Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry

Budgeting for Environmental Health Services in Healthcare Facilities: A Ten-Step Model for Planning and Costing

Environmental health services (EHS) in healthcare facilities (HCFs) are critical for safe care provision, yet their availability in low- and middle-income countries is low. A poor understanding of costs hinders progress towards adequate provision. Methods are inconsistent and poorly documented in costing literature, suggesting opportunities to improve evidence. The goal of this research was to develop a model to guide budgeting for EHS in HCFs. Based on 47 studies selected through a systematic review, we identified discrete budgeting steps, developed codes to define each step, and ordered steps into a model. We identified good practices based on a review of additional selected guidelines for costing EHS and HCFs. Our model comprises ten steps in three phases: planning, data collection, and synthesis. Costing-stakeholders define the costing purpose, relevant EHS, and cost scope; assess the EHS delivery context; develop a costing plan; and identify data sources (planning). Stakeholders then execute their costing plan and evaluate the data quality (data collection). Finally, stakeholders calculate costs and disseminate findings (synthesis). We present three hypothetical costing examples and discuss good practices, including using costing frameworks, selecting appropriate indicators to measure the quantity and quality of EHS, and iterating planning and data collection to select appropriate costing approaches and identify data gaps

Sources of and Solutions to Toxic Metal and Metalloid Contamination in Small Rural Drinking Water Systems: A Rapid Review

Exposure to toxic metals and metalloids (TMs) such as arsenic and lead at levels of concern is associated with lifelong adverse health consequences. As exposure to TMs from paint, leaded gasoline, canned foods, and other consumer products has decreased in recent decades, the relative contribution of drinking water to environmental TM exposure and associated disease burdens has increased. We conducted a rapid review from June to September 2019 to synthesize information on the sources of TM contamination in small rural drinking water systems and solutions to TM contamination from these sources, with an emphasis on actionable evidence applicable to small rural drinking water systems worldwide. We reviewed publications from five databases (ProQuest, PubMed, Web of Science, Embase, and Global Health Library) as well as grey literature from expert groups including WHO, IWA, and others; findings from 61 eligible review publications were synthesized. Identified sources of TMs in included studies were natural occurrence (geogenic), catchment pollution, and corrosion of water distribution system materials. The review found general support for preventive over corrective actions. This review informs a useful planning and management framework for preventing and mitigating TM exposure from drinking water based on water supply characteristics, identified contamination sources, and other context-specific variables

Clinical risk factors and atherosclerotic plaque extent to define risk for major events in patients without obstructive coronary artery disease: the long-term coronary computed tomography angiography CONFIRM registry.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both

Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries

Background: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs). Objectives: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management. Methods: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy. Results: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type. Discussion: Ensuring use of lead-free (<0.25% ) components in new water systems and progressively remediating existing systems could reduce drinking-water lead exposures and improve health outcomes for millions. However, reflexive decommissioning of existing systems may deprive users of sufficient water for health or drive them to riskier sources. Because supply chains for many water system components are global, TM monitoring, prevention, and management may be warranted in other LMICs beyond the study area as well. https://doi.org/10.1289/EHP780

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study

Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone

Development and application of tools to cost the delivery of environmental health services in healthcare facilities: a financial analysis in urban Malawi

Background Environmental health services (EHS) in healthcare facilities (HCFs) are critical for providing a safe, functional healthcare environment, but little is known about their costs. Poor understanding of costs impedes progress towards universal access of EHS in HCFs. We developed frameworks of essential expenses required to provide EHS and conducted an ex-post financial analysis of EHS in a network of medical research and training facilities in Lilongwe, Malawi, serving an estimated 42,000 patients annually through seven outpatient buildings. Methods We estimated the cost of providing the following EHS: water, sanitation, hygiene, personal protective equipment use at the point of care, waste management, cleaning, laundry, and vector control. We developed frameworks of essential outputs and inputs for each EHS through review of international guidelines and standards, which we used to identify expenses required for EHS delivery and evaluate the completeness of costs data in our case study. For costing, we use a mixed-methods approach, applying qualitative interviews to understand facility context and review of electronic records to determine costs. We calculated initial costs to establish EHS and annual operations and maintenance. Results Available records contained little information on the upfront, capital costs associated with establishing EHS. Annual operations and maintenance totaled USD 220,427 for all EHS across all facilities (USD 5.21 per patient encounter), although costs of many essential inputs were missing from records. Annual operations and maintenance costs were highest for cleaning (USD 69,372) and waste management (USD 46,752). Discussion Missing expenses suggests that documented costs are substantial underestimates. Costs to establish services were missing predominantly because purchases pre-dated electronic records. Annual operations and maintenance costs were incomplete primarily because administrative records did not record sufficient detail to disaggregate and attribute expenses. Conclusions Electronic health information systems have potential to support efficient data collection. However, we found that existing records systems were decentralized and poorly suited to identify EHS costs. Our research suggests a need to better code and disaggregate EHS expenses to properly leverage records for costing. Frameworks developed in this study are a potential tool to develop more accurate estimates of the cost of providing EHS in HCFs

Geographical inequalities in drinking water in the Solomon Islands

Sustainable Development Goal 6.1 seeks to “by 2030, achieve universal and equitable access to safe and affordable drinking water”, which is challenging particularly in Small Island Developing States (SIDS) and Pacific Island Countries (PIC). We report drinking water sources and services in the Solomon Islands and examine geographical inequalities. Based on two quantitative baseline datasets of n = 1,598 rural and n = 1,068 urban households, we analyzed different drinking water variables (source type, collection time, amount, use, perceived quality, storage, treatment) and a composite index, drinking water service level. We stratified data by urban and rural areas and by province, mapped, and contextualized them. There are substantive rural–urban drinking water inequalities in the Solomon Islands. Overall, urban households are more likely to: use improved drinking water sources, need less time to collect water, collect more water, store their water more safely, treat water prior to consumption, perceive their water quality as better and have an at least basic drinking water service than rural households. There are also provincial and center-periphery inequalities in drinking water access, with more centrally located provinces using piped water supplies and more distant and remote provinces using rainwater and surface water as their primary source. There are also inter-national inequalities. Out of all PICs, the Solomon Islands have among the lowest access to basic drinking water services: 92% of urban and 55% of rural households. Of all SIDS, PICs are least serviced. This study shows that drinking water inequality is a critical issue, and highlights that all identified dimensions of inequality - rural–urban, provincial, center-periphery and inter-national - need to be explicitly recognized and addressed and included in pro-equity monitoring, policy and programming efforts by the Solomon Islands Government and stakeholders to reduce inequalities as per the Agenda 2030

Dietary supplement use among health care professionals enrolled in an online curriculum on herbs and dietary supplements

BACKGROUND: Although many health care professionals (HCPs) in the United States have been educated about and recommend dietary supplements, little is known about their personal use of dietary supplements and factors associated with their use. METHODS: We surveyed HCPs at the point of their enrollment in an on-line course about dietary supplements between September, 2004 and May, 2005. We used multivariable logistic regression to analyze demographic and practice factors associated with use of dietary supplements. RESULTS: Of the 1249 health care professionals surveyed, 81 % reported having used a vitamin, mineral, or other non-herbal dietary supplements in the last week. Use varied by profession with highest rates among nurses (88%), physician assistants or nurse practitioners (84 %) and the lowest rates among pharmacists (66%) and trainees (72%). The most frequently used supplements were multivitamins (60%), calcium (40%), vitamin B (31%), vitamin C (30%), and fish oil (24%). Factors associated with higher supplement use were older age, female, high knowledge of dietary supplements, and discussing dietary supplements with patients. In our adjusted model, nurses were more likely than other professionals to use a multivitamin and students were more likely to use calcium. CONCLUSION: Among HCPs enrolled in an on-line course about dietary supplements, women, older clinicians, those with higher knowledge and those who talk with patients about dietary supplements had higher use of dietary supplements. Additional research is necessary to understand the impact of professionals' personal use of dietary supplements on communication with patients about them