Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.     

(iii) Minimal invasive techniques in the management of tibial plateau fractures

Intra-articular fractures of the proximal tibia present a wide spectrum of injury patterns with associated soft tissue injury. The last two decades have seen the techniques of management evolve from extensive open reduction and rigid internal fixation to arthroscopy-assisted minimal invasive surgery (MIS) and biologically benign internal fixation. The ultimate aim is to prevent the occurrence of late degenerative arthritis. This could be achieved in selected patients using minimal invasive surgery, which offers the advantages of better visualisation and management of intra-articular soft tissue injuries, confirmation of fracture reduction viewed from the joint surface, faster rehabilitation and fewer wound complications.     

Bancroftian filariasis in Pondicherry, south India--epidemiological impact of recovery of the vector population.

An Integrated Vector Management (IVM) strategy was implemented from 1981 to 1985 in one part of Pondicherry, South India, for the control of the bancroftian filariasis vector Culex quinquefasciatus (the IVM area). The rest of the town (the comparison area) received the conventional larvicidal input. After 1985 both the areas were managed conventionally. The switch to conventional strategy resulted in an increase of vector density in both areas. The microfilaraemia prevalence in humans showed a general decline (P less than 0.05) from 1986 to 1989 only in the IVM area whereas its intensity did not change significantly in either area. While the age-specific rate of gain of infection was generally unchanged in the IVM area, an increase in all age classes was observed after 1985 in the comparison area, where the Annual Transmission Index was high during the previous years. In both areas the rate of loss of infection increased during 1986-9 compared to 1981-6. The results suggest that 3 years is too short a period to relate the changes in entomological parameters to those in the microfilaraemia status of the population.     

Effects of amiodarone and desethylamiodarone on rabbit myocardial beta-adrenoceptors and serum thyroid hormones--absence of relationship to serum and myocardial drug concentrations

The antiadrenergic actions of amiodarone (Am) are well known but its effect and that of its metabolite, desethylamiodarone (DAm), on beta-receptor density (Bmax) and affinity (KD) are poorly defined. Thus, the acute and chronic effects of Am and DAm on myocardial beta-receptors in rabbits were determined relative to changes in thyroid hormones and serum and tissue drug concentrations. Bmax and KD were measured by radio-ligand binding, thyroid hormones by RIA, and drug levels by HPLC. Compared with controls, intravenous Am (20 mg/kg) reduced Bmax by 23% (p less than 0.05) and DAm (20 mg/kg) by 32% (p less than 0.05). After 3 weeks of chronic drug, the corresponding value for Am was 24% (p less than 0.05) versus 45% (p less than 0.05) for DAm. The effect of DAm was significantly greater (p less than 0.05) than that of Am, being comparable to that of Am (-44%) after 6 weeks. In the case of Am, doubling the dose (and myocardial level) led to no further decrease in Bmax. DAm also reduced Bmax more following chronic treatment than after acute administration (-45 versus -32%), a difference of borderline significance. Following 3 weeks of p.o. Am, T3 decreased 3% (NS) and reverse T3 (rT3) increased 90% (p less than 0.05); after 6 weeks, the corresponding values were 25% (p less than 0.05) and 181% (p less than 0.01). After 1 week of p.o. DAm, T3 did not change but rT3 increased by 34% (p less than 0.05); after 3 weeks the corresponding values were 21% (p less than 0.01) and 64% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Past exposure and the dynamics of lymphatic filariasis infection in young children.

This study utilizes parallel, longitudinal entomological and parasitological data collected during a 5-year vector control programme in Pondicherry, South India, to quantify Wuchereria bancrofti transmission from the vector to the human population. A simple mathematical model, derived from the standard catalytic model, is used to examine the hypothesis that current infection prevalence in young children is a dynamical function of their cumulative past exposure to infective bites. Maximum likelihood fits of the model to the observed data indicate a constant child infection rate with age, above a threshold representing the pre-patent period, or equivalently, the cumulative biting intensity required to produce patent infections. Extrapolation of the model allows the crude estimation of the equilibrium microfilaria age-prevalence curve due to control. The results suggest that vector control alone may have little impact on the overall age-prevalence of infection even when sustained for long periods. These observations are discussed in terms of the likely impact of density dependent mechanisms, such as acquired immunity, on model predictions.     

Alteration of pulse configuration affects the pain response during diode laser photocoagulation

Background and Objective: The shape of the treatment pulse of the diode laser (810 nm) can be easily altered electronically in contrast to ion laser photocoagulators. We investigated whether changes in laser pulse shape influenced the subjective pain response in patients undergoing retinal photocoagulation when only topical anesthesia was used. Study Design/Materials and Methods: Twenty consecutive patients required peripheral retinal photocoagulation for proliferative diabetic retinopathy or extensive retinal breaks. Three diode pulse waveforms including a square wave, shaped-wave, and an envelope of micropulses were compared to one another. Power was adjusted so that each waveform delivered the same total energy. The patients subjectively ranked the intensity of any pain they experienced for each group of lesions. Responses were compared to one another using an analysis of variance. Results: 40% of patients found the standard square wave pulse to be significantly more painful (P < 0.05) than the shaped pulse mode and 30% found the square wave significantly more painful (P < 0.05) than the micropulse mode. Conclusion: Modification of the laser pulse waveform may ameliorate pain induced by diode laser photocoagulation of the retinal periphery. © 1995 Wiley-Liss, Inc.