Rate versus rhythm control and outcomes in patients with atrial fibrillation and chronic kidney disease: Data from the GUSTO-III Trial

Background: Atrial fi brillation (AF) and chronic kidney disease (CKD) have both beenshown to portend worse outcomes after acute myocardial infarction (MI); however, the benefi tof a rhythm control strategy in patients with CKD post-MI is unclear.Methods: We prospectively studied 985 patients with new-onset AF post-MI in theGUSTO-III trial, of whom 413 (42%) had CKD (creatinine clearance < 60 mL/min).A rhythm control strategy, defi ned as the use of an antiarrhythmic medication and/orelectrical cardioversion, was used in 346 (35%) of patients.Results: A rhythm control strategy was used in 34% of patients with CKD and 36% of patientswith no CKD. At hospital discharge, sinus rhythm was present in 487 (76%) of patients treatedwith a rate control strategy, vs. 276 (80%) in those treated with rhythm control (p = 0.20). CKDwas associated with a lower odds of sinus rhythm at discharge (unadjusted OR 0.56, 95% CI0.38–0.84, p < 0.001). However, in multivariable analyses, treatment with a rhythm controlstrategy was not associated with discharge rhythm (HR 1.068, 95% CI 0.69–1.66, p = 0.77),30-day mortality (HR 0.78, 95% CI 0.54–1.12, p = 0.18) or mortality from day 30 to 1 year(HR 1.00, 95% CI 0.59–1.69, p = 0.99). CKD status did not signifi cantly impact the relationshipbetween rhythm control and outcomes.Conclusions: Treatment with a rhythm or rate control strategy does not signifi cantly impactshort-term or long-term mortality in patients with post-MI AF, regardless of kidney disease status.Future studies to investigate the optimal management of AF in CKD patients are needed

Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction

BACKGROUND: Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. METHODS AND RESULTS: We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12-lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all-cause mortality and investigate race-QRS and sex-QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92-132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98-139) followed by white women (108 ms; IQR, 92-140), black men (100 ms; IQR, 91-120), and black women (94 ms; IQR, 86-118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). CONCLUSIONS: Black individuals with heart failure had a shorter QRS duration and more often had non-left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality

The Database for Aggregate Analysis of ClinicalTrials.gov (AACT) and Subsequent Regrouping by Clinical Specialty

BACKGROUND: The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. METHODS/PRINCIPAL RESULTS: The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. CONCLUSIONS/SIGNIFICANCE: The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups

PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit

BACKGROUND: Pneumonia is the leading infection-related cause of death. Using simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. RESEARCH QUESTION: What are the clinical criteria and contemporary epidemiology trends helpful in identifying patients at high risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: Within the intensive care units of 28 United States hospitals, we conducted a prospective cohort study among adults hospitalized more than 48 hours and considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients developing nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures associated with increased risk of pneumonia development during the intensive care unit admission. RESULTS: Between February 6, 2016 and October 7, 2016, 4613 high-risk patients were enrolled. Among 1464/4613 (32%) high-risk patients treated for possible nosocomial pneumonia, 537/1464 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures associated with increased risk of nosocomial pneumonia development (c-statistic 0.709, 95% confidence interval 0.686 to 0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. INTERPRETATION: Treatment for nosocomial pneumonia is common among intensive care unit patients receiving high levels of respiratory support, yet more than half of patients treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts

Background The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001). Conclusions Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States

Phytoplankton spring bloom initiation: The impact of atmospheric forcing and light in the temperate North Atlantic Ocean

The spring bloom dominates the annual cycle of phytoplankton abundance in large regions of the world oceans. The mechanisms that trigger blooms have been studied for decades, but are still keenly debated, due in part to a lack of data on phytoplankton stocks in winter and early spring. Now however autonomous underwater gliders can provide high-resolution sampling of the upper ocean over inter-seasonal timescales and advance our understanding of spring blooms. In this study, we analyze bio-optical and physical observations collected by gliders at the Porcupine Abyssal Plain observatory site to investigate the impact of atmospheric forcing and light conditions on phytoplankton blooms in the temperate North Atlantic. We contrast three hypotheses for the mechanism of bloom initiation: the critical depth, critical turbulence, and dilution-recoupling hypotheses. Bloom initiation at our study site corresponded to an improvement in growth conditions for phytoplankton (increasing light, decreasing mixing layer depth) and was most consistent with the critical depth hypothesis, with the proviso that mixing depth (rather than mixed layer depth) was considered. After initiation, the observed bloom developed slowly: over several months both depth-integrated inventories and surface concentrations of chlorophyll a increased only by a factor of ~2 and ~3 respectively. We find that periods of convective mixing and high winds in winter and spring can substantially decrease (up to an order of magnitude) light-dependent mean specific growth rate for phytoplankton and prevent the development of rapid, high-magnitude blooms

Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short?

<div><p>The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention.</p></div

The Naked Truth

First Line: 'Ere the days of drouth and pillage, when old Greenwich was a villageFirst Line of Chorus: Now you'll find the naked truth in Greenwich VillageTitle of Larger Work: The Greenwich Village Follies of 1920Key: C Majo

Right ventricular longitudinal strain reproducibility using vendor dependent and independent software

Background: Right ventricular peak systolic longitudinal strain (RVLS) has emerged as an approach for quantifying right ventricular function in diseases such as pulmonary hypertension and congenital heart disease. A major limitation in applying RVLS is that strain imaging and analysis are proprietary, which may result in systematic differences from vendor to vendor. The goal of this study was to test the reproducibility of right ventricular strain analysis among selected vendor-specific software (VSS) and vendor-independent software (VIS) on images obtained from different ultrasound scanners, as would be common in clinical practice or in a multicenter clinical trial. Methods: In this prospective, single-center study, 35 patients (5 healthy subjects and 30 with pulmonary hypertension) each underwent two echocardiographic scans, one using GE (Vivid E9) and the other using Philips (iE33) ultrasound systems. Images were analyzed using both VSS and VIS (TomTec) software for determination of RVLS. A repeated-measures analysis of variance was used to assess for any systematic differences among methods, as well as effects of scanner and software and a possible interaction between scanner and software for each strain measurement. Results: Differences for global strains were not statistically significant among VSS packages (P ≥ .05), but some differences were noted between VSS and VIS. Wide variability between regional peak strain measurements was noted, but no systematic differences were found. Conclusion: Global RVLS values between VSS systems are not significantly different but may differ slightly from VIS. When comparing regional strain between VSS and VIS analyses, there is widespread variability without clear systematic differences