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BACKGROUND Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Context: Midazolam and propofol are effective sedatives for use in upper gastrointestinal endoscopy (UGIE); however, their utility is limited when used alone. In this regard, dexmedetomidine seems to be a promising sedative. Aims: The aim was to compare the hemodynamic effects and sedation efficacy of these drugs in patients undergoing elective diagnostic UGIE. Settings and Design: Randomized control double-blind study was conducted at a teaching hospital. Subjects and Methods: Patients belonging to ASA Grade I or II, undergoing diagnostic elective UGIE were enrolled in the study and randomized into three groups; Group I received midazolam infusion, Group II received propofol infusion and Group III received dexmedetomidine infusion. Hemodynamic parameters and adverse events were recorded during the procedure (intra-operative period [IOP]). Both patient and endoscopist satisfaction were rated on visual analog scale (0 = no pain/least difficulty to 10 = worst pain/maximum difficulty). Recovery was recorded as time to achieve modified Aldrete score of 10/10. Statistical Analysis: Parametric test analysis of variance was applied to compare the means of three groups of continuous data. Results: Ninety patients were analyzed. Mean arterial pressure was significantly lower in the propofol group at IOP2, IOP4, IOP8, and IOP10 compared with dexmedetomidine and midazolam group. The endoscopist satisfaction level was significantly higher in dexmedetomidine group as compared to propofol and midazolam (60%, 56.7%, 13.3%; P < 0.001). Significantly faster recovery was observed in dexmedetomidine group compared to midazolam and propofol group (7.7 ± 3.9, 18.3 ± 3.8, 12.7 ± 2.9 min; P = 0.001). Conclusions: Use of dexmedetomidine was associated with greater hemodynamic stability and faster recovery when compared to propofol and midazolam.

Context Sedation is commonly used to improve patients' tolerance and comfort during flexible bronchoscopy (FB). Dexmedetomidine is a relatively novel sedative for use in FB. Aims The aim of this study was to compare dexmedetomidine and propofol as sole sedative agent in terms of hemodynamics, efficacy, safety and tolerance to the procedure among patients undergoing FB. Settings and design This study was carried out in a tertiary care teaching hospital, and was a double-blind randomized-controlled trial. Patients and methods Sixty patients were analyzed. Group 1 received propofol (1 mg/kg bolus, then 5 mg/kg/h infusion); group 2 received dexmedetomidine (1 mg/kg bolus, followed by 0.7 mg/kg/h infusion). Intraoperative (IOP) SpO 2 , heart rate, mean arterial pressure, and respiratory rate were recorded at nine time points. Primary outcome variables were hemodynamic variables, level of sedation, and recovery time (to reach an Aldrete score 10/10). Results The dexmedetomidine group showed significantly lower mean heart rate than the propofol group at IOP 0 , IOP 2 , and IOP 4 . The mean arterial pressure was significantly higher throughout the procedure in the dexmedetomidine group compared with the propofol group ( P 4 and IOP 6 ( P 2 was noted in the dexmedetomidine group (97.0 ± 1.1). Incidences of bucking and coughing were significantly higher in the dexmedetomidine group. Bronchoscopist visual analogue scale scores for coughing and satisfaction were significantly lower in the propofol group ( P P < 0.001). Conclusion Propofol showed superiority over dexmedetomidine in terms of safety, efficacy, adverse-effect profile, and tolerance to the procedure in patients undergoing diagnostic flexible bronchoscopy.

Introduction Predictive accuracy of severity scoring systems in Indian ICUs does not fit well owing to differences in case mix from the west. We hypothesized that 24 h is too early to predict the outcome and that the predictive accuracy of these scores might be better at 48 h of ICU admission. Objective The aim of this study was to evaluate and compare Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology (SAPS) II, and Sequential Organ Failure Assessment (SOFA) as a predictor of outcome in critically ill patients at 24 and at 48 h in a tertiary care hospital ICU. Patients and methods A prospective cohort study was conducted on 169 patients over 2 years at a single medical surgical ICU. Eighty-five critically ill patients were included. For each patient, APACHE II, SAPS II, and SOFA scores were calculated at two time frames (first at 24 and then at 48 h) after ICU admission. The accuracies and comparisons of outcome prediction by the three scores were assessed with standardized mortality ratio and area under the receiver operating characteristic (AUROC) curves. Results All scoring systems (except SOFA) underestimated the deaths (standardized mortality ratio>1). All scoring systems displayed larger AUROC curves at 48 h than those at 24 h. APACHE II 48 showed the largest AUROC of 0.933. Conclusion All scores performed better when calculated at 48 h rather than at 24 h. Overall, APACHE II 48 is the best predictor of 28-day mortality in critically ill patients. A worsening APACHE II score at 48 h after ICU admission may identify the patients at high risk of mortality.