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.

     

Initiatives to reduce postoperative surgical site infections of the head and neck cancer surgery with a special emphasis on developing countries

Introduction: Surgery in patients with head and neck cancers is frequently complicated by multiple stages of procedure that includes significant surgical removal of all or part of an organ with cancer, tissue reconstruction, and extensive neck dissection. Postoperative wound infections, termed ‘surgical site infections’ (SSIs) are a significant impediment to head-and-neck cancer surgery and recovery, and need to be addressed.

Areas covered: Approximately 10–45% of patients undergoing head-and-neck cancers surgery develop SSIs. SSIs can lead to delayed wound healing, increased morbidity and mortality as well as costs. Consequently, SSIs need to be avoided where possible, as even the surgery itself impacts on patients’ subsequent activities and their quality of life, which is exacerbated by SSIs. Several risk factors for SSIs need to be considered to reduce future rates, and care is also needed in the selection and duration of antibiotic prophylaxis.

Expert commentary: Head and neck surgeons should give personalized care especially to patients at high risk of SSIs. Such patients include those who have had chemoradiotherapy and need reconstructive surgery, and patients from lower and middle-income countries and from poorer communities in high income countries, who often have high levels of co-morbidity because of resource constraints.     

Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol

We performed genome-wide tests for association between haplotype clusters and each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were body mass index, C-reactive protein, diastolic blood pressure, glucose, high-density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood pressure, and triglycerides. Haplotype clusters were determined using Beagle. There were LDL-associated clusters in the chromosome 4q13.3-q21.1 region containing the albumin (ALB) and platelet factor 4 (PF4) genes. This region has not been associated with LDL in previous genome-wide association studies. The most significant haplotype cluster in this region was associated with 0.488 mmol/l higher LDL (95% CI: 0.361–0.615 mmol/l, P-value: 6.4 × 10⁻¹⁴). We also observed three previously reported associations: Chromosome 16q13 with HDL, chromosome 1p32.3-p32.2 with LDL and chromosome 19q13.31-q13.32 with LDL. The chromosome 1 and chromosome 4 LDL associations do not reach genome-wide significance in single-marker analyses of these data, illustrating the power of haplotypic association testing.     

伴随结节性硬化的浸润性视网膜星形细胞瘤4例

众所周知，视网膜星形细胞瘤常伴有结节性硬化的表现。视网膜星形细胞瘤一般是发生在视网膜神经纤维层的无蒂轻度隆起性病变。临床上可以是单侧发生，也可以是双侧发生。可以单个病灶，也可以多个病灶。可以是透明的，也可以是不透明的。可以有钙化，也可以没有钙化。视网膜星形细胞瘤相对固定的伴有眼内结节性硬化，很少表现为浸润性增长。在很少的情况下视网膜星形细胞瘤可以表现出浸润性增长，造成局部严重并发症。