Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Intrastromal injection of 5% voriconazole solution may provide a safe and effective treatment option for corneal stromal abscessation in horses. In all reported cases, administration of injection early in the treatment period appeared to contribute to rapid resolution of clinical disease without significant complications. The authors present this technique as an alternative to traditional surgical intervention, being more economical, having shorter treatment duration, and potentially resulting in less scar formation.
Case series summary This case series describes the clinical utility of antigen testing for the diagnosis of feline ocular histoplasmosis. Four cats with suspected (n = 2) or confirmed (n = 2) ocular histoplasmosis are described: three from Oklahoma and one from California. In one case, serial urine antigen tests, as well as a serum antigen test for Histoplasma capsulatum, were negative; however, light microscopy identified microorganisms consistent with H capsulatum in ocular tissues at necropsy. In a further two cats with recurrent ocular histoplasmosis following long-term systemic antifungal therapy, Histoplasma species urine antigen concentrations were negative, but both cats improved clinically following systemic antifungal therapy and remained in apparent clinical remission after treatment cessation (9-16 months). The final cat displayed profound bilateral endophthalmitis; however, Histoplasma species antigen testing of vitreous humor and subretinal fluid from the left eye was negative. Intralesional organisms were detected on histopathology of both eyes, and H capsulatum was subsequently isolated and sequenced from tissue of one eye. Relevance and novel information These cases highlight the potential difficulty in definitively diagnosing ocular histoplasmosis in cats when conducting antigen testing of serum, urine and even ocular fluids. Although antigen testing has previously proven useful in the diagnosis of disseminated feline histoplasmosis, it may not be adequate in cats with only ocular signs.
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