Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. METHODS: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. RESULTS: Mean age was 55 +/- 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (>/=40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio /= 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos >/= 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu >/= 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT 1.5. CONCLUSION: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies

In silico analysis of gene expression in V3a and the superior occipital gyrus. Relevance for migraine

Introduction: Visual manifestations are the most prominent non-painful features of migraine. During the last decades, visual area V3a has gathered attention of headache scientists because of its apparent implication on aura initiation, photophobia and cortical hyper-responsiveness related to visual motion perception. In this hypothesis-generating study, we performed an in silico analysis of gene expression in left V3a and the cerebral gyrus that harbours it (left superior occipital gyrus (lSOG)) searching for transcriptomic patterns that could be linked with migraine’s pathophysiology. Materials and methods: Neurotransmitter receptor gene expression levels in left V3a were extracted from validated brain mRNA expression models using a probabilistic volumetric mask of this region. The primary visual cortex and other sensory cortices (auditory, olfactory and somatosensory) were used as comparators. Genome-wide transcriptomic differences between the gyrus harbouring left V3a (lSOG) and the rest of the cerebral cortex were assessed using the Allen Brain Institute Human RNA micro array atlas/database. Results: Adrenergic receptor β1, dopaminergic receptor D3 and serotoninergic receptors 1B, 1F and 2A, which have been previously implicated in migraine’s pathophysiology and/or treatment, showed significantly higher expression levels on left V3a. Transcriptomic differences between the lSOG harbouring V3a and the rest of the cortex comprise genes whose products are involved in neuronal excitability (SLC17A6, KCNS1, KCNG1 and GABRQ), activation of multiple signal transduction pathways (MET) and cell metabolism (SPHKAP via its interaction with cAMP-dependent protein kinase). Conclusions: Focal gene expression analysis of V3a suggests some clues about its implication in migraine. Further studies are warranted

Antibiotics and Antimicrobial Resistance in the COVID-19 Era: Perspective from Resource-Limited Settings

The dissemination of COVID-19 around the globe has been followed by an increased consumption of antibiotics. This is related to the concern for bacterial superinfection in COVID-19 patients. The identification of bacterial pathogens is challenging in low and middle income countries (LMIC), as there are no readily-available and cost-effective clinical or biological markers that can effectively discriminate between bacterial and viral infections. Fortunately, faced with the threat of COVID-19 spread, there has been a growing awareness of the importance of antimicrobial stewardship programs, as well as infection prevention and control measures that could help reduce the microbial load and hence circulation of pathogens, with a reduction in dissemination of antimicrobial resistance. These measures should be improved particularly in developing countries. Studies need to be conducted to evaluate the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders. This issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal

Study protocol for a randomised controlled trial assessing the impact of pulmonary rehabilitation on maximal exercise capacity for adults living with post-TB lung disease: Global RECHARGE Uganda

Introduction: The burden of post-tuberculosis (TB) lung disease (PTBLD) is steadily increasing in sub-Saharan Africa, causing disability among TB survivors. Without effective medicines, the mainstay of PTBLD treatment evolves around disease prevention and supportive treatment. Pulmonary rehabilitation (PR), a low-cost, non-pharmacological intervention has shown effectiveness in a group of PTBLD individuals but has not been tested in a clinical trial. This study aims to assess the impact of a 6-week PR programme on maximal exercise capacity and other outcomes among adults in Uganda living with PTBLD. Methods and analysis: This is a randomised waiting-list controlled trial with blinded outcome measures, comparing PR versus usual care for patients with PTBLD. A total of 114 participants will be randomised (1:1) to receive either usual care (on the waiting list) or PR, with follow-up assessments at 6 weeks and 12 weeks postintervention. The primary outcome is change in walking distance measured by the Incremental Shuttle Walk Test from baseline to the end of 6 weeks of PR. All secondary outcomes will be compared between the PR and usual care arms from baseline to 6-week and 12-week follow-ups. Secondary outcomes include self-reported respiratory symptoms, physical activity, psychological well-being, health-related quality of life and cost–benefit analysis. All randomised participants will be included in the intention-to-treat analysis population. The primary efficacy analysis will be based on both per-protocol and modified intention-to-treat populations. Ethics and dissemination: The trial has received ethical clearance from the Mulago Hospital Research and Ethics Committee (MHREC 1478), Kampala, Uganda as well as the Uganda National Council for Science and Technology (SS 5105). Ethical approval has been obtained from the University of Leicester, UK research ethics committee (Ref No. 22349). Study findings will be published in appropriate peer-reviewed journals and disseminated at appropriate local, regional and international scientific meetings and conferences. Trial registration number: ISRCTN18256843. Protocol version: Version 1.0 July 2019

Outcomes of Invasive and Noninvasive Ventilation in a Haitian Emergency Department

Background: Limited data exist on the outcomes of patients requiring invasive ventilation or noninvasive positive pressure ventilation (NIPPV) in low-income countries. To our knowledge, no study has investigated this topic in Haiti. Objectives: We describe the clinical epidemiology, treatment, and outcomes of patients requiring NIPPV or intubation in an emergency department (ED) in rural Haiti. Methods: This is an observational study utilizing a convenience sample of adult and pediatric patients requiring NIPPV or intubation in the ED at an academic hospital in central Haiti from January 2019–February 2021. Patients were prospectively identified at the time of clinical care. Data on demographics, clinical presentation, management, and ED disposition were extracted from patient charts using a standardized form and analyzed in SAS v9.4. The primary outcome was survival to discharge. Findings: Of 46 patients, 27 (58.7%) were female, mean age was 31 years, and 14 (30.4%) were pediatric (age <18 years). Common diagnoses were cardiogenic pulmonary edema, pneumonia/pulmonary sepsis, and severe asthma. Twenty-three (50.0%) patients were initially treated with NIPPV, with 4 requiring intubation; a total of 27 (58.7%) patients were intubated. Among those for whom intubation success was documented, first-pass success was 57.7% and overall success was 100% (one record missing data); intubation was associated with few immediate complications. Twenty-two (47.8%) patients died in the ED. Of the 24 patients who survived, 4 were discharged, 19 (intubation: 12; NIPPV: 9) were admitted to the intensive care unit or general ward, and 1 was transferred. Survival to discharge was 34.8% (intubation: 22.2%; NIPPV: 52.2%); 1 patient left against medical advice following admission. Conclusions: Patients with acute respiratory failure in this Haitian ED were successfully treated with both NIPPV and intubation. While overall survival to discharge remains relatively low, this study supports developing capacity for advanced respiratory interventions in low-resource settings

Protocol for the cultural adaptation of pulmonary rehabilitation and subsequent testing in a randomised controlled feasibility trial for adults with chronic obstructive pulmonary disease in Sri Lanka

Introduction: International guidelines recommend pulmonary rehabilitation (PR) should be offered to adults living with chronic obstructive pulmonary disease (COPD), but PR availability is limited in Sri Lanka. Culturally appropriate PR needs to be designed and implemented in Sri Lanka. The study aims to adapt PR to the Sri Lankan context and determine the feasibility of conducting a future trial of the adapted PR in Sri Lanka. Methods and analysis: Eligible participants will be identified and will be invited to take part in the randomised controlled feasibility trial, which will be conducted in Central Chest Clinic, Colombo, Sri Lanka. A total of 50 participants will be recruited (anticipated from April 2021) to the trial and randomised (1:1) into one of two groups; control group receiving usual care or the intervention group receiving adapted PR. The trial intervention is a Sri Lankan-specific PR programme, which will consist of 12 sessions of exercise and health education, delivered over 6 weeks. Focus groups with adults living with COPD, caregivers and nurses and in-depth interviews with doctors and physiotherapist will be conducted to inform the Sri Lankan specific PR adaptations. After completion of PR, routine measures in both groups will be assessed by a blinded assessor. The primary outcome measure is feasibility, including assessing eligibility, uptake and completion. Qualitative evaluation of the trial using focus groups with participants and in-depth interviews with PR deliverers will be conducted to further determine feasibility and acceptability of PR, as well as the ability to run a larger future trial. Ethics and dissemination: Ethical approval was obtained from the ethics review committee of Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka and University of Leicester, UK. The results of the trial will be disseminated through patient and public involvement events, local and international conference proceedings, and peer-reviewed journals. Trial registration number ISRCTN1336773

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2&nbsp;m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0\u20135 and 5\u201315&nbsp;cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10\ub0C (mean&nbsp;=&nbsp;3.0&nbsp;\ub1&nbsp;2.1\ub0C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6&nbsp;\ub1&nbsp;2.3\ub0C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler ( 120.7&nbsp;\ub1&nbsp;2.3\ub0C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications