Predictors of Mortality Amongst Recipients of Implantable Cardioverter Defibrillators for Secondary Prevention of Cardiac Arrest

BACKGROUND: Implantable Cardioverter-defibrillators (ICD) reduce mortality in survivors of cardiac arrest (CA). We investigated the predictors of mortality after ICD implantation in survivors of CA. METHODS: Retrospective review of clinical records and social security death index of all patients who received an ICD in a preexisting database of survivors of CA at the University of Pittsburgh Medical Center was performed. Multivariate analyses using the Cox proportional hazard model were performed with backward elimination to identify independent predictors of the time to death, and Kaplan-Meier curves were plotted. RESULTS: Eighty patients (64 men) with a mean age of 64.4+/-12.5 years were followed for 4.7+/-2.3 years after ICD implantation. Survival rates were 93.8%, 65% and 50% at 1, 5, and 10 years, respectively. Independent predictors of time to death were determined to include age (hazard ratio (HR) = 1.91 per 10-year increase, p = 0.003), serum creatinine > or = 1.3 mg/dL (HR = 2.56, p = 0.004), and QRS width >120 ms (HR = 5.14, p = 0.012). CONCLUSIONS: In this sample of ICD recipients secondary to CA, older age, elevated serum creatinine, and wider QRS duration were independent predictors of mortality. The presence of more than one risk factor in the same patient was associated with higher mortality rates. Whether interventions such as biventricular pacing can offset this increase risk of death warrants further investigation

Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells

BACKGROUND: Hypermethylation of the promoter of the tumor suppressor gene RASSF1A silences its expression and has been found to be associated with advanced grade prostatic tumors. The DNA methyltransferase (DNMT) family of enzymes are known to be involved in the epigenetic silencing of gene expression, including RASSF1A, and are often overexpressed in prostate cancer. The present study demonstrates how mahanine, a plant-derived carbazole alkaloid, restores RASSF1A expression by down-regulating specific members of the DNMT family of proteins in prostate cancer cells. RESULTS: Using methylation-specific PCR we establish that mahanine restores the expression of RASSF1A by inducing the demethylation of its promoter in prostate cancer cells. Furthermore, we show that mahanine treatment induces the degradation of DNMT1 and DNMT3B, but not DNMT3A, via the ubiquitin-proteasome pathway; an effect which is rescued in the presence of a proteasome inhibitor, MG132. The inactivation of Akt by wortmannin, a PI3K inhibitor, results in a similar down-regulation in the levels DNMT1 and DNMT3B. Mahanine treatment results in a decline in phospho-Akt levels and a disruption in the interaction of Akt with DNMT1 and DNMT3B. Conversely, the exogenous expression of constitutively active Akt inhibits the ability of mahanine to down-regulate these DNMTs, suggesting that the degradation of DNMT1 and DNMT3B by mahanine occurs via Akt inactivation. CONCLUSIONS: Taken together, we show that mahanine treatment induces the proteasomal degradation of DNMT1 and DNMT3B via the inactivation of Akt, which facilitates the demethylation of the RASSF1A promoter and restores its expression in prostate cancer cells. Therefore, mahanine could be a potential therapeutic agent for advanced prostate cancer in men when RASSF1A expression is silenced

Outpatient Management of Heart Failure in the United States, 2006–2008

Better outpatient management of heart failure might improve outcomes and reduce the number of rehospitalizations. This study describes recent outpatient heart-failure management in the United States

Relation of Ventricular Premature Complexes to Heart Failure (from the Atherosclerosis Risk In Communities [ARIC] Study)

Analogous to rapid ventricular pacing, frequent ventricular premature complexes (VPCs) may predispose over time to cardiomyopathy and subsequent heart failure (HF). We examined the association of frequent VPCs with HF incidence in a population-based cohort, free of HF and coronary heart disease (CHD) at baseline. At study baseline (1987-89), at least one VPC on a 2-minute rhythm ECG strip was seen in 5.5% (739/13486) of the middle aged (45-64 years old at baseline), white and African-American, men and women of the ARIC cohort. Incident HF was defined as the first appearance of ICD code ‘428.x’ in hospital discharge record or death certificate through 2005. Over an average follow up of 15.6 years, incident HF was seen in 10% subjects (19.4% in those with VPCs vs. 9.4% in those without). The age, race, and gender adjusted hazard ratio (HR) of HF for VPCs was 1.89 (95% CI = 1.59, 2.24). After multivariable adjustment for potential confounders, HR (95% CI) of HF for those with any VPC vs. no VPCs was 1.63 (1.36, 1.96). After additional adjustment for incident CHD as a time-varying covariate, the HR (95% CI) was 1.71 (1.42, 2.08). Presence of higher frequency of VPCs or complex VPCs had similar rates of HF as compared to single VPC and all were higher than no VPC group. In conclusion, in this large population based cohort, presence of VPCs is associated with incident HF independent of incident CHD

Surface charging and electrostatic dust acceleration at the nucleus of comet 67P during periods of low activity

We have investigated through simulation the electrostatic charging of the nucleus of Comet 67 P/Churyumov-Gerasimenko during periods of weak outgassing activity. Specifically, we have modeled the surface potential and electric field at the surface of the nucleus during the initial Rosetta rendezvous at 3.5 AU and the release of the Philae lander at 3 AU. We have also investigated the possibility of dust acceleration and ejection above the nucleus due to electrostatic forces. Finally, we discuss these modeling results in the context of possible observations by instruments on both the Rosetta orbiter and the Philae lander

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London