PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V).

BACKGROUND: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to SARS-CoV-2 infection by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. METHODS: PROTECT-V is a platform trial testing pre-exposure prophylactic interventions against SARS-CoV-2 infection in vulnerable patient populations (organ transplant recipients; individuals with oncological/haematological diagnoses, immune deficiency or autoimmune diseases requiring immunosuppression or on dialysis). Multiple agents can be evaluated across multiple vulnerable populations sharing placebo groups, with the option of adding additional treatments at later time points as these become available. The primary endpoint is symptomatic SARS-CoV-2 infection, and each agent will be independently evaluated in real time when the required number of events occurs. Presently, three agents are approved in the platform: intranasal niclosamide, nasal and inhaled ciclesonide and intravenous sotrovimab. DISCUSSION: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to COVID-19 disease by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04870333. EudraCT 2020-004144-28.

Clinical outcomes associated with the emergency treatment of hyperkalaemia with intravenous insulin-dextrose.

BACKGROUND: Hyperkalaemia occurs in up to 10% of hospital admissions but its treatment in the emergency setting is inconsistent. OBJECTIVES: To describe the emergency management of hyperkalaemia in adults with insulin-dextrose (IDex) and to explore clinical outcomes associated with IDex treatment. DESIGN AND SETTING: Cohort study using comprehensive electronic health records of all emergency admissions to a large university hospital in the United Kingdom between April 2015 and August 2018. PARTICIPANTS: Adult patients aged ≥16 years with at least one emergency admission and one blood potassium result during the study period. MAIN OUTCOMES AND MEASURES: Emergency hyperkalaemia treatment was evaluated including the requirement for re-treatment with IDex, episodes of glucose dysregulation, intensive care (ICU) admission and length of hospital stay. Associations with hyperkalaemia, adverse events and IDex treatment were explored by logistic regression. RESULTS: Amongst 211,993 patients attending the Emergency Department (ED) we identified 11,107 hyperkalaemic adult patients, of whom 1,284 were treated with IDex. Multiple doses were required in 542 patients (42.2%). Hypoglycaemia (plasma glucose < 4 mmol/L) occurred in 249 patients (19.4%) within 6 hours of IDex. Repeated doses were associated with an increased risk of hypoglycaemia (OR 2.94, 95% CI 2.20 to 3.93) compared to patients receiving a single dose, which, after adjustment was also associated with an increased risk of death (OR 1.56, 95% CI 1.16 to 2.09) during the study period. Patients who received multiple doses of IDex (OR 2.2, 95% CI 1.6-3.1) and those who received a dose of insulin above the guideline recommended limit (OR 5.6 3.1-10.3) were more likely to be admitted to ICU following IDex than those who received a single dose or the guideline recommended dose of insulin. CONCLUSIONS AND RELEVANCE: This study provides novel insight into the emergency management of hyperkalaemia in a large population, demonstrates the high risk of hypoglycaemia and highlights the urgent need for an improved, evidence-based approach to the emergency management of hyperkalaemia.

Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD).

BACKGROUND: Users of guideline-recommended renin-angiotensin-aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. METHODS: This exploratory, retrospective analysis utilized data from the UK's Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. RESULTS: Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8-75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. CONCLUSIONS: These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.