OUTdoor Swimming as a nature-based Intervention for DEpression (OUTSIDE): study protocol for a feasibility randomised control trial comparing an outdoor swimming intervention to usual care for adults experiencing mild to moderate symptoms of depression

Background Depression is common and the prevalence increasing worldwide; at least 1 in 10 people will experience depression in their lifetime. It is associated with economic costs at the individual, healthcare and societal level. Recommended treatments include medication and psychological therapies. However, given the long waiting times, and sometimes poor concordance and engagement with these treatments, a greater range of approaches are needed. Evidence for the potential of outdoor swimming as an intervention to support recovery from depression is emerging, but randomised controlled trials (RCTs) evaluating clinical and cost-effectiveness are lacking. This study seeks to investigate the feasibility of conducting a definitive superiority RCT, comparing an 8-session outdoor swimming course offered in addition to usual care compared to usual care only, in adults who are experiencing mild to moderate symptoms of depression. Feasibility questions will examine recruitment and retention rates, acceptability of randomisation and measures, and identify the primary outcome measure that will inform the sample size calculation for a definitive full-scale RCT. This study will also explore potential facilitators and barriers of participation through evaluation questionnaires, focus-group discussions and interviews. Methods/design To address these aims and objectives, a feasibility superiority RCT with 1:1 allocation will be undertaken. We will recruit 88 participants with mild to moderate symptoms of depression through social prescribing organisations and social media in three sites in England. Participants will be randomised to either (1) intervention (8-session outdoor swimming course) plus usual care or (2) usual care only. Both groups will be followed up for a further 8 weeks. Discussion If findings from this feasibility RCT are favourable, a fully powered RCT will be conducted to investigate the clinical- and cost-effectiveness of the intervention. Findings from the definitive trial will provide evidence about outdoor swimming for depression for policymakers and has the potential to lead to greater choice of interventions for adults experiencing symptoms of depression. Trial registration Current controlled trial registration number is ISRCTN 90851983 registered on 19 May 2022

Clinical effectiveness and cost-effectiveness of supported mindfulness-based cognitive therapy self-help compared with supported cognitive behavioral therapy self-help for adults experiencing depression

Importance Depression is prevalent. Treatment guidelines recommend practitioner-supported cognitive behavioral therapy self-help (CBT-SH) for mild to moderate depression in adults; however, dropout rates are high. Alternative approaches are required. Objective To determine if practitioner-supported mindfulness-based cognitive therapy self-help (MBCT-SH) is superior to practitioner-supported CBT-SH at reducing depressive symptom severity at 16 weeks postrandomization among patients with mild to moderate depression and secondarily to examine if practitioner-supported MBCT-SH is cost-effective compared with practitioner-supported CBT-SH. Design, Setting, and Participants This was an assessor- and participant-blinded superiority randomized clinical trial with 1:1 automated online allocation stratified by center and depression severity comparing practitioner-supported MBCT-SH with practitioner-supported CBT-SH for adults experiencing mild to moderate depression. Recruitment took place between November 24, 2017, and January 31, 2020. The study took place in 10 publicly funded psychological therapy services in England (Improving Access to Psychological Therapies [IAPT]). A total of 600 clients attending IAPT services were assessed for eligibility, and 410 were enrolled. Participants met diagnostic criteria for mild to moderate depression. Data were analyzed from January to October 2021. Interventions Participants received a copy of either an MBCT-SH or CBT-SH workbook and were offered 6 support sessions with a trained practitioner. Main Outcomes and Measures The preregistered primary outcome was Patient Health Questionnaire (PHQ-9) score at 16 weeks postrandomization. The primary analysis was intention-to-treat with treatment arms masked. Results Of 410 randomized participants, 255 (62.2%) were female, and the median (IQR) age was 32 (25-45) years. At 16 weeks postrandomization, practitioner-supported MBCT-SH (n = 204; mean [SD] PHQ-9 score, 7.2 [4.8]) led to significantly greater reductions in depression symptom severity compared with practitioner-supported CBT-SH (n = 206; mean [SD] PHQ-9 score, 8.6 [5.5]), with a between-group difference of −1.5 PHQ-9 points (95% CI, −2.6 to −0.4; P = .009; d = −0.36). The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%. However, although between-group effects on secondary outcomes were in the hypothesized direction, they were mostly nonsignificant. Three serious adverse events were reported, all deemed not study related. Conclusions and Relevance In this randomized clinical trial, practitioner-supported MBCT-SH was superior to standard recommended treatment (ie, practitioner-supported CBT-SH) for mild to moderate depression in terms of both clinical effectiveness and cost-effectiveness. Findings suggest that MBCT-SH for mild to moderate depression should be routinely offered to adults in primary care services

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Excellent hepatitis C virus cure rates despite increasing complexity of people who use drugs: integrated-test-stage-treat study final outcomes

Achieving hepatitic C virus (HCV) elimination requires linking people who use drugs (PWUD) into care. We report final direct-acting antivirals (DAAs)-based outcomes from the Integrated-Test-stage -Treat (ITTREAT) study. Project ITTREAT (2013–2021), based at an addiction centre, was a ‘one-stop’ service with innovative linkage to care strategies. Primary outcome was sustained virological response (SVR12) (intention to treat ITT) including whether individuals were recruited in first (period 1) versus last four (period 2 included the COVID-19 pandemic) years of the study. Number recruited were n = 765, mean age 40.9 ± 10.1 years, 78% males, history of current/past injecting drug use (IDU) and alcohol use being 77% and 90%, respectively. Prevalence of a positive HCV PCR was 84% with 19% having cirrhosis. Comparing those recruited in period 2 versus period 1, there was increasing prevalence of IDU, 90% versus 72% (p < .001); homelessness, 67% versus 50% (p < .001); psychiatric diagnosis, 84% versus 50% (p < .001); overdose history 71% versus 31% (p < .001), receiving opioid agonist treatment (OAT) 75% versus 52% (p < .001) and comorbidity 44% versus 25% (p < .001). Of those treated with DAAs (n = 272), ITT SVR rates were 86% (95% CI: 81%–90%), being similar in period 2 versus period 1. Predictors of non-SVR were receiving OAT (OR 0.33, 95% CI: 0.12–0.87, p = .025) and ≥80% adherence (OR 0.01, 95% CI: 0.003–0.041, p < .001). Reinfection rates period 2 versus period 1 (per 100 person-years) were 1.84 versus 1.70, respectively. In the treated cohort, mortality was 15%, being mostly drug-related. Despite increasing complexity of PWUD, high SVR12 rates are achievable with use of OAT and good adherence.</p

Multi-modal hallucinations across diagnoses: what relationships do they have with voice-related distress?

BackgroundResearch into hallucinatory experiences has focused primarily upon hallucinations within the auditory modality, to the relative neglect of other modalities. Furthermore, the exploration of auditory hallucinations (or ‘voices’) has focused primarily upon the experiences of people with a diagnosis of psychosis. The presence of multi-modal hallucinations may have implications across diagnoses for levels of distress, formulation and the targeting of psychological interventions.MethodsThis study presents a cross-sectional analysis of observational data from the PREFER survey (N = 335). Linear regression was used to explore the relationships between voice-related distress and the presence, number, type and timing of multi-modal hallucinations.ResultsSimple relationships were not found between distress and the presence of hallucinations in visual, tactile, olfactory or gustatory modalities, or in the number of modalities experienced. When considering the degree to which another modality hallucination was experienced simultaneously with voices, there was some evidence that the degree of co-occurrence with visual hallucinations was predictive of distress.ConclusionsThe co-occurrence of voices with visual hallucinations may be associated with relatively greater distress, but not consistently, and the association between multimodal hallucinations and clinical impact appear complex and potentially variable from individual to individual. Further study of associated variables such as perceived voice power may further illuminate these relationships.</p

Trialling an optimised social groups intervention in services to enhance social connectedness and mental health in vulnerable young people (TOGETHER): Study protocol for a feasibility randomised controlled trial

BackgroundCalls have been made to rethink the mental health support currently available for young people. This study aims to help re-focus and reduce the inaccessibility of mental health services by offering an adapted version of a theoretically-driven, evidence-based, guided psychosocial intervention known as ‘Groups 4 Health’ (G4H). To date, the G4H intervention has mainly been trialled in Australia, with promising positive effects on social connection, mental health and well-being. The present study examines the feasibility of running a randomised controlled trial when delivering the G4H intervention for young people in the UK.MethodsThe TOGETHER study is a feasibility randomised controlled trial of an adapted version of the G4H intervention. Participants are aged 16–25, currently experiencing mental health difficulties and recruited from mental health services. The target sample size is 30, with 15 in each trial arm. Participants are randomly allocated to either G4H plus treatment as usual, or treatment as usual alone. The primary outcomes of interest are the feasibility of recruitment, randomisation, data collection and retention to the study at 10 and 14 week follow up, as well as the acceptability, and accessibility of the study protocol and G4H intervention.DiscussionThe results of this study will indicate if further optimisation is required to improve the feasibility, acceptability and accessibility of the intervention and study protocol procedures as perceived by end users and practitioners. This offers a significant opportunity to support the local and national demand for accessible, innovative, and effective psychosocial youth mental health support.Trial registrationISRCTN registry (ISRCTN12505807). Registration date: 11/04/2022.</p