Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s

Context  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. Objective  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). Design, Setting, and Participants  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. Main Outcome Measures  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. Results  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). Conclusion  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.      

Depressive symptoms and health-related quality of life: the Heart and Soul Study

Context  Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease. Objective  To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease. Design, Setting, and Participants  Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures  Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor. Results  Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score =" BORDER="0">10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P = .002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not. Conclusions  Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function—ejection fraction and ischemia—are not. Efforts to improve health status should include assessment and treatment of depressive symptoms.      

Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial

Context  Few depressed older adults receive effective treatment in primary care settings. Objective  To determine the effectiveness of the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. Design  Randomized controlled trial with recruitment from July 1999 to August 2001. Setting  Eighteen primary care clinics from 8 health care organizations in 5 states. Participants  A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). Intervention  Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care. Main Outcome Measures  Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. Results  At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. Conclusion  The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.      

Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial

Context  Varenicline, a partial agonist at the 42 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine. Objective  To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR). Design, Setting, and Participants  A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study. Intervention  Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling. Main Outcome Measures  Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52). Results  During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%). Conclusions  Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR. Trial Registration  clinicaltrials.gov Identifier: NCT00143364      

Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials

Context  Patients with unstable angina or non–ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention. Objective  To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies. Data Sources  Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews. Study Selection  Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy. Data Extraction  Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials. Data Synthesis  A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14-2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy. Conclusions  A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies.      

Acute renal failure in critically ill patients: a multinational, multicenter study

Context  Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. Objectives  To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. Design, Setting, and Patients  Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. Main Outcome Measures  Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. Results  Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). Conclusion  In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.      

Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s

Context  The outcome into school age of regional cohorts of children born in the 1990s with birth weights less than 1000 g (extremely low birth weight, ELBW) or earlier than 28 weeks' gestation (very preterm) is not known. Objective  To determine the cognitive, educational, and behavioral outcome of ELBW or very preterm infants born in the 1990s compared with normal birth weight (NBW) controls. Design  Regional cohort study. Setting  Victoria, Australia. Participants  The ELBW or very preterm cohort was composed of 298 consecutive survivors born during 1991-1992. The NBW cohort was composed of 262 randomly selected children with birth weights of more than 2499 g. Main Outcome Measures  Cognitive ability, educational progress, and behavioral problems. Results  The follow-up rates from birth to 8 years of age for survivors were 92.3% (275/298) for the ELBW or very preterm cohort and 85.1% (223/262) for the NBW cohort. The ELBW or very preterm children scored significantly below NBW controls on full-scale IQ (mean difference, –9.4; 95% confidence interval [CI], –12.1 to –6.7; P<.001) and indices of verbal comprehension (mean difference, –6.8; 95% CI, –9.5 to –4.2; P<.001), perceptual organization (mean difference, –9.9; 95% CI, –12.7 to –7.2; P<.001), freedom from distractibility (mean difference, –8.1; 95% CI, –10.8 to –5.5; P<.001), and processing speed (mean difference, –6.7; 95% CI, –9.4 to –4.0; P<.001). The ELBW or very preterm children performed significantly worse than the NBW cohort on tests of reading (mean difference, –6.7; 95% CI, –9.5 to –3.9; P<.001), spelling (mean difference, –5.6; 95% CI, –8.0 to –3.3; P<.001), and arithmetic (mean difference, –8.8; 95% CI, –11.3 to –6.2; P<.001). Attentional difficulties, internalizing behavior problems, and immature adaptive skills were more prevalent in the ELBW or very preterm cohort. Conclusion  School-aged ELBW or very preterm children born in the 1990s continue to display cognitive, educational, and behavioral impairments.      

Obesity, weight gain, and the risk of kidney stones

Context  Larger body size may result in increased urinary excretion of calcium, oxalate, and uric acid, thereby increasing the risk for calcium-containing kidney stones. It is unclear if obesity increases the risk of stone formation, and it is not known if weight gain influences risk. Objective  To determine if weight, weight gain, body mass index (BMI), and waist circumference are associated with kidney stone formation. Design, Setting, and Participants  A prospective study of 3 large cohorts: the Health Professionals Follow-up Study (N = 45 988 men; age range at baseline, 40-75 years), the Nurses’ Health Study I (N = 93 758 older women; age range at baseline, 34-59 years), and the Nurses’ Health Study II (N = 101 877 younger women; age range at baseline, 27-44 years). Main Outcome Measures  Incidence of symptomatic kidney stones. Results  We documented 4827 incident kidney stones over a combined 46 years of follow-up. After adjusting for age, dietary factors, fluid intake, and thiazide use, the relative risk (RR) for stone formation in men weighing more than 220 lb (100.0 kg) vs men less than 150 lb (68.2 kg) was 1.44 (95% confidence interval [CI], 1.11-1.86; P = .002 for trend). In older and younger women, RRs for these weight categories were 1.89 (95% CI, 1.52-2.36; P<.001 for trend) and 1.92 (95% CI, 1.59-2.31; P<.001 for trend), respectively. The RR in men who gained more than 35 lb (15.9 kg) since age 21 years vs men whose weight did not change was 1.39 (95% CI, 1.14-1.70; P = .001 for trend). Corresponding RRs for the same categories of weight gain since age 18 years in older and younger women were 1.70 (95% CI, 1.40-2.05; P<.001 for trend) and 1.82 (95% CI, 1.50-2.21; P<.001 for trend). Body mass index was associated with the risk of kidney stone formation: the RR for men with a BMI of 30 or greater vs those with a BMI of 21 to 22.9 was 1.33 (95% CI, 1.08-1.63; P<.001 for trend). Corresponding RRs for the same categories of BMI in older and younger women were 1.90 (95% CI, 1.61-2.25; P<.001 for trend) and 2.09 (95% CI, 1.77-2.48; P<.001 for trend). Waist circumference was also positively associated with risk in men (P = .002 for trend) and in older and younger women (P<.001 for trend for both). Conclusions  Obesity and weight gain increase the risk of kidney stone formation. The magnitude of the increased risk may be greater in women than in men.      

Short-term prognosis after emergency department diagnosis of TIA

Context  Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation. Objective  To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. Design and Setting  Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients  A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA. Main Outcome Measures  Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events. Results  During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P = .01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P = .005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P = .01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). Conclusions  Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.      

Comparison of Lifestyle and Structured Interventions to Increase Physical Activity and Cardiorespiratory Fitness: A Randomized Trial

Context  Even though the strong association between physical inactivity and ill health is well documented, 60% of the population is inadequately active or completely inactive. Traditional methods of prescribing exercise have not proven effective for increasing and maintaining a program of regular physical activity. Objective  To compare the 24-month intervention effects of a lifestyle physical activity program with traditional structured exercise on improving physical activity, cardiorespiratory fitness, and cardiovascular disease risk factors. Design  Randomized clinical trial conducted from August 1, 1993, through July 31, 1997. Participants  Sedentary men (n = 116) and women (n = 119) with self-reported physical activity of less than 36 and 34 kcal/kg per day, respectively. Interventions  Six months of intensive and 18 months of maintenance intervention on either a lifestyle physical activity or a traditional structured exercise program. Main Outcome Measures  Primary outcomes were physical activity assessed by the 7-Day Physical Activity Recall and peak oxygen consumption (VO_2peak) by a maximal exercise treadmill test. Secondary outcomes were plasma lipid and lipoprotein cholesterol concentrations, blood pressure, and body composition. All measures were obtained at baseline and at 6 and 24 months. Results  Both the lifestyle and structured activity groups had significant and comparable improvements in physical activity and cardiorespiratory fitness from baseline to 24 months. Adjusted mean changes (95% confidence intervals [CIs]) were 0.84 (95% CI, 0.42-1.25 kcal/kg per day; P<.001) and 0.69 (95% CI, 0.25-1.12 kcal/kg day; P = .002) for activity, and 0.77 (95% CI, 0.18-1.36 mL/kg per minute; P = .01) and 1.34 (95% CI, 0.72-1.96 mL/kg per minute; P<.001) for VO_2peak for the lifestyle and structured activity groups, respectively. There were significant and comparable reductions in systolic blood pressure (-3.63 [95% CI, -5.54 to -1.72 mm Hg; P<.001] and -3.26 [95% CI, -5.26 to -1.25 mm Hg; P = .002]) and diastolic blood pressure (-5.38 [95% CI, -6.90 to -3.86 mm Hg; P<.001] and -5.14 [95% CI, -6.73 to -3.54 mm Hg; P<.001) for the lifestyle and structured activity groups, respectively. Neither group significantly changed their weight (-0.05 [95% CI, -1.05 to 0.96 kg; P = .93] and 0.69 [95% CI, -0.37 to 1.74 kg; P = .20]), but each group significantly reduced their percentage of body fat (-2.39% [95% CI, -2.92% to -1.85%; P<.001] and -1.85% [95% CI, -2.41% to -1.28%; P<.001]) in the lifestyle and structured activity groups, respectively. Conclusions  In previously sedentary healthy adults, a lifestyle physical activity intervention is as effective as a structured exercise program in improving physical activity, cardiorespiratory fitness, and blood pressure.      

Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults

Context  Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans. Objective  To examine associations between urinary BPA concentrations and adult health status. Design, Setting, and Participants  Cross-sectional analysis of BPA concentrations and health status in the general adult population of the United States, using data from the National Health and Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urinary BPA and urine creatinine concentrations. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, body mass index, waist circumference, and urinary creatinine concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) of 1.4 for diagnoses of 5% prevalence per 1-SD change in BPA concentration, or standardized regression coefficients of 0.075 for liver enzyme concentrations, at a significance level of P < .05. Main Outcome Measures  Chronic disease diagnoses plus blood markers of liver function, glucose homeostasis, inflammation, and lipid changes. Results  Higher urinary BPA concentrations were associated with cardiovascular diagnoses in age-, sex-, and fully adjusted models (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.18-1.63; P = .001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.21-1.60; P < .001) but not with other studied common diseases. In addition, higher BPA concentrations were associated with clinically abnormal concentrations of the liver enzymes -glutamyltransferase (OR per 1-SD increase in BPA concentration, 1.29; 95% CI, 1.14-1.46; P < .001) and alkaline phosphatase (OR per 1-SD increase in BPA concentration, 1.48; 95% CI, 1.18-1.85; P = .002). Conclusion  Higher BPA exposure, reflected in higher urinary concentrations of BPA, may be associated with avoidable morbidity in the community-dwelling adult population.      

Contemporary clinical profile and outcome of prosthetic valve endocarditis

Context  Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. Objectives  To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care–associated infection, and to determine prognostic factors associated with in-hospital mortality. Design, Setting, and Participants  Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. Main Outcome Measure  In-hospital mortality. Results  Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care–associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care–associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care–associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P<.001), stroke (34/101 [33.7%]; adjusted OR, 2.25; 95% CI, 1.25-4.03; P = .007), intracardiac abscess (47/144 [32.6%]; adjusted OR, 1.86; 95% CI, 1.10-3.15; P = .02), and persistent bacteremia (27/49 [55.1%]; adjusted OR, 4.29; 95% CI, 1.99-9.22; P<.001). Conclusions  Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care–associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.      

Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria

Context  There are concerns that malaria control measures such as use of insecticide-treated bed nets, by delaying acquisition of immunity, might result in an increase in the more severe manifestations of malaria. An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely. Objective  To describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in varying levels of transmission. Design, Setting, and Patients  A total of 1984 patients admitted for severe malaria to 10 hospitals serving populations living at levels of transmission varying from very low (altitude >1200 m) to very high (altitude <600 m) in a defined area of northeastern Tanzania, studied prospectively from February 2002 to February 2003. Data were analyzed in a logistic regression model and adjusted for potential clustering within hospitals. Main Outcome Measures  Specific syndromes of severe malaria; mortality. Results  The median age of patients was 1 year in high transmission, 3 years in moderate transmission, and 5 years in low transmission areas. The odds of severe malarial anemia (hemoglobin <5 g/dL) peaked at 1 year of age at high transmission and at 2 years at moderate and low transmission intensities and then decreased with increasing age (P = .002). Odds were highest in infants (0-1 year: referent; 2-4 years: odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.96), 5 to <15 years: OR, 0.44; 95% CI, 0.27-0.72; 15 years: OR, 0.44; 95% CI, 0.27-0.73; P<.001) and high transmission intensity areas (altitude <600 m: referent; 600 m to 1200 m: OR, 0.55; 95% CI, 0.35-0.84; >1200 m: OR, 0.55; 95% CI, 0.26-1.15; P for trend = .03). The odds of cerebral malaria were significantly higher in low transmission intensity areas (altitude of residence <600 m: referent; 600 m to 1200 m: OR, 3.17; 95% CI, 1.32-7.60; >1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to <15 years: OR, 6.07; 95% CI, 2.98-12.38; 15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths) was similar at high and moderate levels of transmission but increased to 13% in low transmission areas (P = .03), an increase explained by the increase in the proportion of cases with cerebral malaria. Conclusions  Age and level of exposure independently influence the clinical presentation of severe malaria. Our study suggests that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence is likely to be low.      

Differences in mortality and use of revascularization in black and white patients with acute MI admitted to hospitals with and without revascularization services

Context  Racial differences in the use of coronary revascularization after acute myocardial infarction (AMI) have been widely reported. However, few studies have examined patterns of care for AMI patients admitted to hospitals with and without revascularization services. Objective  To compare rates of hospital transfer, coronary revascularization, and mortality after AMI for black and white patients admitted to hospitals with and without revascularization services. Design, Setting, and Participants  Retrospective cohort study of 1 215 924 black and white Medicare beneficiaries aged 68 years and older, admitted with AMI between January 1, 2000, and June 30, 2005, to 4627 US hospitals with and without revascularization services. Main Outcome Measures  For patients admitted to nonrevascularization hospitals, transfer to another hospital with revascularization services; for all patients, risk-adjusted rates of 30-day coronary revascularization and 1-year mortality. Results  Black patients admitted to hospitals without revascularization were less likely (25.2% vs 31.0%; P<.001) to be transferred. Black patients admitted to hospitals with or without revascularization services were less likely to undergo revascularization than white patients (34.3% vs 50.2% and 18.3% vs 25.9%; P<.001) and had higher 1-year mortality (35.3% vs 30.2% and 39.7% vs 37.6%; P<.001). After adjustment for sociodemographics, comorbidity, and illness severity, blacks remained less likely to be transferred (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.75-0.81; P<.001) and undergo revascularization (HR, 0.71; 95% CI, 0.69-0.74; P<.001; and HR, 0.68; 95% CI, 0.65-0.70; P<.001 in hospitals with and without revascularization, respectively). Risk-adjusted mortality was lower for blacks during the first 30 days after admission (HR, 0.91; 95% CI, 0.88-0.93; P<.001; and HR, 0.90; 95% CI, 0.87-0.92; P<.001 in hospitals with and without revascularization, respectively) but was higher (P<.001) thereafter. Conclusions  Black patients admitted to hospitals with and without coronary revascularization services are less likely to receive coronary revascularization. The higher long-term mortality of black patients may reflect the lower use of revascularization or other aspects of AMI care.      

Cytomegalovirus reactivation in critically ill immunocompetent patients

Ajit P. Limaye, MD; Katharine A. Kirby, MSc; Gordon D. Rubenfeld, MD; Wendy M. Leisenring, ScD; Eileen M. Bulger, MD; Margaret J. Neff, MD; Nicole S. Gibran, MD; Meei-Li Huang, PhD; Tracy K. Santo Hayes, BSc; Lawrence Corey, MD; Michael Boeckh, MD

JAMA. 2008;300(4):413-422.

Context  Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined.

Objective  To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons.

Design, Setting, and Participants  We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models.

Main Outcome Measures  Association of CMV reactivation with prolonged hospital length of stay or death.

Results  The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log₁₀ copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days.

Conclusions  These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.

     

Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials

Context  Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. Objective  To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. Data Sources and Study Selection  MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. Data Extraction  Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). Data Synthesis  Among 51 342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44 114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). Conclusions  For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.      

Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places

Context  Scotland prohibited smoking in confined public places on March 26, 2006. Objective  To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. Design, Setting, and Participants  This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. Main Outcome Measures  Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. Results  For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, –26%; 95% confidence interval [CI], –13.8% to –38.1%; P<.001) and 46.8% (n = 38) (–32.5%; 95% CI, –19.8% to –45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, –1.93 ng/mL; 95% CI, –2.83 to –1.03 ng/mL; P<.001) and then 2.93 ng/mL (–2.22 ng/mL; 95% CI, –3.10 to –1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/µL at 2 months (–630 cells/µL; 95% CI, –1010 to –260 cells/µL; P = .002) and from 4440 to 4030 cells/µL (–410 cells/µL; 95% CI, –740 to –90 cells/µL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). Conclusions  Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.      

Prognostic value of placental growth factor in patients with acute chest pain

Context  Experimental data suggest that placental growth factor (PlGF), a member of the vascular endothelial growth factor family, acts as a primary inflammatory instigator of atherosclerotic plaque instability and thus may be useful as a risk-predicting biomarker in patients with acute coronary syndromes (ACS). Objective  To determine whether blood levels of PlGF predict risk for death or nonfatal myocardial infarction in patients with acute chest pain. Design, Setting, and Patients  Measurement of PlGF levels as well as levels of markers of myocardial necrosis (troponin T [TnT]), platelet activation (soluble CD40 ligand [sCD40L]), and inflammation (high-sensitivity C-reactive protein [hsCRP]) in an inception cohort of 547 patients with angiographically validated ACS participating in the CAPTURE (c7E3 Fab Anti-Platelet Therapy in Unstable Refractory Angina) trial and in a heterogeneous cohort of 626 patients presenting with acute chest pain to an emergency department in Germany between December 1996 and March 1999. Main Outcome Measure  Risk for death or nonfatal myocardial infarction after 30 days. Results  In patients with ACS, elevated PlGF levels (>27.0 ng/L; 40.8% of patients) indicated a markedly increased risk of events at 30 days (14.8% vs 4.9%; unadjusted hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.79-6.24; P<.001). In a multivariable model, elevated levels of TnT (HR, 1.83; 95% CI, 1.05-3.86; P = .03), sCD40L (HR, 2.65; 95% CI, 1.41-4.99; P = .002), and PlGF (HR, 3.03; 95% CI, 1.54-5.95; P<.001) were independent predictors, while elevated hsCRP level was not (HR, 0.98; 95% CI, 0.53-1.98; P = .94). In patients with acute chest pain, elevated levels of PlGF predicted risk (21.2% vs 5.3%) (unadjusted: HR, 4.80; 95% CI, 2.81-8.21; P<.001; adjusted: HR, 3.00; 95% CI, 1.68-5.38; P<.001). Patients negative for all 3 markers (TnT, sCD40L, and PlGF) were at very low cardiac risk (7 days: no event; 30 days: 2.1% event rate). Conclusions  Plasma PlGF levels may be an independent biomarker of adverse outcome in patients with suspected ACS. A single initial measurement of plasma PlGF appears to extend the predictive and prognostic information gained from traditional inflammatory markers.      

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease

Context  Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. Objectives  To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. Design, Setting, and Participants  Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. Main Outcome Measures  The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. Results  The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by ² test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD. Conclusions  In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.      

Dietary phytoestrogens and lung cancer risk

Context  Despite lung-specific in vitro and in vivo studies that support a chemopreventive role for phytoestrogens, there has been little epidemiologic research focused on dietary intake of phytoestrogens and risk of lung cancer. Objective  To examine the relationship between dietary intake of phytoestrogens and risk of lung cancer. Design, Setting, and Participants  Ongoing US case-control study of 1674 patients with lung cancer (cases) and 1735 matched healthy controls. From July 1995 through October 2003, participants were personally interviewed with epidemiologic and food frequency questionnaires to collect demographic information and to quantify dietary intake of 12 individual phytoestrogens. Main Outcome Measure  Risk of lung cancer, estimated using unconditional multivariable logistic regression analyses stratified by sex and smoking status and adjusted for established and putative lung cancer risk factors. Results  Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.64-0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42-0.70; P<.001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56-1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41-0.76; P<.001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46-0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31-0.68; P = .04 for interaction) reduction in risk of lung cancer. Conclusions  While there are limitations and concerns regarding case-control studies of diet and cancer, these data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer. Confirmation of these findings is still required in large-scale, hypothesis-driven, prospective studies.