Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151 ; ClinicalTrials.gov number, NCT04315948 .)
All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.
Background and purposeLithuania is one of the countries with the highest incidence of tick‐borne encephalitis (TBE) in Europe. The aim of this study was to describe the epidemiological patterns of TBE in Lithuania, and characterize clinical features in adults in the light of the high incidence in recent years.MethodsSurveillance data available on the website of the Centre for Communicable Diseases and AIDS of Lithuania were used to describe the epidemiological patterns of TBE. The retrospective study included 712 patients hospitalized in the Centre for Infectious Diseases and the Centre for Neurology of Vilnius University in the years 2005–2014.ResultsTick‐borne encephalitis incidence rates have been increasing by 8.5% per year for the 45‐year period from 1970 to 2014. The joinpoint model finds two joinpoints at 1991 and 1994, with a significant decrease of 8.4% per year (P < 0.05) prior to the joinpoint at 1991, and a rise of 195.2% afterwards. TBE presented with meningoencephalitis in 556 cases (81.3%). A total of 129 patients (18%) had a severe case of the disease. The most common neurological signs were ataxia (579, 81.3%), meningeal signs (474, 66.5%) and tremor (338, 47.5%). Limb paresis was observed in 6.3% of patients. Five patients (0.7%) died, and 544 patients (76.7%) were discharged with sequelae.ConclusionsIntensified efforts in promoting TBE vaccination will be needed in the light of the high incidence and expanded spatial distribution. Significant prognostic factors for severe cases of the disease were age above 61 and delayed immune response of specific immunoglobulin G.
The coronavirus (COVID‐19) pandemic is evolving very quickly and has affected healthcare systems worldwide. Many uncertainties remain about transplantation from a SARS‐CoV‐2‐positive donor as only a few cases have been reported. Here, we present the successful transplantation of two kidneys from a 52‐year‐old male donor with active (2 weeks of COVID‐19‐like symptoms and positive nasopharyngeal swab SARS‐CoV‐2 PCR on the day of organ recovery) SARS‐CoV‐2 disease. The immediate postoperative course of both recipients was uneventful. This case emphasizes that patients with SARS‐CoV‐2 may be safe organ donors.
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