Showing papers in "JAMA Internal Medicine in 2007"

Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials

Abstract: Background Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D 2 ] or cholecalciferol [vitamin D 3 ]) on any health condition. Methods The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. Results We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size–adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size–adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. Conclusions Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

Bringing the War Back Home: Mental Health Disorders Among 103 788 US Veterans Returning From Iraq and Afghanistan Seen at Department of Veterans Affairs Facilities

Abstract: Background Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) have endured high combat stress and are eligible for 2 years of free military service–related health care through the Department of Veterans Affairs (VA) health care system, yet little is known about the burden and clinical circumstances of mental health diagnoses among OEF/OIF veterans seen at VA facilities. Methods US veterans separated from OEF/OIF military service and first seen at VA health care facilities between September 30, 2001 (US invasion of Afghanistan), and September 30, 2005, were included. Mental health diagnoses and psychosocial problems were assessed usingInternational Classification of Diseases, Ninth Revision, Clinical Modificationcodes. The prevalence and clinical circumstances of and subgroups at greatest risk for mental health disorders are described herein. Results Of 103 788 OEF/OIF veterans seen at VA health care facilities, 25 658 (25%) received mental health diagnosis(es); 56% of whom had 2 or more distinct mental health diagnoses. Overall, 32 010 (31%) received mental health and/or psychosocial diagnoses. Mental health diagnoses were detected soon after the first VA clinic visit (median of 13 days), and most initial mental health diagnoses (60%) were made in nonmental health clinics, mostly primary care settings. The youngest group of OEF/OIF veterans (age, 18-24 years) were at greatest risk for receiving mental health or posttraumatic stress disorder diagnoses compared with veterans 40 years or older. Conclusions Co-occurring mental health diagnoses and psychosocial problems were detected early and in primary care medical settings in a substantial proportion of OEF/OIF veterans seen at VA facilities. Targeted early detection and intervention beginning in primary care settings are needed to prevent chronic mental illness and disability.

Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.

Abstract: Background: The results from small clinical studies suggest that therapy with adult bone marrow (BM)– derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. Methods: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. Results: Eighteen studies (N=999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P.001); reduced infarct scar size (�5.49%; 95% CI, �9.10% to �1.88%; P=.003); and reduced left ventricular end-systolic volume (�4.80 mL; 95% CI, �8.20 to �1.41 mL; P=.006). Conclusions: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes. Arch Intern Med. 2007;167:989-997

Prediction of Incident Diabetes Mellitus in Middle-aged Adults: The Framingham Offspring Study

Abstract: Background Prediction rules for type 2 diabetes mellitus (T2DM) have been developed, but we lack consensus for the most effective approach. Methods We estimated the 7-year risk of T2DM in middle-aged participants who had an oral glucose tolerance test at baseline. There were 160 cases of new T2DM, and regression models were used to predict new T2DM, starting with characteristics known to the subject (personal model, ie, age, sex, parental history of diabetes, and body mass index [calculated as the weight in kilograms divided by height in meters squared]), adding simple clinical measurements that included metabolic syndrome traits (simple clinical model), and, finally, assessing complex clinical models that included (1) 2-hour post–oral glucose tolerance test glucose, fasting insulin, and C-reactive protein levels; (2) the Gutt insulin sensitivity index; or (3) the homeostasis model insulin resistance and the homeostasis model insulin resistance β-cell sensitivity indexes. Discrimination was assessed with area under the receiver operating characteristic curves (AROCs). Results The personal model variables, except sex, were statistically significant predictors of T2DM (AROC, 0.72). In the simple clinical model, parental history of diabetes and obesity remained significant predictors, along with hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and impaired fasting glucose findings but not a large waist circumference (AROC, 0.85). Complex clinical models showed no further improvement in model discriminations (AROC, 0.850-0.854) and were not superior to the simple clinical model. Conclusion Parental diabetes, obesity, and metabolic syndrome traits effectively predict T2DM risk in a middle-aged white population sample and were used to develop a simple T2DM prediction algorithm to estimate risk of new T2DM during a 7-year follow-up interval.

Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey.

Abstract: Background Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. Methods We examined the association between serum levels of 25-hydroxyvitamin D (25[OH]D) and select cardiovascular disease risk factors in US adults. A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey, a national probability survey conducted by the National Center for Health Statistics between January 1, 1988, and December 31, 1994, with oversampling of persons 60 years and older, non-Hispanic black individuals, and Mexican American individuals. Results There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey. The mean 25(OH)D level in the overall sample was 30 ng/mL (75 nmol/L). The 25(OH)D levels were lower in women, elderly persons (≥60 years), racial/ethnic minorities, and participants with obesity, hypertension, and diabetes mellitus. The adjusted prevalence of hypertension (odds ratio [OR], 1.30), diabetes mellitus (OR, 1.98), obesity (OR, 2.29), and high serum triglyceride levels (OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels (P Conclusions Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults. Prospective studies to assess a direct benefit of cholecalciferol (vitamin D) supplementation on cardiovascular disease risk factors are warranted.

Health literacy and mortality among elderly persons.

Abstract: Background Individuals with low levels of health literacy have less health knowledge, worse self-management of chronic disease, lower use of preventive services, and worse health in cross-sectional studies We sought to determine whether low health literacy levels independently predict overall and cause-specific mortality Methods We designed a prospective cohort study of 3260 Medicare managed-care enrollees in 4 US metropolitan areas who were interviewed in 1997 to determine their demographic characteristics, chronic conditions, self-reported physical and mental health, and health behaviors Participants also completed the shortened version of the Test of Functional Health Literacy in Adults Main outcome measures included all-cause and cause-specific (cardiovascular, cancer, and other) mortality using data from the National Death Index through 2003 Results The crude mortality rates for participants with adequate (n = 2094), marginal (n = 366), and inadequate (n = 800) health literacy were 189%, 287%, and 394%, respectively ( P Conclusions Inadequate health literacy, as measured by reading fluency, independently predicts all-cause mortality and cardiovascular death among community-dwelling elderly persons Reading fluency is a more powerful variable than education for examining the association between socioeconomic status and health

Relations of Serum Phosphorus and Calcium Levels to the Incidence of Cardiovascular Disease in the Community

Abstract: Background Higher levels of serum phosphorus and the calcium-phosphorus product are associated with increased mortality from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) or prior CVD. However, it is unknown if serum phosphorus levels influence vascular risk in individuals without CKD or CVD. Methods We prospectively evaluated 3368 Framingham Offspring study participants (mean age, 44 years; 51% were women) free of CVD and CKD. We used multivariable Cox models to relate serum phosphorus and calcium levels to CVD incidence. Results On follow-up (mean duration, 16.1 years), there were 524 incident CVD events (159 in women). In multivariable analyses and adjusting for established risk factors and additionally for glomerular filtration rate and for hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, a higher level of serum phosphorus was associated with an increased CVD risk in a continuous fashion (adjusted hazard ratio per increment of milligrams per deciliter, 1.31; 95% confidence interval, 1.05-1.63; P = .02; P value for trend across quartiles = .004). Individuals in the highest serum phosphorus quartile experienced a multivariable-adjusted 1.55-fold CVD risk (95% confidence interval, 1.16%-2.07%; P = .004) compared with those in the lowest quartile. These findings remained robust in time-dependent models that updated CVD risk factors every 4 years and in analyses restricted to individuals without proteinuria and an estimated glomerular filtration rate greater than 90 mL/min per 1.73 m 2 . Serum calcium was not related to CVD risk. Conclusion Higher serum phosphorus levels are associated with an increased CVD risk in individuals free of CKD and CVD in the community. These observations emphasize the need for additional research to elucidate the potential link between phosphorus homeostasis and vascular risk.

Interventions to Enhance Medication Adherence in Chronic Medical Conditions: A Systematic Review

Abstract: Background Approximately 20% to 50% of patients are not adherent to medical therapy. This review was performed to summarize, categorize, and estimate the effect size (ES) of interventions to improve medication adherence in chronic medical conditions. Methods Randomized controlled trials published from January 1967 to September 2004 were eligible if they described 1 or more unconfounded interventions intended to enhance adherence with self-administered medications in the treatment of chronic medical conditions. Trials that reported at least 1 measure of medication adherence and 1 clinical outcome, with at least 80% follow-up during 6 months, were included. Study characteristics and results for adherence and clinical outcomes were extracted. In addition, ES was calculated for each outcome. Results Among 37 eligible trials (including 12 informational, 10 behavioral, and 15 combined informational, behavioral, and/or social investigations), 20 studies reported a significant improvement in at least 1 adherence measure. Adherence increased most consistently with behavioral interventions that reduced dosing demands (3 of 3 studies, large ES [0.89-1.20]) and those involving monitoring and feedback (3 of 4 studies, small to large ES [0.27-0.81]). Adherence also improved in 6 multisession informational trials (small to large ES [0.35-1.13]) and 8 combined interventions (small to large ES [absolute value, 0.43-1.20]). Eleven studies (4 informational, 3 behavioral, and 4 combined) demonstrated improvement in at least 1 clinical outcome, but effects were variable (very small to large ES [0.17-3.41]) and not consistently related to changes in adherence. Conclusion Several types of interventions are effective in improving medication adherence in chronic medical conditions, but few significantly affected clinical outcomes.

Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study.

Abstract: Background: Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of proinflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods: This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results: A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8-39.0) (P.001). Conclusions: The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest w hen b oth p roinflammatory a nd a ntiinflammatory cytokine levels are high.

Efficacy of communication skills training for giving bad news and discussing transitions to palliative care.

Abstract: Background Few studies have assessed the efficacy of communication skills training for postgraduate physician trainees at the level of behaviors. We designed a residential communication skills workshop (Oncotalk) for medical oncology fellows. The intervention design built on existing successful models by teaching specific communication tasks linked to the patient's trajectory of illness. This study evaluated the efficacy of Oncotalk in changing observable communication behaviors. Methods Oncotalk was a 4-day residential workshop emphasizing skills practice in small groups. This preintervention and postintervention cohort study involved 115 medical oncology fellows from 62 different institutions during a 3-year study. The primary outcomes were observable participant communication skills measured during standardized patient encounters before and after the workshop in giving bad news and discussing transitions to palliative care. The standardized patient encounters were audiorecorded and assessed by blinded coders using a validated coding system. Before-after comparisons were made using each participant as his or her own control. Results Compared with preworkshop standardized patient encounters, postworkshop encounters showed that participants acquired a mean of 5.4 bad news skills (P Conclusion Oncotalk represents a successful teaching model for improving communication skills for postgraduate medical trainees.

German Acupuncture Trials (Gerac) For Chronic Low Back Pain: Randomized, Multicenter, Blinded, Parallel-Group Trial With 3 Groups

Abstract: Methods A patient- and observer-blinded randomized controlled trial conducted in Germany involving 340 outpatient practices, including 1162 patients aged 18 to 86 years (mean ± SD age, 50 ± 15 years) with a history of chronic low back pain for a mean of 8 years. Patients underwent ten 30-minute sessions, generally 2 sessions per week, of verum acupuncture (n = 387) according to principles of traditional Chinese medicine; sham acupuncture (n = 387) consisting of superficial needling at nonacupuncture points; or conventional therapy, a combination of drugs, physical therapy, and exercise (n = 388). Five additional sessions were offered to patients who had a partial response to treatment (10%-50% reduction in pain intensity). Primary outcome was response after 6 months, defined as 33% improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale questionnaire or 12% improvement or better on the back-specific Hanover Functional Ability Questionnaire. Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement. Results At 6 months, response rate was 47.6% in the verum acupuncture group, 44.2% in the sham acupuncture group, and 27.4% in the conventional therapy group. Differences among groups were as follows: verum vs sham, 3.4% (95% confidence interval, –3.7% to 10.3%; P = .39); verum vs conventional therapy, 20.2% (95% confidence interval, 13.4% to 26.7%; P < .001); and sham vs conventional therapy, 16.8% (95% confidence interval, 10.1% to 23.4%; P < .001.

Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life

Abstract: Background Depressive symptoms are common among patients with chronic obstructive pulmonary disease (COPD), but depression’s impact on COPD outcomes has not been fully investigated. We evaluated the impact of comorbid depression on mortality, hospital readmission, smoking behavior, respiratory symptom burden, and physical and social functioning in patients with COPD. Methods In this prospective cohort study, 376 consecutive patients with COPD hospitalized for acute exacerbation were followed up for 1 year. The independent associations of baseline comorbid depression (designated as a Hospital Anxiety and Depression Scale score of ≥8) with mortality, hospital readmission, length of stay, persistent smoking, and quality of life (determined by responses to the St George Respiratory Questionnaire) were evaluated after adjusting for potential confounders. Results The prevalence of depression at admission was 44.4%. The median follow-up duration was 369 days, during which 57 patients (15.2%) died, and 202 (53.7%) were readmitted at least once. Multivariate analyses showed that depression was significantly associated with mortality (hazard ratio, 1.93; 95% confidence interval, 1.04-3.58), longer index stay (mean, 1.1 more days;P = .02) and total stay (mean, 3.0 more days;P = .047), persistent smoking at 6 months (odds ratio, 2.30; 95% confidence interval, 1.17-4.52), and 12% to 37% worse symptoms, activities, and impact subscale scores and total score on the St George Respiratory Questionnaire at the index hospitalization and 1 year later, even after controlling for chronicity and severity of COPD, comorbidities, and behavioral, psychosocial, and socioeconomic variables. Conclusions Comorbid depressive symptoms in patients with COPD are associated with poorer survival, longer hospitalization stay, persistent smoking, increased symptom burden, and poorer physical and social functioning. Interventions that reduce depressive symptoms may potentially affect COPD outcomes.

Comparison of Outcomes Among Patients Randomized to Warfarin Therapy According to Anticoagulant Control: Results From SPORTIF III and V

Abstract: Background Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) may be related to INR control. Methods We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials. The mean±SD follow-up was 16.6 ± 6.3 months. Patients were divided into 3 equal groups (those with good control [>75%], those with moderate control [60%-75%], or those with poor control [ Results The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good control group (1.69% and 1.58%, respectively) ( P P = .04) and of stroke or SEE (2.10% vs 1.07%, P = .02). Conclusions In patients with atrial fibrillation taking warfarin, the risks of death, MI, major bleeding, and stroke or SEE are related to INR control. Good INR control is important to improve patient outcomes.

Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons.

Abstract: Background: The extent to which moderate overweight (body mass index [BMI], 25.0-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI, 30.0) are associated with increased risk of coronary heart disease (CHD) through adverse effects on blood pressure and cholesterol levels is unclear, as is the risk of CHD that remains after these mediating effects are considered. Methods: Relative risks (RRs) of CHD associated with moderate overweight and obesity with and without adjustment for blood pressure and cholesterol concentrations were calculated by the members of a collaboration of prospective cohort studies of healthy, mainly white persons and pooled by means of random-effects models (RRs for categories of BMI in 14 cohorts and for continuous BMI in 21 cohorts; total N=302 296). Results: A total of 18 000 CHD events occurred during follow-up. The age-, sex-, physical activity–, and smokingadjusted RRs (95% confidence intervals) for moderate overweight and obesity compared with normal weight were 1.32 (1.24-1.40) and 1.81 (1.56-2.10), respectively. Additional adjustment for blood pressure and cholesterol levels reduced the RR to 1.17 (1.11-1.23) for moderate overweight and to 1.49 (1.32-1.67) for obesity. The RR associated with a 5-unit BMI increment was 1.29 (1.221.35) before and 1.16 (1.11-1.21) after adjustment for blood pressure and cholesterol levels. Conclusions: Adverse effects of overweight on blood pressure and cholesterol levels could account for about 45% of the increased risk of CHD. Even for moderate overweight, there is a significant increased risk of CHD independent of these traditional risk factors, although confounding (eg, by dietary factors) cannot be completely ruled out.

Bleeding Complications With Warfarin Use: A Prevalent Adverse Effect Resulting in Regulatory Action

Abstract: Background Warfarin sodium is widely used and causes bleeding; a review might suggest the need for regulatory action by the US Food and Drug Administration (FDA). Methods We accessed warfarin prescriptions from the National Prescription Audit Plus database of IMS Health (Plymouth Meeting, Pennsylvania), adverse event reports submitted to the FDA, deaths due to therapeutic use of anticoagulants from vital statistics data, and warfarin bleeding complications from national hospital emergency department data. Results The number of dispensed outpatient prescriptions for warfarin increased 45%, from 21 million in 1998 to nearly 31 million in 2004. The FDA's Adverse Event Reporting System indicated that warfarin is among the top 10 drugs with the largest number of serious adverse event reports submitted during the 1990 and 2000 decades. From US death certificates, anticoagulants ranked first in 2003 and 2004 in the number of total mentions of deaths for drugs causing “adverse effects in therapeutic use.” Data from hospital emergency departments for 1999 through 2003 indicated that warfarin was associated with about 29 000 visits for bleeding complications per year, and it was among the drugs with the most visits. These data are consistent with literature reports of major bleeding frequencies for warfarin as high as 10% to 16%. Conclusions Use of warfarin has increased, and bleeding from warfarin use is a prevalent reaction and an important cause of mortality. Consequently, a “black box” warning about warfarin's bleeding risk was added to the US product labeling in 2006. Physicians and nurses should tell patients to immediately report signs and symptoms of bleeding. A Medication Guide, which is required to be provided with each prescription, reinforces this message.

A Drug Burden Index to Define the Functional Burden of Medications in Older People

Abstract: Background Older people carry a high burden of illness for which medications are indicated, along with increased risk of adverse drug reactions. We developed an index to determine drug burden based on pharmacologic principles. We evaluated the relationship of this index to physical and cognitive performance apart from disease indication. Methods Data from the Health, Aging, and Body Composition Study on 3075 well-functioning community-dwelling persons aged 70 to 79 years were analyzed by multiple linear regression to assess the cross-sectional association of drug burden index with a validated composite continuous measure for physical function, and with the Digit Symbol Substitution Test for cognitive performance. Results Use of anticholinergic and sedative medications was associated with poorer physical performance score (anticholinergic exposure, 2.08 vs 2.21, P P P = .045; sedative exposure, 34.0 vs 35.5, P = .01). Associations were strengthened when exposure was calculated by principles of dose response. An increase of 1 U in drug burden index was associated with a deficit of 0.15 point ( P P = .01) on the Digit Symbol Substitution Test. These values were more than 3 times those associated with a single comorbid illness. Conclusions The drug burden index demonstrates that anticholinergic and sedative drug exposure is associated with poorer function in community-dwelling older people. This pharmacologic approach provides a useful evidence-based tool for assessing the functional effect of exposure to medications in this population.

The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials.

Abstract: Background: Continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea syndrome (OSAS) might lower blood pressure, but evidence from clinical studies is inconsistent, perhaps as a result of small sample size or heterogeneity in study design. This study aimed to assess whether CPAP reduces ambulatory blood pressure in patients with OSAS, to quantify the effect size with precision, and to identify trial characteristics associated with the greatest blood pressure reductions.

Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis

Abstract: Background Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies. Methods Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level. Results Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P Conclusions Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.

Fiber and Magnesium Intake and Incidence of Type 2 Diabetes A Prospective Study and Meta-analysis

Abstract: Background Prospective studies on fiber and magnesium intake and risk of type 2 diabetes mellitus were inconsistent. We examined associations between fiber and magnesium intake and risk of type 2 diabetes and summarized existing prospective studies by meta-analysis. Methods We conducted a prospective cohort study of 9702 men and 15 365 women aged 35 to 65 years who were observed for incident diabetes from 1994 to 2005. Dietary intake of fiber and magnesium were measured with a validated food-frequency questionnaire. We estimated the relative risk (RR) by means of Cox proportional hazards analysis. We searched PubMed through May 2006 for prospective cohort studies of fiber and magnesium intake and risk of type 2 diabetes. We identified 9 cohort studies of fiber and 8 studies of magnesium intake and calculated summary RRs by means of a random-effects model. Results During 176 117 person-years of follow-up, we observed 844 incident cases of type 2 diabetes in the European Prospective Investigation Into Cancer and Nutrition–Potsdam. Higher cereal fiber intake was inversely associated with diabetes risk (RR for extreme quintiles, 0.72 [95% confidence interval [CI], 0.56-0.93]), while fruit fiber (0.89 [95% CI, 0.70-1.13]) and vegetable fiber (0.93 [95% CI, 0.74-1.17]) were not significantly associated. Meta-analyses showed a reduced diabetes risk with higher cereal fiber intake (RR for extreme categories, 0.67 [95% CI, 0.62-0.72]), but no significant associations for fruit (0.96 [95% CI, 0.88-1.04]) and vegetable fiber (1.04 [95% CI, 0.94-1.15]). Magnesium intake was not related to diabetes risk in the European Prospective Investigation Into Cancer and Nutrition–Potsdam (RR for extreme quintiles, 0.99 [95% CI, 0.78-1.26]); however, meta-analysis showed a significant inverse association (RR for extreme categories, 0.77 [95% CI, 0.72-0.84]). Conclusion Higher cereal fiber and magnesium intakes may decrease diabetes risk.

Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis.

Abstract: Background There is no consensus whether tobacco smoking increases risk of tuberculosis (TB) infection, disease, or mortality. Whether this is so has substantial implications for tobacco and TB control policies. Objective To quantify the relationship between active tobacco smoking and TB infection, pulmonary disease, and mortality using meta-analytic methods. Methods Eight databases (PubMed, Current Contents, BIOSIS, EMBASE, Web of Science, Centers for Disease Control and Prevention Tobacco Information and Prevention Source [TIPS], Smoking and Health Database [Institute for Science and Health], and National Library of Medicine Gateway) and the Cochrane Tobacco Addiction Group Trials Register were searched for relevant articles published between 1953 and 2005. Study Selection Included were epidemiologic studies that provided a relative risk (RR) estimate for the association between TB (infection, pulmonary disease, or mortality) and active tobacco smoking stratified by (or adjusted for) at least age and sex and a corresponding 95% confidence interval (CI) (or data for calculation). Excluded were reports of extrapulmonary TB, studies conducted in populations prone to high levels of smoking or high rates of TB, and case-control studies in which controls were not representative of the population that generated the cases, as well as case series, case reports, abstracts, editorials, and literature reviews. Data Extraction Twenty-four studies were included in the meta-analysis. Extracted data included study design, population and diagnostic details, smoking type, and TB outcomes. Data Synthesis A random-effects model was used to pool data across studies. Separate analyses were performed for TB infection (6 studies), TB disease (13 studies), and TB mortality (5 studies). For TB infection, the summary RR estimate was 1.73 (95% CI, 1.46-2.04); for TB disease, estimates ranged from 2.33 (95% CI, 1.97-2.75) to 2.66 (95% CI, 2.15-3.28). This suggests an RR of 1.4 to 1.6 for development of disease in an infected population. The TB mortality RRs were mostly below the TB disease RRs, suggesting no additional mortality risk from smoking in those with active TB. Conclusions The meta-analysis produced evidence that smoking is a risk factor for TB infection and TB disease. However, it is not clear that smoking causes additional mortality risk in persons who already have active TB. Tuberculosis control policies should in the future incorporate tobacco control as a preventive intervention.

Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study.

Abstract: Background: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality. Methods: Study participants included 214 284 men and 166 012 women in the National Institutes of Health (NIH)-AARP ( formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27 799 deaths were documented. In the first 5 years of follow-up, 5985 cancer deaths and 3451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern ( components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models. Results: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 ( 95% CI, 0.76-0.83), 0.78 ( 95% CI, 0.69-0.87), and 0.83 ( 95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P=.04 and P <.001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged. Conclusion: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population.

A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women: Results From the Women's Antioxidant Cardiovascular Study

Abstract: Background Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD. Methods The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 × 2 × 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005. Results A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04];Pvalue for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (Pvalue for interaction, .03). Conclusion There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD. Trial Registration clinicaltrials.gov Identifier:NCT00000541

Electronic health record use and the quality of ambulatory care in the United States.

Abstract: Background: Electronic health records (EHRs) have been proposed as a sustainable solution for improving the quality of medical care. We assessed the association betweenEHRuse,asimplemented,andthequalityofambulatory care in a nationally representative survey. Methods: We performed a retrospective, crosssectional analysis of visits in the 2003 and 2004 National Ambulatory Medical Care Survey. We examined EHR use throughout the United States and the association of EHR use with 17 ambulatory quality indicators. Performanceonqualityindicatorswasdefinedasthepercentageofapplicablevisitsinwhichpatientsreceivedrecommended care. Results:Electronichealthrecordswereusedin18%(95% confidence interval [CI], 15%-22%) of the estimated 1.8 billion ambulatory visits (95% CI, 1.7-2.0 billion) in the United States in 2003 and 2004. For 14 of the 17 quality indicators, there was no significant difference in performance between visits with vs without EHR use. Categories of these indicators included medical management of common diseases, recommended antibiotic prescribing, preventive counseling, screening tests, and avoiding potentially inappropriate medication prescribing in elderly patients. For 2 quality indicators, visits to medical practices using EHRs had significantly better performance:avoidingbenzodiazepineuseforpatientswithde

Obesity, Waist Circumference, Weight Change, and the Risk of Psoriasis in Women: Nurses' Health Study II

Abstract: Background Psoriasis is a common, chronic, inflammatory skin disorder. Higher adiposity may increase the risk of psoriasis, but, to our knowledge, no prospective data are available on this relationship. Methods We prospectively examined the relationships between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight change, waist circumference, hip circumference, waist-hip ratio, and incident psoriasis in 78 626 women over a 14-year period (1991-2005) in the Nurses’ Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis. Results During the 14 years of follow-up, there were 892 self-reported incident cases of psoriasis. There was a graded positive association between BMI measured at multiple time points and the risk of incident psoriasis. When we analyzed BMI updated every 2 years, compared with a BMI of 21.0 through 22.9, the multivariate relative risks of psoriasis were 1.40 (95% confidence interval [CI], 1.13-1.73) for a BMI of 25.0 through 29.9; 1.48 (95% CI, 1.15-1.91) for a BMI of 30.0 through 34.9; and 2.69 (95% CI, 2.12-3.40) for a BMI of 35.0 or greater ( P for trend, P for trend, P values for trend, Conclusion This large prospective study indicates that increased adiposity and weight gain are strong risk factors for incident psoriasis in women.

Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998-2005

Abstract: Background The US Food and Drug Administration has operated the Adverse Event Reporting System since 1998. It collects all voluntary reports of adverse drug events submitted directly to the agency or through drug manufacturers. Methods Using extracts published for research use, we analyzed all serious adverse drug events and medication errors in the United States reported to the Food and Drug Administration from 1998 through 2005. Results From 1998 through 2005, reported serious adverse drug events increased 2.6-fold from 34 966 to 89 842, and fatal adverse drug events increased 2.7-fold from 5519 to 15 107. Reported serious events increased 4 times faster than the total number of outpatient prescriptions during the period. In a subset of drugs with 500 or more cases reported in any year, drugs related to safety withdrawals accounted for 26% of reported events in that group in 1999, declining to less than 1% in 2005. For 13 new biotechnology products, reported serious events grew 15.8-fold, from 580 reported in 1998 to 9181 in 2005. The increase was influenced by relatively few drugs: 298 of the 1489 drugs identified (20%) accounted for 407 394 of the 467 809 events (87%). Conclusions These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period. The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs.

Prognostic Factors in Heat Wave–Related Deaths: A Meta-analysis

Abstract: Background Although identifying individuals who are at increased risk of dying during heat waves and instituting protective measures represent an established strategy, the evidence supporting the components of this strategy and their strengths has yet to be evaluated. We conducted a meta-analysis of observational studies on risk and protective factors in heat wave–related deaths. Methods Using the OVID interface, we searched Medline (1966-2006) and CINHAL (1982-2006) databases. The Web sites of the World Health Organization, Institut National de Veille Sanitaire, and Centers for Disease Control and Prevention were also visited. The search terms included heat wave , heat stroke , heatstroke , sunstroke , and heat stress disorders . Eligible studies were case-control or cohort studies. Odds ratios (ORs) and information on study quality were abstracted by 2 investigators independently. Six case-control studies involving 1065 heat wave–related deaths were identified. Results Being confined to bed (OR, 6.44; 95% confidence interval [CI], 4.5-9.2), not leaving home daily (OR, 3.35; 95% CI, 1.6-6.9), and being unable to care for oneself (OR, 2.97; 95% CI, 1.8-4.8) were associated with the highest risk of death during heat waves. Preexisting psychiatric illness (OR, 3.61; 95% CI, 1.3-9.8) tripled the risk of death, followed by cardiovascular (OR, 2.48; 95% CI, 1.3-4.8) and pulmonary (OR, 1.61; 95% CI, 1.2-2.1) illness. Working home air-conditioning (OR, 0.23; 95% CI, 0.1-0.6), visiting cool environments (OR, 0.34; 95% CI, 0.2-0.5), and increasing social contact (OR, 0.40; 95% CI, 0.2-0.8) were strongly associated with better outcomes. Taking extra showers or baths (OR, 0.32; 95% CI, 0.1-1.1) and using fans (OR, 0.60; 95% CI, 0.4-1.1) were associated with a trend toward lower risk of death. Conclusion The present study identified several prognostic factors that could help to detect those individuals who are at highest risk during heat waves and to provide a basis for potential risk-reducing interventions in the setting of heat waves. Published online August 13, 2007 (doi:10.1001/archinte.167.20.ira70009).

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.

Abstract: Background Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation. Methods A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevencion con Dieta Mediterranea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n = 121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months. Results After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (−10.6 U/L [−14.2 to −6.1]) and TMD + nuts (−7.3 U/L [−11.2 to −3.3]) groups, without changes in the low-fat diet group (−2.9 U/L [−7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group ( P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. Conclusions Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD. Trial Registration isrctn.org Identifier:ISRCTN35739639

Prospective study of dietary carbohydrates, glycemic index, glycemic load, and incidence of type 2 diabetes mellitus in middle-aged Chinese women.

Abstract: Background Much uncertainty exists about the role of dietary glycemic index and glycemic load in the development of type 2 diabetes mellitus, especially in populations that traditionally subsist on a diet high in carbohydrates. Methods We observed a cohort of 64 227 Chinese women with no history of diabetes or other chronic disease at baseline for 4.6 years. In-person interviews were conducted to collect data on dietary habits, physical activity, and other relevant information using a validated questionnaire. Incident diabetes cases were identified via in-person follow-up. Associations between dietary carbohydrate intake, glycemic index, and glycemic load and diabetes incidence were evaluated using multivariable Cox proportional hazards models. Results We identified 1608 incident cases of type 2 diabetes mellitus in 297 755 person-years of follow-up. Dietary carbohydrate intake and consumption of rice were positively associated with risk of developing type 2 diabetes mellitus. The multivariable-adjusted estimates of relative risk comparing the highest vs the lowest quintiles of intake were 1.28 (95% confidence interval, 1.09-1.50) for carbohydrates and 1.78 (95% confidence interval, 1.48-2.15) for rice. The relative risk for increasing quintiles of intake was 1.00, 1.04, 1.02, 1.09, and 1.21 (95% confidence interval, 1.03-1.43) for dietary glycemic index and 1.00, 1.06, 0.97, 1.23, and 1.34 (95% confidence interval, 1.13-1.58) for dietary glycemic load. Conclusion High intake of foods with a high glycemic index and glycemic load, especially rice, the main carbohydrate-contributing food in this population, may increase the risk of type 2 diabetes mellitus in Chinese women.

Physical activity recommendations and decreased risk of mortality.

Abstract: Background: Whether national physical activity recommendations are related to mortality benefit is incompletely understood. Methods: We prospectively examined physical activity guidelines in relation to mortality among 252925 women and men aged 50 to 71 years in the National Institutes of Health–American Association of Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed using 2 self-administered baseline questionnaires. Results: During 1265347 person-years of follow-up, 7900 participants died. Compared with being inactive, achievement of activity levels that approximate the recommendations for moderate activity (at least 30 minutes on most days of the week) or vigorous exercise (at least 20 minutes 3 times per week) was associated with a 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.68-0.78) and 32% (RR, 0.68; 95% CI, 0.64-0.73) decreased mortality risk, respectively. Physical activity reflective of meeting both recommendations was relatedtosubstantiallydecreasedmortalityriskoverall(RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers (RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers (RR, 0.54; 95% CI, 0.45-0.64), normal weight (RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals (RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d (RR, 0.53; 95% CI, 0.44-0.63) and more than 2 h/d of television or video watching (RR, 0.50; 95% CI, 0.450.55). Engaging in physical activity at less than recommended levels was also related to reduced mortality risk (RR, 0.81; 95% CI, 0.76-0.86). Conclusions: Following physical activity guidelines is associatedwithlowerriskofdeath.Mortalitybenefitmay also be achieved by engaging in less than recommended activity levels.

Association of Laboratory-Defined Aspirin Resistance With a Higher Risk of Recurrent Cardiovascular Events: A Systematic Review and Meta-analysis

Abstract: Background The risk of recurrence of cardiovascular events among patients using aspirin (acetylsalicylic acid) for secondary prevention of such events remains high. Persistent platelet reactivity despite aspirin therapy, a laboratory-defined phenomenon called aspirin resistance (hereinafter, laboratory aspirin resistance), might explain this in part, but its actual contribution to the risk remains unclear. The objective of this study was to systematically review all available evidence on whether laboratory aspirin resistance is related to a higher risk of cardiovascular recurrent events. Methods Using a predefined search strategy, we searched electronic databases. To be included in our analysis, articles had to report on patients who used aspirin for secondary cardiovascular prevention, had to contain a clear description of a method to establish the effects of aspirin on platelet reactivity, and had to report recurrence rates of cardiovascular events. Odds ratios of cardiovascular outcome of eligible studies were pooled in a random-effects model. Results We included 15 full-text articles and 1 meeting abstract. Fifteen of these studies revealed an adverse association between laboratory aspirin resistance and occurrence of cardiovascular events. The pooled odds ratio of all cardiovascular outcomes was 3.8 (95% confidence interval, 2.3-6.1) for laboratory aspirin resistance. Conclusion This systematic review and meta-analysis shows that patients biochemically identified as having laboratory aspirin resistance are more likely to also have “clinical resistance” to aspirin because they exhibit significantly higher risks of recurrent cardiovascular events compared with patients who are identified as (laboratory) aspirin sensitive.