Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Context  Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status. Objectives  To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes. Design, Setting, and Participants  Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study, a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings (n = 2916) served as a comparison group. Main Outcome Measures  Six health status domains were assessed: general health, mental health, functional status, activity limitations, cancer-related pain, and cancer-related anxiety/fears. The first 4 domains were assessed in the control group. Results  Survivors were significantly more likely to report adverse general health (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.0; P<.001), mental health (OR, 1.8; 95% CI, 1.6-2.1; P<.001), activity limitations (OR, 2.7; 95% CI, 2.3-3.3; P<.001), and functional impairment (OR, 5.2; 95% CI, 4.1-6.6; P<.001), compared with siblings. Forty-four percent of survivors reported at least 1 adversely affected health status domain. Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female (OR, 1.4; 95% CI, 1.3-1.6; P<.001), lower level of educational attainment (OR, 2.0; 95% CI, 1.8-2.2; P<.001), and annual income less than $20 000 (OR, 1.8; 95% CI, 1.6-2.1; P<.001). Relative to those survivors with childhood leukemia, an increased risk was observed for at least 1 adverse health status domain among those with bone tumors (OR, 2.1; 95% CI, 1.8-2.5; P<.001), central nervous system tumors (OR, 1.7; 95% CI, 1.5-2.0; P<.001), and sarcomas (OR, 1.2; 95% CI, 1.1-1.5; P = .01). Conclusion  Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status, especially among females, those with low educational attainment, and those with low household incomes.      

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.      

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.      

Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial

Context  No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers. Objective  To compare the effects of an insulin sensitizer, pioglitazone, with an insulin secretagogue, glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. Design, Setting, and Participants  Double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. Interventions  A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. Main Outcome Measure  Change in percent atheroma volume (PAV) from baseline to study completion. Results  Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with glimepiride and decreased 0.16% (95% CI, –0.57% to 0.25%) with pioglitazone(P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for glimepiride and a decrease of 0.06% (–0.47% to 0.35%) for pioglitazone (between-group P = .02). Mean (SD) baseline HbA_1c levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, –0.68% to –0.42%) with pioglitazone and 0.36% (95% CI, –0.48% to –0.24%) with glimepiride (between-group P = .03). In the pioglitazone group, compared with glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, –0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, –27.7 to –11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, –10.7 to 11.7 mg/dL; 0.6%) (P < .001 for both comparisons). Median fasting insulin levels decreased with pioglitazone and increased with glimepiride (P < .001). Hypoglycemia was more common in the glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the pioglitazone group. Conclusion  In patients with type 2 diabetes and coronary artery disease, treatment with pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride. Trial Registration  clinicaltrials.gov Identifier: NCT00225277      

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.      

The Use of Information Technologies Among Rural and Urban Physicians in Florida

This study examines rural–urban differences in the use of various information technologies (IT) applications by physicians in the ambulatory setting. Findings suggest that no differences exist between rural and urban physicians with respect to the use of a computer (77.4 vs 81.4; p = .144) or with the availability of an Internet connection (95.0 vs 96.5; p = .249) in the office. However, rural physicians were significantly less likely than urban doctors to indicate using e-mail with patients (7.9 vs 17.2%; p < .001) and slightly less likely to use a personal digital assistant (PDA) (32.3 vs 37.9; p = .091). Rural doctors were significantly less likely to indicate routinely using an electronic health records (EHR) system (17.6 vs 24.1; p = .020). EHR differences between rural and urban physicians were not significant (p = .124) in multivariate analyses and were explained away by practice size (p < .001) and practice type (p = .015). Most barriers to EHR did not differ between rural and urban physicians. However, rural physicians more commonly cited barriers associated with temporary disruptions to productivity or disruptions in access to records when computers systems fail. In sum, EHR use and patient e-mailing is less common in rural areas. While much of this variability can be explained by rural practice characteristics, these findings illustrate the need for further efforts to identify and alleviate barriers and encourage health IT adoption in rural areas.     

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.      

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.      

Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial

Beverly B. Green, MD, MPH; Andrea J. Cook, PhD; James D. Ralston, MD, MPH; Paul A. Fishman, PhD; Sheryl L. Catz, PhD; James Carlson, PharmD; David Carrell, PhD; Lynda Tyll, RN, MS; Eric B. Larson, MD, MPH; Robert S. Thompson, MD

JAMA. 2008;299(24):2857-2867.

Context  Treating hypertension decreases mortality and disability from cardiovascular disease, but most hypertension remains inadequately controlled.

Objective  To determine if a new model of care that uses patient Web services, home blood pressure (BP) monitoring, and pharmacist-assisted care improves BP control.

Design, Setting, and Participants  A 3-group randomized controlled trial, the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model. The trial was conducted at an integrated group practice in Washington state, enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access. Care was delivered over a secure patient Web site from June 2005 to December 2007.

Interventions  Participants were randomly assigned to usual care, home BP monitoring and secure patient Web site training only, or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications.

Main Outcome Measures  Percentage of patients with controlled BP (<140/90 mm Hg) and changes in systolic and diastolic BP at 12 months.

Results  Of 778 patients, 730 (94%) completed the 1-year follow-up visit. Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP (<140/90 mm Hg) compared with usual care (36% [95% confidence interval {CI}, 30%-42%] vs 31% [95% CI, 25%-37%]; P = .21). Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP (56%; 95% CI, 49%-62%) compared with usual care (P < .001) and home BP monitoring and Web training only (P < .001). Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care. Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups. Compared with usual care, the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP (–13.2 mm Hg [95% CI, –19.2 to –7.1]; P < .001) and diastolic BP (–4.6 mm Hg [95% CI, –8.0 to –1.2]; P < .001), and improved BP control (relative risk, 3.32 [95% CI, 1.86 to 5.94]; P<.001).

Conclusion  Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension.

Trial Registration  clinicaltrials.gov Identifier: NCT00158639

     

Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction

Context  In the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)–Thrombolysis in Myocardial Infarction (TIMI) 18 trial, patients with either unstable angina or non–ST-segment elevation myocardial infarction (UA/NSTEMI) treated with the platelet glycoprotein (Gp IIb/IIIa) inhibitor tirofiban had a significantly reduced rate of major cardiac events at 6 months with an early invasive vs a conservative strategy. Objective  To examine total 6-month costs and long-term cost-effectiveness of an invasive vs a conservative strategy. Design  Randomized controlled trial including a priori economic end points. Setting  Hospitalization for UA/NSTEMI with 6-month follow-up period. Patients  A total of 2220 patients with UA/NSTEMI; economic data from 1722 patients at US–non-VA hospitals. Intervention  Early invasive strategy with routine catheterization and revascularization as appropriate vs a conservative strategy with catheterization performed only for recurrent ischemia or a positive stress test. Main Outcome Measure  Total 6-month costs and incremental cost-effectiveness ratio. Results  The average initial hospitalization costs among those in the invasive strategy group were $15714 vs $14047 among those in the conservative stategy group, a difference of $1667 (95% confidence interval [CI], $387-3091). The in-hospital costs were offset significantly at the 6-month follow-up, with an average cost in the invasive group of $6098 vs $7180 in the conservative group, a difference of $1082 (95% CI, -$2051 to $76). The average total costs at 6 months, including productivity costs, for the invasive group was $21 813 vs $21 227 for the conservative group, a $586 difference (95% CI, -$1087 to $2486). The average 6-month costs excluding productivity costs in the invasive group was $19 780 vs $19 111 in the conservative group, a difference of $670, 95% CI; (-$1035 to $2321). Estimated cost per year of life gained for the invasive strategy, based on projected life expectancy, was $12739 for the base case, and ranged from $8371 to $25769, based on model assumptions. Conclusions  In patients with UA/NSTEMI treated with the Gp IIb/IIIa inhibitor tirofiban, the clinical benefit of an early invasive strategy was achieved with a small increase in cost, yielding favorable projected estimates of cost per year of life gained. These results support the broader use of an early invasive strategy in these patients.      

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.      

Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial

Context  Atherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. Objective  To assess whether statin therapy could slow progression and/or cause regression of carotid intima-media thickness (CIMT) over 2 years. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled study (Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin [METEOR]) of 984 individuals, with either age (mean, 57 years) as the only coronary heart disease risk factor or a 10-year FRS of less than 10%, modest CIMT thickening (1.2-<3.5 mm), and elevated LDL cholesterol (mean, 154 mg/dL); conducted at 61 primary care centers in the United States and Europe between August 2002 and May 2006. Intervention  Participants received either a 40-mg dose of rosuvastatin or placebo. Main Outcome Measures  Rate of change in maximum CIMT (assessed with B-mode ultrasound) for 12 carotid sites; changes in maximum CIMT of the common carotid artery, carotid bulb, and internal carotid artery sites and in mean CIMT of the common carotid artery sites. CIMT regression was assessed in the rosuvastatin group only. Results  Among participants in the rosuvastatin group, the mean (SD) baseline LDL cholesterol level of 155 (24.1) mg/dL declined to 78 (27.5) mg/dL, a mean reduction of 49% (P<.001 vs placebo group). The change in maximum CIMT for the 12 carotid sites was –0.0014 (95% CI, –0.0041 to 0.0014) mm/y for the rosuvastatin group vs 0.0131 (95% CI, 0.0087-0.0174) mm/y for the placebo group (P<.001). The change in maximum CIMT for the rosuvastatin group was –0.0038 (95% CI, –0.0064 to –0.0013) mm/y for the common carotid artery sites (P<.001), –0.0040 (95% CI, –0.0090 to 0.0010) mm/y for the carotid bulb sites (P<.001), and 0.0039 (95% CI, –0.0009 to 0.0088) mm/y for the internal carotid artery sites (P = .02). The change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 (95% CI, –0.0011 to 0.0019) mm/y (P<.001). All P values are vs placebo group. Overall, rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events (6 participants [0.86%] had 8 events [1.1%] over 2 years). Conclusions  In middle-aged adults with an FRS of less than 10% and evidence of subclinical atherosclerosis, rosuvastatin resulted in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo. Rosuvastatin did not induce disease regression. Larger, longer-term trials are needed to determine the clinical implications of these findings. Trial Registration  clinicaltrials.gov Identifier: NCT00225589      

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.      

Opening of specialty cardiac hospitals and use of coronary revascularization in medicare beneficiaries

Context  Although proponents argue that specialty cardiac hospitals provide high-quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization. Objective  To determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization. Design, Setting, and Patients  In a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151). Main Outcome Measures  Rates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations. Results  Overall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P<.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P<.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P<.001) and HRRs with no new programs (7.4% [95% CI, 3.2%-11.5%], P<.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P<.001). Conclusion  The opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries.      

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial

Context  Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. Objective  To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. Design, Setting, and Patients  Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. Intervention  Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative -blockers. Main Outcome Measure  Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. Results  Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative -blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative -blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. Conclusion  Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251706      

Medicine residents' understanding of the biostatistics and results in the medical literature

Context  Physicians depend on the medical literature to keep current with clinical information. Little is known about residents' ability to understand statistical methods or how to appropriately interpret research outcomes. Objective  To evaluate residents' understanding of biostatistics and interpretation of research results. Design, Setting, and Participants  Multiprogram cross-sectional survey of internal medicine residents. Main Outcome Measure  Percentage of questions correct on a biostatistics/study design multiple-choice knowledge test. Results  The survey was completed by 277 of 367 residents (75.5%) in 11 residency programs. The overall mean percentage correct on statistical knowledge and interpretation of results was 41.4% (95% confidence interval [CI], 39.7%-43.3%) vs 71.5% (95% CI, 57.5%-85.5%) for fellows and general medicine faculty with research training (P < .001). Higher scores in residents were associated with additional advanced degrees (50.0% [95% CI, 44.5%-55.5%] vs 40.1% [95% CI, 38.3%-42.0%]; P < .001); prior biostatistics training (45.2% [95% CI, 42.7%-47.8%] vs 37.9% [95% CI, 35.4%-40.3%]; P = .001); enrollment in a university-based training program (43.0% [95% CI, 41.0%-45.1%] vs 36.3% [95% CI, 32.6%-40.0%]; P = .002); and male sex (44.0% [95% CI, 41.4%-46.7%] vs 38.8% [95% CI, 36.4%-41.1%]; P = .004). On individual knowledge questions, 81.6% correctly interpreted a relative risk. Residents were less likely to know how to interpret an adjusted odds ratio from a multivariate regression analysis (37.4%) or the results of a Kaplan-Meier analysis (10.5%). Seventy-five percent indicated they did not understand all of the statistics they encountered in journal articles, but 95% felt it was important to understand these concepts to be an intelligent reader of the literature. Conclusions  Most residents in this study lacked the knowledge in biostatistics needed to interpret many of the results in published clinical research. Residency programs should include more effective biostatistics training in their curricula to successfully prepare residents for this important lifelong learning skill.      

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