UNASSIGNED: Smoke from biomass fuels used for cooking in traditional cookstoves contains a variety of health-damaging pollutants. Inhalation of these pollutants by pregnant women has been linked to abnormal foetal development and adverse pregnancy outcomes, including low birthweight (LBW). There is a dearth of data on environmental interventions that have the potential to reduce exposure to biomass fuel during pregnancy and improve birth outcomes. International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) therefore, designed a low-cost kitchen with an improved cookstove and examined the impact of this intervention on the birthweight of neonates.
UNASSIGNED: icddr,b conducted a cluster-randomised controlled trial of a \'low-cost kitchen with improved cookstove\' intervention among 1,267 pregnant women who used traditional cookstoves in a rural sub-district of Bangladesh. All participants were enrolled during the first trimester of pregnancy among 104 randomly selected clusters after obtaining informed consent. The model kitchens were installed in 628 participants\' households of the intervention group, and 639 participants continued to use traditional cookstoves as the control group. The primary outcome was the proportion of LBW neonates between the intervention and control groups. The study also examined if the intervention would reduce CO exposure, measured by the differences in maternal blood carbon monoxide saturation (SpCO) levels and prevalence of LBW in neonates. We performed a generalized structural equation model for jointly assessing the simultaneous relationships of biomass fuel exposure to LBW of neonates and the relationships of LBW of neonates to maternal blood SpCO level. This trial was registered with ClinicalTrials.gov (NCT02923882).
UNASSIGNED: We found that in the intervention group using \'low-cost kitchen with improved cookstove\', the risk of LBW reduced by 37% (adjusted risk ratio: 0.63, 95% CI [0.45, 0.89]). Between the second and third trimester, the mean maternal blood SpCO level was significantly reduced from 10.4% to 8.9% (p-value <0.01) in the intervention group but remained unchanged in the control group (11.6% and 11.5%). Of the total effects of the intervention on the risk of LBW, 48.3% was mediated through maternal blood SpCO level.
UNASSIGNED: The risk of LBW among rural neonates was reduced in the intervention group using \'low-cost kitchen with improved cookstove\', which may be attributed to the reduction in maternal blood SpCO level. Additional research is needed to identify other mechanisms through which biomass fuel exposure might lead to adverse pregnancy outcomes.
UNASSIGNED: Grand Challenges Canada: Rising Stars in Global Health Programme.

BACKGROUND: Diarrheal disease is a significant cause of morbidity and mortality in under-fives in many low- and middle-income countries. Changes in food safety, hygiene practices, and nutrition around the weaning period may reduce the risk of disease and improve infant development. The MaaCiwara study aims to evaluate the effectiveness of a community-based educational intervention designed to improve food safety and hygiene behaviours, as well as child nutrition. This update article describes the statistical analysis plan for the MaaCiwara study in detail.
METHODS: The MaaCiwara study is a parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures, involving 120 clusters of rural and urban communities. These clusters are randomised to either receive the community-based behaviour change intervention or to the control group. The study participants will be mother-child pairs, with children aged between 6 and 36 months. Data collection involves a day of observation and interviews with each participating mother-child pair, conducted at baseline, 4 months, and 15 months post-intervention. The primary analysis aims to estimate the effectiveness of the intervention on changes to complementary food safety and preparation behaviours, food and water contamination, and diarrhoea. The primary outcomes will be analysed generalised linear mixed models, at individual level, accounting for clusters and rural/urban status to estimate the difference in outcomes between the intervention and control groups. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. In addition, structural equation analysis will be conducted to examine the causal relationships between the different outcomes.
BACKGROUND: International Standard Randomised Controlled Trial Number (ISRCTN) register: ISRCTN14390796 . Registered on 13 December 2021.

BACKGROUND: This update outlines amendments to the CHAMPION2/STRIPES2 cluster randomised trial protocol primarily made due to the COVID-19 pandemic and nationwide lockdown in India in 2020. These amendments were in line with national guidelines for health research during the COVID-19 pandemic.
METHODS: We did not change the original trial design, eligibility, and outcomes. Amendments were introduced to minimise the risk of COVID-19 transmission and ensure safety and wellbeing of trial staff, participants, and other villagers. CHAMPION2 intervention: participatory learning and action (PLA) and fixed day service (FDS) meeting were revised to incorporate social distancing and hygiene precautions. During the COVID-19 pandemic, PLA participation was limited to pregnant women and birthing partners. STRIPES2 intervention: before/after-school classes were halted for a period and then modified temporarily (reducing class sizes, and/or changing meeting places) with hygiene and safe distancing practices introduced.
METHODS: The research team gathered as much information as possible from participants by telephone. If the participant had no telephone or could not be contacted by telephone, data were collected in person. COVID-19 precautions: trial teams were trained on COVID-19 precautions and used personal protective equipment whilst in the villages for trial-related activities. After restarting the trial between June and September 2020 in a phased manner, some trial activities were suspended again in all the trial villages from April to June 2021 due to the second wave of COVID-19 cases and lockdown imposed in Satna, Madhya Pradesh. Trial timelines were also revised, with outcomes measured later than originally planned.
BACKGROUND: Clinical Trial Registry of India CTRI/2019/05/019296. Registered 23 May 2019. https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MzExOTg=&Enc=&userName=champion2 .

BACKGROUND: The purpose of this study was to examine the effects of a brief family psychoeducation (BFP) programme provided by psychiatric visiting nurses on caregiver burden of family caregivers of people with schizophrenia through a cluster randomised controlled trial (cRCT).
METHODS: The study was a two-arm, parallel-group cRCT. Forty-seven psychiatric visiting nurse agencies were randomly allocated to the BFP programme group (intervention group) or treatment as usual group (TAU; control group). Caregivers of people with schizophrenia were recruited by psychiatric visiting nurses using a randomly ordered list. The primary outcome was caregiver burden, measured using the Japanese version of the Zarit Burden Interview. Outcome assessments were conducted at baseline, 1-month follow-up, and 6-month follow-up. Intention-to-treat analysis was conducted to examine the effects of the BFP programme on caregiver burden.
RESULTS: Thirty-four psychiatric visiting nurse agencies and 83 family caregivers of people with schizophrenia participated in the study. The participant attrition rate was less than 20%. Adherence to the program was 100%. Compared with TAU group, the BFP programme group had decreased caregiver burden. However, this improvement was not significant at 1-month follow-up (adjusted mean difference [aMD] = 0.27, 95% CI = - 5.48 to 6.03, p = 0.93, d = 0.01) or 6-month follow-up (aMD = - 2.12, 95% CI = - 7.80 to 3.56, p = 0.45, d = 0.11).
CONCLUSIONS: The BFP programme provided by psychiatric visiting nurses did not achieve significant decreases in caregiver burden. This result may be attributed to the difficulty in continuing the research due to the COVID-19 pandemic, which prevented us from achieving the targeted sample size necessary to meet the statistical power requirements, as well as to the participation of caregivers with relatively low burden. However, the program had the advantage of high adherence to treatment plan. Further studies should be conducted with a larger sample size and a more diverse sample that includes caregivers with a higher care burden.
BACKGROUND: The study protocol was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000038044) on 2019/09/18.

UNASSIGNED: Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery.
UNASSIGNED: The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care.
UNASSIGNED: This was a two-arm cluster randomised controlled trial.
UNASSIGNED: The trial was set in 30 NHS general practice sites in England.
UNASSIGNED: Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms.
UNASSIGNED: Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons\' patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention.
UNASSIGNED: The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms.
UNASSIGNED: A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of -1.81 points, 95% confidence interval -2.66 to -0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of -£29.99, 95% confidence interval -£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval -0.011 to 0.014).
UNASSIGNED: The intervention showed a small, sustained benefit for men\'s lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population..
UNASSIGNED: This trial is registered as ISRCTN11669964.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.
Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice’s usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice.

BACKGROUND: Pulmonary rehabilitation (PR) is a programme of exercise and education and the most effective treatment for the symptoms and disability associated with chronic obstructive pulmonary disease. However, the benefits of PR are limited by poor uptake and completion. This trial will determine whether using trained volunteer lay health workers, called \"PR buddies,\" improves uptake and completion of PR and is cost-effective. This trial protocol outlines the methods for evaluating effectiveness, cost-effectiveness, and acceptability.
METHODS: The IMPROVE trial is a pragmatic, open, cluster randomised controlled trial planned in 38 PR services across England and Wales. PR services will be randomised to either intervention arm-offering support from PR buddies to patients with chronic obstructive pulmonary disease-or to usual care as the control arm. PR staff in trial sites randomised to the intervention arm will receive training in recruiting and training PR buddies. They will deliver training to volunteers, recruited from among people who have recently completed PR in their service. The 3-day PR-buddy training programme covers communication skills, confidentiality, boundaries of the PR-buddy role and behaviour change techniques to help patients overcome obstacles to attending PR. An internal pilot will test the implementation of the trial in eight sites (four intervention sites and four in control arm). The primary outcome of the trial is the uptake and completion of PR. A process evaluation will investigate the acceptability of the intervention to patients, PR staff and the volunteer PR buddies, and intervention fidelity. We will also conduct a cost-effectiveness analysis.
CONCLUSIONS: Improving outcomes for chronic obstructive pulmonary disease and access to PR are priorities for the UK National Health Service (NHS) in its long-term plan. The trial hypothesis is that volunteer PR buddies, who are recruited and trained by local PR teams, are an effective and cost-effective way to improve the uptake and completion rates of PR. The trial is pragmatic, since it will test whether the intervention can be incorporated into NHS PR services. Information obtained in this trial may be used to influence policy on the use of PR buddies in PR and other similar services in the NHS.
BACKGROUND: ISRCTN12658458. Registered on 23/01/2023.

BACKGROUND: The Identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i) trial is being conducted to establish whether \'screening and intervention\', consisting of usual school practice plus a pathway comprising screening, feedback and a brief parent-led online intervention (OSI: Online Support and Intervention for child anxiety), bring clinical and health economic benefits compared to usual school practice and assessment only - \'usual school practice\', for children aged 8-9 years in the following: (1) the \'target population\', who initially screen positive for anxiety problems according to a two-item parent-report child anxiety questionnaire - iCATS-2, and (2) the \'total population\', comprising all children in participating classes. This article describes the detailed statistical analysis plan for the trial.
METHODS: iCATS-i2i is a definitive, superiority, pragmatic, school-based cluster randomised controlled trial (with internal pilot), with two parallel groups. Schools are randomised 1:1 to receive either screening and intervention or usual school practice. This article describes the following: trial objectives and outcomes; statistical analysis principles, including detailed estimand information necessary for aligning trial objectives, conduct, analyses and interpretation when there are different analysis populations and outcome measures to be considered; and planned main analyses, sensitivity and additional analyses.
BACKGROUND: ClinicalTrials.gov ISRCTN76119074. Registered on 4 January 2022.

Using four case studies, we aim to provide practical guidance and recommendations for the analysis of cluster randomised controlled trials.
Four modelling approaches (Generalized Linear Mixed Models with parameters estimated by maximum likelihood/restricted maximum likelihood; Generalized Linear Models with parameters estimated by Generalized Estimating Equations (1st order or second order) and Quadratic Inference Function, for analysing correlated individual participant level outcomes in cluster randomised controlled trials were identified after we reviewed the literature. We systematically searched the online bibliography databases of MEDLINE, EMBASE, PsycINFO (via OVID), CINAHL (via EBSCO), and SCOPUS. We identified the above-mentioned four statistical analytical approaches and applied them to four case studies of cluster randomised controlled trials with the number of clusters ranging from 10 to 100, and individual participants ranging from 748 to 9,207. Results were obtained for both continuous and binary outcomes using R and SAS statistical packages.
The intracluster correlation coefficient (ICC) estimates for the case studies were less than 0.05 and are consistent with the observed ICC values commonly reported in primary care and community-based cluster randomised controlled trials. In most cases, the four methods produced similar results. However, in a few analyses, quadratic inference function produced different results compared to the generalized linear mixed model, first-order generalized estimating equations, and second-order generalized estimating equations, especially in trials with small to moderate numbers of clusters.
This paper demonstrates the analysis of cluster randomised controlled trials with four modelling approaches. The results obtained were similar in most cases, however, for trials with few clusters we do recommend that the quadratic inference function should be used with caution, and where possible a small sample correction should be used. The generalisability of our results is limited to studies with similar features to our case studies, for example, studies with a similar-sized ICC. It is important to conduct simulation studies to comprehensively evaluate the performance of the four modelling approaches.

OBJECTIVE: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis.
METHODS: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion.
CONCLUSIONS: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice.
BACKGROUND: Netherlands Trial Registry (NL8852). Prospectively registered.

BACKGROUND: Older patients often experience safety issues when transitioning from hospital to home. The \'Your Care Needs You\' (YCNY) intervention aims to support older people to \'know more\' and \'do more\' whilst in hospital so that they are better prepared for managing at home.
METHODS: A multi-centre cluster randomised controlled trial (cRCT) will evaluate the effectiveness and cost-effectiveness of the YCNY intervention. Forty acute hospital wards (clusters) in England from varying medical specialities will be randomised to deliver YCNY or care-as-usual on a 1:1 basis. The primary outcome will be unplanned hospital readmission rates within 30 days of discharge. This will be extracted from routinely collected data of at least 5440 patients (aged 75 years and older) discharged to their own homes during the 4- to 5-month YCNY intervention period. A nested cohort of up to 1000 patients will be recruited to the study to collect secondary outcomes via follow-up questionnaires at 5-, 30- and 90-day post-discharge. These will include measures of patient experience of transitions, patient-reported safety events, quality of life and healthcare resource use. Unplanned hospital readmission rates at 60 and 90 days of discharge will be collected from routine data. A process evaluation (primarily interviews and observations with patients, carers and staff) will be conducted to understand the implementation of the intervention and the contextual factors that shape this, as well as the intervention\'s underlying mechanisms of action. Fidelity of intervention delivery will also be assessed across all intervention wards.
CONCLUSIONS: This study will establish the effectiveness and cost-effectiveness of the YCNY intervention which aims to improve patient safety and experience for older people during transitions of care. The process evaluation will generate insights about how the YCNY intervention was implemented, what elements of the intervention work and for whom, and how to optimise its implementation so that it can be delivered with high fidelity in routine service contexts.
BACKGROUND: UK Clinical Research Network Portfolio: 44559; ISTCRN: ISRCTN17062524. Registered on 11/02/2020.