of cases. Chronic cough is often caused by multiple, simultaneously contributing causes. Postnasal drip syndrome, asthma, and gastroesophageal reflux disease remain the 3 most common causes of chronic cough and there is a clinical profile that nearly always predicts their presence in immunocompetent patients. (Arch Intern Med. 1996;156:997-1003)

The Role of Hypertension in the Pathogenesis of Heart Failure: A Clinical Mechanistic Overview

Abstract: Hypertension plays a key role in the evolution of the syndrome of heart failure. Hypertension has been identified as the chief precursor of left ventricular hypertrophy. Hypertensive left ventricular hypertrophy can lead to ventricular diastolic dysfunction; it is also a risk factor for myocardial infarction, which is a principal cause of left ventricular systolic dysfunction. Asymptomatic left ventricular dysfunction, whether systolic or diastolic, culminates in clinically overt heart failure when a threshold is exceeded or when other precipitating factors are superimposed. The onset of overt heart failure heralds a bleak outcome. These structural and functional changes associated with hypertension evolve over decades and are preventable with effective antihypertensive treatment. These observations emphasize the importance of early diagnosis and effective treatment of hypertension to prevent cardiac complications.

Diagnosis of Pulmonary Embolism by a Decision Analysis-Based Strategy Including Clinical Probability, D-Dimer Levels, and Ultrasonography: A Management Study

Abstract: Background: Assessment of the clinical probability of pulmonary embolism, plasma D-dimer measurement, and lower-limb venous compression ultrasonography have all been advocated in the workup of suspected pulmonary embolism, to minimize the requirement for pulmonary angiography in patients with nondiagnostic lung scans. However, their contribution has not been assessed prospectively. Methods: Three hundred eight consecutive patients who came to the emergency department with suspected pulmonary embolism were managed according to a diagnostic protocol that included clinical probability assessment, lung scan, and sequential noninvasive tests: plasma D-dimer measurement by enzyme-linked immunosorbent assay (a concentration Results: Of the 308 patients, 106 (34%) had a diagnostic lung scan (normal in 43 and high probability in 63). For the remaining 202 patients, noninvasive workup was diagnostic in 125 (62%). Pulmonary embolism was ruled out by a low clinical probability and a nondiagnostic scan in 48 patients and a D-dimer level less than 500 μg/L in 53; pulmonary embolism was established by a high clinical probability and a nondiagnostic scan in seven patients and by a finding of a deep vein thrombosis on ultrasonography in 17. Therefore, only 77 of these 202 patients underwent pulmonary angiography (negative in 55; positive in 22). At 6-month follow-up (completed for 99.4% of the study population), only two of the 199 patients in whom the diagnostic protocol had ruled out pulmonary embolism (1.0% [95% confidence interval, 0.1 to 3.6]) had a thromboembolic event (pulmonary embolism, one; deep vein thrombosis, one). Conclusions: This decision analysis strategy yielded a definitive noninvasive diagnosis in 62% of patients with a nondiagnostic scan and appears to be safe. (Arch Intern Med. 1996;156:531-536)

Prevalence of Undiagnosed Pernicious Anemia in the Elderly

Abstract: Background: Existing information about the prevalence of pernicious anemia is largely based on older surveys that favored florid manifestations, tended to be retrospective analyses of previously diagnosed disease, and usually studied homogeneous European populations. The lack of current data in the United States has, among other things, hampered discussions of the proposal to increase folate intake by the general population. Objective: To estimate the prevalence of undiagnosed and untreated pernicious anemia among the elderly. Methods: A prospective survey of cobalamin levels and anti—intrinsic factor antibody was done in the elderly. Blood testing was done in 729 people aged 60 years or older and follow-up assessment with the Schilling test and other tests was offered when results were abnormal. Results: Seventeen subjects were found to have pernicious anemia, usually with only minimal clinical manifestations of cobalamin deficiency. Although cobalamin deficiency had been suspected by the physicians of three subjects, they had been treated inadequately and still had evidence of deficiency. Excluding these three partially treated subjects from the analysis, 1.9% of the survey population had unrecognized and untreated pernicious anemia. The prevalence was 2.7% in women and 1.4% in men; 4.3% of the black women and 4.0% of the white women had pernicious anemia. Conclusions: Undiagnosed pernicious anemia is a common finding in the elderly, especially among black and white women. If these findings can be extrapolated, almost 800000 elderly people in the United States have undiagnosed and untreated pernicious anemia, and, thus, would be at possible risk for masked cobalamin deficiency if exposed to large amounts of folate. This number does not include those elderly with cobalamin deficiency caused by other disorders or the still unknown number of younger people with unrecognized pernicious anemia and other causes of deficiency. ( Arch Intern Med. 1996;156:1097-1100 )

National Patterns of Warfarin Use in Atrial Fibrillation

Abstract: Background: Despite consensus that patients with atrial fibrillation benefit from warfarin sodium anticoagulation, little is known about national trends and predictors of anticoagulant use. Methods: We analyzed 1062 visits by patients with atrial fibrillation to randomly selected office-based physicians included in the National Ambulatory Medical Care Surveys in 1980, 1981,1985, and 1989 through 1993. Warfarin and aspirin use in these patients was extrapolated to national patterns and logistic regression was used to determine independent predictors. Results: Patients with atrial fibrillation made an estimated 1.3 (1980) to 3.1 (1992) million annual visits to physicians. Warfarin use in atrial fibrillation increased from 7% in 1980 and 1981 to 32% in 1992 and 1993 (P Conclusions: Anticoagulant use for atrial fibrillation has increased dramatically. The substantial increase from 1989 and 1990 to 1992 and 1993 coincided with the publication of several randomized clinical trials reporting the benefits of warfarin. Although it is unrealistic to expect universal warfarin use, the 1992 and 1993 rate of 32% is probably suboptimal given the benefit of anticoagulation in preventing embolic strokes. The oldest patients, in whom warfarin may have its greatest benefit, appear to have the lowest rates of anticoagulant use. Arch Intern Med. 1996;156:2537-2541