Background.
Tocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients.
Methods: In a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2<96% despite O2-support >6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days.
Results: 246 patients were included (106 treated by tocilizumab). They were 67.6 +/-15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 +/-4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n=168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR)=0.49 (95% confidence interval (95CI)=0.3-0.81), p-value=0.005). These results were similar in the overall cohort (n=246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR=0.26 (95CI=0.135-0.51, p=0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results.
Conclusion: In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML).It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV strains between urine, cerebrospinal fluid, and cerebellum, specific rearrangements in the JCV regulatory region were observed in the cerebellum, resulting in alterations of transcription factor binding sites. Our data underline the importance of searching for JCV in HIV-infected patients with cerebellar disorders and suggest that mutations in the regulatory region may be involved in cerebellar degeneration.
We report a retrospective study of an epidemic of dengue in New-Caledonia (South Pacific) in 2003 among adult inpatients. The aim was to establish clinical and biological criteria for the severity of the infection at the time of admission. During 7 months, all inpatients older than 15 y having a laboratory-confirmed diagnosis of dengue fever (IgM or PCR) were included (n=170). Two groups were defined: severe cases (death and/or transfer to intensive care unit, n=24) and benign cases (n=146). Data were analysed using Epi-Info software. Univariate analysis showed that shock, haemorrhage and neurological complications were significantly more frequent in serious cases, respectively 37.5% vs 0.7%, 62.5% vs 32.2%, 25% vs 9.6% (p<0.05). Relevant biological criteria were: creatinine > 140 micromol/l (OR 12 (95% CI 3.93-37.44)), free bilirubin > 18 micromol/l (OR 12.69 ( 95% CI 2.88-59.5)), amylase > 220 UI/l (OR 27.34 (95% CI 4.57-210)) and platelets < 45,000/mm3 (OR 4.35 (95% CI 1.43-14.2)) with p<0.005 (VPP = 100% for association of 3 criteria). We suggest this combination of 4 biological criteria inclines to severity.
Appropriate advice for malaria prophylaxis, yellow fever, and hepatitis A vaccinations was provided in a travel medicine and vaccine center where trained physicians used a computerized decision support system. Even in this setting, however, errors can occur and professional practices should be regularly assessed to improve health care.
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