Effect of Surfactant Mixtures on Skin Structure and Barrier Properties

We investigated the effect of two commonly studied surfactants, sodium dodecyl sulfate (SDS) and dodecyl trimethylammonium bromide (C12TAB), on skin barrier properties. Using skin conductivity, FT-IR of stratum corneum samples, and penetration of radiolabelled SDS, we determined that addition of C12TAB lowers the ability of SDS to perturb skin’s barrier properties. Ultrafiltration experiments revealed that addition of C12TAB serves to decrease the concentration of monomers and sub-micellar aggregates. None of the measured skin properties including enhancement of skin conductivity, perturbation of lipid structure and skin concentration of SDS correlated with the total SDS concentration in the donor compartment (i.e., the total SDS concentration). However, all these parameters correlated well against the concentration of monomers and sub-micellar aggregates. These findings provide the evidence of the importance of monomer and sub-micellar components in altering skin barrier properties

A Population-Based Study of the Association of Medical Manpower with County Trauma Death Rates in the United States

OBJECTIVE: To determine the association between measures of medical manpower available to treat trauma patients and county trauma death rates in the United States. The primary hypothesis was that greater availability of medical manpower to treat trauma injury would be associated with lower trauma death rates. SUMMARY BACKGROUND DATA: When viewed from the standpoint of the number of productive years of life lost, trauma has a greater effect on health care and lost productivity in the United States than any disease. Allocation of health care manpower to treat injuries seems logical, but studies have not been done to determine its efficacy. The effect of medical manpower and hospital resource allocation on the outcome of injury in the United States has not been fully explored or adequately evaluated. METHODS: Data on trauma deaths in the United States were obtained from the National Center for Health Statistics. Data on the number of surgeons and emergency medicine physicians were obtained from the American Hospital Association and the American Medical Association. Data on physicians who have participated in the American College of Surgeons (ACS) Advanced Trauma Life Support Course (ATLS) were obtained from the ACS. Membership information for the American Association for Surgery of Trauma (AAST) was obtained from that organization. Demographic data were obtained from the United States Census Bureau. Multivariate stepwise linear regression and cluster analysis were used to model the county trauma death rates in the United States. The Statistical Analysis System (Cary, NC) for statistical analysis was used. RESULTS: Bivariate and multivariate analyses showed that a variety of medical manpower measures and demographic factors were associated with county trauma death rates in the United States. As in other studies, measures of low population density and high levels of poverty were found to be strongly associated with increased trauma death rates. After accounting for these variables, using multivariate analysis and cluster analysis, an increase in the following medical manpower measures were associated with decreased county trauma death rates: number of board-certified general surgeons, number of board-certified emergency medicine physicians, number of AAST members, and number of ATLS-trained physicians. CONCLUSIONS: This study confirms previous work that showed a strong relation among measures of poverty, rural setting, and increased county trauma death rates. It also found that counties with more board-certified surgeons per capita and with more surgeons with an increased interest (AAST membership) or increased training (ATLS) in trauma care have lower per-capita trauma death rates

COVID-19 outbreak and pediatric diabetes: perceptions of health care professionals worldwide

This is the peer reviewed version of the following article: "COVID-19 outbreak and pediatric diabetes: perceptions of health care professionals worldwide". Pediatric Diabetes (2020): 20 July, which has been published in final form at 10.1111/pedi.13084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsCoronavirus diasease (COVID-19) is an infectious disease that startedin Wuhan, China in late 2019 and later spread around the world. Diabetes has beenrecognized as a possible risk factor for COVID-19 complications.Objective: International Society for Pediatric and Adolescent Diabetes (ISPAD) investi-gated perceptions, challenges and experience of health care professionals (HCP) takingcare of children and young people with diabetes worldwide during COVID-19 pandemic.Methods: From 21st April to 17th May 2020, during COVID-19 pandemic, a web-based survey was sent to ISPAD members and former participants of ISPAD confer-ences by email.Results: Responders from 215 diabetes centers from 75 countries completed the sur-vey. Majority were from UK (35; 16.3%), USA (20; 9.3%), and India (15; 7%). HCPwere mostly pediatric endocrinologists (64%). During COVID-19 pandemic, 16.5% ofresponders continued face-to-face consultation while most changed to telephone(32%) or video (18%) consultations. 19% reported a shortage of medical supplies.22% reported a delay in diagnosis of patients with new-onset diabetes, while 15%reported a higher incidence of DKA. 12% reported having one or more patients withCOVID-19. Most of the 86 children and adolescents with diabetes and COVID-19had only mild/moderate symptoms, while 5 required admission to an intensive careunit. No deaths were reported.Conclusions: This large global survey during COVID-19 pandemic showed that manyHCP adapted to the pandemic by resorting to telemedicine. One fourth of HCPreported delays in diagnosis and an increased rate of DKA. The emergence ofCOVID-19 pandemic had an important impact on family's behavior that might haveled to increase in diabetic ketoacidosis presentatio

Substantial effect of efavirenz monotherapy on bilirubin levels in healthy volunteers

BACKGROUND: Efavirenz exhibits multiple interactions with drug-metabolizing enzymes and transporters, and for this reason efavirenz-based HIV therapy is associated with altered pharmacokinetics of coadministered drugs. Probably by the same mechanism, efavirenz-based HIV therapy affects the disposition of endogenous compounds, but this effect is difficult to directly link with efavirenz because it is used in combination with other drugs. OBJECTIVES: To explore the effect of efavirenz monotherapy on biochemical laboratory values in a clinical trial of healthy volunteers. METHODS: Men and women (aged 18-49 years) with body mass index ≤32 who were assessed to be healthy based on medical history, physical examination, and standard laboratory screening received a single (600 mg) and multiple doses (600 mg/d for 17 days) of efavirenz orally. This trial was designed to determine the pharmacokinetics and drug interactions of efavirenz. As part of this study, analysis of serum chemistries that were measured at study entry (screening) and 1 week after completion of the multiple dose study (exit) is reported. RESULTS: Data from 60 subjects who fully completed and 13 subjects who partially completed the study are presented. Total bilirubin was substantially reduced at exit (by ~30%, with large intersubject variability) compared with screening values (P < 0.0001). The percent changes were in part explained by the intersubject differences in baseline total bilirubin because there was a significant correlation between baseline (screening) values and percent change at exit (r = 0.50; P < 0.0001). Hemoglobin and absolute neutropenia were also substantially decreased at exit compared with screening, but this may be due to intensive blood sampling rather than direct effect of efavirenz on these parameters. No significant correlation was found between percent change in hemoglobin versus percent change in bilirubin, indicating the effect of efavirenz on bilirubin is independent of its effects on hemoglobin. CONCLUSIONS: Efavirenz monotherapy significantly lowers plasma total bilirubin concentration in healthy volunteers independent of its effect on hemoglobin, probably through its effects on bilirubin metabolism and transport (uptake and efflux). These findings help explain reversal by efavirenz of hyperbilirubinemia induction observed by some protease inhibitor antiretroviral drugs (eg, atazanavir). Besides its well-documented role on drug interactions, efavirenz may alter the disposition of endogenous compounds relevant in physiologic homeostasis through its interaction with drug metabolizing enzymes and/or drug transporters. ClinicalTrials.gov identifier: NCT00668395

Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000-2016: a spatial and temporal modelling study.

BACKGROUND: Routine childhood vaccination is among the most cost-effective, successful public health interventions available. Amid substantial investments to expand vaccine delivery throughout Africa and strengthen administrative reporting systems, most countries still require robust measures of local routine vaccine coverage and changes in geographical inequalities over time. METHODS: This analysis drew from 183 surveys done between 2000 and 2016, including data from 881 268 children in 49 African countries. We used a Bayesian geostatistical model calibrated to results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, to produce annual estimates with high-spatial resolution (5 ×    5 km) of diphtheria-pertussis-tetanus (DPT) vaccine coverage and dropout for children aged 12-23 months in 52 African countries from 2000 to 2016. FINDINGS: Estimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval [UI] 64·6-80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola. INTERPRETATION: Despite substantial progress in Africa, marked national and subnational inequalities in DPT coverage persist throughout the continent. These results can help identify areas of low coverage and vaccine delivery system vulnerabilities and can ultimately support more precise targeting of resources to improve vaccine coverage and health outcomes for African children. FUNDING: Bill & Melinda Gates Foundation

Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US$10 trillion (95$20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only $40 (24–65) to$413 (263–668) in 2040 in low-income countries, and from $140 (90–200) to$1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC. Funding: The Bill & Melinda Gates Foundation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI)

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030