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.

High prevalence of latent tuberculosis and bloodborne virus infection in a homeless population.

INTRODUCTION: Urban homeless populations in the UK have been shown to have high rates of active tuberculosis, but less is known about the prevalence of latent tuberculosis infection (LTBI). This study aimed to estimate the prevalence of LTBI among individuals using homeless hostels in London. METHODS: We performed a cross-sectional survey with outcome follow-up in homeless hostels in London. Our primary outcome was prevalence of LTBI. Recruitment for the study took place between May 2011 and June 2013. To estimate an LTBI prevalence of 10% with 95% CIs between 8% and 13%, we required 500 participants. RESULTS: 491/804 (61.1%) individuals agreed to be screened. The prevalence of LTBI was 16.5% (81/491; 95% CI 13.2 to 19.8). In UK-born individuals, a history of incarceration was associated with increased risk of LTBI (OR 3.49; 95% CI 1.10 to 11.04; P=0.018) after adjusting for age, length of time spent homeless and illicit drug use. Of the three subjects who met English treatment guidelines for LTBI at the time of the study, none engaged with services after referral for treatment. Prevalence of past hepatitis B infection was 10.4% (51/489; 95% CI 7.7 to 13.1), and 59.5% (291/489; 95% CI 55.1 to 63.9) of individuals were non-immune. Prevalence of current hepatitis C infection was 10.4% (51/489; 95% CI 7.8 to 13.1). CONCLUSIONS: This study demonstrates the high prevalence of LTBI in homeless people in London and the associated poor engagement with care. There is a large unmet need for LTBI and hepatitis C infection treatment, and hepatitis B vaccination, in this group.

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

TRIAL DESIGN: Cluster randomised controlled trial. OBJECTIVE: 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. PARTICIPANTS: 46 hostels took part in the study, with a total of 2342 residents eligible for screening. The study took place between February 2012 and October 2013 at homeless hostels in London, UK. INTERVENTION: At intervention sites, volunteer peer educators agreed to a work plan that involved moving around the hostel in conjunction with the hostel staff, and speaking to residents in order to encourage them to attend the screening. RANDOMISATION: Cluster randomisation (by hostel) was performed using an internet-based service to ensure allocation concealment, with minimisation by hostel size and historical screening uptake. BLINDING: Only the study statistician was blinded to the allocation of intervention or control arms. PRIMARY OUTCOME: The primary outcome was the number of eligible clients at a hostel venue screened for active pulmonary tuberculosis by the mobile X-ray unit. RESULTS: A total of 59 hostels were considered for eligibility and 46 were randomised. Control sites had a total of 1192 residents, with a median uptake of 45% (IQR 33-55). Intervention sites had 1150 eligible residents with a median uptake of 40% (IQR 25-61). Using Poisson regression to account for the clustered study design, hostel size and historical screening levels, there was no evidence that peer educators increased uptake (adjusted risk ratio 0.98; 95% CIs 0.80 to 1.20). The study team noted no adverse events. CONCLUSIONS: This study found no evidence that volunteer peer educators increased client uptake of mobile X-ray unit screening for tuberculosis. Further qualitative work should be undertaken to explore the possible ancillary benefits to peer volunteers. TRIAL REGISTRATION NUMBER: ISRCTN17270334.