To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 .Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. Results:We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (-1 to 15), 0 (-1 to 9) and-1 (-1 to 7), respectively,

Background Pneumothorax (PTX) and pneumomediastinum (PM), collectively termed here “air leak”, are now well described complications of severe COVID-19 pneumonia across several case series. The incidence is thought to be approximately 1% but is not definitively known. Objectives To report the incidence and describe the demographic features, risk factors and outcomes of patients with air leak as a complication of COVID-19. Methods A retrospective observational study on all adult patients with COVID-19 admitted to Watford General Hospital, West Hertfordshire NHS Trust between March 1st 2020 and Feb 28th 2021. Patients with air leak were identified after reviewing both chest radiographs (CXRs) and axial imaging (CT Thorax) with confirmatory radiology reports inclusive of the terms PTX and/or PM. Results Air leak occurred with an incidence of 0.56%. Patients with air leak were younger and had evidence of more severe disease at presentation, including a higher median CRP and number of abnormal zones affected on chest radiograph. Asthma was a significant risk factor in the development of air leak (OR 13.4 [4.7-36.4]), both spontaneously and following positive pressure ventilation. CPAP and IMV were also associated with a greater than six fold increase in the risk of air leak (OR 6.4 [2.5-16.6] and 9.8 [3.7-27.8] respectively). PTX, with or without PM, in the context of COVID-19 pneumonia was almost universally fatal whereas those with alone PM had a lower risk of death. Conclusion Despite the global vaccination programme, patients continue to develop severe COVID-19 disease and may require respiratory support. This study demonstrates the importance of identifying that deterioration in such patients may be resultant from PTX or PM, particularly in asthmatics and those managed with positive pressure ventilation.

Background The homeobox B13 ( HOXB13 ) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain. Objective To obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors. Design, setting, and participants Two-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11 983 PCa patients enrolled during 1993–2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E. Outcome measurements and statistical analysis Relative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort. Results and limitations A meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95–33.0, p < 0.001) and differences by case selection ( p = 0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78–4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history ( p < 0.001). There was a suggestion that RRs decrease with age, but this was not significant ( p = 0.068). We found higher RR estimates for men from more recent birth cohorts ( p = 0.004): 3.09 (95% CI 2.03–4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01–8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history. Conclusions PCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers’ family history and birth cohort. Patient summary Men who carry a hereditary mutation in the homeobox B13 ( HOXB13 ) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to he...

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Introduction: Coronavirus Disease 2019 is a contagious infection that has infected millions worldwide. The objective of this systematic review is to identify studies pertaining to antivirals, both as sole and combined therapies, in COVID-19 patients and review the clinical outcomes of these treatment methods. Areas covered: A systematic review was conducted using Preferred Reporting Items or Systematic Reviews and Meta-analysis (PRISMA) guidelines. A literature search was done on Medline, Global Health, and EMBASE using keywords and MeSH terms relevant to COVID-19 and antivirals. Limits were put on date to obtain articles between December 2019 to May 2020 (the time at which the search was performed). 776 articles were identified and screened. After screening, 16 studies were included. The narrative synthesis revealed three key themes (1) Use of antivirals only (such as lopinavir, umifenovir, and remdesivir), (2) Use of lopinavir-ritonavir alongside other treatments, and (3) Use of other antivirals in combination with other treatments. Expert opinion: Using antivirals in combination with other treatments has potential; however, further randomized controlled trials with larger sample sizes are required to identify the best candidate components that should comprise combined treatments for COVID-19. This should optimize treatment efficacy and improve patient outcomes.