Mortality of Care Home Residents and Community-Dwelling Controls During the COVID-19 Pandemic in 2020: Matched Cohort Study.

OBJECTIVE: This study aimed to estimate and compare mortality of care home residents, and matched community-dwelling controls, during the COVID-19 pandemic from primary care electronic health records in England. DESIGN: Matched cohort study. SETTING AND PARTICIPANTS: Family practices in England in the Clinical Practice Research Datalink Aurum database. There were 83,627 care home residents in 2020, with 26,923 deaths; 80,730 (97%) were matched on age, sex, and family practice with 300,445 community-dwelling adults. METHODS: All-cause mortality was evaluated and adjusted rate ratios by negative binomial regression were adjusted for age, sex, number of long-term conditions, frailty category, region, calendar month or week, and clustering by family practice. RESULTS: Underlying mortality of care home residents was higher than community controls (adjusted rate ratio 5.59, 95% confidence interval 5.23‒5.99, P < .001). During April 2020, there was a net increase in mortality of care home residents over that of controls. The mortality rate of care home residents was 27.2 deaths per 1000 patients per week, compared with 2.31 per 1000 for controls. Excess deaths for care home residents, above that predicted from pre-pandemic years, peaked between April 13 and 19 (men, 27.7, 95% confidence interval 25.1‒30.3; women, 17.4, 15.9‒18.8 per 1000 per week). Compared with care home residents, long-term conditions and frailty were differentially associated with greater mortality in community-dwelling controls. CONCLUSIONS AND IMPLICATIONS: Individual-patient data from primary care electronic health records may be used to estimate mortality in care home residents. Mortality is substantially higher than for community-dwelling comparators and showed a disproportionate increase in the first wave of the COVID-19 pandemic. Care home residents require particular protection during periods of high infectious disease transmission.

The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection-study protocol for a two-stage randomised phase II trial.

BACKGROUND: Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. METHODS: RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. DISCUSSION: The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. TRIAL REGISTRATION: The protocol is registered on Clinical. TRIALS: gov and EudraCT and has approval from UK Ethics and MHRA.

Randomised controlled trial of a just-in-time adaptive intervention (JITAI) smoking cessation smartphone app: the Quit Sense feasibility trial protocol.

INTRODUCTION: A lapse (any smoking) early in a smoking cessation attempt is strongly associated with reduced success. A substantial proportion of lapses are due to urges to smoke triggered by situational cues. Currently, no available interventions proactively respond to such cues in real time. Quit Sense is a theory-guided just-in-time adaptive intervention smartphone app that uses a learning tool and smartphone sensing to provide in-the-moment tailored support to help smokers manage cue-induced urges to smoke. The primary aim of this randomised controlled trial (RCT) is to assess the feasibility of delivering a definitive online efficacy trial of Quit Sense. METHODS AND ANALYSES: A two-arm parallel-group RCT allocating smokers willing to make a quit attempt, recruited via online adverts, to usual care (referral to the NHS SmokeFree website) or usual care plus Quit Sense. Randomisation will be stratified by smoking rate (<16 vs ≥16 cigarettes/day) and socioeconomic status (low vs high). Recruitment, enrolment, baseline data collection, allocation and intervention delivery will be automated through the study website. Outcomes will be collected at 6 weeks and 6 months follow-up via the study website or telephone, and during app usage. The study aims to recruit 200 smokers to estimate key feasibility outcomes, the preliminary impact of Quit Sense and potential cost-effectiveness, in addition to gaining insights on user views of the app through qualitative interviews. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Wales NHS Research Ethics Committee 7 (19/WA/0361). The findings will be disseminated to the public, the funders, relevant practice and policy representatives and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN12326962.