Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction. A report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve)

Background—In patients with HF and preserved ejection fraction (HFpEF), little is known about the characteristics of and outcomes in those with and without diabetes. Methods—We examined clinical and echocardiographic characteristics and outcomes in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), according to history of diabetes. Cox regression models were used to estimate hazard ratios (HR) for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results—Overall, 1134 of 4128 patients (27%) had diabetes. Compared to those without diabetes, they were more likely to have a history of myocardial infarction (28% vs. 22%), higher BMI (31kg/m2 vs. 29kg/m2), worse Minnesota living with HF score (48 vs. 40), higher median NT-proBNP concentration (403 vs 320 pg/ml; all p<0.01), more signs of congestion but no significant difference in LVEF. Patients with diabetes had a greater left ventricular (LV) mass and left atrial area than patients without diabetes. Doppler E wave velocity (86 vs 76 cm/sec, p<0.0001) and the ratio of E/e' (11.7 vs 10.4, p=0.010) were higher in patients with diabetes. Over a median follow-up of 4.1 years, cardiovascular death or HF hospitalization occurred in 34% of patients with diabetes vs. 22% of those without diabetes; adjusted HR 1.75 (95% CI 1.49-2.05) and 28% vs. 19% of patients with and without diabetes died; adjusted HR 1.59 (1.33-1.91). Conclusions—In HFpEF, patients with diabetes have more signs of congestion, worse quality of life, higher NT-proBNP levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes on outcomes in HFPEF, and whether they are modifiable

Combined Cisplatinum and Laser Thermal Therapy for Palliation of Recurrent Head and Neck Tumors

In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m2) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients

Sudden cardiac death in patients with ischemic heart failure undergoing coronary artery bypass grafting results from the STICH randomized clinical trial (Surgical Treatment for Ischemic Heart Failure)

Background—The risk of sudden cardiac death (SCD) in patients with heart failure following CABG has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing and clinical predictors of SCD after CABG. Methods—Patients enrolled in the Surgical Treatment of Ischemic Heart Failure (STICH) trial who underwent CABG with or without surgical ventricular reconstruction (SVR) were included. We excluded patients with prior ICD and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. Results—Over a median follow-up of 46 months, 113 patients of 1411 patients who received CABG without (n = 934) or with SVR (n = 477) had SCD; 311 died of other causes. The mean LVEF at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than those who died for reasons other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31-90 day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy and LV function, ESVI and BNP were most strongly associated with SCD. Conclusions—The monthly risk of SCD shortly after CABG among patients with a low LVEF is highest between the first and third month, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative ESVI and/or BNP

Fermion sea along the sphaleron barrier

In this revised version we have improved the treatment of the top and bottom quark mass. This leads to slight changes of the numerical results, especially of those presented in Fig.4. The discussion of the numerical procedure and accuracy has been extended.Comment: 39 pages (LaTex) plus 5 figures (uuencoded postscript files); RUB-TPII-62/93, to appear in Phys.Rev.

Irbesartan in patients with heart failure and preserved ejection fraction

Background: Approximately 50% of patients with heart failure have a left ventricular ejection fraction of at least 45%, but no therapies have been shown to improve the outcome of these patients. Therefore, we studied the effects of irbesartan in patients with this syndrome. Methods: We enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II, III, or IV heart failure and an ejection fraction of at least 45% and randomly assigned them to receive 300 mg of irbesartan or placebo per day. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke). Secondary outcomes included death from heart failure or hospitalization for heart failure, death from any cause and from cardiovascular causes, and quality of life. Results: During a mean follow-up of 49.5 months, the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group. Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P=0.35). Overall rates of death were 52.6 and 52.3 per 1000 patient-years, respectively (hazard ratio, 1.00; 95% CI, 0.88 to 1.14; P=0.98). Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% CI, 0.85 to 1.08; P=0.44). There were no significant differences in the other prespecified outcomes. Conclusions: Irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction. (ClinicalTrials.gov number, NCT00095238.)

Drought and the Sacramento-San Joaquin Delta, 2012–2016: Environmental Review and Lessons

This paper reviews environmental management and the use of science in the Sacramento–San Joaquin Delta during California’s 2012–2016 drought. The review is based on available reports and data, and guided by discussions with 27 agency staff, stake-holders, and researchers. Key management actions for the drought are discussed relative to four major drought water management priorities stated by water managers: support public health and safety, control saltwater intrusion, preserve cold water in Shasta Reservoir, and maintain minimum protections for endangered species. Despite some success in streamlining communication through interagency task forces, conflicting management mandates sometimes led to confusion about priorities and actions during the drought (i.e., water delivery, the environment, etc.). This report highlights several lessons and offers suggestions to improve management for future droughts. Recommendations include use of pre-drought warnings, timely drought declarations, improved transparency and useful documentation, better scientific preparation, development of a Delta drought management plan (including preparing for salinity barriers), and improved water accounting. Finally, better environmental outcomes occur when resources are applied to improving habitat and bolstering populations of native species during inter-drought periods, well before stressful conditions occur.

Systematic Review of the Relationships Between Objectively Measured Physical Activity and Health Indicators in School-Aged Children and Youth

Moderate-to-vigorous physical activity (MVPA) is essential for disease prevention and health promotion. Emerging evidence suggests other intensities of physical activity (PA), including light-intensity activity (LPA), may also be important, but there has been no rigorous evaluation of the evidence. The purpose of this systematic review was to examine the relationships between objectively measured PA (total and all intensities) and health indicators in school-aged children and youth. Online databases were searched for peer-reviewed studies that met the a priori inclusion criteria: population (apparently healthy, aged 5–17 years), intervention/exposure/comparator (volumes, durations, frequencies, intensities, and patterns of objectively measured PA), and outcome (body composition, cardiometabolic biomarkers, physical fitness, behavioural conduct/pro-social behaviour, cognition/academic achievement, quality of life/well-being, harms, bone health, motor skill development, psychological distress, self-esteem). Heterogeneity among studies precluded meta-analyses; narrative synthesis was conducted. A total of 162 studies were included (204 171 participants from 31 countries). Overall, total PA was favourably associated with physical, psychological/social, and cognitive health indicators. Relationships were more consistent and robust for higher (e.g., MVPA) versus lower (e.g., LPA) intensity PA. All patterns of activity (sporadic, bouts, continuous) provided benefit. LPA was favourably associated with cardiometabolic biomarkers; data were scarce for other outcomes. These findings continue to support the importance of at least 60 min/day of MVPA for disease prevention and health promotion in children and youth, but also highlight the potential benefits of LPA and total PA. All intensities of PA should be considered in future work aimed at better elucidating the health benefits of PA in children and youth

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines

Cause of Death in Patients With Acute Heart Failure: Insights From RELAX-AHF-2

OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. METHODS: Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. RESULTS: By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. CONCLUSIONS: Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)