Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

INTERNATIONAL JOURNAL OF AGRICULTURE & BIOLOGY Full Length Article Evaluation of a Saponin Adjuvanted Inactivated Mycoplasma bovis (A Field Isolate from Cattle Lungs in Balochistan, Pakistan) Vaccine

Abstract An inactivated saponin adjuvanted vaccine was prepared from Mycoplasma bovis local field isolate and its efficacy was evaluated. Nine calves (n=9) were split in three groups (three calves in each group). Calves in group A were vaccinated with M. bovis saponin adjuvanted (inactivated) vaccine and challenged with live M. bovis strain by nasal spray at day 21 post vaccination. Calves in group B were only challenged with live M. bovis culture through same route and Group C was kept as control. All groups of calves were monitored for 7 weeks. The antibody profile of all vaccinated and challenged animal were assessed through IHA test. The saponated M. bovis (inactivated) vaccines with protein concentration (2 mg/mL) was found very effective. Any pathological lesion, mortality and any other clinical manifestation was not observed in vaccinated group of calves. Over all the immune status with a GMT (40.3) was found satisfactory with this vaccine, which was achieved 3 weeks post-vaccination and this titer has risen to a GMT (80.6) after four week and was maintained to a GMT of (64.0) on 49 th days at the end of experiment

Water Pollution in Balochistan Province of Pakistan

Water pollution is one of the main environmental issues in Balochistan. This serious environment issue leads to many deaths in Balochistan. In most of the places of Balochistan clean and safe water is now totally converted to polluted water. Drinking water sources, both surface and groundwater are contaminated with coliforms, toxic metals and pesticides throughout the Balochistan. Various drinking water quality parameters set by WHO are frequently violated. Human activities like improper disposal of municipal and industrial effluents and indiscriminate applications of agrochemicals in agriculture are the main factors contributing to the deterioration of water quality. Microbial and chemical pollutants are the main factors responsible exclusively or in combination for various public health problems. People of these areas are drinking polluted water due to unavailability of clean water. Drinking of polluted water can causes major health disease. Major diseases connected with polluted drinking water in Balochistan are diarrhea, gastroenteritis, typhoid, cryptosporidium infections, giardiasis intestinal worms, some strains of hepatitis and infant deaths are caused by waterborne diarrhea in Balochistan

Crystal structures of 2,2′-bipyridin-1-ium 1,1,3,3-tetracyano-2-ethoxyprop-2-en-1-ide and bis(2,2′-bipyridin-1-ium) 1,1,3,3-tetracyano-2-(dicyano-methylene) propane-1,3-diide (dataset)

CCDC 1059033, 105903