Summary Background Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of ...published and unpublished data whether any relation exists between statin use and development of diabetes. Methods We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I2 statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis. Findings We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio OR 1·09; 95% CI 1·02–1·17), with little heterogeneity ( I2 =11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150–852) patients with statins for 4 years resulted in one extra case of diabetes. Interpretation Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change. Funding None.
Study objective Survival after out-of-hospital cardiac arrest depends on the links in the chain of survival. The Utstein elements are designed to assess these links and provide the basis for ...comparing outcomes within and across communities. We assess whether these measures sufficiently predict survival and explain outcome differences. Methods We used an observational, prospective data collection, case-series of adult persons with nontraumatic out-of-hospital cardiac arrest from December 1, 2005, through March 1, 2007, from the multisite, population-based Resuscitation Outcomes Consortium Epistry–Cardiac Arrest. We used logistic regression, receiver operating curves, and measures of variance to estimate the extent to which the Utstein elements predicted survival to hospital discharge and explained outcome variability overall and between 7 Resuscitation Outcomes Consortium sites. Analyses were conducted for all emergency medical services–treated cardiac arrests and for the subset of bystander-witnessed patient arrests because of presumed cardiac cause presenting with ventricular fibrillation or ventricular tachycardia. Results Survival was 7.8% overall (n=833/10,681) and varied from 4.6% to 14.7% across Resuscitation Outcomes Consortium sites. Among bystander-witnessed ventricular fibrillation or ventricular tachycardia, survival was 22.1% overall (n=323/1459) and varied from 12.5% to 41.0% across sites. The Utstein elements collectively predicted 72% of survival variability among all arrests and 40% of survival variability among bystander-witnessed ventricular fibrillation. The Utstein elements accounted for 43.6% of the between-site survival difference among all arrests and 22.3% of the between-site difference among the bystander-witnessed ventricular fibrillation subset. Conclusion The Utstein elements predict survival but account for only a modest portion of outcome variability overall and between Resuscitation Outcomes Consortium sites. The results underscore the need for ongoing investigation to better understand characteristics that influence cardiac arrest survival.
In observational studies of patients hospitalized for heart failure (HHF), risk of death is highest immediately after discharge and decreases over time. It is unclear whether this population risk ...trajectory reflects (1) lowering of individual patient mortality risk with increasing time from index hospitalization or (2) temporal changes in population case-mix with earlier postdischarge death for “sicker” patients. Survival rate and longitudinal models were used to estimate temporal changes in postdischarge all-cause mortality risk in 3,993 HHF patients discharged alive in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. After median follow-up of 9.9 months, 971 patients died (24.2%). Predicted mortality rate decreased from 15.9 per 100 patient-years immediately after discharge to 13.4 at 30 days and 12.8 at 90 days; mortality rate increased steadily thereafter. Risk variation between quintiles of risk was considerably larger than the temporal variation within risk strata. In a longitudinal model serially reassessing predicted patient mortality risk after each follow-up visit using data collected at these visits, predicted mortality risk increased during the 90 days preceding subsequent heart failure readmission and then followed a postdischarge trajectory similar to the index admission. In conclusion, although there is transiently elevated individual patient risk in the 90 days before and after discharge, the patient's individual risk profile, rather than temporal change in risk relative to hospitalization, remains the main determinant of mortality. For purposes of reducing all-cause mortality in HF patients, preventative and therapeutic measures may be best implemented as long-term interventions for high mortality risk patients based on serial risk assessments, irrespective of recent hospitalization.
The CLAS12 drift chamber system Mestayer, M.D.; Adhikari, K.; Bennett, R.P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Letnik:
959, Številka:
C
Journal Article
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The CEBAF Large Acceptance Spectrometer at 12 GeV (CLAS12) is located in Hall B, one of the experimental halls at Jefferson Lab. The forward part of CLAS12 is built around a superconducting toroidal ...magnet. The six coils of the toroid divide the detector azimuthally into six sectors. Each sector contains three multi-layer drift chambers for reconstructing the trajectories of charged particles originating from a fixed target.
Each of the 18 planar chambers has two “superlayers” of six layers each, with the wires in the two adjacent superlayers oriented at ±6° stereo angles. Each layer has 112 hexagonal cells spanning a range from about 5° to 40° in polar angle. The six-layer structure provides redundancy in track segment finding and good tracking efficiency even in the presence of some individual wire inefficiency. The design, construction, operation, and calibration methods are described, and estimates of the efficiency and resolution are presented from in-beam measurements.
Contemporary results of open aortic arch surgery Thomas, Mathew, MBBS; Li, Zhuo, MS; Cook, David J., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
10/2012, Letnik:
144, Številka:
4
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Objectives The success of endovascular therapies for descending thoracic aortic disease has turned attention toward stent graft options for repair of aortic arch aneurysms. Defining the role of such ...techniques demands understanding of contemporary results of open surgery. Methods The outcomes of open arch procedures performed on a single surgical service from July 1, 2001 to August 30, 2010, were examined as defined per The Society of Thoracic Surgeons national database. Results During the study period, 209 patients (median age, 65 years; range, 26-88) underwent arch operations, of which 159 were elective procedures. In 65 the entire arch was replaced, 22 of whom had portions of the descending thoracic aorta simultaneously replaced via bilateral thoracosternotomy. Antegrade cerebral perfusion was used in 78 patients and retrograde cerebral perfusion in 1. Operative mortality was 2.5% in elective circumstances and 10% in emergency cases ( P = .04). The stroke rate was 5.0% when procedures were performed electively and 11.8% when on an emergency basis ( P = .11). Procedure-specific mortality rates were 5.5% for elective and 10% for emergency procedures with total arch replacement, and 1.0% for elective and 10% for emergency procedures with hemiarch replacement. Stratified by extent, neurologic event rates were 5.5% for elective and 10% for emergency procedures with total arch and 4.8% for elective and 12.5% for emergency procedures with hemiarch replacement. Conclusions Open aortic arch replacement can be performed with low operative mortality and stroke rates, especially in elective circumstances, by a team with particular focus on the procedure. The results of novel endovascular therapies should be benchmarked against contemporary open series performed in such a setting.
Background The postdischarge rehospitalization and death rates are high in patients with acute heart failure (HF) syndromes despite optimization of standard therapy for chronic HF. To the best of our ...knowledge, there has been no systematic analysis of the causes of death and rehospitalization in this patient population. Methods This was a prespecified analysis of adjudicated cause-specific all-cause mortality and cardiovascular (CV) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, a randomized, double-blind, placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction ≤40% comparing tolvaptan, an oral vasopressin receptor antagonist to placebo, in addition to standard care. Results Of the 4,133 randomized, there were 5,239 rehospitalizations and 1,080 deaths during a median of 9.9 months. Of all deaths, 41.0% were due to HF, 26.0% due to sudden cardiac death (SCD), 2.6% due to acute myocardial infarction (MI), 2.2% due to stroke, and 13.2% due to non-CV causes. Of all hospitalizations, 39.2% were non-CV, whereas 46.3% were for HF, and a minority of hospitalizations was due to stroke, MI, arrhythmia, or other CV causes. Conclusions Despite close follow-up and evidence-based therapy within a clinical trial, rehospitalization and death remain high. Although most deaths were from HF, one quarter of patients had SCD. In addition, there were almost as many non-CV hospitalizations as HF hospitalizations. Knowledge of the causes of death and rehospitalization may be essential for proper management and early initiation of therapy.
Scientists have feared that emerging infectious diseases could complicate efforts to conserve rare and endangered species, but quantifying impacts has proven difficult until now. We report unexpected ...impacts of West Nile virus (WNv) on radio-marked greater sage-grouse (Centrocercus urophasianus), a species that has declined 45–80% and is endangered in Canada and under current consideration for federal listing in the US. We show that WNv reduced late-summer survival an average of 25% in four radio-marked populations in the western US and Canada. Serum from 112 sage-grouse collected after the outbreak show that none had antibodies, suggesting that they lack resistance. The spread of WNv represents a significant new stressor on sage-grouse and probably other at-risk species. While managing habitat might lessen its impact on sage-grouse populations, WNv has left wildlife and public health officials scrambling to address surface water and vector control issues in western North America.
Introduction A demonstration project in Richmond, Virginia involved patients and other stakeholders in the creation of a research agenda on dietary and behavioral management of diabetes and ...hypertension. Given the impact of these diseases on morbidity and mortality, considerable research has been directed at the challenges patients face in chronic disease management. The continuing need to understand disparities and find evidence-based interventions to improve outcomes has been fruitful, but disparities and unmet needs persist. Methods The Stakeholder Engagement in Question Development (SEED) method is a stakeholder engagement methodology that combines engagement with a review of available evidence to generate research questions that address current research gaps and are important to patients and other stakeholders. Using the SEED method, patients and other stakeholders participated in research question development through a combination of collaborative, participatory, and consultative engagement. Steps in the process included: (1) identifying the topic and recruiting participants; (2) conducting focus groups and interviews; (3) developing conceptual models; (4) developing research questions; and (5) prioritizing research questions. Results Stakeholders were involved in the SEED process from February to August 2015. Eighteen questions were prioritized for inclusion in the research agenda, covering diverse domains, from healthcare provision to social and environmental factors. Data analysis took place September to May 2016. During this time, researchers conducted a literature review to target research gaps. Conclusions The stakeholder-prioritized, novel research questions developed through the SEED process can directly inform future research and guide the development of evidence that translates more directly to clinical practice.
Apolipoprotein A-I (apoA-I), the major protein in high density lipoprotein (HDL) regulates cholesterol homeostasis and is protective against atherosclerosis. An examination of the amino acid sequence ...of apoA-I among 21 species shows a high conservation of positively and negatively charged residues within helix 6, a domain responsible for regulating the rate of cholesterol esterification in plasma. These observations prompted an investigation to determine if charged residues in helix 6 maintain a structural conformation for protein−protein interaction with lecithin−cholesterol acyltransferase (LCAT) the enzyme for which apoA-I acts as a cofactor. Three apoA-I mutants were engineered; the first, 3/4 no negative apoA-I, eliminated 3 of the 4 negatively charged residues in helix 6, no negative apoA-I (NN apoA-I) eliminated all four negative charges, while all negative (AN apoA-I) doubled the negative charge. Reconstituted phospholipid-containing HDL (rHDL) of two discrete sizes and compositions were prepared and tested. Results showed that LCAT activation was largely influenced by both rHDL particle size and the net negative charge on helix 6. The 80 Å diameter rHDL showed a 12-fold lower LCAT catalytic efficiency when compared to 96 Å diameter rHDL, apparently resulting from an increased protein−protein interaction, at the expense of lipid−protein association on the 80 Å rHDL. When mutant apoproteins were compared bound to the two different sized rHDL, a strong inverse correlation (r = 0.85) was found between LCAT catalytic efficiency and apoA-I helix 6 net negative charge. These results support the concept that highly conserved negatively charged residues in apoA-I helix 6 interact directly and attenuate LCAT activation, independent of the overall particle charge.
Prior studies suggest that allergist care improves asthma outcomes, but many of these studies have methodological shortcomings.
We sought to compare patient-based and medical utilization outcomes in ...randomly selected asthmatic patients cared for by allergists versus primary care providers.
A random sample of 3568 patients enrolled in a staff model health maintenance organization who were given diagnoses of persistent asthma completed surveys. Of these participants, 1679 (47.1%) identified a primary care provider as their regular source of asthma care, 884 (24.8%) identified an allergist, 693 (19.4%) reported no regular source of asthma care, and 195 (5.5%) identified a pulmonologist. Validated quality of life, control, severity, patient satisfaction, and self-management knowledge tools and linked administrative data that captured medication use were compared between groups, adjusting for demographics and baseline hospital and corticosteroid use.
Compared with those followed by primary care providers, patients of allergists reported significantly higher (P < .001) generic physical and asthma-specific quality of life, less asthma control problems, less severe symptoms, higher satisfaction with care, and greater self-management knowledge. Patients of allergists were less likely than patients of primary care providers to require an asthma hospitalization (odds ratio, 0.45) or unscheduled visit (odds ratio, 0.71) and to overuse β-agonists (odds ratio, 0.47) and were more likely to receive inhaled steroids (odds ratio, 1.81) during their past year.
Allergist care is associated with a wide range of improved outcomes in asthmatic patients compared with care provided by primary care providers.
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