Showing papers in "JAMA in 2009"

International Study of the Prevalence and Outcomes of Infection in Intensive Care Units

Abstract: Context Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. Objective To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. Design, Setting, and Patients The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14 414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13 796 adult (>18 years) patients. Results On the day of the study, 7087 of 13 796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively; P Conclusions Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.

Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women: A Meta-analysis

Abstract: Context Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants. Objective To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women. Data Sources and Study Selection A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included. Data Extraction Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF ( Data Synthesis Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P Conclusions Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with a MAC of less 7.9 METs.

Major lipids, apolipoproteins, and risk of vascular disease

Abstract: CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes. MAIN OUTCOME MEASURES: Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non-HDL-C. CONCLUSION: Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.

Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention

Abstract: A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways—either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease. From both basic research and policy perspectives, confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood.

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Abstract: Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. Design, Setting, and Participants A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. Interventions Oral selenium (200 μg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. Main Outcome Measures Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. Results As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. Trial Registration clinicaltrials.gov identifier: NCT00006392Published online December 9, 2008 (doi:10.1001/jama.2008.864).

Diabetes in Asia: epidemiology, risk factors, and pathophysiology.

Abstract: Context With increasing globalization and East-West exchanges, the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implications. Objective To review recent data in epidemiologic trends, risk factors, and complications of type 2 diabetes in Asia. Evidence Acquisition Search of MEDLINE using the term diabetes and other relevant keywords to identify meta-analyses, systematic reviews, large surveys, and cohort studies. Separate searches were performed for specific Asian countries. The review was limited to English-language articles published between January 1980 and March 2009; publications on type 1 diabetes were excluded. Evidence Synthesis The prevalence of diabetes in Asian populations has increased rapidly in recent decades. In 2007, more than 110 million individuals in Asia were living with diabetes, with a disproportionate burden among the young and middle aged. Similarly, rates of overweight and obesity are increasing sharply, driven by economic development, nutrition transition, and increasingly sedentary lifestyles. The “metabolically obese” phenotype (ie, normal body weight with increased abdominal adiposity) is common in Asian populations. The increased risk of gestational diabetes, combined with exposure to poor nutrition in utero and overnutrition in later life in some populations, may contribute to the increasing diabetes epidemic through “diabetes begetting diabetes” in Asia. While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications, cancer is emerging as an important cause of morbidity and mortality. Conclusions Type 2 diabetes is an increasing epidemic in Asia, characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index. Prevention and control of diabetes should be a top public health priority in Asian populations.

Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.

Abstract: Context Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes. Objective To test the efficacy and safety of exercise training among patients with heart failure. Design, Setting, and Patients Multicenter, randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months. Interventions Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone. Main Outcome Measures Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization. Results The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Heart failure etiology was ischemic in 51%, and median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 patients (65%) in the exercise training group died or were hospitalized compared with 796 patients (68%) in the usual care group (hazard ratio [HR], 0.93 [95% confidence interval {CI}, 0.84-1.02]; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 patients [16%] in the exercise training group vs 198 patients [17%] in the usual care group; HR, 0.96 [95% CI, 0.79-1.17]; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise training group vs 677 [58%] in the usual care group; HR, 0.92 [95% CI, 0.83-1.03]; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise training group vs 393 [34%] in the usual care group; HR, 0.87 [95% CI, 0.75-1.00]; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81-0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82-1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74-0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups. Conclusions In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization. Trial Registration clinicaltrials.gov Identifier: NCT00047437

Association of Torture and Other Potentially Traumatic Events With Mental Health Outcomes Among Populations Exposed to Mass Conflict and Displacement: A Systematic Review and Meta-analysis

Abstract: Context Uncertainties continue about the roles that methodological factors and key risk factors, particularly torture and other potentially traumatic events (PTEs), play in the variation of reported prevalence rates of posttraumatic stress disorder (PTSD) and depression across epidemiologic surveys among postconflict populations worldwide. Objective To undertake a systematic review and meta-regression of the prevalence rates of PTSD and depression in the refugee and postconflict mental health field. Data Sources An initial pool of 5904 articles, identified through MEDLINE, PsycINFO and PILOTS, of surveys involving refugee, conflict-affected populations, or both, published in English-language journals between 1980 and May 2009. Study Selection Surveys were limited to those of adult populations (n ≥ 50) reporting PTSD prevalence, depression prevalence, or both. Excluded surveys comprised patients, war veterans, and civilian populations (nonrefugees/asylum seekers) from high-income countries exposed to terrorist attacks or involved in distal conflicts (≥25 years). Data Extraction Methodological factors (response rate, sample size and design, diagnostic method) and substantive factors (sociodemographics, place of survey, torture and other PTEs, Political Terror Scale score, residency status, time since conflict). Data Synthesis A total of 161 articles reporting results of 181 surveys comprising 81 866 refugees and other conflict-affected persons from 40 countries were identified. Rates of reported PTSD and depression showed large intersurvey variability (0%-99% and 3%-85.5%, respectively). The unadjusted weighted prevalence rate reported across all surveys for PTSD was 30.6% (95% CI, 26.3%-35.2%) and for depression was 30.8% (95% CI, 26.3%-35.6%). Methodological factors accounted for 12.9% and 27.7% PTSD and depression, respectively. Nonrandom sampling, small sample sizes, and self-report questionnaires were associated with higher rates of mental disorder. Adjusting for methodological factors, reported torture (Δ total R 2 between base methodological model and base model + substantive factor [ΔR 2 ] = 23.6%; OR, 2.01; 95% CI, 1.52-2.65) emerged as the strongest factor associated with PTSD, followed by cumulative exposure to PTEs (ΔR 2 = 10.8%; OR, 1.52; 95% CI, 1.21-1.91), time since conflict (ΔR 2 = 10%; OR, 0.77; 95% CI, 0.66-0.91), and assessed level of political terror (ΔR 2 = 3.5%; OR, 1.60; 95% CI, 1.03-2.50). For depression, significant factors were number of PTEs (ΔR 2 = 22.0%; OR, 1.64; 95% CI, 1.39-1.93), time since conflict (ΔR 2 = 21.9%; OR, 0.80; 95% CI, 0.69-0.93), reported torture (ΔR 2 = 11.4%; OR, 1.48; 95% CI, 1.07-2.04), and residency status (ΔR 2 = 5.0%; OR, 1.30; 95% CI, 1.07-1.57). Conclusion Methodological factors and substantive population risk factors, such as exposure to torture and other PTEs, after adjusting for methodological factors account for higher rates of reported prevalence of PTSD and depression.

Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression: A Meta-analysis

Abstract: Context Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. Objective To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Data Sources Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Study Selection Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, ≥3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Data Extraction Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14 250 participants, 1769 were classified as having depression; 12 481 as not having depression. Results In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. Conclusion This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

Association of an Educational Program in Mindful Communication With Burnout, Empathy, and Attitudes Among Primary Care Physicians

Abstract: Context Primary care physicians report high levels of distress, which is linked to burnout, attrition, and poorer quality of care. Programs to reduce burnout before it results in impairment are rare; data on these programs are scarce. Objective To determine whether an intensive educational program in mindfulness, communication, and self-awareness is associated with improvement in primary care physicians' well-being, psychological distress, burnout, and capacity for relating to patients. Design, Setting, and Participants Before-and-after study of 70 primary care physicians in Rochester, New York, in a continuing medical education (CME) course in 2007-2008. The course included mindfulness meditation, self-awareness exercises, narratives about meaningful clinical experiences, appreciative interviews, didactic material, and discussion. An 8-week intensive phase (2.5 h/wk, 7-hour retreat) was followed by a 10-month maintenance phase (2.5 h/mo). Main Outcome Measures Mindfulness (2 subscales), burnout (3 subscales), empathy (3 subscales), psychosocial orientation, personality (5 factors), and mood (6 subscales) measured at baseline and at 2, 12, and 15 months. Results Over the course of the program and follow-up, participants demonstrated improvements in mindfulness (raw score, 45.2 to 54.1; raw score change [Δ], 8.9; 95% confidence interval [CI], 7.0 to 10.8); burnout (emotional exhaustion, 26.8 to 20.0; Δ = −6.8; 95% CI, −4.8 to −8.8; depersonalization, 8.4 to 5.9; Δ = −2.5; 95% CI, −1.4 to −3.6; and personal accomplishment, 40.2 to 42.6; Δ = 2.4; 95% CI, 1.2 to 3.6); empathy (116.6 to 121.2; Δ = 4.6; 95% CI, 2.2 to 7.0); physician belief scale (76.7 to 72.6; Δ = −4.1; 95% CI, −1.8 to −6.4); total mood disturbance (33.2 to 16.1; Δ = −17.1; 95% CI, −11 to −23.2), and personality (conscientiousness, 6.5 to 6.8; Δ = 0.3; 95% CI, 0.1 to 5 and emotional stability, 6.1 to 6.6; Δ = 0.5; 95% CI, 0.3 to 0.7). Improvements in mindfulness were correlated with improvements in total mood disturbance (r = −0.39, P Conclusions Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care. Because before-and-after designs limit inferences about intervention effects, these findings warrant randomized trials involving a variety of practicing physicians.

Extracorporeal membrane oxygenation for 2009 Influenza A (H1N1) Acute Respiratory Distress Syndrome

Abstract: Context The novel influenza A(H1N1) pandemic affected Australia and New Zealand during the 2009 southern hemisphere winter. It caused an epidemic of critical illness and some patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO). Objectives To describe the characteristics of all patients with 2009 influenza A(H1N1)-associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes. Design, setting, and patients An observational study of all patients (n = 68) with 2009 influenza A(H1N1)-associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009. Main outcome measures Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival. Results Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n = 53) or influenza A not subtyped (n = 8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 (26.6-43.1) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H(2)O, and an acute lung injury score of 3.8 (3.5-4.0). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO. Conclusions During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)-associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period.

Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy

Abstract: Context Clopidogrel therapy improves cardiovascular outcomes in patients with acute coronary syndromes and following percutaneous coronary intervention by inhibiting adenosine diphosphate (ADP)–dependent platelet activation. However, nonresponsiveness is widely recognized and is related to recurrent ischemic events. Objective To identify gene variants that influence clopidogrel response. Design, Setting, and Participants In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 healthy Amish persons and measured response by ex vivo platelet aggregometry. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention. Main Outcome Measure ADP-stimulated platelet aggregation in response to clopidogrel treatment and cardiovascular events. Results Platelet response to clopidogrel was highly heritable (h 2 = 0.73; P −13 for rs12777823, additive model). The rs12777823 polymorphism was in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished clopidogrel response, accounting for 12% of the variation in platelet aggregation to ADP (P = 4.3 × 10 −11 ). The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention (P = .02). Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death during 1 year of follow-up (hazard ratio, 2.42; 95% confidence interval, 1.18-4.99; P = .02). Conclusion CYP2C19*2 genotype was associated with diminished platelet response to clopidogrel treatment and poorer cardiovascular outcomes.

Mortality Risk Associated With Low-Trauma Osteoporotic Fracture and Subsequent Fracture in Men and Women

Abstract: 2.93] and 3.51 [95% CI, 2.65-4.66]), vertebral fractures (SMRs, 1.82 [95% CI, 1.522.17] and 2.12 [95% CI, 1.66-2.72]), major fractures (SMRs, 1.65 [95% CI, 1.312.08] and 1.70 [95% CI, 1.23-2.36]), and minor fractures (SMRs, 1.42 [95% CI, 1.19-1.70] and 1.33 [95% CI, 0.99-1.80]) for both women and men, respectively. Mortality was increased for all ages for all fractures except minor fractures for which increased mortality was only apparent for those older than 75 years. Increased mortality risk persisted for 5 years for all fractures and up to 10 years for hip fractures. Increases in absolute mortality that were above expected, for 5 years after fracture, ranged from 1.3 to 13.2 per 100 person-years in women and from 2.7 to 22.3 per 100 person-years in men, depending on fracture type. Subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men. Mortality risk following a subsequent fracture then declined but beyond 5 years still remained higher than in the general population (SMR, 1.41 [95% CI, 1.01-1.97] and SMR, 1.78 [95% CI, 0.96-3.31] for women and men, respectively). Predictors of mortality after any fragility fracture for both men and women included age, quadriceps weakness, and subsequent fracture but not comorbidities. Low bone mineral density, having smoked, and sway were also predictors for women and less physical activity for men. Conclusions In a sample of older women and men, all low-trauma fractures were associated with increased mortality risk for 5 to 10 years. Subsequent fracture was associated with increased mortality risk for an additional 5 years.

Critically ill patients with 2009 influenza A(H1N1) infection in Canada.

Abstract: Context Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. Objective To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. Design, Setting, and Patients A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. Main Outcome Measures The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. Results Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of PaO 2 to fraction of inspired oxygen [FIO 2 ] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). Conclusion Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.Published online October 12, 2009 (doi:10.1001/jama.2009.1496).

Effects of a Palliative Care Intervention on Clinical Outcomes in Patients With Advanced Cancer: The Project ENABLE II Randomized Controlled Trial

Abstract: Context There are few randomized controlled trials on the effectiveness of palliative care interventions to improve the care of patients with advanced cancer. Objective To determine the effect of a nursing-led intervention on quality of life, symptom intensity, mood, and resource use in patients with advanced cancer. Design, Setting, and Participants Randomized controlled trial conducted from November 2003 through May 2008 of 322 patients with advanced cancer in a rural, National Cancer Institute–designated comprehensive cancer center in New Hampshire and affiliated outreach clinics and a VA medical center in Vermont. Interventions A multicomponent, psychoeducational intervention (Project ENABLE [Educate, Nurture, Advise, Before Life Ends]) conducted by advanced practice nurses consisting of 4 weekly educational sessions and monthly follow-up sessions until death or study completion (n = 161) vs usual care (n = 161). Main Outcome Measures Quality of life was measured by the Functional Assessment of Chronic Illness Therapy for Palliative Care (score range, 0-184). Symptom intensity was measured by the Edmonton Symptom Assessment Scale (score range, 0-900). Mood was measured by the Center for Epidemiological Studies Depression Scale (range, 0-60). These measures were assessed at baseline, 1 month, and every 3 months until death or study completion. Intensity of service was measured as the number of days in the hospital and in the intensive care unit (ICU) and the number of emergency department visits recorded in the electronic medical record. Results A total of 322 participants with cancer of the gastrointestinal tract (41%; 67 in the usual care group vs 66 in the intervention group), lung (36%; 58 vs 59), genitourinary tract (12%; 20 vs 19), and breast (10%; 16 vs 17) were randomized. The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of 4.6 (2) for quality of life (P = .02), −27.8 (15) for symptom intensity (P = .06), and −1.8 (0.81) for depressed mood (P = .02). The estimated treatment effects in participants who died during the study were a mean (SE) of 8.6 (3.6) for quality of life (P = .02), −24.2 (20.5) for symptom intensity (P = .24), and −2.7 (1.2) for depressed mood (P = .03). Intensity of service did not differ between the 2 groups. Conclusion Compared with participants receiving usual oncology care, those receiving a nurse-led, palliative care–focused intervention addressing physical, psychosocial, and care coordination provided concurrently with oncology care had higher scores for quality of life and mood, but did not have improvements in symptom intensity scores or reduced days in the hospital or ICU or emergency department visits. Trial Registration clinicaltrials.gov Identifier: NCT00253383

Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.

Abstract: CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION: Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION: Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS: Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION: Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

Incidence and mortality of hip fractures in the United States.

Abstract: Context Understanding the incidence and subsequent mortality following hip fracture is essential to measuring population health and the value of improvements in health care. Objective To examine trends in hip fracture incidence and resulting mortality over 20 years in the US Medicare population. Design, Setting, and Patients Observational study using data from a 20% sample of Medicare claims from 1985-2005. In patients 65 years or older, we identified 786 717 hip fractures for analysis. Medication data were obtained from 109 805 respondents to the Medicare Current Beneficiary Survey between 1992 and 2005. Main Outcome Measures Age- and sex-specific incidence of hip fracture and age- and risk-adjusted mortality rates. Results Between 1986 and 2005, the annual mean number of hip fractures was 957.3 per 100 000 (95% confidence interval [CI], 921.7-992.9) for women and 414.4 per 100 000 (95% CI, 401.6-427.3) for men. The age-adjusted incidence of hip fracture increased from 1986 to 1995 and then steadily declined from 1995 to 2005. In women, incidence increased 9.0%, from 964.2 per 100 000 (95% CI, 958.3-970.1) in 1986 to 1050.9 (95% CI, 1045.2-1056.7) in 1995, with a subsequent decline of 24.5% to 793.5 (95% CI, 788.7-798.3) in 2005. In men, the increase in incidence from 1986 to 1995 was 16.4%, from 392.4 (95% CI, 387.8-397.0) to 456.6 (95% CI, 452.0-461.3), and the subsequent decrease to 2005 was 19.2%, to 369.0 (95% CI, 365.1-372.8). Age- and risk-adjusted mortality in women declined by 11.9%, 14.9%, and 8.8% for 30-, 180-, and 360-day mortality, respectively. For men, age- and risk-adjusted mortality decreased by 21.8%, 25.4%, and 20.0% for 30-, 180-, and 360-day mortality, respectively. Over time, patients with hip fracture have had an increase in all comorbidities recorded except paralysis. The incidence decrease is coincident with increased use of bisphosphonates. Conclusion In the United States, hip fracture rates and subsequent mortality among persons 65 years and older are declining, and comorbidities among patients with hip fractures have increased.

Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial.

Abstract: Context γ-Aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the α 2 agonist dexmedetomidine may have distinct advantages Objective To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients Design, Setting, and Patients Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU Interventions Dexmedetomidine (02-14 μg/kg per hour [n = 244]) or midazolam (002-01 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between −2 and +1) from enrollment until extubation or 30 days Main Outcome Measures Percentage of time within target RASS range Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events Results There was no difference in percentage of time within the target RASS range (773% for dexmedetomidine group vs 751% for midazolam group; difference, 22% [95% confidence interval {CI}, −32% to 75%]; P = 18) The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 766% (n = 93/122) in midazolam-treated patients (difference, 226% [95% CI, 14% to 33%]; P Conclusions There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension The most notable adverse effect of dexmedetomidine was bradycardia Trial Registration clinicaltrialsgov Identifier: NCT00216190Published online February 2, 2009 (doi:101001/jama200956)

Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease: A Randomized Controlled Trial

Abstract: Context Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. Objective To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Design, Setting, and Patients Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age ( Intervention Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. Main Outcome Measures The primary outcome was time spent in the “on” state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Results Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P Conclusion In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. Trial Registration clinicaltrials.gov Identifier: NCT00056563

Maternal Overweight and Obesity and the Risk of Congenital Anomalies: A Systematic Review and Meta-analysis

Abstract: Context Evidence suggests an association between maternal obesity and some congenital anomalies. Objective To assess current evidence of the association between maternal overweight, maternal obesity, and congenital anomaly. Data Sources MEDLINE, EMBASE, CINAHL, and Scopus (January 1966 through May 2008) were searched for English-language studies using a list of keywords. Reference lists from relevant review articles were also searched. Study Selection Observational studies with an estimate of prepregnancy or early pregnancy weight or body mass index (BMI) and data on congenital anomalies were considered. Of 1944 potential articles, 39 were included in the systematic review and 18 in the meta-analysis. Data Extraction and Synthesis Information was extracted on study design, quality, participants, congenital anomaly groups and subtypes, and risk estimates. Pooled odds ratios (ORs) comparing risk among overweight, obese, and recommended-weight mothers (defined by BMI) were determined for congenital anomaly groups and subtypes for which at least 150 cases had been reported in the literature. Results Pooled ORs for overweight and obesity were calculated for 16 and 15 anomaly groups or subtypes, respectively. Compared with mothers of recommended BMI, obese mothers were at increased odds of pregnancies affected by neural tube defects (OR, 1.87; 95% confidence interval [CI], 1.62-2.15), spina bifida (OR, 2.24; 95% CI, 1.86-2.69), cardiovascular anomalies (OR, 1.30; 95% CI, 1.12-1.51), septal anomalies (OR, 1.20; 95% CI, 1.09-1.31), cleft palate (OR, 1.23; 95% CI, 1.03-1.47), cleft lip and palate (OR, 1.20; 95% CI, 1.03-1.40), anorectal atresia (OR, 1.48; 95% CI, 1.12-1.97), hydrocephaly (OR, 1.68; 95% CI, 1.19-2.36), and limb reduction anomalies (OR, 1.34; 95% CI, 1.03-1.73). The risk of gastroschisis among obese mothers was significantly reduced (OR, 0.17; 95% CI, 0.10-0.30). Conclusions Maternal obesity is associated with an increased risk of a range of structural anomalies, although the absolute increase is likely to be small. Further studies are needed to confirm whether maternal overweight is also implicated.

CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.

Abstract: Context Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. Objective To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (A beta 42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. Design, Setting, and Participants The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. Main Outcome Measures Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF A beta 42, T-tau, and P-tau for identifying incipient AD. Results During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The A beta 42 assay in particular had considerable intersite variability. Patients who developed AD had lower median A beta 42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 1211420 ng/L for A beta 42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for A beta 42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of A beta 42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. Conclusions This multicenter study found that CSF A beta 42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures. JAMA. 2009;302(4):385-393 (Less)

Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California.

Abstract: Context Pandemic influenza A(H1N1) emerged rapidly in California in April 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A(H1N1) disproportionately affects younger ages and causes generally mild disease. Objective To describe the clinical and epidemiologic features of pandemic 2009 influenza A(H1N1) cases that led to hospitalization or death. Design, setting, and participants Statewide enhanced public health surveillance of California residents who were hospitalized or died with laboratory evidence of pandemic 2009 influenza A(H1N1) infection reported to the California Department of Public Health between April 23 and August 11, 2009. Main outcome measure Characteristics of hospitalized and fatal cases. Results During the study period there were 1088 cases of hospitalization or death due to pandemic 2009 influenza A(H1N1) infection reported in California. The median age was 27 years (range, Conclusions In the first 16 weeks of the current pandemic, the median age of hospitalized infected cases was younger than is common with seasonal influenza. Infants had the highest hospitalization rates and persons aged 50 years or older had the highest mortality rates once hospitalized. Most cases had established risk factors for complications of seasonal influenza.

Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.

Abstract: Context High levels of lipoprotein(a) are associated with increased risk of myocardial infarction (MI). Objective To assess whether genetic data are consistent with this association being causal. Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a prospective general population study with 16 years of follow-up (1991-2007, n = 8637, 599 MI events); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (2003-2006, n = 29 388, 994 MI events); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (1991-2004, n = 2461, 1231 MI events). Main Outcome Measures Plasma lipoprotein(a) levels, lipoprotein(a) kringle IV type 2 (KIV-2) size polymorphism genotype, and MIs recorded from 1976 through July 2007 for all participants. Results In the CCHS, multivariable-adjusted hazard ratios (HRs) for MI for elevated lipoprotein(a) levels were 1.2 (95% confidence interval [CI], 0.9-1.6; events/10 000 person-years, 59) for levels between the 22nd and 66th percentile, 1.6 (95% CI, 1.1-2.2; events/10 000 person-years, 75) for the 67th to 89th percentile, 1.9 (95% CI, 1.2-3.0; events/10 000 person-years, 84) for the 90th to 95th percentile, and 2.6 (95% CI, 1.6-4.1; events/10 000 person-years, 108) for levels greater than the 95th percentile, respectively, vs levels less than the 22nd percentile (events/10 000 person-years, 55) (trend P Conclusion These data are consistent with a causal association between elevated lipoprotein(a) levels and increased risk of MI.

Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial

Abstract: Context Limited data are available to assess whether endovascular repair of abdominal aortic aneurysm (AAA) improves short-term outcomes compared with traditional open repair. Objective To compare postoperative outcomes up to 2 years after endovascular or open repair of AAA in a planned interim report of a 9-year trial. Design, Setting, and Patients A randomized, multicenter clinical trial of 881 veterans (aged ≥49 years) from 42 Veterans Affairs Medical Centers with eligible AAA who were candidates for both elective endovascular repair and open repair of AAA. The trial is ongoing and this report describes the period between October 15, 2002, and October 15, 2008. Intervention Elective endovascular (n = 444) or open (n = 437) repair of AAA. Main Outcome Measures Procedure failure, secondary therapeutic procedures, length of stay, quality of life, erectile dysfunction, major morbidity, and mortality. Results Mean follow-up was 1.8 years. Perioperative mortality (30 days or inpatient) was lower for endovascular repair (0.5% vs 3.0%; P = .004), but there was no significant difference in mortality at 2 years (7.0% vs 9.8%, P = .13). Patients in the endovascular repair group had reduced median procedure time (2.9 vs 3.7 hours), blood loss (200 vs 1000 mL), transfusion requirement (0 vs 1.0 units), duration of mechanical ventilation (3.6 vs 5.0 hours), hospital stay (3 vs 7 days), and intensive care unit stay (1 vs 4 days), but required substantial exposure to fluoroscopy and contrast. There were no differences between the 2 groups in major morbidity, procedure failure, secondary therapeutic procedures, aneurysm-related hospitalizations, health-related quality of life, or erectile function. Conclusions In this report of short-term outcomes after elective AAA repair, perioperative mortality was low for both procedures and lower for endovascular than open repair. The early advantage of endovascular repair was not offset by increased morbidity or mortality in the first 2 years after repair. Longer-term outcome data are needed to fully assess the relative merits of the 2 procedures. Trial Registration clinicaltrials.gov Identifier: NCT00094575

Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome

Abstract: Context Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear. Objective To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS). Design, Setting, and Patients Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006. Main Outcome Measures All-cause mortality or rehospitalization for ACS. Results Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI (adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI (compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) (AOR, 0.98; 95% CI, 0.85-1.13). Conclusion Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.

Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus

Abstract: Context Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes.

Targeted muscle reinnervation for real-time myoelectric control of multifunction artificial arms.

Abstract: Context Improving the function of prosthetic arms remains a challenge, because access to the neural-control information for the arm is lost during amputation. A surgical technique called targeted muscle reinnervation (TMR) transfers residual arm nerves to alternative muscle sites. After reinnervation, these target muscles produce electromyogram (EMG) signals on the surface of the skin that can be measured and used to control prosthetic arms. Objective To assess the performance of patients with upper-limb amputation who had undergone TMR surgery, using a pattern-recognition algorithm to decode EMG signals and control prosthetic-arm motions. Design, Setting, and Participants Study conducted between January 2007 and January 2008 at the Rehabilitation Institute of Chicago among 5 patients with shoulder-disarticulation or transhumeral amputations who underwent TMR surgery between February 2002 and October 2006 and 5 control participants without amputation. Surface EMG signals were recorded from all participants and decoded using a pattern-recognition algorithm. The decoding program controlled the movement of a virtual prosthetic arm. All participants were instructed to perform various arm movements, and their abilities to control the virtual prosthetic arm were measured. In addition, TMR patients used the same control system to operate advanced arm prosthesis prototypes. Main Outcome Measure Performance metrics measured during virtual arm movements included motion selection time, motion completion time, and motion completion (“success”) rate. Results The TMR patients were able to repeatedly perform 10 different elbow, wrist, and hand motions with the virtual prosthetic arm. For these patients, the mean motion selection and motion completion times for elbow and wrist movements were 0.22 seconds (SD, 0.06) and 1.29 seconds (SD, 0.15), respectively. These times were 0.06 seconds and 0.21 seconds longer than the mean times for control participants. For TMR patients, the mean motion selection and motion completion times for hand-grasp patterns were 0.38 seconds (SD, 0.12) and 1.54 seconds (SD, 0.27), respectively. These patients successfully completed a mean of 96.3% (SD, 3.8) of elbow and wrist movements and 86.9% (SD, 13.9) of hand movements within 5 seconds, compared with 100% (SD, 0) and 96.7% (SD, 4.7) completed by controls. Three of the patients were able to demonstrate the use of this control system in advanced prostheses, including motorized shoulders, elbows, wrists, and hands. Conclusion These results suggest that reinnervated muscles can produce sufficient EMG information for real-time control of advanced artificial arms.

Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.

Abstract: Context Cardiometabolic effects of second-generation antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to antipsychotic medication. Objective To study the association of second-generation antipsychotic medications with body composition and metabolic parameters in patients without prior antipsychotic medication exposure. Design, Setting, and Patients Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients who completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group. Intervention Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks. Main Outcome Measures Weight gain and changes in lipid and metabolic parameters. Results After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, −1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P Conclusions First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.

Estimated Radiation Dose Associated With Cardiac CT Angiography

Abstract: Context Cardiac computed tomography (CT) angiography (CCTA) has emerged as a useful diagnostic imaging modality in the assessment of coronary artery disease. However, the potential risks due to exposure to ionizing radiation associated with CCTA have raised concerns. Objectives To estimate the radiation dose of CCTA in routine clinical practice as well as the association of currently available strategies with dose reduction and to identify the independent factors contributing to radiation dose. Design, Setting, and Patients A cross-sectional, international, multicenter, observational study (50 study sites: 21 university hospitals and 29 community hospitals) of estimated radiation dose in 1965 patients undergoing CCTA between February and December 2007. Linear regression analysis was used to identify independent predictors associated with dose. Main Outcome Measure Dose-length product (DLP) of CCTA. Results The median DLP of 1965 CCTA examinations performed at 50 study sites was 885 mGy × cm (interquartile range, 568-1259 mGy × cm), which corresponds to an estimated radiation dose of 12 mSv (or 1.2 × the dose of an abdominal CT study or 600 chest x-rays). A high variability in DLP was observed between study sites (range of median DLPs per site, 331-2146 mGy × cm). Independent factors associated with radiation dose were patient weight (relative effect on DLP, 5%; 95% confidence interval [CI], 4%-6%), absence of stable sinus rhythm (10%; 95% CI, 2%-19%), scan length (5%; 95% CI, 4%-6%), electrocardiographically controlled tube current modulation (−25%; 95% CI, −23% to −28%; applied in 73% of patients), 100-kV tube voltage (−46%; 95% CI, −42% to −51%; applied in 5% of patients), sequential scanning (−78%; 95% CI, −77% to −79%; applied in 6% of patients), experience in cardiac CT (−1%; 95% CI, −1% to 0%), number of CCTAs per month (0%; 95% CI, 0%-1%), and type of 64-slice CT system (for highest vs lowest dose system, 97%; 95% CI, 88%-106%). Algorithms for dose reduction were not associated with deteriorated diagnostic image quality in this observational study. Conclusions Median doses of CCTA differ significantly between study sites and CT systems. Effective strategies to reduce radiation dose are available but some strategies are not frequently used. The comparable diagnostic image quality may support an increased use of dose-saving strategies in adequately selected patients.

Estimated Radiation Dose Associated With Cardiac CT Angiography. Commentary

Abstract: Context Cardiac computed tomography (CT) angiography (CCTA) has emerged as a useful diagnostic imaging modality in the assessment of coronary artery disease. However, the potential risks due to exposure to ionizing radiation associated with CCTA have raised concerns. Objectives To estimate the radiation dose of CCTA in routine clinical practice as well as the association of currently available strategies with dose reduction and to identify the independent factors contributing to radiation dose. Design, Setting, and Patients A cross-sectional, international, multicenter, observational study (50 study sites: 21 university hospitals and 29 community hospitals) of estimated radiation dose in 1965 patients undergoing CCTA between February and December 2007. Linear regression analysis was used to identify independent predictors associated with dose. Main Outcome Measure Dose-length product (DLP) of CCTA. Results The median DLP of 1965 CCTA examinations performed at 50 study sites was 885 mGy × cm (interquartile range, 568-1259 mGy × cm), which corresponds to an estimated radiation dose of 12 mSv (or 1.2 x the dose of an abdominal CT study or 600 chest x-rays). A high variability in DLP was observed between study sites (range of median DLPs per site, 331-2146 mGy x cm). Independent factors associated with radiation dose were patient weight (relative effect on DLP, 5%; 95% confidence interval [Cl], 4%-6%), absence of stable sinus rhythm (10%; 95% Cl, 2%-19%), scan length (5%; 95% Cl, 4%-6%), electrocardiographically controlled tube current modulation (-25%; 95% Cl, -23% to -28%; applied in 73% of patients), 100-kV tube voltage (-46%; 95% Cl, -42% to -51 %; applied in 5% of patients), sequential scanning (-78%; 95% Cl, -77% to -79%; applied in 6% of patients), experience in cardiac CT (-1%; 95% Cl, -1 % to 0%), number of CCTAs per month (0%; 95% Cl, 0%-1 %), and type of 64-slice CT system (for highest vs lowest dose system, 97%; 95% Cl, 88%-106%). Algorithms for dose reduction were not associated with deteriorated diagnostic image quality in this observational study. Conclusions Median doses of CCTA differ significantly between study sites and CT systems. Effective strategies to reduce radiation dose are available but some strategies are not frequently used. The comparable diagnostic image quality may support an increased use of dose-saving strategies in adequately selected patients.