What is the best beta-blocker for systolic heart failure?

Q: What is the best beta-blocker for systolic heart failure? Evidence-based answer: Three beta-blockers--carvedilol, metoprolol succinate, and bisoprolol--reduce mortality equally (by about 30% over one year) in patients with Class III or IV systolic heart failure. Insufficient evidence exists comparing equipotent doses of these medications head-to-head to recommend any one over the others (strength of recommendation [SOR]: A, systematic review/meta-analysis)

Sustainability Assessment of the Biosand Filter in Bonao, Dominican Republic

Access to clean drinking water is not a reality for approximately 1.1 billion people in the world, leading to approximately 1.6 million children dying each year due to diarrheal diseases linked to unsafe drinking water. Household water treatment at the point-of-use (POU) has proven effective in improving microbiological water quality and reducing diarrheal disease among users in both laboratory and field studies. The Biosand filter (BSF), an intermittently operated, slow sand filter, is a promising POU technology, although little follow-up of the initial positive study and trial results has occurred to assess BSF sustainability. The purpose of this study was to assess the sustainability of previously implemented BSFs in and around Bonao, Dominican Republic (DR) through two approaches: 1) cross-sectional analysis of continued use, performance effectiveness, and sustained water quality improvement, and 2) longitudinal analysis of sustained health impact, measured as diarrheal disease, and sustained water quality improvement. Over 90% of the BSFs were found still in use after an average of one year since installation. Incidence rates of diarrheal disease were reduced by 61% for BSF intervention households in comparison with non-BSF control households. Water quality improvement, as measured by reduction of fecal indicator bacteria, was found to be low (84 to 88%) ) in comparison to reductions seen in the laboratory but comparable to analogous rates seen for the BSF in other field assessments. Together, the results suggest the BSF is a highly sustainable POU water treatment technology.Master of Science in Public Healt

An Assessment of Continued Use and Health Impact of the Concrete Biosand Filter in Bonao, Dominican Republic.

The biosand filter (BSF) is a promising point of use (POU) technology for water treatment; however there has been little follow-up of initial implementation to assess sustainability. The purpose of this study was to examine continued use, performance, and sustainability of previously implemented concrete BSFs in Bonao, Dominican Republic. Of 328 households visited and interviewed, 90% of BSFs were still in use after approximately 1 year since installation. Waterquality improvement, measured by fecal indicator bacteria reduction, was found to be 84–88%, which is lower than reductions in controlled laboratory studies but similar to other field assessments. In a short prospective cohort study comparing BSF to non-BSF households, odds of reported diarrheal disease in BSF households were 0.39 times the odds of reported diarrheal disease in non-BSF households. These results document high levels of sustained and effective concrete BSF use and associated improvements in water quality and health

Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance.

Maternal obesity is a global problem that increases the risk of short- and long-term adverse outcomes for mother and child, many of which are linked to gestational diabetes mellitus. Effective treatments are essential to prevent the transmission of poor metabolic health from mother to child. Metformin is an effective glucose lowering drug commonly used to treat gestational diabetes mellitus; however, its wider effects on maternal and fetal health are poorly explored. In this study we used a mouse (C57Bl6/J) model of diet-induced (high sugar/high fat) maternal obesity to explore the impact of metformin on maternal and feto-placental health. Metformin (300 mg kg-1  day-1 ) was given to obese females via the diet and was shown to achieve clinically relevant concentrations in maternal serum (1669 ± 568 nM in late pregnancy). Obese dams developed glucose intolerance during pregnancy and had reduced uterine artery compliance. Metformin treatment of obese dams improved maternal glucose tolerance, reduced maternal fat mass and restored uterine artery function. Placental efficiency was reduced in obese dams, with increased calcification and reduced labyrinthine area. Consequently, fetuses from obese dams weighed less (P < 0.001) at the end of gestation. Despite normalisation of maternal parameters, metformin did not correct placental structure or fetal growth restriction. Metformin levels were substantial in the placenta and fetal circulation (109.7 ± 125.4 nmol g-1 in the placenta and 2063 ± 2327 nM in fetal plasma). These findings reveal the distinct effects of metformin administration during pregnancy on mother and fetus and highlight the complex balance of risk vs. benefits that are weighed in obstetric medical treatments. KEY POINTS: Maternal obesity and gestational diabetes mellitus have detrimental short- and long-term effects for mother and child. Metformin is commonly used to treat gestational diabetes mellitus in many populations worldwide but the effects on fetus and placenta are unknown. In a mouse model of diet-induced obesity and glucose intolerance in pregnancy we show reduced uterine artery compliance, placental structural changes and reduced fetal growth. Metformin treatment improved maternal metabolic health and uterine artery compliance but did not rescue obesity-induced changes in the fetus or placenta. Metformin crossed the placenta into the fetal circulation and entered fetal tissue. Metformin has beneficial effects on maternal health beyond glycaemic control. However, despite improvements in maternal physiology, metformin did not prevent fetal growth restriction or placental ageing. The high uptake of metformin into the placental and fetal circulation highlights the potential for direct immediate effects of metformin on the fetus with possible long-term consequences postnatally

Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study

BACKGROUND: Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness. METHODS: From March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews. RESULTS: Some 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2-1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3-2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing. CONCLUSION: In Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability

Failing better: The stochastic art of evaluating community-led environmental action programs

This article provides insights into the evaluation of a government-funded action for climate change program. The UK-based program aimed to reduce CO2 emissions and encourage behavioral change through community-led environmental projects. It, thus, employed six community development facilitators, with expertise in environmental issues. These facilitators supported and learnt from 18 community groups over an 18-month period. The paper explores the narratives of the six professional facilitators. These facilitators discuss their experiences of supporting community groups. They also explain their contribution to the wider evaluation of the community-led projects. This paper reflects on the facilitator experience of the program’s outcome-led evaluation process. In turn, it also explores how the groups they supported experienced the process. The facilitator’s narratives reveal that often community-group objectives did not align with predefined outcomes established through theory of change or logic model methodologies, which had been devised in attempt to align to program funder aims. Assisting community action emerges in this inquiry as a stochastic art that requires funder and facilitator willingness to experiment and openness to the possibilities of learning from failure. Drawing on in-depth accounts, the article illustrates that a reflexive, interpretive evaluation approach can enhance learning opportunities and provides funders with more trustworthy representations of community-led initiatives. Yet, it also addresses why such an approach remains marginal within policy circles

Interrater Reliability of NI-RADS on Posttreatment PET/Contrast-enhanced CT Scans in Head and Neck Squamous Cell Carcinoma

Purpose: To evaluate the interrater reliability among radiologists examining posttreatment head and neck squamous cell carcinoma (HNSCC) fluorodeoxyglucose PET/contrast-enhanced CT (CECT) scans using Neck Imaging Reporting and Data System (NI-RADS). Materials and Methods: In this retrospective study, images in 80 patients with HNSCC who underwent posttreatment surveillance PET/CECT and immediate prior comparison CECT or PET/CECT (from June 2014 to July 2016) were uploaded to the American College of Radiology's cloud-based website, Cortex. Eight radiologists from seven institutions with variable NI-RADS experience independently evaluated each case and assigned an appropriate prose description and NI-RADS category for the primary site and the neck site. Five of these individuals were experienced readers (> 5 years of experience), and three were novices (< 5 years of experience). In total, 640 lexicon-based and NI-RADS categories were assigned to lesions among the 80 included patients by the eight radiologists. Light generalization of Cohen κ for interrater reliability was performed. Results: Of the 80 included patients (mean age, 63 years ± 10 [standard deviation]), there were 58 men (73%); 60 patients had stage IV HNSCC (75%), and the most common tumor location was oropharynx (n = 32; 40%). Light κ for lexicon was 0.30 (95% CI: 0.23, 0.36) at the primary site and 0.31 (95% CI: 0.24, 0.37) at the neck site. Light κ for NI-RADS category was 0.55 (95% CI: 0.46, 0.63) at the primary site and 0.60 (95% CI: 0.48, 0.69) at the neck site. Percent agreement between lexicon and correlative NI-RADS category was 84.4% (540 of 640) at the primary site and 92.6% (593 of 640) at the neck site. There was no significant difference in interobserver agreement among the experienced versus novice raters. Conclusion: Moderate agreement was achieved among eight radiologists using NI-RADS at posttreatment HNSCC surveillance imaging

Revisiting HIV-1 uncoating

HIV uncoating is defined as the loss of viral capsid that occurs within the cytoplasm of infected cells before entry of the viral genome into the nucleus. It is an obligatory step of HIV-1 early infection and accompanies the transition between reverse transcription complexes (RTCs), in which reverse transcription occurs, and pre-integration complexes (PICs), which are competent to integrate into the host genome. The study of the nature and timing of HIV-1 uncoating has been paved with difficulties, particularly as a result of the vulnerability of the capsid assembly to experimental manipulation. Nevertheless, recent studies of capsid structure, retroviral restriction and mechanisms of nuclear import, as well as the recent expansion of technical advances in genome-wide studies and cell imagery approaches, have substantially changed our understanding of HIV uncoating. Although early work suggested that uncoating occurs immediately following viral entry in the cell, thus attributing a trivial role for the capsid in infected cells, recent data suggest that uncoating occurs several hours later and that capsid has an all-important role in the cell that it infects: for transport towards the nucleus, reverse transcription and nuclear import. Knowing that uncoating occurs at a later stage suggests that the viral capsid interacts extensively with the cytoskeleton and other cytoplasmic components during its transport to the nucleus, which leads to a considerable reassessment of our efforts to identify potential therapeutic targets for HIV therapy. This review discusses our current understanding of HIV uncoating, the functional interplay between infectivity and timely uncoating, as well as exposing the appropriate methods to study uncoating and addressing the many questions that remain unanswered

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic