A person-centred consultation intervention to improve shared decision-making about, and uptake of, osteoporosis medicines (iFraP): a pragmatic, parallel-group, individual randomised controlled trial protocol.

Background: Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person's life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations.Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods: The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion: The iFraP trial will answer important questions about the effectiveness of the new 'iFraP' osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration ISRCTN: 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407.

Background: For people with osteoporosis, broken bones (called 'fragility fractures') can occur from low or no trauma and cause significant disability. Medicines can strengthen bone and lower the chance of fragility fractures. However, many people who experience a fragility fracture do not start or continue taking osteoporosis medicines. People commonly choose not to take osteoporosis medicines because they are unsure what medicines are for, confused about fracture 'risk' and/or worried about side-effects. To address this, we developed the 'iFraP intervention': 1. The iFraP 'decision-support tool': to support patients and healthcare professionals talk together to make decisions about medicines2. iFraP training for healthcare professionals to:a. use the tool in appointments with patientsb. give understandable, clear and consistent information c. listen to and address patient concerns This trial investigates whether the iFraP intervention makes decision-making about osteoporosis medicines easier, and whether it is cost-effective, acceptable and practical to deliver. Methods: 380 patients will take part who will be 50 years and older and referred to a fracture prevention service, because they have broken a bone. Patients taking part will be allocated to receive either a usual NHS appointment or an appointment using the iFraP intervention. Patients will complete a questionnaire before their appointment, and 2 weeks and 3 months afterwards. Some patients will be asked if they consent to have their appointment recorded and/or be interviewed, to understand how the decision-support tool is being used, and patient's views of the iFraP intervention. Outputs: If successful, the iFraP intervention will benefit patients and the NHS by helping patients make decisions about osteoporosis medicine. If the iFraP intervention increases the number of people with osteoporosis that start and continue taking osteoporosis medicines, iFraP will lower the number of future fractures, and reduce the negative outcomes that result from fractures (e.g. significant disability).

Rapid qualitative analysis of recruitment obstacles in the FORVAD (Posterior Cervical Foraminotomy surgery versus Anterior Cervical Discectomy surgery in the treatment of cervical brachialgia) randomised, controlled trial.

BACKGROUND: The number of surgical trials is increasing but such trials can be complex to deliver and pose specific challenges. A multi-centre, Phase III, RCT comparing Posterior Cervical Foraminotomy versus Anterior Cervical Discectomy and Fusion in the Treatment of Cervical Brachialgia (FORVAD Trial) was unable to recruit to target. A rapid qualitative study was conducted during trial closedown to understand the experiences of healthcare professionals who participated in the FORVAD Trial, with the aim of informing future research in this area. METHODS: Semi-structured interviews were conducted with 18 healthcare professionals who had participated in the FORVAD Trial. Interviews explored participants' experiences of the FORVAD trial. A rapid qualitative analysis was conducted, informed by Normalisation Process Theory. RESULTS: Four main themes were generated in the data analysis: (1) individual vs. community equipoise; (2) trial set-up and delivery; (3) identifying and approaching patients; and (4) timing of randomisation. The objectives of the FORVAD trial made sense to participants and they supported the idea that there was clinical or collective equipoise regarding the two FORVAD interventions; however, many surgeons had treatment preferences and lacked individual equipoise. The site which had most recruitment success had adopted a more structured process for identification and recruitment of patients, whereas other sites that adopted more "ad hoc" screening strategies struggled to identify patients. Randomisation on the day of surgery caused both medico-legal and practical concerns at some sites. CONCLUSIONS: Organisation and implementation of a surgical trial in neurosurgery is complex and presents many challenges. Sites often reported low recruitment and discussed the logistical issues of conducting a complex surgical RCT. Future trials in neurosurgery may need to offer more flexibility and time during set-up to maximise opportunities for larger recruitment numbers. Rapid qualitative analysis informed by Normalisation Process Theory was able to quickly identify key issues with trial implementation so rapid qualitative analysis may be a useful approach for teams conducting qualitative research in trials. TRIAL REGISTRATION: ISRCTN, ISRCTN reference: 10,133,661. Registered 23rd November 2018.

Protocol of a cost-effectiveness analysis of a combined intervention for depression and parenting compared with enhanced standard of care for perinatally depressed, HIV-positive women and their infants in rural South Africa.

INTRODUCTION: Poverty, HIV and perinatal depression represent a triple threat to public health in sub-Saharan Africa because of their combined negative effects on parenting and child development. In the resource-constrained context of low-income and middle-income countries, a lay-counsellor-delivered intervention that combines a psychological and parenting intervention could offer the potential to mitigate the consequences of perinatal depression while also optimising scarce resources for healthcare.Measuring the cost-effectiveness of such a novel intervention will help decision-makers to better understand the relative costs and effects associated with replicating the intervention, thereby supporting evidence-based decision-making. This protocol sets out the methodological framework for analysing the cost-effectiveness of a cluster randomised controlled trial (RCT) that compares a combined intervention to enhanced standard of care when treating depressed, HIV-positive pregnant women and their infants in rural South Africa. METHODS AND ANALYSIS: This cost-effectiveness analysis (CEA) protocol complies with the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. A societal perspective will be chosen.The proposed methods will determine the cost and efficiency of implementing the intervention as per the randomised control trial protocol, as well as the cost of replicating the intervention in a non-research setting. The costs will be calculated using an appropriately adjusted version of the Standardised Early Childhood Development Costing Tool.Primary health outcomes will be used in combination with costs to determine the cost per improvement in maternal perinatal depression at 12 months postnatal and the cost per improvement in child cognitive development at 24 months of age. To facilitate priority setting, the incremental cost-effectiveness ratios for improvements in child cognitive development will be ranked against six other child cognitive-development interventions according to Verguet et al's methodology (2022).A combination of activity-based and ingredient-based costing approaches will be used to identify, measure and value activities and inputs for all alternatives. Outcomes data will be sourced from the RCT team. ETHICS AND DISSEMINATION: The University of Oxford is the sponsor of the CEA. Ethics approval has been obtained from the Human Sciences Research Council (HSRC, #REC 5/23/08/17), South Africa and the Oxford Tropical Research Ethics Committee (OxTREC #31-17), UK.Consent for publication is not applicable since no participant data are used in this protocol.We plan to disseminate the CEA results to key policymakers and researchers in the form of a policy brief, meetings and academic papers. TRIAL REGISTRATION DETAILS: ISRCTN registry #11 284 870 (14/11/2017) and SANCTR DOH-27-102020-9097 (17/11/2017).

Cognitive behavioural treatment for mild Alzheimer's patients and their caregivers (CBTAC): results of a randomised controlled trial.

OBJECTIVES: This study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer's dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms. METHOD: The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver. RESULTS: Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL. CONCLUSION: The results are very encouraging and support an adequately powered multicentre study.Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011.

Effects of a waiting list control design on alcohol consumption among online help-seekers: A randomised controlled trial.

BACKGROUND: Indirect evidence suggests that using waiting list control designs in behavioural research may have unintended consequences. The aim of this study was to estimate the effects of a waiting list design on alcohol consumption among individuals who had looked online for help. METHODS: A two-arm randomised controlled trial was employed. The intervention group was informed that they belonged to the intervention group and would receive immediate access to a digital alcohol intervention. The waiting list control group was informed that they belonged to the group that had to wait four weeks to be given access to the intervention and in the meantime, they would be given a summary of their drinking. However, both groups received immediate access to the same digital alcohol intervention; the experimental contrast was thus between being told to wait or not. RESULTS: We randomised 3388 participants (intervention: 1692, waiting list: 1696). Data were available for 954 participants at 1-month follow-up. We found no strong evidence that alcohol consumption differed between groups, but the evidence pointed towards the intervention group reporting lowering weekly alcohol consumption compared to the waiting list control group (IRR = 0.95, 95 % CI = 0.83; 1.08, probability of effect = 78.8 %). CONCLUSION: We found no strong evidence that being informed that access to an intervention would be delayed produced differential self-reported alcohol consumption compared to being informed that access would be immediate. We did find a difference in engagement with the intervention materials, indicating that the experimental manipulation was successful.

Allied rehabilitation using caregiver-mediated exercises combined with telerehabilitation for stroke (ARMed4Stroke): A randomised controlled trial.

OBJECTIVE: To assess the added value of caregiver-mediated exercises combined with telerehabilitation in addition to usual care compared to usual care alone on the self-reported mobility outcome after subacute stroke. DESIGN: Multicentre, observer-blinded, parallel randomised controlled trial. An off-site researcher allocated treatments using minimisation. SETTING: Four rehabilitation centres in the Netherlands. PARTICIPANTS: Forty-one patient-caregiver dyads within 3 months poststroke. INTERVENTION: Eight-week blended care program with caregiver-mediated mobility exercises for 2.5 h per week supported by telerehabilitation and four face-to-face sessions in addition to usual care. MAIN MEASURES: Self-reported mobility domain of the Stroke Impact Scale postintervention. Secondary outcomes were functional outcome, dyads' psychosocial wellbeing, care transition to the community postintervention and after 6 months. RESULTS: Forty-one dyads (21 intervention, 20 control) were randomised, and 37 (N = 18; N = 19) were analysed following intention-to-treat. The Stroke Impact Scale mobility was not significantly different between groups postintervention (B 0.8, 95% CI -6.8-8.5, p = 0.826). The secondary outcomes, namely, (a) caregivers' quality of life postintervention (p = 0.013), (b) caregivers' symptoms of depression postintervention (p = 0.025), and (c) independence in leisurely activities at 6 months (p = 0.024), showed significant benefits in favour of caregiver-mediated exercises with telerehabilitation. A significant difference favouring controls was found in self-reported muscle strength at 6 months (p = 0.002). CONCLUSIONS: Caregiver-mediated exercises combined with telerehabilitation yielded no differential effect on our primary outcome self-reported mobility. Although the trial is underpowered, current findings are in line with previous trials. Future studies should further explore beneficial effects of caregiver involvement in stroke rehabilitation targeting psychosocial wellbeing.

Significance of phosphoinositide 3-kinase inhibitors in advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: The Phosphoinositide 3-kinase (PI3K) inhibitors may be used in cancer progression and mortality along with standard therapy to improve therapeutic efficacy of Advanced Breast Cancer (ABC). PURPOSE: This systematic review and meta- analysis were conducted to understand the therapeutic and toxicity profile of PI3K inhibitors in ABC. METHODS: The electronic databases were searched for suitable trials as per the criteria. The outcomes assessed were Progression- Free Survival, Objective Response Rate and Disease Control Rate. The data were systematically reviewed and meta-analyzed by Mantele- Haenszel method. RESULTS: Seven studies were included in the systematic review and meta- analysis. The co- administration of PI3K inhibitors with standard therapy improved the Progression- Free Survival significantly, while a marginal improvement was observed in Objective Response Rate, no difference in Disease Control Rate and toxicity significantly increased. CONCLUSIONS: The addition of PI3K inhibitors decreased the risk of progression but increased the risk of toxicity.

Promoting resilience in mental health nurses: A partially clustered randomised controlled trial.

BACKGROUND: There is a critical global shortage of nurses in mental health, with workforce attrition due in large part to workplace stressors. Proactive strengths-based interventions to strengthen nurses' capacity to manage stress and improve mental health, wellbeing and resilience may also support workforce retention. OBJECTIVE: To determine the effects of a resilience-building programme on mental health nurses' coping self-efficacy (primary outcome), and psychological distress, wellbeing, resilience, posttraumatic growth, emotional intelligence behaviours, workplace belonging, and turnover intention (secondary outcomes). DESIGN: Partially clustered randomised controlled trial. SETTING: Large tertiary metropolitan mental health service in Australia. PARTICIPANTS: A total of 144 registered and enrolled nurses working clinically ≥0.6 full-time equivalent (73/intervention, 71/control), with 122 completing 3-month follow-up. METHODS: The Promoting Resilience in Nurses programme is an evidence-based workplace intervention delivered by trained facilitators across two workshops. Surveys were administered online upon registration and prior to randomisation (Time 1) into Intervention or Control (no intervention) arms, and immediately after the final workshop (Time 2), and at three months follow-up (Time 3). Linear mixed models for outcome measures were fitted to Time 2 and 3 responses. RESULTS: There were seven intervention groups, with seven to 13 participants per group. Coping self-efficacy improved at Time 2 (estimated intervention effect 21.2 units, 95 % Confidence Intervals: 13.3 to 29.0) and Time 3 (12.1 units, 4.7 to 19.6), as well as wellbeing (Time 2: 9.2 units, 5.0 to 13.4), resilience (Time 2: 0.24 units, 0.01 to 0.46) and posttraumatic growth (Time 2: 16.1 units, 7.0 to 25.3). Psychological distress reduced (Time 2: -3.7 units, -6.2 to -1.31). All were sustained at three months. Emotional intelligence behaviours were improved (Time 2: 3.5 units, 0.6 to 6.5) but not sustained. Workplace belonging improved at Time 3 (0.34 units, 0.02 to 0.65) only. No statistically significant effects for turnover intention. CONCLUSIONS: Despite major contextual challenges, the Promoting Resilience in Nurses programme achieved the aims of promoting nurses' efficacy to cope with stress and regulate their emotions and improving mental health and wellbeing. The findings support the programme as a feasible and successful intervention for nurses across other settings and contexts. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12620001052921). Registered 15/10/2020. First recruitment 04/02/2021. TWEETABLE ABSTRACT: Promoting Resilience in Nurses intervention improved coping self-efficacy, wellbeing, resilience, posttraumatic growth, emotional intelligence and psychological distress.

BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial.

OBJECTIVES: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19. DESIGN: Phase III double blind randomised controlled trial. SETTING: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic. PARTICIPANTS: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG. INTERVENTION: Randomised 1:1 using a web-based procedure to receive a single 0.1mL intradermal dose of BCG-Denmark (BCG group, n=1999) or saline (placebo group, n=1989). MAIN OUTCOME MEASURES: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12-months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion). RESULTS: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6% to 24.5%) compared with the placebo group (19.6%; 95%CI 17.6% to 21.5%); adjusted difference +3.0 percentage points (95%CI 0.2% to 5.8%; p=0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95%CI 9.5% to 12.4%) compared with 9.6% in the placebo group (95%CI 8.3% to 11.1%); adjusted difference +1.3 percentage points (95%CI -0.7% to 3.3%, p=0.2). Breakthrough COVID-19 (post COVID-19 vaccination), and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95%CI 0.60 to 4.02, p=0.4) and two deaths due to COVID-19, both in the placebo group. CONCLUSIONS: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among health care workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.

Nordic inflammatory bowel disease treatment strategy trial: protocol for the NORDTREAT randomised controlled biomarker-strategy trial.

INTRODUCTION: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. METHODS AND ANALYSIS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. ETHICS AND DISSEMINATION: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.

A case management strategy to reduce falls in older people with a history of falls: A randomized controlled trial.

The present study aimed to determine whether a remotely delivered intervention, based on an individual case management, can reduce falls and their consequences in community-dwelling older people with a history of multiple falls. In this randomized controlled trial, 32 participants were randomized to the intervention group, which comprised a 16-week case management program involving a multidimensional assessment, targeted interventions according to the identified fall risk factors, and development of individualized care plans. The intervention was performed by trained gerontologists, under weekly supervision of professionals with experience in falls. The control group (n = 30) received usual care. Falls were monitored over 12 months with monthly falls calendars and telephone calls. Remotely delivered case management presented an 82 % uptake of recommendations. There was a trend toward a reduced fall incidence in the intervention vs control group, with lower fall, fall injury and fracture rates in the intervention group compared with the control group at both the 16-week and 12-month time-points, with the difference statistically significant for injurious fall rates at 12 months - IRR=0.18 (95 % CI = 0.04 to 0.74).

Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial.

BACKGROUND: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. OBJECTIVE: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. DESIGN: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. SUBJECTS: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). MEASUREMENTS: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. RESULTS: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. CONCLUSION: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.

Study protocol for an adaptive, multi-arm, multi-stage (MAMS) randomised controlled trial of brief remotely delivered psychosocial interventions for people with serious mental health problems who have experienced a recent suicidal crisis: Remote Approaches to Psychosocial Intervention Delivery (RAPID).

BACKGROUND: People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. METHODS: A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). DISCUSSION: There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. TRIAL REGISTRATION: ISRCTN33079589. Registered on June 20, 2022.

Statistical analysis plan for cluster randomised trial to evaluate a community-level complementary food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study.

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 AND DESIGN: 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. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) register: ISRCTN14390796 . Registered on 13 December 2021.

Effect of low-cost kitchen with improved cookstove on birthweight of neonates in Shahjadpur, Bangladesh: a cluster-randomised controlled trial.

Background: 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. Methods: 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). Findings: 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. Interpretation: 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. Funding: Grand Challenges Canada: Rising Stars in Global Health Programme.

Randomised controlled trials in vascular access devices in emergency departments: a scoping review protocol.

BACKGROUND: The significance of vascular access devices for patients in the emergency department (ED) is undeniable. When it comes to evaluating the effectiveness of interventions, randomised controlled trials (RCTs) stand out as the most reliable sources of evidence compared with other study designs. AIM: To explore and synthesise the findings from RCTs related to vascular access devices in the ED setting. METHODS: A systematic search will be conducted in electronic medical databases including the Cochrane Central Register of Controlled Trials, Pubmed, CINAHL and Embase databases. All RCTs focusing on peripheral intravenous catheters, central venous catheters and intraosseous catheters, published in English and Chinese in peer-reviewed journals within the past decade, will be included. CONCLUSION: This scoping review will summarise the current state of evidence for vascular access devices in the ED setting. This will identify gaps in the literature and, in turn, assist clinicians and researchers in pinpointing areas for future exploration and provide a valuable guide for future research.

Components of pharmacist-led medication reviews and their relationship to outcomes: a systematic review and narrative synthesis.

INTRODUCTION: Pharmacist-led medication reviews are an established intervention to support patients prescribed multiple medicines or with complex medication regimes. For this systematic review, a medication review was defined as 'a consultation between a pharmacist and a patient to review the patient's total medicines use with a view to improve patient health outcomes and minimise medicines-related problems'. It is not known how varying approaches to medication reviews lead to different outcomes. AIM: To explore the common themes associated with positive outcomes from pharmacist-led medication reviews. METHOD: Randomised controlled trials of pharmacist-led medication reviews in adults aged 18 years and over were included. The search terms used in MEDLINE, EMBASE and Web of Science databases were "medication review", "pharmacist", "randomised controlled trial" and their synonyms, time filter 2015 to September 2023. Studies published before 2015 were identified from a previous systematic review. Risk of bias was assessed using the Cochrane risk of bias 2 tool. Descriptions of medication reviews' components, implementation and outcomes were narratively synthesised to draw out common themes. Results are presented in tables. RESULTS: Sixty-eight papers describing 50 studies met the inclusion criteria. Common themes that emerged from synthesis include collaborative working which may help reduce medicines-related problems and the number of medicines prescribed; patient involvement in goal setting and action planning which may improve patients' ability to take medicines as prescribed and help them achieve their treatment goals; additional support and follow-up, which may lead to improved blood pressure, diabetes control, quality of life and a reduction of medicines-related problems. CONCLUSION: This systematic review identified common themes and components, for example, goal setting, action planning, additional support and follow-up, that may influence outcomes of pharmacist-led medication reviews. Researchers, health professionals and commissioners could use these for a comprehensive evaluation of medication review implementation. PROSPERO REGISTRATION NUMBER: CRD42020173907.

Developing and testing personalised nutrition feedback for more sustainable healthy diets: the MyPlanetDiet randomised controlled trial protocol.

PURPOSE: Agriculture and food production contribute to climate change. There is mounting pressure to transition to diets with less environmental impact while maintaining nutritional adequacy. MyPlanetDiet aimed to reduce diet-related greenhouse gas emissions (GHGE) in a safe, nutritionally adequate, and acceptable manner. This paper describes the trial protocol, development, and testing of personalised nutrition feedback in the MyPlanetDiet randomised controlled trial (RCT). METHODS: MyPlanetDiet was a 12-week RCT that provided standardised personalised nutrition feedback to participants based on new sustainable healthy eating guidelines (intervention) or existing healthy eating guidelines (control) using decision trees and corresponding feedback messages. To test the personalised nutrition feedback, we modelled a sample of 20 of the MyPlanetDiet participants baseline diets. Diets were modelled to adhere to control and intervention decision trees and feedback messages. Modelled nutrient intakes and environmental metrics were compared using repeated measure one-way analysis of covariance. RESULTS: Intervention diets had significantly lower (p < 0.001) diet-related GHGE per 2500 kilocalories (kcal) (4.7 kg CO2-eq) relative to control (6.6 kg CO2-eq) and baseline (7.1 kg CO2-eq). Modelled control and intervention diets had higher mean daily intakes of macronutrients (carbohydrates, fibre, and protein) and micronutrients (calcium, iron, zinc, and iodine). Modelled control and intervention diets had lower percent energy from fat and saturated fat relative to baseline. CONCLUSIONS: Adherence to the MyPlanetDiet personalised nutrition feedback would be expected to lead to better nutrient intakes and reduced diet-related GHGE. The MyPlanetDiet RCT will test the effectiveness and safety of personalised feedback for a more sustainable diet. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Clinical trials registration number: NCT05253547, 23 February 2022.