Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Exploring the Housing and Household Energy Pathways to Stress: A Mixed Methods Study

Chronic stress, known to contribute to negative physical and mental health outcomes, is closely associated with broader issues of material hardship, poor neighborhood conditions, residential instability, and inadequate housing conditions. However, few studies have comprehensively explored pathways to stress in a low-income housing environment. A mixed-methods pilot study investigated the concept of energy insecurity by looking at the impacts of weatherization and energy efficiency interventions on low-income households in the South Bronx neighborhood of New York City. In-depth interviews were conducted with 20 low-income heads of household; participants also completed health, housing and budget assessments. Physical deficiencies, economic hardship, and health issues all interacted to directly and indirectly produce living conditions that contribute to chronic stress. Households with higher stress reported more health problems. Poor quality housing led to coping responses that increased expenses, which in turn increased stress around housing and energy affordability. This study provides further support for the connections between both health and the built environment and between low socio-economic status populations and net negative health outcomes. Energy insecurity is an important contributor to chronic stress in low-income households, and isolating pathways to stress where there is potential for interventions is important for future policy and housing-based strategies

Effects of Polybrominated Diphenyl Ethers on Child Cognitive, Behavioral, and Motor Development

Polybrominated Diphenyl Ether (PBDE) flame retardants are environmental chemicals that cross the placenta during pregnancy and have shown evidence of neurotoxicity. As the in utero period is a sensitive developmental window, such exposure may result in adverse childhood outcomes. Associations between in utero PBDE exposure and neurodevelopment are found in animal models and increasingly in human population studies. Here, we review the epidemiological evidence of the association between prenatal exposure to PBDEs and motor, cognitive, and behavioral development in infants and children. Published work suggests a negative association between PBDE concentrations and neurodevelopment despite varying PBDE congeners measured, bio-specimen matrix used, timing of the biological sampling, geographic location of study population, specific developmental tests used, age of children at time of testing, and statistical methodologies. This review includes 16 published studies that measured PBDE exposure in maternal blood during pregnancy or in cord blood at delivery and performed validated motor, cognitive, and/or behavioral testing at one or more time during childhood. We evaluate possible mediation through PBDE-induced perturbations in thyroid function and effect measure modification by child sex. While the majority of studies support an adverse association between PBDEs and neurodevelopment, additional research is required to understand the mechanism of action, possibly through the perturbations in thyroid function either in the pregnant woman or in the child, and the role of biologically relevant effect modifiers such as sex

Real-time drug detection using a diathermic knife combined to rapid evaporative ionisation mass spectrometry

Fast, accurate and sensitive detection of drugs in human tissue is of crucial importance in an investigation of a suspicious death. Here, we aimed to screen cocaine, diazepam, methadone and morphine in post-mortem muscle samples without sample preparation and in quasi-real time using rapid evaporative ionisation mass spectrometry (REIMS). REIMS enables the online MS analysis of vapours generated from tissue dissection by a diathermic knife. Human muscle samples were soaked in solutions of 4 drugs at different concentrations and multiple incubation times to check the feasibility of REIMS for this innovative application. Muscle samples soaked in blank saline were used as a control. The classification model was able to distinguish between 30 μg g-1 cocaine (m/z 304.2), 200 μg g-1 morphine (m/z 286.2), 10 μg g-1 methadone (m/z 310.2) and 10 μg g-1 muscle of diazepam (m/z 285.1). REIMS tandem MS confirmed that the mass peaks that contributed to the class separation, originated from the drugs of interest. As a proof-of-concept, a forensic case muscle sample from a methadone overdose was investigated using REIMS. Here, using our classification model, the recognition software was able to detect methadone, demonstrating that the REIMS method opens new possibilities in forensic toxicology and during autopsy, leading to faster crime solving and decreased costs

Predictors of Urinary Pyrethroid and Organophosphate Compound Concentrations among Healthy Pregnant Women in New York

Our study aimed to investigate dietary and non-dietary predictors of exposure to pyrethroids, organophosphates pesticides and 2,4-D herbicide in two cohorts of pregnant women in New York City: 153 women from the Thyroid Disruption and Infant Development (TDID) cohort and 121 from the Sibling/Hermanos Cohort(S/H). Baseline data on predictors were collected from the women at time of recruitment. We used three different modeling strategies to address missing data due to biomarker values below the limit of detection (<LOD): (1) logistic regression models with biomarkers categorized as (<median, ≥median); (2) linear regression models, imputing the <LOD values with (LOD/√2); (3) regression models, considering <LOD values as left-censored. Generally, all three models identified similar predictors of exposure. We found that ethnicity, higher income and education predicted higher concentrations of most of the biomarkers in both cohorts. Mothers who consumed processed meat in the TDID cohort, and broiled, barbequed food or burgers in the S/H cohort, tended to have lower concentrations of organophosphates and 2,4-D. The choice of modeling led to a few different predictors identified, and the selection of modeling strategy should be based on the study question

Towards real-time intraoperative tissue interrogation for REIMS-guided glioma surgery

Introduction: The main goal of brain tumour surgery is to maximize tumour resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are, therefore, essential to achieve optimal surgical results. Objectives: The primary objective of this study was to develop and validate a mass spectrometry- based technique for the molecular characterization of high- and low-grade glioma tissue during surgery. Methods: An electrosurgical knife is connected to a mass spectrometer (iKnife). Using this system, an aerosol created during electrosurgical resection is aspirated to a mass spectrometer to determine the molecular profile of the tissue within seconds. This rapid evaporative ionization mass spectrometry (REIMS) technique is used to create a chemical profile database and develop a real-time tissue recognition system based on machine learning. Results: Classification models were built by analysing biopsies from 36 patients who underwent brain tumour resection. Our multivariate statistical model could differentiate between astrocytoma grade II and III, glioblastoma, oligodendroglioma grade II and III, and normal brain tissue with an 88% overall accuracy. Astrocytoma and oligodendroglioma grade II were separated from normal brain with a 96% correct classification rate. REIMS could differentiate between different percentages of GBM with 99.2% sensitivity and different percentages of astrocytoma grade II with 97.5% sensitivity. Conclusion: Real-time information during electrosurgical dissection can improve intra-operative decision-making, leading to a more accurate tumour removal for different glioma subtypes

Towards real-time intraoperative tissue interrogation for REIMS-guided glioma surgery

INTRODUCTION: The main goal of brain tumour surgery is to maximize tumour resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are, therefore, essential to achieve optimal surgical results. OBJECTIVES: The primary objective of this study was to develop and validate a mass spectrometry- based technique for the molecular characterization of high- and low-grade glioma tissue during surgery. METHODS: An electrosurgical knife is connected to a mass spectrometer (iKnife). Using this system, an aerosol created during electrosurgical resection is aspirated to a mass spectrometer to determine the molecular profile of the tissue within seconds. This rapid evaporative ionization mass spectrometry (REIMS) technique is used to create a chemical profile database and develop a real-time tissue recognition system based on machine learning. RESULTS: Classification models were built by analysing biopsies from 36 patients who underwent brain tumour resection. Our multivariate statistical model could differentiate between astrocytoma grade II and III, glioblastoma, oligodendroglioma grade II and III, and normal brain tissue with an 88% overall accuracy. Astrocytoma and oligodendroglioma grade II were separated from normal brain with a 96% correct classification rate. REIMS could differentiate between different percentages of GBM with 99.2% sensitivity and different percentages of astrocytoma grade II with 97.5% sensitivity. CONCLUSION: Real-time information during electrosurgical dissection can improve intra-operative decision-making, leading to a more accurate tumour removal for different glioma subtypes

[DNVF Memorandum Health Literacy (Part 1) - Background, Relevance, Research Topics and Questions in Health Services Research: Short Version].

Ernstmann N, Bauer U, Berens E-M, et al. DNVF Memorandum Gesundheitskompetenz (Teil 1) – Hintergrund, Relevanz, Gegenstand und Fragestellungen in der Versorgungsforschung: Kurzfassung. Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)). 2020;82(7):639-645.Mehr als die Hälfte der deutschen Bevölkerung hat Schwierigkeiten im Umgang mit Gesundheitsinformationen. Es ist eine wichtige Aufgabe der Versorgungsforschung zu untersuchen, wie sich die Professionen und Organisationen des Gesundheitssystems dieser Herausforderung stellen können. Die vorliegende Kurzfassung des DNVF Memorandums Gesundheitskompetenz (Teil 1) nimmt Begriffsbestimmungen der individuellen und organisationalen Gesundheitskompetenz vor, präsentiert den nationalen und internationalen Forschungsstand und stellt ethische Aspekte der versorgungsbezogenen Gesundheitskompetenzforschung dar. Vor diesem Hintergrund werden zentrale Forschungsgegenstände und zukünftige Forschungsdesiderata abgeleitet.More than half of the German population has difficulties in dealing with health information. It is an important task of health services research to examine how healthcare professionals and health care organizations can meet this challenge. This short version of the DNVF Memorandum Health Literacy (Part 1) defines the terms of individual and organizational health literacy, presents the national and international state of research and ethical aspects of health literacy research in health care settings. Central research topics and future research desiderata are derived. © Georg Thieme Verlag KG Stuttgart · New York