Performance of the subcutaneous implantable cardioverter-defibrillator in patients with a primary prevention indication with and without a reduced ejection fraction versus patients with a secondary prevention indication

Background: The subcutaneous implantable defibrillator (S-ICD) provides an alternative to the transvenous ICD for the prevention of sudden cardiac death, but has not been well studied in the most commonly treated transvenous ICD patient population, namely, primary prevention (PP) patients with left ventricular dysfunction. Objective: The analyses in the present study were designed to compar

The Sloan Digital Sky Survey: Technical Summary

The Sloan Digital Sky Survey (SDSS) will provide the data to support detailed investigations of the distribution of luminous and non- luminous matter in the Universe: a photometrically and astrometrically calibrated digital imaging survey of pi steradians above about Galactic latitude 30 degrees in five broad optical bands to a depth of g' about 23 magnitudes, and a spectroscopic survey of the approximately one million brightest galaxies and 10^5 brightest quasars found in the photometric object catalog produced by the imaging survey. This paper summarizes the observational parameters and data products of the SDSS, and serves as an introduction to extensive technical on-line documentation.Comment: 9 pages, 7 figures, AAS Latex. To appear in AJ, Sept 200

Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Optimizing the trade-off between offspring number and quality in unpredictable environments: Testing the role of differential androgen transfer to collared flycatcher eggs

According to the brood reduction hypothesis, parents adjust their brood size in response to current environmental conditions. When resources are abundant, parents can successfully raise all hatched offspring, but when resources are scarce, brood reduction, i.e., the sacrifice of some siblings to secure the quality of a subset of offspring, may maximize fitness. Differential transfer of maternal androgens is one potential proximate mechanism through which female birds may facilitate brood reduction because it may alter the relative competitive ability of sibling nestlings. We tested the hypothesis that female collared flycatchers (Ficedula albicollis) manipulate sibling competition by transferring less androgens to eggs late in the laying sequence. We experimentally elevated androgen levels in i) whole clutches and ii) only the two last laid eggs, and compared growth and begging behavior of offspring from these treatments with a control treatment. By using three treatments and video assessment of begging, we examined the effects of within-clutch patterns of yolk androgen transfer on levels of sibling competition in situ. When androgens were elevated in only the two last laid eggs, begging was more even among siblings compared to control nests. We also found that female nestlings receiving additional yolk androgens showed higher mass gain later in the breeding season, while their male counterparts did not. Our results suggest that females may improve reproductive success in unpredictable environments by altering within-clutch patterns of yolk androgen transfer. We discuss the possibility that life-history divergence between the co-occurring collared and pied flycatcher (Ficedula hypoleuca) is amplified by patterns of yolk androgen transfer. (C) 2013 Elsevier Inc. All rights reserved

Performance of the subcutaneous implantable cardioverter-defibrillator in patients with a primary prevention indication with and without a reduced ejection fraction versus patients with a secondary prevention indication

textabstractBackground: The subcutaneous implantable defibrillator (S-ICD) provides an alternative to the transvenous ICD for the prevention of sudden cardiac death, but has not been well studied in the most commonly treated transvenous ICD patient population, namely, primary prevention (PP) patients with left ventricular dysfunction. Objective: The analyses in the present study were designed to compar

Safety and Efficacy of the Totally Subcutaneous Implantable Defibrillator: 2-Year Results From a Pooled Analysis of the IDE Study and EFFORTLESS Registry

The entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) is the first implantable defibrillator that avoids placing electrodes in or around the heart. Two large prospective studies (IDE [S-ICD System IDE Clinical Investigation] and EFFORTLESS [Boston Scientific Post Market S-ICD Registry]) have reported 6-month to 1-year data on the S-ICD. The objective of this study was to evaluate the safety and efficacy of the S-ICD in a large diverse population. Data from the IDE and EFFORTLESS studies were pooled. Shocks were independently adjudicated, and complications were measured with a standardized classification scheme. Enrollment date quartiles were used to assess event rates over time. Eight hundred eighty-two patients who underwent implantation were followed for 651±345 days. Spontaneous ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) events (n=111) were treated in 59 patients; 100 (90.1%) events were terminated with 1 shock, and 109 events (98.2%) were terminated within the 5 available shocks. The estimated 3-year inappropriate shock rate was 13.1%. Estimated 3-year, all-cause mortality was 4.7% (95% confidence interval: 0.9% to 8.5%), with 26 deaths (2.9%). Device-related complications occurred in 11.1% of patients at 3 years. There were no electrode failures, and no S-ICD-related endocarditis or bacteremia occurred. Three devices (0.3%) were replaced for right ventricular pacing. The 6-month complication rate decreased by quartile of enrollment (Q1: 8.9%; Q4: 5.5%), and there was a trend toward a reduction in inappropriate shocks (Q1: 6.9% Q4: 4.5%). The S-ICD demonstrated high efficacy for VT/VF. Complications and inappropriate shock rates were reduced consistently with strategic programming and as operator experience increased. These data provide further evidence for the safety and efficacy of the S-ICD. (Boston Scientific Post Market S-ICD Registry [EFFORTLESS]; NCT01085435; S-ICD® System IDE Clinical Study; NCT01064076

Inappropriate shocks in the subcutaneous ICD:Incidence, predictors and management

The entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) eliminates the need for transvenous leads, and therefore has the potential to improve lead-longevity and reduce lead-related complications. The S-ICD has a morphology-based sensing algorithm of which inappropriate shocks have been reported. We analyzed the incidence, predictors and management of inappropriate shocks in the EFFORTLESS S-ICD Registry, which collects S-ICD implantation information and follow-up data from clinical centers in Europe and New Zealand. During a follow-up of 21 ± 13 months, 48 out of 581 S-ICD patients (71% male, age 49 ± 18 years) experienced 101 inappropriate shocks (8.3%). The most common cause was cardiac signal oversensing (73%), such as T-wave oversensing. Eighteen shocks (18%) were due to supraventricular tachycardias (SVT), of which 15 occurred in the shock-only zone. Cox-proportional hazard modeling using time-dependent covariates demonstrated that patients with a history of atrial fibrillation (HR 2.4) and patients with hypertrophic cardiomyopathy (HR 4.6) had an increased risk for inappropriate shocks, while programming the primary vector for sensing (from xyphoid to V6) reduced the risk. Reprogramming or optimization of SVT treatment after the first clinical event of inappropriate shock was successful in preventing further inappropriate shocks for cardiac oversensing and SVT events. Inappropriate shocks, mainly due to cardiac oversensing, occurred in 8.3% of the S-ICD patients. Patients with hypertrophic cardiomyopathy or a history of atrial fibrillation were at increased risk, warranting specific attention for sensing and programming in this populatio

Preferred habitat of breeding birds may be compromised by climate change: unexpected effects of an exceptionally cold, wet spring

Previous studies of the consequences for breeding birds of climate change have explored how their populations may respond to increasing temperatures. However, few have considered the likely outcome of predicted extreme conditions and the relative vulnerability of populations in different habitats. Here, we compare phenology and breeding success in great tits and blue tits over a 10 year period, including the extremely harsh conditions during spring 2012, at three sites in eastern England – mixed deciduous woodland, riparian and urban habitat. Production, measured as brood biomass, was significantly lower in 2012 compared with the previous 9 years, with the decrease in productivity relatively greatest in woodland habitat. Production was related to hatch delay, i.e. birds not initiating incubation immediately after clutch completion, which was more common in 2012 than in previous years. The best predictor of hatch delay was daytime temperature (not nighttime minimum temperature) and rainfall, which convincingly reflected low growth and activity of caterpillar prey. We found that birds breeding in riparian and urban habitats were less vulnerable to the extremes of weather than those breeding in mixed deciduous woodland

Implant and Midterm Outcomes of the Subcutaneous Implantable Cardioverter-Defibrillator Registry

BACKGROUND The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to defibrillate ventricular arrhythmias, avoiding drawbacks of transvenous leads. The global EFFORTLESS S-ICD (Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD) registry is collecting outcomes in 985 patients during a 5-year follow-up. OBJECTIVES The primary goal of the EFFORTLESS registry is to determine the safety of the S-ICD by evaluating complications and inappropriate shock rate. METHODS This is the first report on the full patient cohort and study endpoints with follow-up $1 year. The predefined endpoints are 30- and 360-day complications, and shocks for atrial fibrillation or supraventricular tachycardia. RESULTS Patients were followed for 3.1 ± 1.5 years and 82 completed the study protocol 5-year visit. Average age was 48 years, 28% were women, ejection fraction was 43 ± 18%, and 65% had a primary prevention indication. The S-ICD system and procedure complication rate was 4.1% at 30 days and 8.4% at 360 days. The 1-year complication rate trended toward improvement from the first to last quartile of enrollment (11.3% [quartile 1]) to 7.8% [quartile 2], 6.6% [quartile 3], and 7.4% [quartile 4]; quartile 1 vs. quartiles 2 to 4; p ¼ 0.06). Few device extractions occurred due to need for antitachycardia (n ¼ 5), or biventricular (n ¼ 4) or bradycardia pacing (n ¼ 1). Inappropriate shocks occurred in 8.1% at 1 year and 11.7% after 3.1 years. At implant, 99.5% of patients had a successful conversion of induced ventricular tachycardia or ventricular fibrillation. The 1- and 5-year rates of appropriate shock were 5.8% and 13.5%, respectively. Conversion success for discrete spontaneous episodes was 97.4% overall. CONCLUSIONS This registry demonstrates that the S-ICD fulfills predefined endpoints for safety and efficacy. Midterm performance rates on complications, inappropriate shocks, and conversion efficacy were comparable to rates observed in transvenous implantable cardioverter-defibrillator studies