Effectiveness of peer educators on the uptake of mobile X-ray tuberculosis screening at homeless hostels: a cluster randomised controlled trial.

To compare current practice for encouraging homeless people to be screened for tuberculosis on a mobile digital X-ray unit in London, UK, with the additional use of volunteer peer educators who have direct experience of tuberculosis, homelessness or both

Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs

Background: Socially complex groups, including people experiencing homelessness, prisoners and drug users, have very high levels of tuberculosis, often complicated by late diagnosis and difficulty in adhering to treatment. / Objective: To assess a series of interventions to improve tuberculosis control in socially complex groups. / Design: A series of observational surveys, evaluations and trials of interventions. / Setting: The pan-London Find&Treat service, which supports tuberculosis screening and case management in socially complex groups across London. / Participants: Socially complex groups with tuberculosis or at risk of tuberculosis, including people experiencing homelessness, prisoners, drug users and those at high risk of poor adherence to tuberculosis treatment. Interventions and main outcome measures We screened 491 people in homeless hostels and 511 people in prison for latent tuberculosis infection, human immunodeficiency virus, hepatitis B and hepatitis C. We evaluated an NHS-led prison radiographic screening programme. We conducted a cluster randomised controlled trial (2348 eligible people experiencing homelessness in 46 hostels) of the effectiveness of peer educators (22 hostels) compared with NHS staff (24 hostels) at encouraging the uptake of mobile radiographic screening. We initiated a trial of the use of point-of-care polymerase chain reaction diagnostics to rapidly confirm tuberculosis alongside mobile radiographic screening. We undertook a randomised controlled trial to improve treatment adherence, comparing face-to-face, directly observed treatment with video-observed treatment using a smartphone application. The primary outcome was completion of ≥ 80% of scheduled treatment observations over the first 2 months following enrolment. We assessed the cost-effectiveness of latent tuberculosis screening alongside radiographic screening of people experiencing homelessness. The costs of video-observed treatment and directly observed treatment were compared. / Results: In the homeless hostels, 16.5% of people experiencing homelessness had latent tuberculosis infection, 1.4% had current hepatitis B infection, 10.4% had hepatitis C infection and 1.0% had human immunodeficiency virus infection. When a quality-adjusted life-year is valued at £30,000, the latent tuberculosis screening of people experiencing homelessness was cost-effective provided treatment uptake was ≥ 25% (for a £20,000 quality-adjusted life-year threshold, treatment uptake would need to be > 50%). In prison, 12.6% of prisoners had latent tuberculosis infection, 1.9% had current hepatitis B infection, 4.2% had hepatitis C infection and 0.0% had human immunodeficiency virus infection. In both settings, levels of latent tuberculosis infection and blood-borne viruses were higher among injecting drug users. A total of 1484 prisoners were screened using chest radiography over a total of 112 screening days (new prisoner screening coverage was 43%). Twenty-nine radiographs were reported as potentially indicating tuberculosis. One prisoner began, and completed, antituberculosis treatment in prison. In the cluster randomised controlled trial of peer educators to increase screening uptake, the median uptake was 45% in the control arm and 40% in the intervention arm (adjusted risk ratio 0.98, 95% confidence interval 0.80 to 1.20). A rapid diagnostic service was established on the mobile radiographic unit but the trial of rapid diagnostics was abandoned because of recruitment and follow-up difficulties. We randomly assigned 112 patients to video-observed treatment and 114 patients to directly observed treatment. Fifty-eight per cent of those recruited had a history of homelessness, addiction, imprisonment or severe mental health problems. Seventy-eight (70%) of 112 patients on video-observed treatment achieved the primary outcome, compared with 35 (31%) of 114 patients on directly observed treatment (adjusted odds ratio 5.48, 95% confidence interval 3.10 to 9.68; p < 0.0001). Video-observed treatment was superior to directly observed treatment in all demographic and social risk factor subgroups. The cost for 6 months of treatment observation was £1645 for daily video-observed treatment, £3420 for directly observed treatment three times per week and £5700 for directly observed treatment five times per week. / Limitations: Recruitment was lower than anticipated for most of the studies. The peer advocate study may have been contaminated by the fact that the service was already using peer educators to support its work. / Conclusions: There are very high levels of latent tuberculosis infection among prisoners, people experiencing homelessness and drug users. Screening for latent infection in people experiencing homelessness alongside mobile radiographic screening would be cost-effective, providing the uptake of treatment was 25–50%. Despite ring-fenced funding, the NHS was unable to establish static radiographic screening programmes. Although we found no evidence that peer educators were more effective than health-care workers in encouraging the uptake of mobile radiographic screening, there may be wider benefits of including peer educators as part of the Find&Treat team. Utilising polymerase chain reaction-based rapid diagnostic testing on a mobile radiographic unit is feasible. Smartphone-enabled video-observed treatment is more effective and cheaper than directly observed treatment for ensuring that treatment is observed. / Future work: Trials of video-observed treatment in high-incidence settings are needed. / Trial registration: Current Controlled Trials ISRCTN17270334 and ISRCTN26184967. / Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information

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

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

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

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Smartphone-enabled video observed versus directly observed treatment for tuberculosis: a randomised controlled trial

Background Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but delivery entails substantial inconvenience to patients and service providers. Remote video observed therapy (VOT) has recently been conditionally recommended by the WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. Methods We conducted a randomised controlled trial of VOT (daily remote observation using a smartphone app) compared to DOT (three or five-weekly observation in home, community or clinic settings). Tuberculosis patients eligible for DOT at 22 clinics in England were allocated to trial arms by the SealedEnvelopeTM service using randomisation by minimisation. The primary outcome was completion of 80% or more scheduled treatment observations over the first two months following enrolment. Intention-to-treat and restricted (including only patients with at least one week of observation on allocated arm) analyses were conducted. The trial is registered with the ISRCTN, number ISRCTN26184967. Findings Between September 1, 2014 and October 1, 2016, we enrolled 226 patients; 112 randomised to VOT and 114 to DOT. Overall, 58% (131 of 226) had a history of homelessness, imprisonment, drug use, alcohol problems or mental health problems. Seventy percent of patients on VOT (78 of 112) had the primary outcome compared to 31% (35 of 114) of those on DOT (adjusted odds ratio 5·48; 95% confidence interval 3·10-9·68; p<0·0001). Drop-out during the first week of observation was less for VOT (10%, 11 of 112) than DOT (51%, 58 of 114). High observation levels were sustained throughout treatment for VOT patients, but declined rapidly for DOT patients. 4 Interpretation VOT is a more effective approach to observation of tuberculosis treatment than clinic- , community- or home-based DOT

Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial

BACKGROUND: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. METHODS: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN26184967. FINDINGS: Between Sept 1, 2014, and Oct 1, 2016, we randomly assigned 226 patients; 112 to VOT and 114 to DOT. Overall, 131 (58%) patients had a history of homelessness, imprisonment, drug use, alcohol problems or mental health problems. In the ITT analysis, 78 (70%) of 112 patients on VOT achieved ≥80% scheduled observations successfully completed during the first 2 months compared with 35 (31%) of 114 on DOT (adjusted odds ratio [OR] 5·48, 95% CI 3·10-9·68; p<0·0001). In the restricted analysis, 78 (77%) of 101 patients on VOT achieved the primary outcome compared with 35 (63%) of 56 on DOT (adjusted OR 2·52; 95% CI 1·17-5·54; p=0·017). Stomach pain, nausea, and vomiting were the most common adverse events reported (in 16 [14%] of 112 on VOT and nine [8%] of 114 on DOT). INTERPRETATION: VOT was a more effective approach to observation of tuberculosis treatment than DOT. VOT is likely to be preferable to DOT for many patients across a broad range of settings, providing a more acceptable, effective, and cheaper option for supervision of daily and multiple daily doses than DOT. FUNDING: National Institute for Health Research