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Showing papers in "JAMA in 2003"


Journal ArticleDOI
21 May 2003-JAMA
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

24,313 citations


Journal ArticleDOI
18 Jun 2003-JAMA
TL;DR: Notably, major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment, and while the recent increase in treatment is encouraging, inadequate treatment is a serious concern.
Abstract: ContextUncertainties exist about prevalence and correlates of major depressive disorder (MDD).ObjectiveTo present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R).DesignFace-to-face household survey conducted from February 2001 to December 2002.SettingThe 48 contiguous United States.ParticipantsHousehold residents ages 18 years or older (N = 9090) who responded to the NCS-R survey.Main Outcome MeasuresPrevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV.ResultsThe prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence.ConclusionsMajor depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.

7,295 citations


Journal ArticleDOI
01 Jan 2003-JAMA
TL;DR: Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status, and increases in obesity and diabetes continue in both sexes, all ages, all races, all educational levels, and all smoking levels.
Abstract: Context Obesity and diabetes are increasing in the United States. Objective To estimate the prevalence of obesity and diabetes among US adults in 2001. Design, Setting, and Participants Random-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001. Main Outcome Measures Body mass index, based on self-reported weight and height and self-reported diabetes. Results In 2001 the prevalence of obesity (BMI ≥30) was 20.9% vs 19.8% in 2000, an increase of 5.6%. The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an increase of 8.2%. The prevalence of BMI of 40 or higher in 2001 was 2.3%. Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status. Compared with adults with normal weight, adults with a BMI of 40 or higher had an odds ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50) for diagnosed diabetes, 6.38 (95% CI, 5.67-7.17) for high blood pressure, 1.88 (95% CI,1.67-2.13) for high cholesterol levels, 2.72 (95% CI, 2.38-3.12) for asthma, 4.41 (95% CI, 3.91-4.97) for arthritis, and 4.19 (95% CI, 3.68-4.76) for fair or poor health. Conclusions Increases in obesity and diabetes among US adults continue in both sexes, all ages, all races, all educational levels, and all smoking levels. Obesity is strongly associated with several major health risk factors.

5,576 citations


Journal ArticleDOI
08 Jan 2003-JAMA
TL;DR: Mortality associated with both influenza and RSV circulation disproportionately affects elderly persons, and influenza deaths have increased substantially in the last 2 decades, in part because of aging of the population, highlighting the need for better prevention measures, including more effective vaccines and vaccination programs for elderly persons.
Abstract: Context Influenza and respiratory syncytial virus (RSV) cause substantial morbidity and mortality. Statistical methods used to estimate deaths in the United States attributable to influenza have not accounted for RSV circulation. Objective To develop a statistical model using national mortality and viral surveillance data to estimate annual influenza- and RSV-associated deaths in the United States, by age group, virus, and influenza type and subtype. Design, Setting, and Population Age-specific Poisson regression models using national viral surveillance data for the 1976-1977 through 1998-1999 seasons were used to estimate influenza-associated deaths. Influenza- and RSV-associated deaths were simultaneously estimated for the 1990-1991 through 1998-1999 seasons. Main Outcome Measures Attributable deaths for 3 categories: underlying pneumonia and influenza, underlying respiratory and circulatory, and all causes. Results Annual estimates of influenza-associated deaths increased significantly between the 1976-1977 and 1998-1999 seasons for all 3 death categories (P Conclusions Mortality associated with both influenza and RSV circulation disproportionately affects elderly persons. Influenza deaths have increased substantially in the last 2 decades, in part because of aging of the population, underscoring the need for better prevention measures, including more effective vaccines and vaccination programs for elderly persons.

3,416 citations


Journal ArticleDOI
08 Jan 2003-JAMA
TL;DR: In the community, systolic dysfunction is frequently present in individuals without recognized CHF and diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognizedCHF, and associated with marked increases in all-cause mortality.
Abstract: Context Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined. Objectives To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality. Design, Setting, Participants Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000. Main Outcome Measures Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction. Results The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF ≤50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF ≤40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1],P Conclusions In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.

2,687 citations


Journal ArticleDOI
22 Oct 2003-JAMA
TL;DR: Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.
Abstract: ContextMore persons in the United States die from non–small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.ObjectiveTo assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Design, Setting, and PatientsDouble-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.InterventionDaily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).Main Outcome MeasuresImprovement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).ResultsOf 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P = .54). The 500-mg dose was associated more frequently with transient acne-like rash (P = .04) and diarrhea (P = .006).ConclusionsGefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

2,374 citations


Journal ArticleDOI
08 Jan 2003-JAMA
TL;DR: Obesity appears to lessen life expectancy markedly, especially among younger adults, and Marked race and sex differences were observed in estimated YLL.
Abstract: ContextPublic health officials and organizations have disseminated health messages regarding the dangers of obesity, but these have not produced the desired effect.ObjectiveTo estimate the expected number of years of life lost (YLL) due to overweight and obesity across the life span of an adult.Design, Setting, and SubjectsData from the (1) US Life Tables (1999); (2) Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994); and (3) First National Health and Nutrition Epidemiologic Follow-up Study (NHANES I and II; 1971-1992) and NHANES II Mortality Study (1976-1992) were used to derive YLL estimates for adults aged 18 to 85 years. Body mass index (BMI) integer-defined categories were used (ie, <17; 17 to <18; 18 to <19; 20 to <21; 21 to 45; or ≥45). A BMI of 24 was used as the reference category.Main Outcome MeasureThe difference between the number of years of life expected if an individual were obese vs not obese, which was designated YLL.ResultsMarked race and sex differences were observed in estimated YLL. Among whites, a J- or U-shaped association was found between overweight or obesity and YLL. The optimal BMI (associated with the least YLL or greatest longevity) is approximately 23 to 25 for whites and 23 to 30 for blacks. For any given degree of overweight, younger adults generally had greater YLL than did older adults. The maximum YLL for white men aged 20 to 30 years with a severe level of obesity (BMI >45) is 13 and is 8 for white women. For men, this could represent a 22% reduction in expected remaining life span. Among black men and black women older than 60 years, overweight and moderate obesity were generally not associated with an increased YLL and only severe obesity resulted in YLL. However, blacks at younger ages with severe levels of obesity had a maximum YLL of 20 for men and 5 for women.ConclusionObesity appears to lessen life expectancy markedly, especially among younger adults.

2,300 citations


Journal ArticleDOI
09 Jul 2003-JAMA
TL;DR: In a multiple regression analysis, increasing age, increasing body mass index, and non-Hispanic black race/ethnicity were independently associated with increased rates of hypertension.
Abstract: ContextPrior analyses of National Health and Nutrition Examination Survey (NHANES) data through 1991 have suggested that hypertension prevalence is declining, but more recent self-reported rates of hypertension suggest that the rate is increasing.ObjectiveTo describe trends in the prevalence, awareness, treatment, and control of hypertension in the United States using NHANES data.Design, Setting, and ParticipantsSurvey using a stratified multistage probability sample of the civilian noninstitutionalized population. The most recent NHANES survey, conducted in 1999-2000 (n = 5448), was compared with the 2 phases of NHANES III conducted in 1988-1991 (n = 9901) and 1991-1994 (n = 9717). Individuals aged 18 years or older were included in this analysis.Main Outcome MeasuresHypertension, defined as a measured blood pressure of 140/90 mm Hg or greater or reported use of antihypertensive medications. Hypertension awareness and treatment were assessed with standardized questions. Hypertension control was defined as treatment with antihypertensive medication and a measured blood pressure of less than 140/90 mm Hg.ResultsIn 1999-2000, 28.7% of NHANES participants had hypertension, an increase of 3.7% (95% confidence interval [CI], 0%-8.3%) from 1988-1991. Hypertension prevalence was highest in non-Hispanic blacks (33.5%), increased with age (65.4% among those aged ≥60 years), and tended to be higher in women (30.1%). In a multiple regression analysis, increasing age, increasing body mass index, and non-Hispanic black race/ethnicity were independently associated with increased rates of hypertension. Overall, in 1999-2000, 68.9% were aware of their hypertension (nonsignificant decline of −0.3%; 95% CI, −4.2% to 3.6%), 58.4% were treated (increase of 6.0%; 95% CI, 1.2%-10.8%), and hypertension was controlled in 31.0% (increase of 6.4%; 95% CI, 1.6%-11.2%). Women, Mexican Americans, and those aged 60 years or older had significantly lower rates of control compared with men, younger individuals, and non-Hispanic whites.ConclusionsContrary to earlier reports, hypertension prevalence is increasing in the United States. Hypertension control rates, although improving, continue to be low. Programs targeting hypertension prevention and treatment are of utmost importance.

2,298 citations


Journal ArticleDOI
28 May 2003-JAMA
TL;DR: Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older and did not prevent mild cognitive impairment in these women, supporting the conclusion that the risks of estrogen plus progESTin outweigh the benefits.
Abstract: ContextPostmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.ObjectiveTo evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.Design, Setting, and ParticipantsThe Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.InterventionParticipants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).Main Outcome MeasuresIncidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment.ResultsThe mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P = .01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P = .72).ConclusionsEstrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.

1,800 citations


Journal ArticleDOI
09 Apr 2003-JAMA
TL;DR: Severely obeseChildren and adolescents have lower health-related QOL than children and adolescents who are healthy and similar QOL as those diagnosed as having cancer.
Abstract: One in 7 US children and adolescents is obese, yet little is known about their health-related quality of life (QOL) This study was a cross-sectional study of 106 children and adolescents (57 males) between the ages of 5 and 18 years, who had been referred to an academic children's hospital for evaluation of obesity between January and June 2002 Children and adolescents had a mean (SD) body mass index (BMI) of 347 (93) The main outcome measures were child self-report and parent proxy report using a pediatric QOL inventory generic core scale (range, 0-100) The inventory was administered by an interviewer for children aged 5 through 7 years Scores were compared with previously published scores for healthy children and adolescents and children and adolescents diagnosed as having cancer Compared with healthy children and adolescents, obese children and adolescents reported significantly lower health-related QOL in all domains Obese children and adolescents were more likely to have impaired health-related QOL than healthy children and adolescents and were similar to children and adolescents diagnosed as having cancer Children and adolescents with obstructive sleep apnea reported a significantly lower health-related QOL total score than obese children and adolescents without obstructive sleep apnea Overall it is clear that physicians, parents, and teachers need to be informed of the risk for impaired health-related QOL among obese children and adolescents to target interventions that could enhance health outcomes

1,758 citations


Journal ArticleDOI
10 Dec 2003-JAMA
TL;DR: It is suggested that most community-associated MRSA strains did not originate in health care settings, and that their microbiological features may have contributed to their emergence in the community.
Abstract: Context Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been considered a health care–associated pathogen in patients with established risk factors. However, MRSA has emerged in patients without established risk factors (community-associated MRSA). Objective To characterize epidemiological and microbiological characteristics of community-associated MRSA cases compared with health care–associated MRSA cases. Design, Setting, and Patients Prospective cohort study of patients with MRSA infection identified at 12 Minnesota laboratory facilities from January 1 through December 31, 2000, comparing community-associated (median age, 23 years) with health care–associated (median age, 68 years) MRSA cases. Main Outcome Measures Clinical infections associated with either communityassociated or health care–associated MRSA, microbiological characteristics of the MRSA isolates including susceptibility testing, pulsed-field gel electrophoresis, and staphylococcal exotoxin gene testing. Results Of 1100 MRSA infections, 131 (12%) were community-associated and 937 (85%) were health care–associated; 32 (3%) could not be classified due to lack of information. Skin and soft tissue infections were more common among communityassociated cases (75%) than among health care–associated cases (37%) (odds ratio [OR], 4.25; 95% confidence interval [CI], 2.97-5.90). Although communityassociated MRSA isolates were more likely to be susceptible to 4 antimicrobial classes (adjusted OR, 2.44; 95% CI, 1.35-3.86), most community-associated infections were initially treated with antimicrobials to which the isolate was nonsusceptible. Communityassociated isolates were also more likely to belong to 1 of 2 pulsed-field gel electrophoresis clonal groups in both univariate and multivariate analysis. Communityassociated isolates typically possessed different exotoxin gene profiles (eg, Panton Valentine leukocidin genes) compared with health care–associated isolates. Conclusions Community-associated and health care–associated MRSA cases differ demographically and clinically, and their respective isolates are microbiologically distinct. This suggests that most community-associated MRSA strains did not originate in health care settings, and that their microbiological features may have contributed to their emergence in the community. Clinicians should be aware that therapy with -lactam antimicrobials can no longer be relied on as the sole empiric therapy for severely ill outpatients whose infections may be staphylococcal in origin.

Journal ArticleDOI
16 Apr 2003-JAMA
TL;DR: The theory and research on the dissemination of innovations and applications of that theory to health care are examined and at least 7 recommendations for health care executives who want to accelerate the rate of diffusion of innovations within their organizations are suggested.
Abstract: Health care is rich in evidence-based innovations, yet even when such innovations are implemented successfully in one location, they often disseminate slowly-if at all. Diffusion of innovations is a major challenge in all industries including health care. This article examines the theory and research on the dissemination of innovations and suggests applications of that theory to health care. It explores in detail 3 clusters of influence on the rate of diffusion of innovations within an organization: the perceptions of the innovation, the characteristics of the individuals who may adopt the change, and contextual and managerial factors within the organization. This theory makes plausible at least 7 recommendations for health care executives who want to accelerate the rate of diffusion of innovations within their organizations: find sound innovations, find and support "innovators," invest in "early adopters," make early adopter activity observable, trust and enable reinvention, create slack for change, and lead by example.

Journal ArticleDOI
18 Jun 2003-JAMA
TL;DR: The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.
Abstract: CONTEXT Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment. OBJECTIVE To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI. DESIGN, SETTING, AND PATIENTS Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention. INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks. MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months. RESULTS Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients). CONCLUSIONS The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.

Journal ArticleDOI
05 Nov 2003-JAMA
TL;DR: A recombinant ApoA-I Milano/phospholipid complex administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS, and results require confirmation in larger clinical trials with morbidity and mortality end points.
Abstract: ContextAlthough low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano–phospholipid complexes produces rapid regression of atherosclerosis in animal models.ObjectiveWe assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS).DesignThe study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS).SettingTen community and tertiary care hospitals in the United States.PatientsBetween November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol.InterventionsIn a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments.Main Outcome MeasuresThe primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness.ResultsThe mean (SD) percent atheroma volume decreased by −1.06% (3.17%) in the combined ETC-216 group (median, −0.81%; 95% confidence interval [CI], −1.53% to −0.34%; P = .02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, −1.11% to 1.43%; P = .97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was −14.1 mm3 or a 4.2% decrease from baseline (P<.001).ConclusionsA recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points.

Journal ArticleDOI
25 Jun 2003-JAMA
TL;DR: Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms, a pattern which continued for the study duration.
Abstract: ContextThe Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.ObjectiveTo determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.Design, Setting, and ParticipantsFollowing a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.Main Outcome MeasuresBreast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.ResultsIn intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P = .003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P = .04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.ConclusionsRelatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

Journal ArticleDOI
24 Sep 2003-JAMA
TL;DR: In hospitals with higher proportions of nurses educated at the baccalaureate level or higher, surgical patients experienced lower mortality and failure-to-rescue rates.
Abstract: ContextGrowing evidence suggests that nurse staffing affects the quality of care in hospitals, but little is known about whether the educational composition of registered nurses (RNs) in hospitals is related to patient outcomes.ObjectiveTo examine whether the proportion of hospital RNs educated at the baccalaureate level or higher is associated with risk-adjusted mortality and failure to rescue (deaths in surgical patients with serious complications).Design, Setting, and PopulationCross-sectional analyses of outcomes data for 232 342 general, orthopedic, and vascular surgery patients discharged from 168 nonfederal adult general Pennsylvania hospitals between April 1, 1998, and November 30, 1999, linked to administrative and survey data providing information on educational composition, staffing, and other characteristics.Main Outcome MeasuresRisk-adjusted patient mortality and failure to rescue within 30 days of admission associated with nurse educational level.ResultsThe proportion of hospital RNs holding a bachelor's degree or higher ranged from 0% to 77% across the hospitals. After adjusting for patient characteristics and hospital structural characteristics (size, teaching status, level of technology), as well as for nurse staffing, nurse experience, and whether the patient's surgeon was board certified, a 10% increase in the proportion of nurses holding a bachelor's degree was associated with a 5% decrease in both the likelihood of patients dying within 30 days of admission and the odds of failure to rescue (odds ratio, 0.95; 95% confidence interval, 0.91-0.99 in both cases).ConclusionIn hospitals with higher proportions of nurses educated at the baccalaureate level or higher, surgical patients experienced lower mortality and failure-to-rescue rates.

Journal ArticleDOI
24 Sep 2003-JAMA
TL;DR: Increasing the supply of pragmatic or practical clinical trials will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding forThese studies.
Abstract: Decision makers in health care are increasingly interested in using highquality scientific evidence to support clinical and health policy choices; however, the quality of available scientific evidence is often found to be inadequate. Reliable evidence is essential to improve health care quality and to support efficient use of limited resources. The widespread gaps in evidencebased knowledge suggest that systematic flaws exist in the production of scientific evidence, in part because there is no consistent effort to conduct clinical trials designed to meet the needs of decision makers. Clinical trials for which the hypothesis and study design are developed specifically to answer the questions faced by decision makers are called pragmatic or practical clinical trials (PCTs). The characteristic features of PCTs are that they (1) select clinically relevant alternative interventions to compare, (2) include a diverse population of study participants, (3) recruit participants from heterogeneous practice settings, and (4) collect data on a broad range of health outcomes. The supply of PCTs is limited primarily because the major funders of clinical research, the National Institutes of Health and the medical products industry, do not focus on supporting such trials. Increasing the supply of PCTs will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding for these studies. For these changes to occur, clinical and health policy decision makers will need to become more involved in all aspects of clinical research, including priority setting, infrastructure development, and funding.

Journal ArticleDOI
05 Mar 2003-JAMA
TL;DR: Adverse drug events are common and often preventable among older persons in the ambulatory clinical setting and prevention strategies should target the prescribing and monitoring stages of pharmaceutical care.
Abstract: ContextAdverse drug events, especially those that may be preventable, are among the most serious concerns about medication use in older persons cared for in the ambulatory clinical setting.ObjectiveTo assess the incidence and preventability of adverse drug events among older persons in the ambulatory clinical setting.Design, Setting, and PatientsCohort study of all Medicare enrollees (30 397 person-years of observation) cared for by a multispecialty group practice during a 12-month study period (July 1, 1999, through June 30, 2000), in which possible drug-related incidents occurring in the ambulatory clinical setting were detected using multiple methods, including reports from health care providers; review of hospital discharge summaries; review of emergency department notes; computer-generated signals; automated free-text review of electronic clinic notes; and review of administrative incident reports concerning medication errors.Main Outcome MeasuresNumber of adverse drug events, severity of the events (classified as significant, serious, life-threatening, or fatal), and whether the events were preventable.ResultsThere were 1523 identified adverse drug events, of which 27.6% (421) were considered preventable. The overall rate of adverse drug events was 50.1 per 1000 person-years, with a rate of 13.8 preventable adverse drug events per 1000 person-years. Of the adverse drug events, 578 (38.0%) were categorized as serious, life-threatening, or fatal; 244 (42.2%) of these more severe events were deemed preventable compared with 177 (18.7%) of the 945 significant adverse drug events. Errors associated with preventable adverse drug events occurred most often at the stages of prescribing (n = 246, 58.4%) and monitoring (n = 256, 60.8%), and errors involving patient adherence (n = 89, 21.1%) also were common. Cardiovascular medications (24.5%), followed by diuretics (22.1%), nonopioid analgesics (15.4%), hypoglycemics (10.9%), and anticoagulants (10.2%) were the most common medication categories associated with preventable adverse drug events. Electrolyte/renal (26.6%), gastrointestinal tract (21.1%), hemorrhagic (15.9%), metabolic/endocrine (13.8%), and neuropsychiatric (8.6%) events were the most common types of preventable adverse drug events.ConclusionsAdverse drug events are common and often preventable among older persons in the ambulatory clinical setting. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the prescribing and monitoring stages of pharmaceutical care. Interventions focused on improving patient adherence with prescribed regimens and monitoring of prescribed medications also may be beneficial.

Journal ArticleDOI
05 Nov 2003-JAMA
TL;DR: Risk factor profile assessed in 12- to 18-year-old adolescents predicts adult common carotid artery IMT independently of contemporaneous risk factors, suggesting that exposure to cardiovascular risk factors early in life may induce changes in arteries that contribute to the development of atherosclerosis.
Abstract: ContextExposure to cardiovascular risk factors during childhood and adolescence may be associated with the development of atherosclerosis later in life.ObjectiveTo study the relationship between cardiovascular risk factors measured in childhood and adolescence and common carotid artery intima-media thickness (IMT), a marker of preclinical atherosclerosis, measured in adulthood.Design, Setting, and ParticipantsPopulation-based, prospective cohort study conducted at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were examined in childhood and adolescence at ages 3 to 18 years in 1980 and reexamined 21 years later, between September 2001 and January 2002.Main Outcome MeasuresAssociation between cardiovascular risk variables (levels of low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood pressure; body mass index; smoking) measured in childhood and adulthood and common carotid artery IMT measured in adulthood.ResultsIn multivariable models adjusted for age and sex, IMT in adulthood was significantly associated with childhood LDL-C levels (P = .001), systolic blood pressure (P<.001), body mass index (P = .007), and smoking (P = .02), and with adult systolic blood pressure (P<.001), body mass index (P<.001), and smoking (P = .004). The number of risk factors measured in 12- to 18-year-old adolescents, including high levels (ie, extreme age- and sex-specific 80th percentile) of LDL-C, systolic blood pressure, body mass index, and cigarette smoking, were directly related to carotid IMT measured in young adults at ages 33 through 39 years (P<.001 for both men and women), and remained significant after adjustment for contemporaneous risk variables. The number of risk factors measured at ages 3 to 9 years demonstrated a weak direct relationship with carotid IMT at ages 24 to 30 years in men (P = .02) but not in women (P = .63).ConclusionsRisk factor profile assessed in 12- to 18-year-old adolescents predicts adult common carotid artery IMT independently of contemporaneous risk factors. These findings suggest that exposure to cardiovascular risk factors early in life may induce changes in arteries that contribute to the development of atherosclerosis.

Journal ArticleDOI
14 May 2003-JAMA
TL;DR: The 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated and the implication for national prevention strategies should be vigorously explored.
Abstract: ContextGeographic variations in cardiovascular disease (CVD) and associated risk factors have been recognized worldwide. However, little attention has been directed to potential differences in hypertension between Europe and North America.ObjectiveTo determine whether higher blood pressure (BP) levels and hypertension are more prevalent in Europe than in the United States and Canada.Design, Setting, and ParticipantsSample surveys that were national in scope and conducted in the 1990s were identified in Germany, Finland, Sweden, England, Spain, Italy, Canada, and the United States. Collaborating investigators provided tabular data in a consistent format by age and sex for persons at least 35 years of age. Population registries were the main basis for sampling. Survey sizes ranged from 1800 to 23 100, with response rates of 61% to 87.5%. The data were analyzed to provide age-specific and age-adjusted estimates of BP and hypertension prevalence by country and region (eg, European vs North American).Main Outcome MeasuresBlood pressure levels and prevalence of hypertension in Europe, the United States, and Canada.ResultsAverage BP was 136/83 mm Hg in the European countries and 127/77 mm Hg in Canada and the United States among men and women combined who were 35 to 74 years of age. This difference already existed among younger persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm Hg and 115/75 mm Hg, respectively), and the slope with age was steeper in the European countries. For all age groups, BP measurements were lowest in the United States and highest in Germany. The age- and sex-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries at the 140/90 mm Hg threshold. The findings for men and women by region were similar. Hypertension prevalence was strongly correlated with stroke mortality (r = 0.78) and more modestly with total CVD (r = 0.44).ConclusionsDespite extensive research on geographic patterns of CVD, the 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated. The implication of this finding for national prevention strategies should be vigorously explored.

Journal ArticleDOI
23 Jul 2003-JAMA
TL;DR: This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.
Abstract: ContextThe worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns.ObjectiveTo evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an α-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).Design, Setting, and ParticipantsInternational, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years.InterventionPatients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714).Main Outcome MeasuresThe development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (≥140/90 mm Hg).ResultsThree hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P = .03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P = .006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically significant.ConclusionThis study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

Journal ArticleDOI
09 Apr 2003-JAMA
TL;DR: Independent of exercise levels, sedentary behaviors, especially TV watching, were associated with significantly elevated risk of obesity and type 2 diabetes, whereas even light to moderate activity was associated with substantially lower risk.
Abstract: ContextCurrent public health campaigns to reduce obesity and type 2 diabetes have largely focused on increasing exercise, but have paid little attention to the reduction of sedentary behaviors.ObjectiveTo examine the relationship between various sedentary behaviors, especially prolonged television (TV) watching, and risk of obesity and type 2 diabetes in women.Design, Setting, and ParticipantsProspective cohort study conducted from 1992 to 1998 among women from 11 states in the Nurses' Health Study. The obesity analysis included 50 277 women who had a body mass index (BMI) of less than 30 and were free from diagnosed cardiovascular disease, diabetes, or cancer and completed questions on physical activity and sedentary behaviors at baseline. The diabetes analysis included 68 497 women who at baseline were free from diagnosed diabetes mellitus, cardiovascular disease, or cancer.Main Outcome MeasuresOnset of obesity and type 2 diabetes mellitus.ResultsDuring 6 years of follow-up, 3757 (7.5%) of 50 277 women who had a BMI of less than 30 in 1992 became obese (BMI ≥30). Overall, we documented 1515 new cases of type 2 diabetes. Time spent watching TV was positively associated with risk of obesity and type 2 diabetes. In the multivariate analyses adjusting for age, smoking, exercise levels, dietary factors, and other covariates, each 2-h/d increment in TV watching was associated with a 23% (95% confidence interval [CI], 17%-30%) increase in obesity and a 14% (95% CI, 5%-23%) increase in risk of diabetes; each 2-h/d increment in sitting at work was associated with a 5% (95% CI, 0%-10%) increase in obesity and a 7% (95% CI, 0%-16%) increase in diabetes. In contrast, standing or walking around at home (2 h/d) was associated with a 9% (95% CI, 6%-12%) reduction in obesity and a 12% (95% CI, 7%-16%) reduction in diabetes. Each 1 hour per day of brisk walking was associated with a 24% (95% CI, 19%-29%) reduction in obesity and a 34% (95% CI, 27%-41%) reduction in diabetes. We estimated that in our cohort, 30% (95% CI, 24%-36%) of new cases of obesity and 43% (95% CI, 32%-52%) of new cases of diabetes could be prevented by adopting a relatively active lifestyle (<10 h/wk of TV watching and ≥30 min/d of brisk walking).ConclusionsIndependent of exercise levels, sedentary behaviors, especially TV watching, were associated with significantly elevated risk of obesity and type 2 diabetes, whereas even light to moderate activity was associated with substantially lower risk. This study emphasizes the importance of reducing prolonged TV watching and other sedentary behaviors for preventing obesity and diabetes.

Journal ArticleDOI
28 May 2003-JAMA
TL;DR: Cardiac resynchronization improved quality of life, functional status, and exercise capacity in patients with moderate to severe HF, a wide QRS interval, and life-threatening arrhythmias without proarrhythmia or compromised ICD function.
Abstract: ContextCardiac resynchronization therapy (CRT) through biventricular pacing is an effective treatment for heart failure (HF) with a wide QRS; however, the outcomes of patients requiring CRT and implantable cardioverter defibrillator (ICD) therapy are unknown.ObjectiveTo examine the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association (NYHA) class III or IV congestive HF despite appropriate medical management.Design, Setting, and ParticipantsRandomized, double-blind, parallel-controlled trial conducted from October 1, 1999, to August 31, 2001, of 369 patients with left ventricular ejection fraction of 35% or less, QRS duration of 130 ms, at high risk of life-threatening ventricular arrhythmias, and in NYHA class III (n = 328) or IV (n = 41) despite optimized medical treatment.InterventionsOf 369 randomized patients who received devices with combined CRT and ICD capabilities, 182 were controls (ICD activated, CRT off) and 187 were in the CRT group (ICD activated, CRT on).Main Outcome MeasuresThe primary double-blind study end points were changes between baseline and 6 months in quality of life, functional class, and distance covered during a 6-minute walk. Additional outcome measures included changes in exercise capacity, plasma neurohormones, left ventricular function, and overall HF status. Survival, incidence of ventricular arrhythmias, and rates of hospitalization were also compared.ResultsAt 6 months, patients assigned to CRT had a greater improvement in median (95% confidence interval) quality of life score (–17.5 [–21 to –14] vs –11.0 [–16 to –7], P = .02) and functional class (–1 [–1 to –1] vs 0 [–1 to 0], P = .007) than controls but were no different in the change in distance walked in 6 minutes (55 m [44-79] vs 53 m [43-75], P = .36). Peak oxygen consumption increased by 1.1 mL/kg per minute (0.7-1.6) in the CRT group vs 0.1 mL/kg per minute (–0.1 to 0.8) in controls (P = .04), although treadmill exercise duration increased by 56 seconds (30-79) in the CRT group and decreased by 11 seconds (–55 to 12) in controls (P<.001). No significant differences were observed in changes in left ventricular size or function, overall HF status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired.ConclusionsCardiac resynchronization improved quality of life, functional status, and exercise capacity in patients with moderate to severe HF, a wide QRS interval, and life-threatening arrhythmias. These improvements occurred in the context of underlying appropriate medical management without proarrhythmia or compromised ICD function.

Journal ArticleDOI
08 Oct 2003-JAMA
TL;DR: For individuals born in the United States in 2000, the lifetime probability of being diagnosed with diabetes mellitus is substantial and primary prevention of diabetes and its complications are important public health priorities.
Abstract: ContextAlthough diabetes mellitus is one of the most prevalent and costly chronic diseases in the United States, no estimates have been published of individuals' average lifetime risk of developing diabetes.ObjectiveTo estimate age-, sex-, and race/ethnicity-specific lifetime risk of diabetes in the cohort born in 2000 in the United States.Design, Setting, and ParticipantsData from the National Health Interview Survey (1984-2000) were used to estimate age-, sex-, and race/ethnicity-specific prevalence and incidence in 2000. US Census Bureau data and data from a previous study of diabetes as a cause of death were used to estimate age-, sex-, and race/ethnicity-specific mortality rates for diabetic and nondiabetic populations.Main Outcome MeasuresResidual (remaining) lifetime risk of diabetes (from birth to 80 years in 1-year intervals), duration with diabetes, and life-years and quality-adjusted life-years lost from diabetes.ResultsThe estimated lifetime risk of developing diabetes for individuals born in 2000 is 32.8% for males and 38.5% for females. Females have higher residual lifetime risks at all ages. The highest estimated lifetime risk for diabetes is among Hispanics (males, 45.4% and females, 52.5%). Individuals diagnosed as having diabetes have large reductions in life expectancy. For example, we estimate that if an individual is diagnosed at age 40 years, men will lose 11.6 life-years and 18.6 quality-adjusted life-years and women will lose 14.3 life-years and 22.0 quality-adjusted life-years.ConclusionsFor individuals born in the United States in 2000, the lifetime probability of being diagnosed with diabetes mellitus is substantial. Primary prevention of diabetes and its complications are important public health priorities.

Journal ArticleDOI
09 Apr 2003-JAMA
TL;DR: A multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.
Abstract: ContextObesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue.ObjectiveTo determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance.Design and SettingRandomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy.PatientsOne hundred twenty premenopausal obese women (body mass index ≥30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia.InterventionsThe 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise.Main Outcome MeasuresLipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin.ResultsAfter 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P<.001), monounsaturated fat (2%; P = .009), and fiber (7 g/d; P<.001); had a lower ratio of omega-6 to omega-3 fatty acids (−5; P<.001); and had lower energy (−310 kcal/d; P<.001), saturated fat (−3.5%; P = .007), and cholesterol intake (−92 mg/d; P<.001) than controls. Body mass index decreased more in the intervention group than in controls (−4.2; P<.001), as did serum concentrations of IL-6 (−1.1 pg/mL; P = .009), IL-18 (−57 pg/mL; P = .02), and CRP (−1.6 mg/L; P = .008), while adiponectin levels increased significantly (2.2 µg/mL; P = .01). In multivariate analyses, changes in free fatty acids (P = .008), IL-6 (P = .02), and adiponectin (P = .007) levels were independently associated with changes in insulin sensitivity.ConclusionIn this study, a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.

Journal ArticleDOI
22 Jan 2003-JAMA
TL;DR: In this article, the authors reviewed original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research and concluded that financial relationships among industry, scientific investigators, and academic institutions are widespread.
Abstract: ContextDespite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed.ObjectiveTo review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research.Data SourcesStudies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts.Study SelectionAll English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria.Data ExtractionOne investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest.Data SynthesisApproximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals.ConclusionsFinancial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways.

Journal ArticleDOI
12 Nov 2003-JAMA
TL;DR: Pain is an inordinately common and disabling condition in the US workforce and most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.
Abstract: ContextCommon pain conditions appear to have an adverse effect on work, but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain.ObjectiveTo measure lost productive time (absence and reduced performance due to common pain conditions) during a 2-week period.Design and SettingCross-sectional study using survey data from the American Productivity Audit (a telephone survey that uses the Work and Health Interview) of working adults between August 1, 2001, and July 30, 2002.ParticipantsRandom sample of 28 902 working adults in the United States.Main Outcome MeasuresLost productive time due to common pain conditions (arthritis, back, headache, and other musculoskeletal) expressed in hours per worker per week and calculated in US dollars.ResultsThirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition. Headache was the most common (5.4%) pain condition resulting in lost productive time. It was followed by back pain (3.2%), arthritis pain (2.0%), and other musculoskeletal pain (2.0%). Workers who experienced lost productive time from a pain condition lost a mean (SE) of 4.6 (0.09) h/wk. Workers who had a headache had a mean (SE) loss in productive time of 3.5 (0.1) h/wk. Workers who reported arthritis or back pain had mean (SE) lost productive times of 5.2 (0.25) h/wk. Other common pain conditions resulted in a mean (SE) loss in productive time of 5.5 (0.22) h/wk. Lost productive time from common pain conditions among active workers costs an estimated $61.2 billion per year. The majority (76.6%) of the lost productive time was explained by reduced performance while at work and not work absence.ConclusionsPain is an inordinately common and disabling condition in the US workforce. Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.

Journal ArticleDOI
19 Nov 2003-JAMA
TL;DR: In this paper, a study of 1631 football players from 15 US colleges found that players with concussions exhibited more severe symptoms (mean GSC score 20.93 [95% confidence interval {CI, 15.65-26.21] points higher than that of controls), cognitive impairments (mean SAC score 2.94 [ 95% CI, 1.41 to 2.06], cognitive functioning improved to baseline levels within 5 to 7 days (day 7 SAC mean difference, −0.33;
Abstract: ContextLack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury.ObjectiveTo prospectively measure immediate effects and natural recovery course relating to symptoms, cognitive functioning, and postural stability following sport-related concussion.Design, Setting, and ParticipantsProspective cohort study of 1631 football players from 15 US colleges. All players underwent preseason baseline testing on concussion assessment measures in 1999, 2000, and 2001. Ninety-four players with concussion (based on American Academy of Neurology criteria) and 56 noninjured controls underwent assessment of symptoms, cognitive functioning, and postural stability immediately, 3 hours, and 1, 2, 3, 5, 7, and 90 days after injury.Main Outcome MeasuresScores on the Graded Symptom Checklist (GSC), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and a neuropsychological test battery.ResultsNo player with concussion was excluded from participation; 79 players with concussion (84%) completed the protocol through day 90. Players with concussion exhibited more severe symptoms (mean GSC score 20.93 [95% confidence interval {CI}, 15.65-26.21] points higher than that of controls), cognitive impairment (mean SAC score 2.94 [95% CI, 1.50-4.38] points lower than that of controls), and balance problems (mean BESS score 5.81 [95% CI, –0.67 to 12.30] points higher than that of controls) immediately after concussion. On average, symptoms gradually resolved by day 7 (GSC mean difference, 0.33; 95% CI, −1.41 to 2.06), cognitive functioning improved to baseline levels within 5 to 7 days (day 7 SAC mean difference, −0.03; 95% CI, −1.33 to 1.26), and balance deficits dissipated within 3 to 5 days after injury (day 5 BESS mean difference, −0.31; 95% CI, −3.02 to 2.40). Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7. There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion.ConclusionsCollegiate football players may require several days for recovery of symptoms, cognitive dysfunction, and postural instability after concussion. Further research is required to determine factors that predict variability in recovery time after concussion. Standardized measurement of postconcussive symptoms, cognitive functioning, and postural stability may enhance clinical management of athletes recovering from concussion.

Journal ArticleDOI
19 Nov 2003-JAMA
TL;DR: This study suggests thatPlayers with a history of previous concussions are more likely to have future concussive injuries than those with no history; 1 in 15 players with a concussion may have additional concussions in the same playing season; and previous concussion may be associated with slower recovery of neurological function.
Abstract: ContextApproximately 300 000 sport-related concussions occur annually in the United States, and the likelihood of serious sequelae may increase with repeated head injury.ObjectiveTo estimate the incidence of concussion and time to recovery after concussion in collegiate football players.Design, Setting, and ParticipantsProspective cohort study of 2905 football players from 25 US colleges were tested at preseason baseline in 1999, 2000, and 2001 on a variety of measures and followed up prospectively to ascertain concussion occurrence. Players injured with a concussion were monitored until their concussion symptoms resolved and were followed up for repeat concussions until completion of their collegiate football career or until the end of the 2001 football season.Main Outcome MeasuresIncidence of concussion and repeat concusion; type and duration of symptoms and course of recovery among players who were injured with a concussion during the seasons.ResultsDuring follow-up of 4251 player-seasons, 184 players (6.3%) had a concussion, and 12 (6.5%) of these players had a repeat concussion within the same season. There was an association between reported number of previous concussions and likelihood of incident concussion. Players reporting a history of 3 or more previous concussions were 3.0 (95% confidence interval, 1.6-5.6) times more likely to have an incident concussion than players with no concussion history. Headache was the most commonly reported symptom at the time of injury (85.2%), and mean overall symptom duration was 82 hours. Slowed recovery was associated with a history of multiple previous concussions (30.0% of those with ≥3 previous concussions had symptoms lasting >1 week compared with 14.6% of those with 1 previous concussion). Of the 12 incident within-season repeat concussions, 11 (91.7%) occurred within 10 days of the first injury, and 9 (75.0%) occurred within 7 days of the first injury.ConclusionsOur study suggests that players with a history of previous concussions are more likely to have future concussive injuries than those with no history; 1 in 15 players with a concussion may have additional concussions in the same playing season; and previous concussions may be associated with slower recovery of neurological function.

Journal ArticleDOI
23 Apr 2003-JAMA
TL;DR: Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake and the established plus DASH intervention also increased fruit, vegetable, and dairy intake.
Abstract: CONTEXT Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations. OBJECTIVE To determine the effect on BP of 2 multicomponent, behavioral interventions. DESIGN, SETTING, AND PARTICIPANTS Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications. INTERVENTION Participants were randomized to one of 3 intervention groups: (1) "established," a behavioral intervention that implemented established recommendations (n = 268); (2) "established plus DASH,"which also implemented the DASH diet (n = 269); and (3) an "advice only" comparison group (n = 273). MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months. RESULTS Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group). CONCLUSION Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.