Metallomics in pulmonary arterial hypertension patients.

Pulmonary arterial hypertension (PAH) prevalence is increasing worldwide, and the prognosis is poor with 5-year survival < 50% in high risk patients. The relationship between metal exposure/essential metal dyshomeostasis and PAH/right ventricular dysfunction is less investigated. The aim of this study is to investigate vegetable consumptions and metal levels between PAH patients and controls. This was a prospective, single center pilot study. Questionnaires were completed by all study subjects (20 PAH patients and 10 healthy controls) on smoking, metal exposure risks, metal supplements, and vegetable consumptions. Blood and urine samples were collected to measure 25 metal levels in blood, plasma, and urine using an X Series II quadrupole inductively coupled plasma mass spectrometry. Statistical analysis was conducted using SAS 9.5 and results with p value < 0.05 were considered significant. Vegetables consumptions (broccoli risk ratio [RR] = 0.4, CI = (0.2, 0.9)], cabbage [RR = 0.2, CI = (0.1, 0.8)], and brussel sprouts [RR = 0.2, CI = (0.1, 0.5)]) are associated with less risks of PAH. In the plasma samples, silver (p < 0.001), and copper (p = 0.002) levels were significantly higher in PAH patients. There was significant positive correlation between cardiac output and cardiac index with plasma levels of silver (r = 0.665, p = 0.001 and r = 0.678 p = 0.001), respectively. There was significant correlation between mixed venous saturation, 6-min walk distance, and last BNP with plasma levels of chromium (r = -0.520, p = 0.022; r = -0.55, p = 0.014; r = 0.463, p = 0.039), respectively. In conclusion, there are significant differences between PAH and control groups in terms of vegetable consumptions and metal concentrations. Silver and chromium levels are correlated with clinical indicators of PAH severities.

Obesity reprograms the pulmonary polyunsaturated fatty acid-derived lipidome, transcriptome, and gene-oxylipin networks.

Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to external injury are not well studied. Herein, we tested the hypothesis that obesity dysregulates pulmonary PUFA metabolism that is central to inflammation initiation and resolution. We first show that a high-fat diet (HFD) administered to C57BL/6J mice increased the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins (particularly prostaglandins and hydroxyeicosatetraenoic acids), independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity (ob/ob) generally recapitulated the effects of the HFD on the pulmonary oxylipin signature. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. We found the HFD increased pathways related to glycerophospholipid metabolism and immunity, including a unique elevation in B cell differentiation and signaling. Furthermore, we conducted computational integration of lipidomic with transcriptomic data. These analyses identified novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived pulmonary oxylipins. Finally, we confirmed the hypothesis by demonstrating that the concentration of pulmonary oxylipins, in addition to inflammatory markers, were generally increased in mice consuming a HFD upon ozone-induced acute lung injury. Collectively, these data show that a HFD dysregulates pulmonary PUFA metabolism prior to external lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly to infectious and/or inflammatory challenges.

3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.

Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH. Herein, we identified HA synthase-2 (HAS2) in the pulmonary artery smooth muscle cell (PASMC) layer as a predominant locus of HA dysregulation. HA upregulation involves depletion of NUDT21, a master regulator of alternative polyadenylation, resulting in 3'UTR shortening and hyper-expression of HAS2. The ensuing increase of HAS2 and hyper-synthesis of HA promoted bioenergetic dysfunction of PASMC characterized by impaired mitochondrial oxidative capacity and a glycolytic shift. The resulting HA accumulation stimulated pro-remodeling phenotypes such as cell proliferation, migration, apoptosis-resistance, and stimulated pulmonary artery contractility. Transgenic mice, mimicking HAS2 hyper-synthesis in smooth muscle cells, developed spontaneous PH, whereas targeted deletion of HAS2 prevented experimental PH. Pharmacological blockade of HAS2 restored normal bioenergetics in PASMC, ameliorated cell remodeling phenotypes, and reversed experimental PH in vivo. In summary, our results uncover a novel mechanism of HA hyper-synthesis and downstream effects on pulmonary vascular cell metabolism and remodeling.

Thunderstorms, Pollen, and Severe Asthma in a Midwestern, USA, Urban Environment, 2007-2018.

BACKGROUND: Previous research has shown an association between individual thunderstorm events in the presence of high pollen, commonly called thunderstorm asthma, and acute severe asthma events, but little work has studied risk over long periods of time, using detailed measurements of storms and pollen. METHODS: We estimated change in the risk of asthma-related emergency room visits related to thunderstorm asthma events in the Minneapolis-St. Paul metropolitan area over the years 2007-2018. We defined thunderstorm asthma events as daily occurrence of two or more lightning strikes during high pollen periods interpolating weather and pollen monitor data and modeling lightning counts. We acquired daily counts of asthma-related emergency department visits from the Minnesota Hospital Association and used a quasi-Poisson time-series regression to estimate overall relative risk of emergency department visits during thunderstorm asthma events. RESULTS: We observed a 1.047 times higher risk (95% confidence interval = 1.012, 1.083) of asthma-related emergency department visits on the day of thunderstorm asthma event. Our findings are robust to adjustment for temperature, humidity, wind, precipitation, ozone, PM 2.5 , day of week, and seasonal variation in asthma cases. Occurrence of lightning alone or pollen alone showed no association with the risk of severe asthma. A two-stage analysis combining individual zip code-level results shows similar RR, and we see no evidence of spatial correlation or spatial heterogeneity of effect. DISCUSSION: Our results support an association between co-occurrence of lightning and pollen and risk of severe asthma events. Our approach incorporates lightning and pollen data and small-spatial area exposure and outcome counts.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Medication taking in a national sample of dependent older people.

BACKGROUND: Polypharmacy is associated with inappropriate medication use, and subsequently increasing older persons' risk of drug-related harm and health-related costs to individuals and society. OBJECTIVE: To examine and describe, using a national sample of patient-level medication data, the prevalence of older people's polypharmacy and medication use across dependency levels. To examine oral and general pain prevalence and associated analgesic usage. METHODS: Medication data from the 2012 New Zealand Older People's Oral Health Survey, a nationally-representative, cross-sectional study of dependent older people's oral health, were analysed descriptively, comparing classes and sub-classes of drugs and nutrient supplements taken across four categories of dependency: very low (own homes receiving in-home support), low, high and psychogeriatric (all receiving aged residential care). Self-reported current general pain and frequency of orofacial pain data were cross-tabulated by sub-classes of analgesics taken. RESULTS: All participants were taking at least one medication overall, 53.2% (95% CI: 50.4, 56.0) took between five and nine (polypharmacy), and 13.9% (95% CI: 17.4, 22.5) took 10 or more (hyperpolypharmacy). Antihypertensives, analgesics, antiulcer drugs, aspirin, laxatives, statins and antidepressants were the most common drug classes taken, the proportions differing between psychogeriatric level care and all other dependency groups. Overall, simple analgesics were taken (34.5%; 95%CI: 30.8, 38.4) more commonly than other analgesics; the use of nonsteroidal anti-inflammatory drugs was low (3.6%; 95% CI: 2.7, 4.7). Of those reporting experiencing extreme general bodily pain, 63.3% (95% CI: 56.6, 69.4) took an analgesic, more than those experiencing mouth pain occasionally or often. Fat-soluble vitamins were the most common vitamin supplement taken (32.0%; 95%CI: 27.0, 37.4). CONCLUSIONS: Polypharmacy and hyperpolypharmacy are common among older people, regardless of dependency level, and pain may be undertreated.

Supernatural explanatory models of health and illness and healthcare use in China among men who have sex with men.

People's beliefs in supernatural explanatory models of health and illness - beliefs in divine and/or supernatural forces to inform how they perceive, interpret, and respond to health and illness - may have important implications for their use of healthcare services, especially among individuals with lower socioeconomic status (SES). However, the relevance of such research for contexts with strong Confucian and Buddhist traditions and sexual minority subpopulations remains unclear. We conducted a nation-wide survey in China of 503 men who have sex with men (MSM) to test hypotheses examining how supernatural beliefs impact commitment to a primary healthcare provider and testing history for HIV and syphilis. We also tested hypotheses regarding how SES may moderate such effects. Results indicate that strength of supernatural beliefs is associated with less commitment to a primary care provider and lower likelihood of HIV testing, particularly among men with lower educational attainment. However, among men with low income, supernatural belief was associated with higher likelihood of testing for HIV and syphilis. Belief in supernatural explanatory models of health and illness may have substantial influence on healthcare use among MSM in China. As religion and spirituality evolves within China, additional research concerning supernatural beliefs and healthcare use is warranted.

Traditional health practitioners and sustainable development: a case study in South Africa.

OBJECTIVES: To highlight legal and regulatory advances relating to South African traditional health practitioners (THPs) over the past 10 years and discuss the implications for the translation of health policies into guidelines for sustainable practice supporting public health. STUDY DESIGN: This is a rapid, structured literature review. METHODS: A rapid, structured literature review was undertaken to identify relevant studies related to South African THPs involving a search of peer-reviewed literature from three databases and a grey literature internet search. The identified citations were screened, critically appraised, and narratively synthesized. RESULTS: Efforts to regulate THPs in South Africa are underway; however, the lack of a regulatory framework for traditional practices is hampering progress. Several efforts to collaborate with THPs have been made over the years, many of which were not systematically evaluated and not based on principles of mutual respect. Existing collaborative examples need to be further supported by cost-effective evidence to suit the South African public health budget. Furthermore, small collaborative research efforts do not take into consideration the scale up of interventions. CONCLUSIONS: THPs in South Africa represent an important healthcare resource. However, the current policy environment does not support indicators to describe, monitor, and/or evaluate the role of THPs in the healthcare system.

Thalamocortical Connections and Executive Function in Pediatric Temporal and Frontal Lobe Epilepsy.

BACKGROUND AND PURPOSE: Largely accepted in the literature is the role the interconnections between the thalamus and cortex play in generalized epilepsy. However, thalamocortical involvement is less understood in focal epilepsy in terms of the effect of seizures on thalamocortical circuitry in the developing brain and subsequent cognitive outcome. We investigated thalamocortical pathway microstructure in pediatric frontal lobe epilepsy and temporal lobe epilepsy and examined the associations between pathway microstructure and measures of executive function. MATERIALS AND METHODS: We examined thalamocortical connections in 24 children with frontal lobe epilepsy, 17 patients with temporal lobe epilepsy, and 25 healthy children using DTI. We investigated several executive function measures in patients and controls, which were distilled into latent executive function components to compare among groups, and the associations between measures of thalamocortical microstructure and executive function. RESULTS: We found no differences in thalamocortical pathway microstructure between the groups, but aspects of executive function (mental flexibility/inhibition/shifting) were impaired in the frontal lobe epilepsy group compared with controls. In patients with frontal lobe epilepsy, younger age at seizure onset and a greater number of antiepileptic drugs were associated with DTI indices indicative of damaged/less developed thalamocortical pathways. In patients with temporal lobe epilepsy, poorer performance on all measures of executive function was associated with DTI indices reflective of damaged/less developed pathways. CONCLUSIONS: Our results give insight into vulnerable neural networks in pediatric focal epilepsy and suggest thalamocortical pathway damage as a potential mechanism of executive function impairment in temporal lobe epilepsy but not frontal lobe epilepsy. Identifying structure-function relations can help inform how we measure functional and cognitive/behavioral outcomes in these populations.

A six week contextualised physical activity intervention for women living with HIV and AIDS of low socioeconomic status: a pilot study.

Research has consistently shown the benefits of regular physical activity (PA) for women living with HIV and AIDS (WLWHA). This study is a pilot, randomised controlled crossover trial, reporting the effects of a contextualised PA intervention amongst a sample of 21 HIV positive Xhosa-speaking women of low socioeconomic status (SES). The study determined total moderate-to-vigorous PA (TMVPA) as measured subjectively by the Global Physical Activity Questionnaire (GPAQ), total weekly steps (TWS) as measured by a pedometer, and self-efficacy for PA as measured by the Physical Exercise Self-efficacy scale (PESES). Multivariate analysis of covariance (MANCOVA) was used to compute the impact of the intervention on TMVPA, TWS, and self-efficacy for PA from baseline to six weeks, and baseline to 12 weeks post-intervention controlling for pre-test differences in TMVPA. Results showed that participants exposed to the intervention had significant increases in PA as measured by TMVPA (p = .027), TWS (p = .032), as well as exercise self-efficacy (p = .000) from pre-test to 6 weeks. Insignificant findings were reported for all three variables when measured from baseline to 12 weeks. In conclusion, the findings of the pilot study suggest that the intervention was effective in producing significant increases in PA in a sample of PLWHA of low SES over six weeks. Careful consideration of behavioural constructs, such as self-efficacy, can help WLWHA of low SES to adopt regular PA as a complementary therapy for managing their health.

Selenium at the redox interface of the genome, metabolome and exposome.

Selenium (Se) is a redox-active environmental mineral that is converted to only a small number of metabolites and required for a relatively small number of mammalian enzymes. Despite this, dietary and environmental Se has extensive impact on every layer of omics space. This highlights a need for global network response structures to provide reference for targeted, hypothesis-driven Se research. In this review, we survey the Se research literature from the perspective of the responsive physical and chemical barrier between an organism (functional genome) and its environment (exposome), which we have previously termed the redox interface. Recent advances in metabolomics allow molecular phenotyping of the integrated genome-metabolome-exposome structure. Use of metabolomics with transcriptomics to map functional network responses to supplemental Se in mice revealed complex network responses linked to dyslipidemia and weight gain. Central metabolic hubs in the network structure in liver were not directly linked to transcripts for selenoproteins but were, instead, linked to transcripts for glucose transport and fatty acid ß-oxidation. The experimental results confirm the survey of research literature in showing that Se interacts with the functional genome through a complex network response structure. The results imply that systematic application of data-driven integrated omics methods to models with controlled Se exposure could disentangle health benefits and risks from Se exposures and also serve more broadly as an experimental paradigm for exposome research.

Ambrosia pollen source inventory for Italy: a multi-purpose tool to assess the impact of the ragweed leaf beetle (Ophraella communa LeSage) on populations of its host plant.

Here, we produce Ambrosia pollen source inventories for Italy that focuses on the periods before and after the accidental introduction of the Ophraella communa beetle. The inventory uses the top-down approach that combines the annual Ambrosia pollen index from a number of monitoring stations in the source region as well as Ambrosia ecology, local knowledge of Ambrosia infestation and detailed land cover information. The final inventory is gridded to a 5 × 5-km resolution using a stereographic projection. The sites with the highest European Infection levels were recorded in the north of Italy at Busto Arsizio (VA3) (European Infection level 2003-2014 = 52.1) and Magenta (MI7) (European Infection level 2003-2014 = 51.3), whereas the sites with the lowest (i.e. around 0.0) were generally located to the south of the country. Analysis showed that the European Infection level in all of Italy was significantly lower in 2013-2014 compared to 2003-2012, and this decrease was even more pronounced at the sites in the area where Ophraella communa was distributed. Cross-validations show that the sensitivity to the inclusion of stations is typically below 1% (for two thirds of the stations) and that the station Magenta (MI7) had the largest impact compared to all other stations. This is the first time that pollen source inventories from different temporal periods have been compared in this way and has implications for simulating interannual variations in pollen emission as well as evaluating the management of anemophilous plants like Ambrosia artemisiifolia.

'Best buys' for surgery in South Africa.

Improving access to basic surgical interventions has great potential to improve the length and quality of life of many people in low- and middle-income countries (LMICs). However, research has shown that current access to surgical interventions is limited, and initiatives such as the Lancet Commission on Global Surgery 2030 advocate for improved access to basic surgical interventions for all. As the needs, health system context and available budgets in each country will be different, a critical component of effective local scale-up of surgical interventions will be to use tools and processes of health technology assessment (HTA). HTA has traditionally been used in high-income countries to make decisions about which medicines and devices should be available in a health system, but its central concepts, such as assessing clinical effectiveness, cost-effectiveness and feasibility, appraising all available evidence, and incorporating wider health systems objectives in decision-making, can be applied to decisons about how LMICs can best utilise basic surgical interventions from within available resources - in essence, to focus spending on the 'best buys'. As South Africa (SA) moves towards National Health Insurance (NHI), HTA functions will be strengthened. There is potential for SA to lead the practice of application of HTA to decisions about how basic surgical interventions are chosen and implemented, contributing to the success and sustainability of NHI in SA and the health of people in LMICs worldwide.

The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes.

BACKGROUND/OBJECTIVE: There is little randomised evidence using a whole food plant-based (WFPB) diet as intervention for elevated body mass index (BMI) or dyslipidaemia. We investigated the effectiveness of a community-based dietary programme. Primary end points: BMI and cholesterol at 6 months (subsequently extended). SUBJECTS: Ages 35-70, from one general practice in Gisborne, New Zealand. Diagnosed with obesity or overweight and at least one of type 2 diabetes, ischaemic heart disease, hypertension or hypercholesterolaemia. Of 65 subjects randomised (control n=32, intervention n=33), 49 (75.4%) completed the study to 6 months. Twenty-three (70%) intervention participants were followed up at 12 months. METHODS: All participants received normal care. Intervention participants attended facilitated meetings twice-weekly for 12 weeks, and followed a non-energy-restricted WFPB diet with vitamin B12 supplementation. RESULTS: At 6 months, mean BMI reduction was greater with the WFPB diet compared with normal care (4.4 vs 0.4, difference: 3.9 kg m-2 (95% confidence interval (CI)±1), P<0.0001). Mean cholesterol reduction was greater with the WFPB diet, but the difference was not significant compared with normal care (0.71 vs 0.26, difference: 0.45 mmol l-1 (95% CI±0.54), P=0.1), unless dropouts were excluded (difference: 0.56 mmol l-1 (95% CI±0.54), P=0.05). Twelve-month mean reductions for the WFPB diet group were 4.2 (±0.8) kg m-2 BMI points and 0.55 (±0.54, P=0.05) mmol l-1 total cholesterol. No serious harms were reported. CONCLUSIONS: This programme led to significant improvements in BMI, cholesterol and other risk factors. To the best of our knowledge, this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or mandate regular exercise.

Correlates of well-being among Canadians with mood and/or anxiety disorders. / Corrélats du bien-être chez les Canadiens présentant des troubles de l'humeur ou d'anxiété.

INTRODUCTION: Our objective was to examine variables associated with well-being as measured by high self-rated mental health (SRMH) and life satisfaction (LS), among Canadian adults (aged 18+) living with a mood and/or an anxiety disorder. METHODS: We used nationally representative data from the 2014 Survey on Living with Chronic Diseases in Canada-Mood and Anxiety Disorders Component (SLCDC-MA) to describe the association between well-being and self-management behaviours (physical activity, sleep and meditation) as well as perceived stress, coping and social support. We used multivariate logistic regression to model the relationship between these factors and measures of well-being. RESULTS: Approximately one in three individuals with mood and/or anxiety disorders reported high SRMH. The logistic regression models demonstrated that several characteristics such as being older, and reporting higher self-rated general health, fewer functional limitations, lower levels of perceived life stress, higher levels of perceived coping and higher levels of perceived social support were associated with higher levels of wellbeing. Self-management behaviours (including starting physical activity, meditation, adopting good sleep habits and attaining a certain number of hours of nightly sleep) were not significantly associated with measures of well-being in our multivariate model. CONCLUSION: Canadian adults with mood and/or anxiety disorders who reported lower levels of perceived stress and higher levels of social support and coping were more likely to report high levels of well-being. This study contributes evidence from a representative population-based sample indicating well-being is achievable, even in the presence of a mood and/or an anxiety disorder.

INTRODUCTION: Notre objectif visait à étudier les variables liées au bien-être, mesurées par une autoévaluation de la santé mentale (AESM) très positive et une satisfaction élevée à l'égard de la vie (SV) chez des adultes canadiens (âgés de 18 ans et plus) présentant un trouble de l'humeur ou d'anxiété. MÉTHODOLOGIE: Nous avons utilisé des données nationales représentatives tirées de l'Enquête sur les personnes ayant une maladie chronique au Canada ­ Composante des troubles de l'humeur et d'anxiété (EPMCC-TAH) de 2014 afin de décrire l'association entre bien-être et comportements d'autogestion (activité physique, sommeil et méditation) ainsi que stress, adaptation et soutien social perçus. Nous avons eu recours à une régression logistique multivariée pour modéliser la relation entre ces facteurs et les mesures du bien-être. RÉSULTATS: Environ une personne sur trois atteinte d'un trouble de l'humeur ou d'anxiété a fait état d'une AESM positive. Les modèles de régression logistique ont révélé que plusieurs caractéristiques, comme un âge plus avancé, une autoévaluation de la santé générale positive, des limitations fonctionnelles moins nombreuses ainsi que la perception d'un moindre stress à l'égard de la vie, de meilleures capacités d'adaptation et d'un plus grand soutien social, étaient associées à des niveaux de bien-être plus élevés. Les comportements d'autogestion (entamer une activité physique, méditer, adopter de saines habitudes de sommeil et atteindre un certain nombre d'heures de sommeil chaque nuit) n'étaient pas significativement associés à des mesures du bien-être dans notre modèle multivarié. CONCLUSION: Les adultes canadiens souffrant de troubles de l'humeur ou d'anxiété qui ont déclaré percevoir un niveau de stress plus faible, un plus grand soutien social et une meilleure capacité d'adaptation étaient plus susceptibles de déclarer également des scores de bien-être plus élevés. Cette étude a fourni des données probantes à partir d'un échantillon représentatif de la population montrant qu'il est possible de vivre dans un état de bien-être même en présence d'un trouble de l'humeur ou d'anxiété.

Mesoscale atmospheric transport of ragweed pollen allergens from infected to uninfected areas.

Allergenic ragweed (Ambrosia spp.) pollen grains, after being released from anthers, can be dispersed by air masses far from their source. However, the action of air temperature, humidity and solar radiation on pollen grains in the atmosphere could impact on the ability of long distance transported (LDT) pollen to maintain allergenic potency. Here, we report that the major allergen of Ambrosia artemisiifolia pollen (Amb a 1) collected in ambient air during episodes of LDT still have immunoreactive properties. The amount of Amb a 1 found in LDT ragweed pollen grains was not constant and varied between episodes. In addition to allergens in pollen sized particles, we detected reactive Amb a 1 in subpollen sized respirable particles. These findings suggest that ragweed pollen grains have the potential to cause allergic reactions, not only in the heavily infested areas but, due to LDT episodes, also in the regions unaffected by ragweed populations.

Knowledge, attitudes, beliefs and practices related to chronic suppurative otitis media and hearing impairment in Pokhara, Nepal.

BACKGROUND: Nepal has a high prevalence of chronic suppurative otitis media and hearing impairment. An improved understanding of patients' knowledge, attitudes, beliefs and practices is therefore important for effective healthcare planning and intervention. METHOD: Questionnaires designed to explore their current knowledge, attitudes, beliefs and practices were completed by 153 participants: 71 were affected by a known ear disease and 82 were unaffected. RESULTS: In the unaffected group, 31.7 per cent considered breast milk to be a risk factor for ear infection. Home remedies (e.g. leaf paste, oils, and urine and/or bodily fluids) had been used by 42.3 per cent of the affected group. Most participants (71.9 per cent) believed that society discriminates against those with hearing impairment. CONCLUSION: Knowledge deficits and false beliefs were found in both groups, along with a significant use of home remedies and a perception of discrimination against people with hearing impairment. These findings are relevant for healthcare providers and may aid the development of policy, interventions and public education initiatives.

Challenges in hemophilia care in Australia and New Zealand.

BACKGROUND: Health and life expectancy for people with hemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services. AIM: This paper aims to highlight such challenges and propose practical solutions. METHODS: Nine hemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in hemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these. RESULTS: Demography, optimizing treatment and assessing treatment success were identified as broad areas of challenge which included: comorbidities in ageing patients; transitioning from pediatric to adult care; equity of care for remote populations; weight-based dosing in obese patients; tailoring prophylaxis; accurate diagnosis of acute joint pain; managing chronic arthropathy; providing psychosocial support; consistency in definitions and assessment; and quantifiable outcome measures. Practice points included increased cross-specialty coordination and including psychologists and rheumatologists as part of comprehensive care teams; close collaboration between pediatric and adult centers to facilitate transition of care; systems such as telehealth that ensure continuity of care for remote populations; using pharmacokinetic data to tailor therapy; rapid and accurate diagnosis of acute joint pain; using data from bleeding registries to assess treatment effects and help with service planning; and ensuring consistency through benchmarking and standardization of HTCs. SUMMARY: Achieving treatment equity, optimal outcomes and cost savings may be possible through investing in national governance structures, expanding the comprehensive model of care and implementing innovative solutions tailored to local needs.

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Ragweed (Ambrosia) pollen source inventory for Austria.

This study improves the spatial coverage of top-down Ambrosia pollen source inventories for Europe by expanding the methodology to Austria, a country that is challenging in terms of topography and the distribution of ragweed plants. The inventory combines annual ragweed pollen counts from 19 pollen-monitoring stations in Austria (2004-2013), 657 geographical observations of Ambrosia plants, a Digital Elevation Model (DEM), local knowledge of ragweed ecology and CORINE land cover information from the source area. The highest mean annual ragweed pollen concentrations were generally recorded in the East of Austria where the highest densities of possible growth habitats for Ambrosia were situated. Approximately 99% of all observations of Ambrosia populations were below 745m. The European infection level varies from 0.1% at Freistadt in Northern Austria to 12.8% at Rosalia in Eastern Austria. More top-down Ambrosia pollen source inventories are required for other parts of Europe. CAPSULE ABSTRACT: A method for constructing top-down pollen source inventories for invasive ragweed plants in Austria, a country that is challenging in terms of topography and ragweed distribution.