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

Solar and Wind Energy Potential Study of Lower Sindh, Pakistan for Power Generation

Global and diffuse solar radiation on horizontal surface of Lower Sindh, namely Karachi, Hyderabad, Nawabshah were carried out using sunshine hour data of the area to assess the feasibility of solar energy utilization for power generation in Sindh province. The results obtained show a large variation in the direct and diffuse component of solar radiation in summer and winter months in Lower Sindh (50% direct and 50% diffuse for Karachi and Hyderabad). In Nawabshah area, the contribution of diffuse solar radiation is low during the monsoon months, July and August. The KT value of Nawabshah indicates a clear sky throughout almost the entire year. The percentage of diffuse radiation does not exceed more than 20%. In Nawabshah, the appearance of cloud is rare even during the monsoon months. The estimated values indicate that Nawabshah has high solar potential, whereas Karachi and Hyderabad have low solar potential. During the monsoon months the Lower part of Sindh can utilize the hybrid system with wind power. Near Karachi and Hyderabad, the wind speed ranges between 6.2 m/sec to 6.9 m/sec. A wind corridor exists near Karachi, Hyderabad, Gharo, Keti Bander and Shah Bander. The short fall of solar can be compensated by wind because in the monsoon months of July and August, wind speeds are higher in the Lower region of Sindh

Pregnancy in lupus: an updated consensus to guide best practice strategies

Abstract Background Systemic lupus erythematosus is a multifaceted chronic relapsing autoimmune disease of unknown etiology. The disease has always been a serious diagnosis in women being a multisystem pathology that is classically encountered during the childbearing age posing serious systemic comorbidities with a potential impact on the functional performance, psychosocial status, and survival. In this article, we review critical issues related to the decision to conceive in female with lupus highlighting the impact of the diagnosis and disease activity status on the mother and the fetus, attempting to suggest a consensus to guide safe decision making for pregnancy with SLE. Main body The pleomorphic dysregulated immune nature of lupus in the presence of uncontrolled disease carries a higher risk of complicated pregnancy. Therefore, SLE pregnancies should be well planned and are usually encouraged if the disease is inactive (at least 6 months prior to conception) to ensure immune quiescence towards a safer outcome. Conclusion With the proper implementation of preconception counseling strategy, choice of the correct timing of conception, close monitoring of SLE flares with tight control, and the appreciation of the value of multidisciplinary management to best practice most young women with SLE can carry on successful pregnancies with favorable outcome

Magnetic resonance three-dimensional steady-state free precession imaging of the thoracic duct in patients with Fontan circulation and its relationship to outcomes

Abstract Background Lymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. Methods This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. Results The study included 189 Fontan patients (median age 16.1 years, IQR 11.0–23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1–23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p < 0.001) in Fontan patients vs. rTOF patients. TD dimension increased mildly with age in Fontan patients, R = 0.19, p = 0.01. In Fontan patients, the TD diameter was larger in those with PLE vs. without PLE (age-adjusted mean 4.11 vs. 2.72, p = 0.005), and was more tortuous in those with NYHA class ≥ II vs. class I (moderate or greater tortuosity 75% vs. 28.5%, p = 0.02). Larger TD diameter was associated with a lower ventricular ejection fraction that was independent of age (partial correlation = − 0.22, p = 0.02). More tortuous TDs had a higher end-systolic volume (mean 70.0 mL/m2 vs. 57.3 mL/m2, p = 0.03), lower creatinine (mean 0.61 mg/dL vs. 0.70 mg/dL, p = 0.04), and a higher absolute lymphocyte count (mean 1.80 K cells/µL vs. 0.76 K cells/µL, p = 0.003). The composite outcome was present in 6% of Fontan patients and was not associated with TD diameter (p = 0.50) or tortuosity (p = 0.09). Conclusions The TD is well visualized in two-thirds of patients with Fontan circulation on 3D-bSSFP images. Larger TD diameter is associated with PLE and increased TD tortuosity is associated with an NYHA class ≥ II