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

When an eddy encounters shelf-slope topography

Thesis: Ph. D., Joint Program in Physical Oceanography (Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences; and the Woods Hole Oceanographic Institution), 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 129-135).Eddies in the ocean move westwards. Those shed by western boundary currents must then interact with continental shelf-slope topography at the western boundary. The presence of other eddies and mean flows complicates this simple picture, yet satellite images show that mesoscale eddies translating near the shelfbreak routinely affect the continental shelves of the Mid-Atlantic Bight, the Gulf of Mexico etc. The consequent cross-shelfbreak transports are currently of unknown importance to shelf budgets of heat, salt and volume. Thus motivated, this thesis uses idealized continuously stratified numerical experiments to explore eddy-slope interactions under four questions: 1. Can the continental slope prevent an eddy from reaching the shelfbreak? 2. What is the structure of the eddy-driven offshore flow? 3. How is the continental shelf affected by an eddy at the shelfbreak? 4. Given surface observations, can one estimate the volume of water transported across the shelfbreak? The experiments show that the efficiency of Rossby wave radiation from the eddy controls whether it can cross isobaths: by radiating energy the eddy becomes shallow enough to move into shallower water. For wide continental slopes, relative to an eddy diameter, a slope can prevent an anticyclone from reaching the shelfbreak by shutting down such radiation. For narrow continental slopes, the interaction repeatedly produces dipoles, whose cyclonic halves contain shelf-slope water stacked over eddy water. The formation of such cyclones is explained. Then, the structure of shelf flows forced by the eddy are studied: their vertical structures are rationalized and scalings derived for their cross-isobath scales; for example, the extent to which the eddy influences the shelf. A recipe for estimating cross-isobath transports based on eddy surface properties is put forward. Finally, the findings are tested against observations in the Middle Atlantic Bight off the northeastern United States.by Deepak Abraham Cherian.Ph. D

Analogies of Ocean/Atmosphere Rotating Fluid Dynamics with Gyroscopes: Teaching Opportunities

The dynamics of the rotating shallow-water (RSW) system include geostrophic f low and inertial oscillation. These classes of motion are ubiquitous in the ocean and atmosphere. They are often surprising to people at first because intuition about rotating fluids is uncommon, especially the counterintuitive effects of the Coriolis force. The gyroscope, or toy top, is a simple device whose dynamics are also surprising. It seems to defy gravity by not falling over, as long as it spins fast enough. The links and similarities between rotating rigid bodies, like gyroscopes, and rotating fluids are rarely considered or emphasized. In fact, the dynamics of the RSW system and the gyroscope are related in specific ways and they exhibit analogous motions. As such, gyroscopes provide important pedagogical opportunities for instruction, comparison, contrast, and demonstration. Gyroscopic precession is analogous to geostrophic flow and nutation is analogous to inertial oscillation. The geostrophic adjustment process in rotating fluids can be illustrated using a gyroscope that undergoes transient adjustment to steady precession from rest. The controlling role of the Rossby number on RSW dynamics is reflected in a corresponding nondimensional number for the gyroscope. The gyroscope can thus be used to illustrate RSW dynamics by providing a tangible system that behaves like rotating fluids do, such as the large-scale ocean and atmosphere. These relationships are explored for their potential use in educational settings to highlight the instruction, comparison, contrast, and demonstration of important fluid dynamics principles.National Science Foundation (U.S.) (Award DUE-0618483

Ultrasound-guided fine-needle aspiration cytology along with clinical and radiological features in predicting thyroid malignancy in nodules ≥1 cm

Aims and Objectives: The aim of the study is to examine the adequacy and accuracy of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in thyroid nodules ≥1 cm and to analyze the clinical, sonological, and cytological features in predicting thyroid malignancy. Materials and Methods: US-FNAC was done on 290 patients from December 2013 to December 2014 by the radiologist. The Thyroid Imaging Reporting and Data System (TIRADS) was used to record the sonological features. FNAC samples were reported by a dedicated cytopathologist. Accuracy was calculated by comparing US-FNAC, clinical features and ultrasound (US) features for those who had final histopathology till April 2017. Results: The adequacy of US-FNAC in this study was 80.2%. Thyroidectomy was performed in 128/290 (44.1%). The sensitivity and specificity of US-FNAC in this study is 83.9 and 76.3%, respectively, with a positive predictive value of 85.2%, negative predictive value of 74.4%, and an accuracy of 81% in predicting malignancy in thyroid nodules ≥1 cm. The malignancy rate in benign FNAC sample was 25% (10/40), and was 69% (8/13) in those with a follicular lesion of undetermined significance (FLUS). Around 80% of benign and 89% of FLUS had follicular variant of papillary carcinoma of thyroid (FVPTC). US-FNAC, a high TIRADS score, and US features such as marked hypoechogenicity, taller than wide, irregular margins, microcalcification, and clinical features, such as hard in consistency and significant cervical lymph nodes, were important in predicting malignancy (P < 0.001). Conclusions: The accuracy of US-FNAC in this study is 81%. The US-FNAC, a high TIRADS score, a hard thyroid nodule, and significant cervical lymph nodes are important in predicting malignancy. The accuracy rate in benign and atypia undetermined significance categories needs to improve in this study. Further research to help in decreasing false negative rates of FVPTC will help in increasing the accuracy of US-FNAC in the present study

Predictors of acute kidney injury in patients undergoing adult cardiac surgery

Background: Acute kidney injury (AKI) after cardiac surgery (CS) is not uncommon and has serious effects on mortality and morbidity. A majority of patients suffer mild forms of AKI. There is a paucity of Indian data regarding this important complication after CS. Aims and Objectives: The primary objective was to study the incidence of AKI associated with CS in an Indian study population. Secondary objectives were to describe the risk factors associated with AKI-CS in our population and to generate outcome data in patients who suffer this complication. Methods: Serial patients (n = 400) presenting for adult CS (emergency/elective) at a tertiary referral care hospital in South India from August 2016 to November 2017 were included as the study individuals. The incidence of AKI-CS AKI network (AKIN criteria), risk factors associated with this condition and the outcomes following AKI-CS are described. Results: Out of 400, 37 (9.25%) patients developed AKI after CS. AKI associated with CS was associated with a mortality of 13.5% (no AKI group mortality 2.8%, P = 0.001 [P < 0.05]). When AKI was severe enough to need renal replacement therapy, the mortality increased to 75%. Patients with AKI had a mean hospital stay 16.92 ± 12.75 days which was comparatively longer than patients without AKI (14 ± 7.98 days). Recent acute coronary syndrome, postoperative atrial fibrillation, and systemic hypertension significantly predicted the onset of AKI-CS in our population. Conclusions: The overall incidence of AKI-CS was 9.25%. The incidence of AKI-CS requiring dialysis (Stage 3 AKIN) AKI-CS was lower (2%). However, mortality risks were disproportionately high in patients with AKIN Stage 3 AKI-CS (75%). There is a need for quality improvement in the care of patients with AKI-CS in its most severe forms since mortality risks posed by the development of Stage 3 AKIN AKI is higher than reported in other index populations from high resource settings

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine