Summary Background Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory therapy for faecal incontinence. Data from case series suggest it has beneficial outcomes in 50–80% patients; ...however its effectiveness against sham electrical stimulation has not been investigated. We therefore aimed to assess the short-term efficacy of PTNS against sham electrical stimulation in adults with faecal incontinence. Methods We did a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal NeuromodulaTion CONFIDeNT) in 17 specialist hospital units in the UK that had the skills to manage patients with faecal incontinence. Eligible participants aged 18 years or older with substantial faecal incontinence for whom conservative treatments (such as dietary changes and pelvic floor exercises) had not worked, were randomly assigned (1:1) to receive either PTNS (via the Urgent PC neuromodulation system) or sham stimulation (via a transcutaneous electrical nerve stimulation machine to the lateral forefoot) once per week for 12 weeks. Randomisation was done with permuted block sizes of two, four, and six, and was stratified by sex and then by centre for women. Patients and outcome assessors were both masked to treatment allocation for the 14-week duration of the trial (but investigators giving the treatment were not masked). The primary outcome was a clinical response to treatment, which we defined as a 50% or greater reduction in episodes of faecal incontinence per week. We assessed this outcome after 12 treatment sessions, using data from patients' bowel diaries. Analysis was by intention to treat, and missing data were multiply imputed. This trial is registered with the ISRCTN registry, number 88559475, and is closed to new participants. Findings Between Jan 23, 2012, and Oct 31, 2013, we randomly assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the PTNS group and five from the sham group (mainly because they could not commit to receiving treatment every week). Two patients (one in each group) withdrew because of an adverse event that was unrelated to treatment (exacerbation of fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from bowel diaries in the PTNS group had a 50% or greater reduction in the number of episodes of faecal incontinence per week compared with 32 (31%) of 102 patients in the sham group (adjusted odds ratio 1·28, 95% CI 0·72–2·28; p=0·396). No serious adverse events related to treatment were reported in the trial. Seven mild, related adverse events were reported in each treatment group, mainly pain at the needle site (four in PTNS, three in sham). Interpretation PTNS given for 12 weeks did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Further studies are warranted to determine its efficacy in the long term, and in patient subgroups (ie, those with urgency). Funding National Institute for Health Research.
Summary Background Most clinicians have no training about domestic violence, fail to identify patients experiencing abuse, and are uncertain about management after disclosure. We tested the ...effectiveness of a programme of training and support in primary health-care practices to increase identification of women experiencing domestic violence and their referral to specialist advocacy services. Methods In this cluster randomised controlled trial, we selected general practices in two urban primary care trusts, Hackney (London) and Bristol, UK. Practices in which investigators from this trial were employed or those who did not use electronic records were excluded. Practices were stratified by proportion of female doctors, postgraduate training status, number of patients registered, and percentage of practice population on low incomes. Within every primary care trust area, we randomised practices with a computer-minimisation programme with a random component to intervention or control groups. The intervention programme included practice-based training sessions, a prompt within the medical record to ask about abuse, and a referral pathway to a named domestic violence advocate, who also delivered the training and further consultancy. The primary outcome was recorded referral of patients to domestic violence advocacy services. The prespecified secondary outcome was recorded identification of domestic violence in the electronic medical records of the general practice. Poisson regression analyses accounting for clustering were done for all practices receiving the intervention. Practice staff and research associates were not masked and patients were not aware they were part of a study. This study is registered at Current Controlled Trials, ISRCTN74012786. Findings We randomised 51 (61%) of 84 eligible general practices in Hackney and Bristol. Of these, 24 received a training and support programme, 24 did not receive the programme, and three dropped out before the trial started. 1 year after the second training session, the 24 intervention practices recorded 223 referrals of patients to advocacy and the 24 control practices recorded 12 referrals (adjusted intervention rate ratio 22·1 95% CI 11·5–42·4). Intervention practices recorded 641 disclosures of domestic violence and control practices recorded 236 (adjusted intervention rate ratio 3·1 95% CI 2·2–4·3). No adverse events were recorded. Interpretation A training and support programme targeted at primary care clinicians and administrative staff improved referral to specialist domestic violence agencies and recorded identification of women experiencing domestic violence. Our findings reduce the uncertainty about the benefit of training and support interventions in primary care settings for domestic violence and show that screening of women patients for domestic violence is not a necessary condition for improved identification and referral to advocacy services. Funding Health Foundation.
This study (MEasurement Reactions In Trials) aimed to produce recommendations on how best to minimize bias from measurement reactivity (MR) in randomized controlled trials of interventions to improve ...health.
The MERIT study consisted of: (1) an updated systematic review that examined whether measuring participants had effects on participants’ health-related behaviors, relative to no-measurement controls, and three rapid reviews to identify: (i) existing guidance on MR; (ii) existing systematic reviews of studies that have quantified the effects of measurement on behavioral or affective outcomes; and (iii) studies that have investigated the effects of objective measurements of behavior on health-related behavior; (2) a Delphi study to identify the scope of the recommendations; and (3) an expert workshop in October 2018 to discuss potential recommendations in groups.
Fourteen recommendations were produced by the expert group to: (1) identify whether bias is likely to be a problem for a trial; (2) decide whether to collect data about whether bias is likely to be a problem; (3) design trials to minimize the likelihood of this bias.
These recommendations raise awareness of how and where taking measurements can produce bias in trials, and are thus helpful for trial design.
Summary Background Depression is common and is associated with poor outcomes among elderly care-home residents. Exercise is a promising low-risk intervention for depression in this population. We ...tested the hypothesis that a moderate intensity exercise programme would reduce the burden of depressive symptoms in residents of care homes. Methods We did a cluster-randomised controlled trial in care homes in two regions in England; northeast London, and Coventry and Warwickshire. Residents aged 65 years or older were eligible for inclusion. A statistician independent of the study randomised each home (1 to 1·5 ratio, stratified by location, minimised by type of home provider local authority, voluntary, private and care home, private and nursing home and size of home <32 or ≥32 residents) into intervention and control groups. The intervention package included depression awareness training for care-home staff, 45 min physiotherapist-led group exercise sessions for residents (delivered twice weekly), and a whole home component designed to encourage more physical activity in daily life. The control consisted of only the depression awareness training. Researchers collecting follow-up data from individual participants and the participants themselves were inevitably aware of home randomisation because of the physiotherapists' activities within the home. A researcher masked to study allocation coded NHS routine data. The primary outcome was number of depressive symptoms on the geriatric depression scale-15 (GDS-15). Follow-up was for 12 months. This trial is registered with ISRCTN Register, number ISRCTN43769277. Findings Care homes were randomised between Dec 15, 2008, and April 9, 2010. At randomisation, 891 individuals in 78 care homes (35 intervention, 43 control) had provided baseline data. We delivered 3191 group exercise sessions attended on average by five study participants and five non-study residents. Of residents with a GDS-15 score, 374 of 765 (49%) were depressed at baseline; 484 of 765 (63%) provided 12 month follow-up scores. Overall the GDS-15 score was 0·13 (95% CI −0·33 to 0·60) points higher (worse) at 12 months for the intervention group compared with the control group. Among residents depressed at baseline, GDS-15 score was 0·22 (95% CI −0·52 to 0·95) points higher at 6 months in the intervention group than in the control group. In an end of study cross-sectional analysis, including 132 additional residents joining after randomisation, the odds of being depressed were 0·76 (95% CI 0·53 to 1·09) for the intervention group compared with the control group. Interpretation This moderately intense exercise programme did not reduce depressive symptoms in residents of care homes. In this frail population, alternative strategies to manage psychological symptoms are required. Funding National Institute for Health Research Health Technology Assessment.
Little research has been done into the effectiveness of mental health supported accommodation services. We did a national survey to investigate provision and costs of services and assess service user ...quality of life and outcomes across England.
We randomly sampled three types of services from 14 nationally representative regions-residential care, supported housing, and floating outreach-and recruited up to ten service users per service. Service quality and costs and service users' quality of life, autonomy, and satisfaction with care were assessed in a standardised manner with validated tools and compared by multilevel modelling.
619 service users were recruited from 22 residential care, 35 supported housing, and 30 floating outreach services. Those in residential care and supported housing had more severe mental health problems than those in floating outreach. 348 (57%) were assessed as being at risk of severe self-neglect and 229 (37%) as being vulnerable to exploitation in the previous 2 years. Residential care was most expensive but provided for people with the greatest needs. The mean annual budget was £466 687 for residential care (range £276 000-777 920), compared with £365 452 for supported housing (£174 877-818 000), and £172 114 for floating outreach (£17 126-491 692). Quality of care was best in supported housing. People in supported housing and floating outreach were more socially included but experienced more crime than those in residential care. After adjustment for service quality and service user sociodemographic and clinical factors, quality of life was similar for service users in residential care and supported housing (mean difference -0·138, 95% CI -0·402 to 0·126, p=0·306) and lower for those in floating outreach than in residential care (-0·424, -0·734 to -0·114, p=0·007). However, autonomy was greater for those in supported housing than for those in residential care (0·145, 0·010 to 0·279, p=0.035). Satisfaction with care was similar across services.
Supported housing might be cost-effective, but the benefits need to be weighed against the risks associated with increased autonomy.
National Institute for Health Research.
The effectiveness of intermittent montelukast for wheeze in young children is unclear. We aimed to assess whether intermittent montelukast is better than placebo for treatment of wheeze in this age ...group. Because copy numbers of the Sp1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter (either 5/5, 5/x, or x/x, where x does not equal 5) modifies response to montelukast in adults, we stratified by this genotype.
We did this multicentre, parallel-group, randomised, placebo-controlled trial between Oct 1, 2010, and Dec 20, 2013, at 21 primary care sites and 41 secondary care sites in England and Scotland. Children aged 10 months to 5 years with two or more wheeze episodes were allocated to either a 5/5 or 5/x+x/x ALOX5 promoter genotype stratum, then randomly assigned (1:1) via a permuted block schedule (size ten), to receive intermittent montelukast or placebo given by parents at each wheeze episode over a 12 month period. Clinical investigators and parents were masked to treatment group and genotype strata. The primary outcome was number of unscheduled medical attendances for wheezing episodes. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01142505.
We randomly assigned 1358 children to receive montelukast (n=669) or placebo (n=677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups (mean 2·0 SD 2·6 vs 2·3 2·7; incidence rate ratio IRR 0·88, 95% CI: 0·77–1·01; p=0·06). Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum (2·0 2·7 vs 2·4 3·0; IRR 0·80, 95% CI 0·68–0·95; p=0·01), but not in those in the 5/x+x/x stratum (2·0 2·5 vs 2·0 2·3; 1·03, 0·83–1·29; p=0·79, pinteraction=0·08). We recorded one serious adverse event, which was a skin reaction in a child allocated to placebo.
Our findings show no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup.
Medical Research Council (UK) and National Institute for Health Research.
Summary Background Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of ...adjunctive vitamin D on sputum culture conversion are absent. Methods We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D3 or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for Taq I and Fok I polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D3 . This trial is registered with ClinicalTrials.gov number NCT00419068. Findings 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90–2·16; p=0.14). Taq I genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction =0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36–48·01; p=0·02). Fok I genotype did not modify the effect of vitamin D supplementation (pinteraction =0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6–88·2; p<0·0001). Interpretation Administration of four doses of 2·5 mg vitamin D3 increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. Funding British Lung Foundation.
Summary Background Tuberculosis is re-emerging as an important health problem in industrialised countries. Uncertainty surrounds the effect of public-health control options. We therefore aimed to ...assess a programme to promote screening for tuberculosis in a UK primary health care district. Methods In a cluster randomised controlled trial, we randomised 50 of 52 (96%) eligible general practices in Hackney, London, UK, to receive an outreach programme that promoted screening for tuberculosis in people registering in primary care, or to continue with usual care. Screening was verbal, and proceeded to tuberculin skin testing, if appropriate. The primary outcome was the proportion of new cases of active tuberculosis identified in primary care. Analyses were done on an intention-to-treat basis. This study was registered at clinicaltrials.gov , number NCT00214708. Findings Between June 1, 2002, and Oct 1, 2004, 44 986 and 48 984 patients registered with intervention and control practices, respectively. In intervention practices 57% (13 478 of 23 573) of people attending a registration health check were screened for tuberculosis compared with 0·4% (84 of 23 051) in control practices. Intervention practices showed increases in the diagnosis of active tuberculosis cases in primary care compared with control practices (66/141 47% vs 54/157 34%, odds ratio (OR) 1·68, 95% CI 1·05–2·68, p=0·03). Intervention practices also had increases in diagnosis of latent tuberculosis (11/59 19% vs 5/68 9%, OR 3·00, 0·98–9·20, p=0·055) and BCG coverage (mean BCG rate 26·8/1000 vs 3·8/1000, intervention rate ratio 9·52, 4·0–22·7, p<0·001). Interpretation Our educational intervention for promotion of screening for tuberculosis in primary care improved identification of active and latent tuberculosis, and increased BCG coverage. Yield from screening was low, but was augmented by improved case-finding. Screening programmes in primary care should be considered as part of tuberculosis control initiatives in industrialised countries.
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