Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Lung health in rural Nepal : multi-state modeling of health status and economic evaluation of integrated respiratory care guidelines

Mensen lopen verschillende gezondheidsrisico’s. Ziekten kunnen worden voorkomen, verzacht of genezen. In arme landen lijden mensen aan ziekten die in rijke landen goed te voorkomen zijn. Kennisoverdracht van rijke naar arme landen en investeringen in de gezondheidszorg kunnen bijdragen aan de vermindering van de gezondheidsverschillen in de wereld. Om hierbij succesvol te zijn dienen interventies te zijn aangepast aan lokale omstandigheden en vooraf te worden onderworpen aan een kosten-baten analyse. Hierbij worden gezondheidseffecten gerelateerd aan de kosten van de interventie. Dit boek presenteert de resultaten van een kosteneffectiviteitsanalyse van een door de Wereldgezondheidsorganisatie (WHO) ontwikkelde ge¨ıntegreerde aanpak van longaandoeningen, de zogenaamde Practical Approach to Lung Health (PAL). De WHO-PAL aanpak werd toegepast in ruraal Nepal waar verschillende longaandoeningen zoals longontsteking, tuberculose (TBC), chronische obstructieve longziekten (COPD) en asthma veel voorkomende kwalen zijn. Veelal ontbreken er goed uitgeruste gezondheidsvoorzieningen en goed opgeleid personeel. De PAL aanpak voor de eerstelijnsgezondheidszorg is ontwikkeld voor gezondheidswerkers met een beperkte opleiding. In 22 willekeurig gekozen centra voor basisgezondheidszorg in een ruraal district (uit een totaal van 42 centra) werd ten minste ´e´en gezondheidswerker opgeleid volgens het PAL richtlijnenprogramma. In hetzelfde district werden de 20 andere centra als controle centra meegenomen. In een vervolgonderzoek werden de gegevens gedurende een periode van een jaar verzameld van alle pati¨enten die deze 42 gezondheidscentra bezochten en die symptomen van longziekten vertoonden i.c. koorts, hoesten en ademhalingsproblemen. In dit boek worden de resultaten van de PAL benadering vergeleken met die van al bestaande gezondheidszorg in de controle centra, in termen van kosten, gezondheidseffecten en kosteneffectiviteit. ... Zie: Samenvatting

Rethinking organic wastes bioconversion: Evaluating the potential of the black soldier fly (Hermetia illucens (L.)) (Diptera: Stratiomyidae) (BSF)

Population growth and unprecedented economic growth and urbanization, especially in low- and middle-income countries, coupled with extreme weather patterns, the high-environmental footprint of agricultural practices, and disposal-oriented waste management practices, require significant changes in the ways we produce food, feed and fuel, and manage enormous amounts of organic wastes. Farming insects such as the black soldier fly (BSF) (Hermetia illucens) on diverse organic wastes provides an opportunity for producing nutrient-rich animal feed, fuel, organic fertilizer, and biobased products with concurrent valorization of wastes. Inclusion of BSF larvae/pupae in the diets of poultry, fish, and swine has shown promise as a potential substitute of conventional feed ingredients such as soybean meal and fish meal. Moreover, the bioactive compounds such as antimicrobial peptides, medium chain fatty acids, and chitin and its derivatives present in BSF larvae/pupae, could also add values to the animal diets. However, to realize the full potential of BSF-based biorefining, more research and development efforts are necessary for scaling up the production and processing of BSF biomass using more mechanized and automated systems. More studies are also needed to ensure the safety of the BSF biomass grown on various organic wastes for animal feed (also food) and legalizing the feed application of BSF biomass to wider categories of animals. This critical review presents the current status of the BSF technology, identifies the research gaps, highlights the challenges towards industrial scale production, and provides future perspectives.</p

Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was$216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with$195 for low FiO2 leading to a −$11 (95$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was$1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease