Cluster-randomized Trial Research Articles

Acupuncture for hypoxic ischemic encephalopathy in neonates.

Peripartum asphyxia affects three to five per 1000 live births, with moderate or severe hypoxic ischemic encephalopathy (HIE) occurring in 0.5 to 1 per 1000 live births, and is associated with high mortality and morbidity. Therapeutic hypothermia is an effective treatment, but alternative therapies such as acupuncture are also used. To determine the benefits and harms of acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure) on mortality and morbidity in neonates with HIE, compared with 1) no treatment, 2) placebo or sham treatment, 3) any pharmacologic treatment, or 4) different types of acupuncture. We searched CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the WHO ICTRP in March 2023. We conducted a search of the grey literature to identify reports of trials conducted by or referenced in research by CORDIS EU, National Institute for Health and Care Excellence (NICE), and NHSGGC Paediatrics for Health Professionals. We also checked the reference lists of relevant articles to identify additional studies. We included randomized controlled trials (RCTs) or quasi-RCTs and cluster-randomized trials. We included studies where participants were term infants (37 weeks or greater) and late preterm infants (34 + 0 to 36 + 6 weeks' gestation) 10 days of age or less, with evidence of peripartum asphyxia. We included studies on acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure). We included studies where acupuncture was compared with: 1) no treatment; 2) placebo or sham treatment; 3) any pharmacologic treatment; or 4) different types of acupuncture. We used standard Cochrane methods. Our primary outcomes were all-cause mortality at the latest follow-up, major neurodevelopmental disability in children aged 18 to 24 months and aged 3 to 5 years, adverse events until hospital discharge, and length of hospital stay. We included four studies (enrolling 464 infants) that compared acupuncture with no treatment. The studies ranged in size from 60 to 200 infants. Three studies were conducted in China and one in Russia. None of the four studies reported on any of the prespecified outcomes of our review. We did not identify any ongoing studies. There is limited availability of studies addressing this specific population. The included studies did not assess mortality, long-term neurodevelopmental outcomes, or adverse effects of acupuncture. We are unable to draw any conclusions about the benefits and harms of acupuncture for HIE in neonates. In light of the current limitations, clinicians are urged to approach the use of acupuncture in neonates with HIE cautiously, as there is no evidence to support its routine application. The available trials assessed surrogate outcomes that have a relatively small impact on newborns, and failed to report important outcomes such as mortality and long-term neurodevelopmental outcomes. Other available trials were performed on older infants who had experienced neonatal HIE. Given the lack of available evidence, well-designed randomized controlled trials with relevant outcomes such as mortality and neurodevelopmental outcomes are essential to evaluate the efficacy and safety of acupuncture for HIE in neonates.

Interventions to improve pharmacists’ competency in chronic disease management: a systematic review of randomized controlled trials

IntroductionEffective chronic disease management (CDM) is vital for addressing chronic disease challenges. Given the importance of ensuring pharmacists’ competence in CDM, interventions targeting knowledge, skills, and attitudes are essential. Therefore, a comprehensive and up-to-date study is needed to analyze these interventions’ effect and potential development. Categorizing the interventions based on the Effective Practice and Organization of Care (EPOC) taxonomy is essential for better informing policymakers. The objectives of this systematic review were to identify interventions to improve pharmacists’ competency in chronic disease management based on the EPOC taxonomy and summarize their effectiveness.MethodsFollowing methods in the Cochrane Handbook, a systematic search was conducted up to April 2024 on MEDLINE and Scopus. The inclusion criteria were an intervention study with a randomized controlled trial (RCT) design published in English, targeting pharmacists, and measuring knowledge, skills, and attitudes in aspects of CDM. The risk of bias was assessed using Cochrane’s RoB 2 tool for either randomized or cluster-randomized trials. Findings are reported narratively and align with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsWe included 11 RCT studies that focused on various aspects of CDM among community and hospital pharmacists. Implementation strategies and combined implementation strategies–delivery arrangements interventions were identified. Six implementation strategies interventions consistently yielded effective results, with scores ranging from 0.99 to 9.17 (p < 0.05). However, the other two implementation strategies interventions reported mixed results, with no significant improvements in knowledge or skills. Two implementation strategies-delivery arrangements interventions showed improvements, with score differences ranging from 4.5% (95% CI: 1.6%-7.4%) to 30% (95% CI: 29%-40%). Conversely, one implementation strategies-delivery arrangements intervention showed no significant improvement. The risk of bias assessment revealed varying levels of bias across the studies.ConclusionsImplementation strategies and combined implementation strategies–delivery arrangements interventions improved pharmacists' competency in CDM. Most interventions consistently resulted in significant improvements in pharmacists' knowledge, skills, and attitudes. These findings underscore the potential of tailored, competency-based interventions to improve pharmacist competencies in CDM. Policymakers can use these insights to create guidelines and policies that promote ongoing professional development for pharmacists.

Training protocol and calibration of the International Caries Detection and Assessment System in a school-based clinical trial of elementary school-age children.

This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting. ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify dental caries lesion severity (0-6), lesion activity (active/inactive), and filling material (0-9) of all visually available primary and permanent tooth surfaces. Inter and intra-examiner reliability between each dental trainee and the "gold standard" trainer was evaluated using Kappa statistics. For lesion severity, the examination indicated an inter-rater weighted Kappa of 0.77 (95% CI 0.71-0.82) and 0.82 (95% CI 0.77-0.87) for each trainee examiner compared to the gold standard examiner. The Kappas increased slightly from the first to second examinations (lesion-weighted Kappa: 0.76 to 0.84 and 0.82 to 0.84). The intra-rater reliability indicated excellent reliability for lesion and filling (0.83 to 0.94) and moderate for activity (0.58). ICDAS training/calibration were essential to ensure accuracy and reliability of dental caries measurements. The study demonstrated that ICDAS training of dentists with no prior criteria experience is feasible in a community setting and can lead to high reliability and repeatability.

Implementation of Breathing Exercises at Home in Hypertension Patients in Adults Aged 36-45 Years

Hypertension is one of the diseases of the cardiovascular system that has high mortality and morbidity rates. High blood pressure in hypertensive patients can be treated with pharmacological and non-pharmacological therapy. One of the non-pharmacological therapies is deep breathing relaxation therapy. This study aims to determine the effectiveness of deep breathing relaxation therapy on reducing blood pressure in patients with hypertension. The sample in this study were patients with hypertension in Kelurahan Jawa, RT 19 and RT 26 Samarinda as many as 40 respondents. The design of this study was to use a Cluster-randomized trial design by conducting a cluster randomized controlled trial with a 1:1 community-based intervention and control group. The results of the study above show that the systolic blood pressure value before being given deep breathing relaxation therapy was 160.451 mmHg and the systolic blood pressure after being given deep breathing therapy was 130 mmHg. And the diastolic blood pressure before being given deep breathing therapy was 98 mmHg and the diastolic blood pressure after being given deep breathing therapy was 84.35 mmHg. In this study, the confidence level taken was 95% with 5% (0.05). Based on statistical analysis using paired sample T-test, the systolic blood pressure value was 0.001. This means that the value is smaller than 5% (0.05) so that H0 is rejected, which means that there is an effect of deep breathing relaxation therapy on reducing blood pressure in people with hypertension. The average systolic blood pressure value after being given deep breathing relaxation therapy was 30.46 mmHg and the average diastolic blood pressure after being given deep breathing relaxation therapy was 84.35 mmHg. There was a decrease in the respondents' blood pressure after being given deep breathing relaxation therapy, namely systolic blood pressure of 130 mmHg and diastolic blood pressure of 84.35 mmHg. Based on statistical analysis using paired sample T-test with a confidence level taken at 95% with 5% (0.05), the diastolic blood pressure value was 0.001 and the diastolic blood pressure value was 0.001. This shows that deep breathing relaxation therapy is effective in lowering blood pressure in hypertensive patients. This study recommends that deep breathing relaxation therapy is effective in lowering blood pressure (systolic and diastolic) in hypertensive patients.

Intraclass Correlation in Cluster Randomized Controlled Trials: A Meta-Analysis of Studies on Major Depression.

Though cluster randomized trials (CRTs) provide robust evidence for intervention by controlling contamination of interventions, there could be some loss of statistical efficiency. The Consolidated Standards of Reporting Trials (CONSORT) recommends reporting intraclass correlation coefficients (ICC) to understand this phenomenon, though not many studies follow this. This meta-analysis explored the compliance of CRTs in major depression for reporting ICC besides deriving the pooled ICC and pooled mean differences of intervention outcomes. Thirty-four articles on CRTs in major depression were identified from PubMed, Cochrane Library, PsychINFO, and Embase, and relevant data were extracted. Only 20 studies were eligible for meta-analysis of intervention, among which 8 reported ICC. We used DerSimonian and Laird's inverse variance method to calculate the pooled estimates. Only eight (40%) of the CRTs reported using ICC both for designing the study and examining intervention outcomes. The pooled ICC was 0.07 (95% confidence interval [CI]: 0.05, 0.09) with a low heterogeneity (I2 = 28%). Among the 20 studies, 65% used different psychosocial methods alone as intervention, with substantial heterogeneity. The pooled standardized mean difference of depression scores (-0.46; 95% CI: -0.79, -0.13) indicated the effectiveness of psychosocial interventions irrespective of combined pharmacotherapy (z = 2.71, p value = 0.01). Further, a subgroup analysis of intervention effects revealed that the results were significant only for the CRTs with ICC conformity. The ICCs can affect the intervention outcomes. Therefore, as indicated by this meta-analysis, CRTs must adhere to the CONSORT guidelines on reporting ICC. Future CRTs on major depression can utilize the pooled ICC estimate from this study, especially for sample size estimations.

Effect of a multicomponent, person-centred care intervention on client experience and HIV treatment outcomes in Zambia: a stepped-wedge, cluster-randomised trial.

Recipients of health services value not only convenience but also respectful, kind, and helpful providers. To date, research to improve person-centred HIV treatment has focused on making services easier to access (eg, differentiated service delivery) rather than the interpersonal experience of care. We developed and evaluated a person-centred care (PCC) intervention targeting practices of health-care workers. Using a stepped-wedge, cluster-randomised design, we randomly allocated 24 HIV clinics stratified by size in Zambia into four groups and introduced a PCC intervention that targeted caring aspects of the behaviour of health-care workers in one group every 6 months. The intervention entailed training and coaching for health-care workers on PCC practices (to capacitate), client experience assessment with feedback to facilities (to create opportunities), and small performance-based incentives (to motivate). In a probability sample of clients who were pre-trained on a client experience exit survey and masked to facility intervention status, we evaluated effects on client experience by use of mean score change and also proportion with poor encounters (ie, score of ≤8 on a 12-point survey instrument). We examined effects on missed visits (ie, >30 days late for next scheduled encounter) in all groups and retention in care at 15 months in group 1 and group 4 by use of electronic health records. We assessed effects on treatment success at 15 months (ie, HIV RNA concentration <400 copies per mL or adjudicated care status) in a prospectively enrolled subset of clients from group 1 and group 4. We estimated treatment effects with mixed-effects logistic regression, adjusting for sex, age, and baseline care status. This trial is registered at the Pan-African Clinical Trials Registry (202101847907585), and is completed. Between Aug 12, 2019, and Nov 30, 2021, 177 543 unique clients living with HIV made at least one visit to one of the 24 study clinics. The PCC intervention reduced the proportion of poor visits based on exit surveys from 147 (23·3%) of 632 during control periods to 33 (13·3%) of 249 during the first 6 months of intervention, and then to eight (3·5%) of 230 at 6 months or later (adjusted risk difference [aRD] for control vs ≥6 months intervention -16·9 percentage points, 95% CI -24·8 to -8·9). Among all adult scheduled appointments, the PCC intervention reduced the proportion of missed visits from 90 593 (25·3%) of 358 741 during control periods to 40 380 (22·6%) of 178 523 in the first 6 months, and then 52 288 (21·5%) of 243 350 at 6 months or later (aRD for control vs the intervention -4·2 percentage points, 95% CI -4·8 to -3·7). 15-month retention improved from 33 668 (80·2%) of 41 998 in control to 35 959 (83·6%) of 43 005 during intervention (aRD 5·9 percentage points, 95% CI 0·6 to 11·2), with larger effects in clients newly starting treatment (aRD 12·7 percentage points, 1·4 to 23·9). We found no effect on treatment success (based on viral load) in a nested subcohort (379 [83·7%] of 453 in the control phase vs 402 [83·8%] of 480 in the intervention phase; aRD 0·9 percentage points, -5·4 to 7·2). Improving the caring aspects of health-care worker behaviour is feasible in public health settings, enhances client experience, reduces missed appointments, and increases retention. The Bill & Melinda Gates Foundation.

Improving Lynch syndrome detection: a mixed-methods process evaluation of a hybrid type III effectiveness-implementation trial

IntroductionTranslating evidence-based practices into real-world healthcare settings is challenging, particularly in the rapidly evolving field of genomics. A pragmatic two-arm cluster-randomized clinical trial (Hide and Seek Project – HaSP) tested two implementation approaches for improving hereditary cancer referral practices with one key distinction: implementation strategies that were designed 1) explicitly using psychological theory, or 2) using healthcare professional intuition. This mixed-methods process evaluation aimed to provide insights into how and why change occurred by examining contextual determinants, identifying mechanisms of action, and exploring the role of theory.MethodsPost-implementation interviews were conducted with Implementation Leads and clinicians from participating HaSP sites. Transcripts were analysed using a mixed inductive and deductive approach, guided by the updated Consolidated Framework for Implementation Research (2.0). Findings were triangulated with other HaSP process evaluation data sources, including HaSP focus group observations, HaSP research team focus groups, MDT observations, and Implementation Lead project logs. Logic models and case studies were developed to articulate causal processes underlying strategy effectiveness and conditions necessary for implementation success.ResultsEighteen participants from seven HaSP sites were interviewed. Qualitative analysis identified themes related to Lynch syndrome complexity, pandemic disruptions, operational challenges, information technology constraints, multidisciplinary collaboration, cultural determinants, attitudes towards change, the value of theory, adaptations, and implementation support. Within these themes, a total of 39 contextual determinants were identified, with barriers and facilitators spanning 18 CFIR constructs across five domains. Logic models and case studies highlighted a number of mechanisms of action, producing variable clinical outcomes. Process evaluation findings, interpreted together with HaSP trial outcomes, indicate that theory-based implementation strategies may better support Lynch syndrome detection practices compared to intuition-based strategies.ConclusionsThe information gained from this process evaluation deepens understanding of the factors influencing the success of hospital-specific implementation strategies within the HaSP framework. Potential pathways for optimising the effectiveness of the overall HaSP implementation approach have been identified.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12618001072202. Registered 27 June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375348&isReview=true.

Factors associated with declining a menstrual cup among female students and their parents in Ugandan secondary schools: a cross-sectional study

IntroductionA greater choice of menstrual products may improve menstrual health (MH). This study assessed factors associated with declining consent to receive a menstrual cup by parents and female students participating...

The impact of a lifestyle promotion program on anthropometric and clinical manifestations in adolescents with polycystic ovarian syndrome: a randomized controlled trial

BackgroundLifestyle modification can have beneficial effects on improving symptoms of ovary syndrome and anthropometric changes, particularly in obese individuals… However, it is not clear whether these affects in obese adolescents with PCOS are the same as non-PCOS adolescents. We had a study question” Can lifestyle promotion programs, which focus on changing behavioral habits, have an effect on anthropometric parameters and the manifestation of polycystic ovary syndrome (PCOS) in adolescents?”MethodsThis was a cluster randomized trial (CRT) that started from January 2021 and follow-up ended in March 2022. 128 participants included adolescent girls (from 14 to 18 years old). The status of PCOS was determined for the participants, following which both the PCOS-afflicted and non-PCOS cohorts were subjected to randomization to either partake in a lifestyle promotion program or to proceed without it. This program included eight sessions that were designed to be implemented for two months. This intervention provides recommendations for a balanced diet and regular exercise, as well as advice on behavior change for adolescents, including those with PCOS, regardless of their weight. All participants were followed up for 12 months and were evaluated at three time points: baseline, 6 and 12 months. Outcomes included changes in the anthropometric indices (weight, hip and waist circumstance), regularity of menstrual cycle, hirsutism score by the modified-Ferriman-Gallwey scale, acne score by the Investigator’s Global Assessment Scale, hair loss scores by the Sinclair Graphic Instrument and then physical activity by the Caspian tool and dietary intake status by the Food Frequency Questionnaire. Data was analyzed using the non-parametric Mann-Whitney test for variables with two-time point assessments and generalized estimation equations (GEE) for variables with three time point assessments.ResultsIn the study, the intervention group of girls with PCOS exhibited a significant reduction in weight and waist circumference, with an average decrease of 3.14 kg and 4.68 cm, respectively (P < 0.001), compared to the PCOS control group. Similarly, the non-PCOS intervention group showed a decrease in these factors by 2.60 kg and 4.95 cm (P < 0.001) when compared to the non-PCOS control group. After 12 months of intervention, the odds ratio (OR) for menstrual regularity in the PCOS intervention group increased to 3.30 (95% CI: 2.06, 5.25), and the acne score significantly decreased with an OR of 0.46 (95% CI: 0.31, 0.70). In contrast, the non-PCOS intervention group experienced an increase in the OR for menstrual regularity to 2.45 (95% CI: 1.33, 4.25) and an improved in acne score with an OR of 0.44 (95% CI: 0.28, 0.69). No notable differences were observed in the nutritional status among all groups post-intervention. However, a significant increase in physical activity levels, measured in metabolic equivalent minutes per week (met/min/week), was recorded in both intervention groups (p < 0.05).ConclusionManifestations of PCOS in adolescents are improved by a lifestyle promotion program and high schools are considered an appropriate setting to identify those with PCOS and the implementation of a lifestyle modification program. This program was also shown to promote healthy lifestyles for non-PCOS adolescents.Trial registrationTrial registration number: irct.ir number: IRCT20200114046123N1.

Effect of vitamin C and hawthorn beverage formula on blood pressure and oxidative stress in heat-exposed workers: a cluster-randomized controlled trial.

There is no evidence on antioxidant-rich diets in preventing hypertension in heat-exposed workers. We aimed to evaluate the effects of formula supplemented with vitamin C (Vit C) and hawthorn beverage on reducing blood pressure (BP) and oxidative stress levels in heat-exposed workers. In the 40-day cluster-randomized controlled trial, four heat-exposed shift-teams were enrolled and randomly assigned to the intervention and control groups. The intervention group was given one Vit C tablet (130 mg) and a 500 mL hawthorn beverage containing 278.7 mg flavonoids daily whereas the control group was given 500 mL of slightly salted water daily; both groups were provided education on a healthy diet. BP and creatinine-corrected urinary 8-isoprostane-prostaglandin F2α (8-iso-PGF2α/Cr) concentrations were assessed at baseline, Day 17 (only BP) and Day 41, respectively. Compared with the control group, the systolic BP (SBP), diastolic BP (DBP), and log10-transformed 8-iso-PGF2α/Cr in the inter-vention group decreased by 7.41 mmHg, 7.93 mmHg and 0.232, respectively, from baseline to day 41 (all p<0.05). When comparing BP levels at baseline, DBP in the intervention group was reduced by 5.46 mmHg when compared to control (p<0.05) among participants with lower baseline BP; SBP and DBP experienced reductions of 9.74 and 9.22 mmHg among participants with higher baseline BP (both p<0.05). Supplementation of Vit C and flavonoids rich hawthorn beverage to heat-exposed workers prevented elevated BP caused by heat exposure which may be attributed to its oxidative stress inhibition effects.

Pathways from poverty to child mental health in Burkina Faso: Longitudinal mediation analyses in a cluster-randomized clinical trial

The study applies the Family Stress Model to examine the impact of an integrated intervention on the mental health of children facing chronic adversity in Burkina Faso. Its primary goal is to enhance understanding of individual and relational factors at the family level as mediators and specific mechanisms through which poverty reduction can impact child well-being. Cross-lagged autoregressive longitudinal mediation analyses tested the intervention effect on child mental health, examining maternal depression, maternal anxiety, harsh parenting, and child exposure to abuse as potential mediators. Longitudinal data were collected over the course of 24 months in a cluster-randomized controlled trial conducted among 360 dyads (children aged 10-15 and their female caregivers) in Burkina Faso. Participants were randomized into a control arm, economic intervention using the Graduation approach (Treatment Arm 1), or a combination of economic strengthening and family coaching (Treatment Arm 2). In Treatment Arm 1, maternal depression fully mediated the intervention effect on child's depression (B=-0.09, 95% confidence interval [CI] from-0.26 to-0.003) and child's self-esteem (B= 0.05, 95% CI from 0.001-0.18). In Treatment Arm 2, violent parenting practices partially mediated the intervention effect on child's depression (B=-0.08, 95% CI from-0.29 to-0.01). Our study underscores the importance of multifaceted interventions merging economic empowerment with family-focused child protection strategies. This approach fosters a supportive family environment, reducing children's vulnerability to mental health issues in resource-poor communities. It enriches our understanding of how parental economic and behavioral interventions impact child mental health outcomes.

Cost-effectiveness of integrating paediatric tuberculosis services into child healthcare services in Africa: a modelling analysis of a cluster-randomised trial

BackgroundIn 2021, over one million children developed tuberculosis, resulting in 214 000 deaths, largely due to inadequate diagnosis and treatment. The diagnosis and treatment of tuberculosis is limited in most...

Effect of a youth-led early childhood care and education programme on children's development and learning in rural Sindh, Pakistan (LEAPS): a stepped-wedge cluster-randomised implementation trial.

In low-income and middle-income countries, an estimated 181·9 million (74·6%) preschool-aged children do not receive adequate nurturing care in health, nutrition, protection, learning, and responsive care, thus jeopardising their healthy development across the life course. Working alongside the health sector, multisectoral actions including social protection and education are necessary to achieve child health and development outcomes. Innovations are needed to expand access to high-quality early childhood care and education (ECCE) for young children and opportunities for youth development. Youth Leaders for Early Childhood Assuring Children are Prepared for School (LEAPS) is a two-generation programme that trains female youth aged 18-24 years to deliver ECCE. We evaluated the effectiveness of LEAPS to improve children's school readiness when delivered at scale in rural Pakistan. We implemented a stepped-wedge cluster-randomised trial with three steps from Dec 3, 2018, to June 30, 2021. 99 villages (clusters) in four districts in rural Sindh, Pakistan, were randomly assigned (1:1:1) to introduce LEAPS across three steps. Eligible clusters were those that had a feeder primary school run by the National Commission for Human Development, a department of the Ministry of Federal Education and Professional Training; were safe; had space for a LEAPS preschool; could identify a female youth to deliver the ECCE service; and had not previously participated in the pilot study. Government partners trained female youth, aged 18-24 years, to provide community-based ECCE, enrolling up to 20 children, aged 3·5-5·0 years, per class. Population-based cross-sectional surveys were conducted at baseline and after each step for children who were eligible if they resided in the cluster, were aged 4·5-5·5 years at the time of the survey, and without any severe clinical health conditions or disability. The primary outcome was children's school readiness using the International Development and Early Learning Assessment (IDELA) composite score comprising emergent numeracy, emergent literacy, socio-emotional development, and motor skills. An intention-to-treat analysis was conducted, using linear mixed models accounting for clustering and the stepped-wedge design. The trial is registered with ClinicalTrials.gov (NCT03764436). LEAPS was implemented in 91 of 99 villages. In eight clusters, a LEAPS preschool could not be set up. For the intervention programme, the average enrolment of children in a LEAPS preschool was 19 (SD 3, range 12-20). A total of 3858 children (n=3852 with complete IDELA data) were assessed across the four survey rounds conducted between Jan 1, 2019, and March 31, 2021. LEAPS increased school readiness (standardised mean difference: 0·30 [95% CI 0·20-0·40]; p<0·0001) as compared with the control condition. LEAPS offers a scalable solution to expand access to high-quality ECCE and promote children's school readiness while providing employment for female youth in rural Pakistan and settings with similarly low ECCE participation. Dubai Cares; and Saving Brains, Grand Challenges Canada. For the Urdu translation of the abstract see Supplementary Materials section.

Leveraging Technology to Address Social-Emotional Learning during the Pandemic: Findings from an Efficacy Trial

We used a cluster-randomized controlled trial to examine the impacts of a technology- and game-based social-emotional program, the Adventures Aboard the S.S. GRIN (Adventures), on students’ social skills development. Eighty-eight third-grade classrooms (N=1,645 third-grade students) across four California public school districts were randomized to treatment or control. Analysis of student demographic data indicated that 49% were male, 51% were female, approximately one-third were Latinx, and about 50% qualified for free and reduced lunch. Two-level hierarchical linear model analysis results indicated that Adventures had significant and meaningful impacts on students’ social-emotional learning (SEL) skills. The findings of Adventures shine new lights on a growing effort to support all students, including those identified by their teachers as having social-emotional challenges. It also expands our knowledge about the potential role of technology in addressing SEL competencies.

Genomic insights for personalised care in lung cancer and smoking cessation: motivating at-risk individuals toward evidence-based health practices

Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardised PRS distributions across all ancestries. We validated our PRSs in 561,776 individuals of diverse ancestry from the GISC Trial, UK Biobank (UKBB), and All of Us Research Program (AoU). Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58-2.18) in UKBB and 2.39 (95% CI: 1.93-2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32-1.41) in UKBB and 1.32 (95% CI: 1.28-1.36) in AoU. Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations, which will be evaluated in two cluster-randomised clinical trials. This approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment. National Institutes of Health, NIH Intramural Research Program, National Science Foundation.

School-age growth and development following infant feeding and/or water, sanitation, and hygiene interventions in rural Zimbabwe: long-term follow-up of a cluster-randomised trial

Few trials have explored long-term effects of interventions designed to reduce child stunting. We evaluated school-age outcomes in rural Zimbabwean children who received cluster-randomised water, sanitation and hygiene (WASH) and/or infant and young child feeding (IYCF) interventions from pregnancy up to 18 months of age. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial enrolled pregnant women from two rural Zimbabwean districts (Chirumanzu and Shurugwi) between 2012 and 2015, and cluster-randomised them using a 2×2 factorial design to standard-of-care, WASH, IYCF, or combined WASH & IYCF, with a co-primary outcome of height-for-age Z-score and haemoglobin at 18 months (clinicaltrials.govNCT01824940). Children who were HIV-unexposed, age 7 years, and still living in Shurugwi district were eligible for this follow-up study (registered at PACTR 202201828512110) and measured between 1st April 2021 and 30th September 2022. The primary outcome at 7 years was cognitive function using the Kaufman Assessment Battery for Children (KABC-II). Secondary outcomes were executive function, literacy and numeracy, fine motor skills, socioemotional function, handgrip strength, broad jump distance, shuttle-run test distance, anthropometry, lean mass index, and skinfold thicknesses. Study nurses conducting assessments were blinded to intervention arm. Analysis followed a pre-registered statistical analysis plan. Intention-to-treat analyses using generalized estimating equations were used to assess the long-term effects of WASH and IYCF on each outcome, leveraging the factorial trial design. A pre-specified subgroup analysis by child sex was also performed. Among 3989 HIV-negative women, 3676 children were assessed at age 18 months; of these, 1002 (510 female) were assessed at mean (SD) age 7.3 (0.2) years. There was no effect of IYCF or WASH on the KABC-II score or secondary cognitive outcomes, except a small improvement in socioemotional function in WASH arms (-0.98 points, 95% CI-1.73,-0.22, p=0.01). Children in IYCF arms had higher handgrip strength (0.28Kg, 95% CI 0.02, 0.53, p=0.03); however, in the pre-specified subgroup analysis, improved handgrip strength was seen only in boys (0.53Kg, 95% CI 0.19, 0.87 p=0.002). There were no significant effects of either intervention on other outcomes. Early-life IYCF and WASH led to few functional benefits by school-age. Interventions that are more comprehensive, delivered for longer, and include nurturing care should be considered to improve long-term cognitive and physical function. Wellcome [220671/Z/20/Z, 108065/Z/15/Z]; NIH [R61HD103101]; Thrasher [15250]; and IMMANA [3.02].

Effect of integrating paediatric tuberculosis services into child healthcare services on case detection in Africa: the INPUT stepped-wedge cluster-randomised trial

IntroductionPaediatric tuberculosis (TB) underdiagnosis is a critical concern. The INPUT stepped-wedge cluster-randomised trial assessed the impact of integrating child TB services into child healthcare on TB case detection among children...

Costs during the first year after stroke by degree of functional disability: A societal perspective.

The aim of this study was to estimate societal costs during the first year after stroke by degree of functional disability. Descriptive study of the cumulative costs incurred during 1-year follow-up of a cohort of patients with stroke in Catalonia (Spain) participating in a multicentre, population-based, cluster-randomised trial (RACECAT). Patients were recruited between September 2017 and January 2019. Costs were collected for each patient from stroke onset to 1-year follow-up through hospital accounting records, electronic healthcare records and structured telephone-based interviews at 6 and 12-months follow-up. Disability was assessed using the 90-day modified Rankin Scale (mRS). Healthcare, community care, and patient/family costs were included. We used complete data from 567 eligible participants. Cost data were analysed using generalised linear models (GLMs) with gamma distributions and log link functions. For variables with >10% zero values, two-part models were applied. We performed sensitivity analyses modifying unit costs for patient/family costs. Of the 567 patients included, 53% had ischaemic large vessel oclusion (LVO) stroke, 24% intracranial haemorrhage and 23% ischaemic non-LVO stroke. Mean cost per patient during the first year after stroke was €29,673 ± 28,632, and increased with degree of disability (mRS 0-2: €18,568 ± 12,244; mRS 3: €38,214 ± 28,172; mRS 4-5: €52,859 ± 36,383). Healthcare costs represented the highest proportion of total costs (63%; €18,724/patient) across all disability levels, with index hospitalisation being the highest (€12,319 ± 17,675); however, community care and patient/family costs represented over 40% of total cost in patients with higher disability levels. Our results are in line with other studies; the costs during the first year after stroke are high and increase with disability. These results are valuable for calculating the cost of severe stroke cases.

Remote Collaborative Specialist Panel Deployment to Address Health Disparities in the RICH LIFE Project.

Individuals with low income or from minoritized racial or ethnic groups experience a high burden of hypertension and other chronic conditions (eg, diabetes, chronic kidney disease, and mental health conditions) and often lack access to specialist care when compared to their more socially advantaged counterparts. We used a mixed-methods approach to describe the deployment of a Remote Collaborative Specialist Panel intervention aimed at the comprehensive and coordinated management of patients with hypertension and comorbid conditions to address health disparities. Participants of the collaborative care/stepped care arm of the Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone (RICH LIFE) Project, a cluster-randomized trial comparing the effectiveness of enhanced standard of care to a multilevel intervention (collaborative care/stepped care) for improving blood pressure control and reducing disparities, were included. Participants were eligible for referral by their care manager to the Specialist Panel if they continued to have poorly controlled hypertension or had uncontrolled comorbid conditions (eg, diabetes, hyperlipidemia, depression) after 3months in the RICH LIFE trial. Referred participant cases were discussed remotely with a panel of specialists in internal medicine, cardiology, nephrology, endocrinology, and psychiatry. Qualitative data on the Specialist Panel recommendations and interviews with care managers to understand barriers and facilitators to the intervention were collected. We used available components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to examine the impact of the intervention. Of 302 participants in the relevant RICH LIFE arm who were potentially eligible for the Specialist Panel, 19 (6.3%) were referred. The majority were women (53%) and of Black race (84%). Referral reasons included uncontrolled blood pressure, diabetes, and other concerns (eg, chronic kidney disease, life-stressors, medication side effects, and medication nonadherence). Panel recommendations centered on guideline-recommended diagnostic and management algorithms, minimizing intolerable medication side effects and costs, and recommendations for additional referrals. Panel utilization was limited. Barriers reported by care managers were lack of perceived need by clinicians due to redundant specialists, a cumbersome referral process, the remote nature of the panel, and the sensitivity of relaying recommendations back to the primary care physician. Care managers who made panel referrals reported it was overwhelmingly valuable. The use of a Remote Collaborative Specialist Panel was limited but well-received by referring clinicians. With modifications to enhance uptake, the Remote Collaborative Specialist Panel may be a practical care model for addressing some disparities in hypertension and multi-morbidity care.

Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam

BackgroundAfter pneumococcal disease and colonization have been controlled through vaccination campaigns, a reduced pneumococcal conjugate vaccine (PCV) schedule may be sufficient to sustain that control at reduced costs.MethodsWe investigated whether a single primary dose and booster dose (1p+1) of the 10-valent PCV (PCV10) would be noninferior to alternative dose schedules in sustaining control of carriage of pneumococcal serotypes included in the vaccine. In Nha Trang, Vietnam, an area in which PCV had not been used previously, a PCV10 catch-up campaign was conducted in which the vaccine was offered to children younger than 3 years of age, after which a cluster-randomized trial was conducted in which children received PCV10 at 2, 3, and 4 months of age (3p+0 group); at 2, 4, and 12 months of age (2p+1 group); at 2 and 12 months of age (1p+1 group); or at 12 months of age (0p+1 group). Annual carriage surveys in infants (4 to 11 months of age) and toddlers (14 to 24 months of age) were conducted from 2016 through 2020. The primary end point was protection against carriage of vaccine serotypes, evaluated in a noninferiority analysis in the 1p+1 group as compared with the 2p+1 and 3p+0 groups, 3.5 years after vaccine introduction (noninferiority margin, 5 percentage points). Noninferiority of the 0p+1 schedule was also evaluated.ResultsIn 2016, before the introduction of PCV10, vaccine-serotype carriage was found in 160 of 1363 infants (11.7%); in 2020, vaccine-serotype carriage was found in 6 of 333 (1.8%), 5 of 340 (1.5%), and 4 of 313 (1.3%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively, indicating noninferiority of 1p+1 to 2p+1 (difference, 0.3 percentage points; 95% confidence interval [CI], −1.6 to 2.2) and to 3p+0 (difference, 0.5 percentage points; 95% CI, −1.4 to 2.4). Similarly, 1p+1 was noninferior to 2p+1 and 3p+0 for protection against vaccine-serotype carriage among toddlers. In 2016, carriage of serotype 6A was found in 99 of 1363 infants (7.3%); in 2020, it was found in 12 of 333 (3.6%), 10 of 340 (2.9%), and 3 of 313 (1.0%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively. The 0p+1 schedule was also noninferior to the other three dose schedules among infants and toddlers, although cross-protection against serotype 6A was less common than with the other vaccination schedules. No PCV10-associated severe adverse effects were observed.ConclusionsA reduced vaccination schedule involving a single primary dose and booster dose of PCV10 was noninferior to alternative schedules in protecting against vaccine-serotype carriage in infants and toddlers. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02961231.)