<u>Background</u> The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision making. Procalcitonin (PCT) is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between PCT and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated. <u>Methods</u> We retrospectively reviewed Covid-19 patients with PCT levels measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak PCT values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality. <u>Results</u> In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak PCT levels significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0, p=0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6, p=0.03). Higher peak PCT levels was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4, p=0.03). There was a significant positive correlation between increased peak PCT levels and duration on invasive mechanical ventilation. No significant difference was found between peak PCT levels of patients with positive and negative bacterial cultures. <u>Conclusions</u> Elevated PCT levels in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.

Spironolactone (50 mg BID) was ineffective in comparison to acetazolamide (250 mg BID) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya.

IMPORTANCEOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.DESIGN, SETTING, AND PARTICIPANTSIn 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).INTERVENTIONSPatients 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 MEASURESThe 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.RESULTSOn 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 RELEVANCEIn 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 REGISTRATIONClinicalTrials.gov Identifier: NCT02735707

The tragic case of Mayra Cabrera who died as a result of wrong route drug administration is notable as it was the first time a verdict of unlawful killing was recorded against an NHS Trust. Error within medicine is a significant cause of patient morbidity and mortality. We explore the costs of error, the dynamics of error causation, the role of both the individual and institution in accountability for error, as well as transferrable lessons from other industries to reduce error.

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This article reviews the case of a patient who ingested ethylene glycol and who presented to hospital but refused treatment while she was assessed as having capacity. The author reviews issues surrounding the Mental Capacity Act 2005, assessment of capacity and a way forward when confronting this difficult situation.

The association between methotrexate therapy and idiosyncratic neurological complications is well recognised in children. This case illustrates the importance of considering the diagnosis of methotrexate toxicity in an adult patient with behavioural and speech disturbances, who received it by intrathecal route only and in whom the only indicator was an abnormal electroencephalographic study

The evolution in communication and digital technologies is revolutionising the practice of medicine. A physician is now able to oversee provision of healthcare at a distance. In this paper, we argue that practice of telemedicine is an essential and evolving aspect of high altitude and expedition medicine. We acknowledge the lack of international consensus, limited legislation as well as possible reservations towards telemedical practice. Given some unique social and medical aspects of participation in remote, high altitude expeditions we propose a number of guiding principles for those involved in provision of telemedical services for such endeavours.