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BackgroundFunctional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.MethodsWe did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475.FindingsBetween Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group.InterpretationInterferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo.FundingThe National Institute of Allergy and Infectious Diseases (USA).

BackgroundExternal ventricular drain (EVD) is a standard approach for both monitoring intracranial pressure (ICP) and draining cerebrospinal fluid (CSF) for patients with subarachnoid hemorrhage. Documenting an accurate ICP value is important to assess the status of the brain, which would require the EVD system to be leveled properly and closed to CSF drainage for an adequate period. It is suggested that a minimum period of 5-minute EVD closure is needed before documenting a true ICP; however, there is no commonly agreed upon standard for documenting ICP. To obtain an insight into how well the intermittent EVD clamping procedure is performed for ICP documentation, we conducted a retrospective analysis of ICP recordings obtained through EVD from 107 patients with subarachnoid hemorrhage.MethodsThe EVD was kept open for continuous CSF drainage and then intermittently closed for ICP documentation. For each EVD closure, mean ICP, standard deviation of ICP, duration of EVD closure, and time interval between 2 adjacent EVD closures were studied. The total number of EVD closures was calculated for each patient. We developed an algorithm to evaluate whether ICP reached a new equilibrium before the EVD was reopened to drainage. The percentage of EVD closures that reach the equilibrium was calculated.ResultsThe 107 patients had 32 755 EVD closures in total, among which 65.9% instances lasted less than 1 minute and only 16.3% of all the EVD closure episodes lasted longer than 5 minutes. The median duration of each EVD closure was 25 seconds (interquartile range, 10.2 seconds to 2.33 minutes). Only 22.9% of the EVD closures reached ICP equilibrium before EVD reopening.ConclusionA standard guideline and proper training are needed for bedside nurses, and a potential tool that can render ICP trend at a proper scale at bedside would help clinicians correctly document ICP.

BackgroundUnhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use.ObjectiveTo examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT.DesignRandomized clinical trial.ParticipantsSix hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use.InterventionParticipants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively.Main measuresParticipant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence.Key resultsAt 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p

Quality of life (QoL) is relevant to people living with HIV (PLWH) with increased life expectancy because of antiretroviral therapy. Our cross-sectional study examined associations between sociodemographic, HIV-related and psychological variables, and QoL, overall and by age. PLWH (n = 614) completed questionnaires at enrollment in an alcohol treatment study. QoL was assessed by the 12-item Short Form Survey, which includes physical and mental domains. Linear regression models evaluated the association of age and other factors with mental and physical QoL. PLWH younger than 50 years (n = 310) reported poorer mental QoL but better physical QoL compared to older PLWH (n = 304). Poorer mental QoL was associated with substance use, depression, and anxiety. Poorer physical QoL was associated with depression and history of injection drug use. We identified age-group differences in QoL for this primary care-based sample. Health care providers can use our findings to guide patient-centered care.

BACKGROUND:Limited primary care-based research has examined hazardous drinking risk factors and motivation to reduce use in persons with HIV (PWH). METHODS:We computed prevalence ratios (PR) for factors associated with recent (5) included: moderate/severe depression (PR: 1.43; 1.03, 2.00) and other substance use (PR: 1.49; 1.11, 2.01). Lower importance was associated with incomes above $50,000 (PR: 0.65; 0.46, 0.91) and marijuana use (PR: 0.65; 0.49, 0.87). HIV-specific factors (e.g., CD4 and HIV RNA levels) were not associated with alcohol outcomes. CONCLUSIONS:This study identified modifiable participant characteristics associated with alcohol outcomes in PWH, including anxiety and depression severity, tobacco use, and other substance use.