Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: a randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU)

BackgroundAfter admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. MethodsIn a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n=192) or SoC only (n=195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. ResultsAdherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P=0.063); PP 40.7% RRR, 9.6% ARR (P=0.017); AT 43.2% RRR, 10.8% ARR (P=0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. ConclusionsIn hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

CT screening for lung cancer in the UK: position statement by UKLS investigators following the NLST report.

BACKGROUND: The imminent publication of a randomised controlled trial from the USA that suggests CT screening reduces mortality from lung cancer by more than 20%, may potentially lead to one of the most important developments in lung cancer care. However, there remain important questions about the applicability of the results to the UK and the clinical effectiveness of this intervention, including its feasibility and cost-effectiveness. OBJECTIVE: To describe the remaining questions that need to be answered by further research and to comment on the use of CT screening in the UK outside a clinical trial. METHODS: The detailed design process of the UKLS protocol and international discussions were used to identify the research questions that remain to be answered and to inform those who may choose to consider offering CT screening, before these questions are answered. RESULTS: A series of research imperatives have been identified and we advise that CT screening should be part of the ongoing clinical trial in the UK, currently in the pilot phase (UKLS). UKLS is randomising 4,000 individuals for the pilot and a total of 32,000 for the main study. CONCLUSION: There remain unresolved issues with respect to CT screening for lung cancer. These include its feasibility, psychosocial and cost-effectiveness in the UK, harmonisation of CT acquisition techniques, management of suspicious screening findings, the choice of screening frequency and the selection of an appropriate risk group for the intervention. UKLS is aimed at resolving these issues.

The current status of decompressive craniectomy.

Decompressive Craniectomy (DC) continues to be widely practiced but remains controversial. The procedure has its origins thousands of years ago, with early trepanation performed for a range of medical and religious reasons. We summarize the history, techniques, complications and pathophysiology and then explore in detail the recent evidence base for the most common indications for DC; Traumatic brain injury (TBI) and Cerebral infarction. An important consideration from the outset is the often forgotten issue of cranioplasty and we summarize advances in materials, technology and discuss the optimum timing. Outcomes of ongoing randomized trials in TBI are awaited with interest but the trend in the nonrandomized literature suggests timely intervention reduces mortality with acceptable morbidity. Level 1 evidence for early DC in young patients with malignant middle cerebral artery infarction has arrived and has implications for neurosurgical practice and rehabilitation services. Current European and North American practice recommends the judicious use of DC in traumatic brain injury and malignant middle cerebral artery infarction in select patients.