Cluster-randomized Trial Research Articles

Symptom monitoring with electronic patient-reported outcomes during cancer treatment: final results of the PRO-TECT cluster-randomized trial.

Symptoms are often underdetected during cancer treatment. To determine if symptom monitoring with electronic patient-reported outcomes (PROs) improves clinical outcomes, we conducted a cluster-randomized trial in which 52 oncology practices were assigned to PRO or usual care. At PRO practices, patients with metastatic cancer were invited to complete weekly symptom surveys. Severe or worsening symptoms generated alerts to the care team. The primary outcome was overall survival, and secondary outcomes included emergency visits, time to deterioration of physical function, symptoms, health-related quality of life (HRQL) and patient satisfaction with PRO. Among 1,191 enrolled patients, there was no difference in survival (hazard ratio (HR) 0.99 (95% confidence interval (CI), 0.83-1.17); P = 0.86). Time to first emergency visit was significantly prolonged with PRO compared to usual care (HR 0.84 ((95% CI, 0.71-0.98); P = 0.03), with a 6.1% reduction in the cumulative incidence of emergency visits and fewer mean visits at 12 months with PRO (1.02 versus 1.30; P < 0.001). Benefits also significantly favored PRO for delayed deterioration of physical function (median 12.6 versus 8.5 months, HR 0.73; P = 0.002), symptoms (12.7 versus 9.9, HR 0.69; P < 0.001) and HRQL (15.6 versus 12.2, HR 0.72; P = 0.001), which remained significant when considering deaths in analyses. Most patients felt that PRO improved discussions with the care team (77.0% (188/244)), made them feel more in control of their care (84.0% (205/244)) and would recommend it to other patients (91.4% (223/244)). Patients completed 91.5% (20,565/22,486) of expected weekly symptom surveys. These findings demonstrate that symptom monitoring with PRO meaningfully improves clinical outcomes, the patient experience and utilization of services and should be included as a standard part of quality cancer clinical care. Future studies of PRO in clinical care should focus on these outcomes rather than mortality as primary endpoints. ClinicalTrials.gov registration: NCT03249090.

Management of volume load for patients undergoing hemodialysis via WeChat and home monitoring in China: a protocol for a cluster-randomized trial

BackgroundVolume overload is a major mortality risk in hemodialysis (HD) patients. Drug therapy and conventional dialysis limitations underscore the importance of managing volume load through effective lifestyle interventions. In this regard, WeChat, along with its built-in self-monitoring function, has demonstrated considerable potential for application. WeChat, a versatile social media platform in China, integrating Facebook, WhatsApp, Twitter, and PayPal functionalities, shows potential in managing volume load, especially when paired with home monitoring. This method may also reduce adverse events and improve patient outcomes.MethodThe study will be conducted at the Hemodialysis Center of the Hospital of Chengdu University of Traditional Chinese Medicine, recruiting 135 participants. All patients will be cluster randomly assigned to three group according to their HD schedules. The control group will receive standard care. The WeChat group will receive volume load management via WeChat message in addition to standard care. The home monitoring-feedback group will be required to monitor their blood pressure and weight at home, and upload the number to WeChat subscription account “Health Dialysis” in addition to standard care and volume load management via WeChat message. Data will be collected during the baseline period, one, two, and three months after the intervention starts, and three months after the intervention ends to evaluate the effectiveness of this intervention measure.DiscussionThis study aims to effectively manage the volume load of HD patients and enhance their quality of life through a combination of intervention methods utilizing the WeChat platform and home monitoring. If this intervention measure proves effective, it will not only provide empirical evidence for managing HD patients through the WeChat platform but also serve as a reference model for other HD centers in addressing patient volume load issues. What’s more, if significant differences are observed between the results of the WeChat groups and the home monitoring-feedback group, this will further substantiate the importance and impact of home monitoring in volume load management.Trial registrationClinicalTrials.gov (NCT06333574). Registered 13 March 2024.

Acceptability of and experiences with menstrual hygiene cups among adolescent girls and young women aged 15–24 in two communities in Lusaka, Zambia: an exploratory study nested in the Yathu Yathu trial

BackgroundMenstrual cups could be a sustainable menstrual material for adolescent girls and young women (AGYW) in sub-Saharan Africa. Yathu Yathu was a cluster-randomized trial of community-based delivery of HIV and sexual and reproductive health services to young people in Lusaka, Zambia. Among services available through the intervention were menstrual products, including menstrual cups. We explored knowledge of menstruation and menstrual products, acceptability, and experiences of using cups among AGYW aged 15–24. We share lessons learned on how to distribute cups through community-based strategies to AGYW in urban communities.MethodsThrough community-based, peer-led spaces (hubs), AGYW could access menstrual products, including pads and menstrual cups. We conducted four focus group discussions, two with AGYW aged 15–19 (n = 9) and 20–21 (n = 8) who had accessed different menstrual products through Yathu Yathu and two with AGYW aged 15–19 (n = 5) and 20–24 (n = 9) who had accessed menstrual cups. Four interviews were conducted with four AGYW (15–19, n = 2; 20–24, n = 2) who had accessed cups, and four with two AGYW who were enrolled in a qualitative cohort. Data were analyzed thematically.Results‘Surprise’ and ‘fear’ were initial reactions from most AGYW who saw the cups for the first time at Yathu Yathu hubs. Misconceptions that cups cause cancer and fears that they could get stuck in the vagina, cause sore, vagina enlargement, and loss of virginity were raised by AGYW. The desire to try the cup, use an alternative menstrual product and information gained at the hubs facilitated access. Use of the cup was comfortable, and cups were said to be cost-effective and durable. Advantages over pads included: the absence of odor, easy to maintain, and environmentally friendly: “it is hygienic, and it is even easy to maintain”. Challenges included pain, discomfort, and failure to or incorrectly inserting the cup at initial use. When faced with challenges using the cup, AGYW reported going back to the hub for additional information and demonstrations on use.ConclusionDespite concerns, misconceptions and initial challenges, cups were acceptable among AGYW. Free distribution of cups provides an opportunity to address menstrual health challenges among AGYW. However, as a new product, there is need to increase awareness and provide detailed information on use.

Effect of Medication Management at Home via Pharmacist-Led Home Televisits: Protocol for a Cluster Randomized Controlled Trial.

Older adults are more likely to have multiple chronic conditions, be prescribed multiple medications, and be more susceptible to adverse drug reactions (ADRs) to their medications. In addition, older adults often use over-the-counter medications and supplements, further complicating their medication regimens. Complex medication regimens are potentially harmful to older adults. Interventions aimed at reducing medication discrepancy in the ambulatory clinic setting, such as reviews of medication lists and the implementation of "brown bag" reconciliation, continue to be challenging, with limited success. Pharmacist-led interventions to improve appropriate medication use in older adults have demonstrated effectiveness in reducing ADRs. Video visits have the potential to provide direct visualization of medications in older adults' homes, thereby reducing medication discrepancy and increasing medication adherence. Pharmacist-led management of older adults' medication regimens may improve appropriate medication use in older adults. The objective of this study is to examine the effect of pharmacist-led medication through home televisits compared to usual care on appropriate medication use, medication discrepancies, medication adherence, and ADRs. We will conduct a 2-site cluster randomized controlled trial (RCT). The intervention will be a pharmacist-led home televisit including medication reconciliation and assessment of actual medication use. The cluster RCT was iteratively adapted after a pilot test. The primary outcome of medication appropriateness of the intervention will be measured using the STOPP (Screening Tool of Older Persons' Prescriptions) criteria for potentially inappropriate medications (PIMs) at 6 months. Medication lists obtained will be compared against electronic medical records (EMRs) by a clinician to establish discrepancies in medications. The clinician will review medications using the validated Medication Appropriateness Index (MAI). This project has been peer-reviewed and selected for support by the Veterans Affairs (VA) Health Services Research Service. The pilot phase of the study was completed December 2021 with 20 veterans and was primarily informed by the Steinman model of the prescribing process adapted to include system- and provider-level factors. The last date of enrollment was August 6, 2021. We anticipate the completion of the ongoing trial in spring 2025. The first results are expected to be submitted for publication in 2025. The cluster RCT will provide evidence on medication management through televisits. If found effective in improving the use of medications, the intervention has the potential to impact older adults with multiple chronic conditions and polypharmacy. ClinicalTrials.gov NCT04340570; https://clinicaltrials.gov/study/NCT04340570. PRR1-10.2196/65141.

Salt Substitution and Recurrent Stroke and Death

The direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear. To evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke. The Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomized clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analyzed from November 2023 to August 2024. Participants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt. The primary outcome was recurrent stroke. After excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was -2.05 mm Hg (95% CI, -3.03 to -1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on hemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96). Results of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke. ClinicalTrials.gov Identifier: NCT02092090.

Implementation of the children and young people’s health partnership model of paediatric integrated care: a mixed-methods process evaluation

ObjectiveA process evaluation of the Children and Young People’s Health Partnership (CYPHP) model of integrated care for the interpretation of trial findings and building evidence on the implementation of integrated...

Effects of preschool staff professional development in physical activity on self-regulation, executive function and early academic learning in 3–5-year-old children: The active learning Norwegian preschool(er)s (ACTNOW) cluster-randomized controlled trial

ABSTRACT We aimed to investigate the effects of preschool staff physical activity (PA) professional development on self-regulation, executive function and early academic learning in 3–5-year-old children. A total of 1265 children from 46 preschools in Norway were randomized to a 7-month intervention or control. Main analyses included 816 3–4-year-olds who provided data at baseline, 7- and 18-month follow-ups. We measured children’s self-regulation (Head-Toes-Knees-Shoulders task), inhibition, cognitive flexibility, working memory, early expressive vocabulary, early mathematical skills (Early Years Toolbox) and physical activity (accelerometry). Linear mixed models were used to analyze the data. Results showed no effect of the intervention on cognitive or learning outcomes in the primary analyses. We found small positive effects on sedentary time (standardized effect size (ES)=-0.17, p = 0.014) and moderate to vigorous-intensity PA (ES = 0.15, p = 0.048) at 7 months, and a negative effect on low-intensity PA at 18 months (EF = −0.15, p = 0.021). Boys had a small positive effect on vocabulary at 7 months (ES = 0.23, p = 0.006), and girls a small negative effect at 18 months (ES = −0.23, p = 0.004). This cluster RCT in preschoolers supports the notion that pragmatic trials within educational settings have difficulties in providing changes to the PA practice and to impact young children’s cognitive development and learning.

Predictors of sickness absence among employees with common mental disorders in Sweden– a longitudinal study

BackgroundThe study aimed to explore which sociodemographic, health-related, and work-related factors were associated with the number of sickness absence days during 18 months among employees on sickness absence due to common mental disorders.MethodsA longitudinal study with participants from a cluster-randomized controlled trial was conducted. Participants from both intervention and control groups were treated as one cohort. Factors included in the analysis were sociodemographic, health-related, and work-related variables collected through questionnaires at baseline. The outcome was cumulative net sickness absence days for sickness absence spells exceeding 14 days and was collected from a national register. Data was analyzed using generalized estimating equations.ResultsThe sample consisted of 197 employees. Lower-rated work ability in relation to physical demands ([exp (B) 1.19], 95% CI 1.02–1.40) and higher-rated job demands ([exp (B) 1.28], 95% CI 1.01–1.61), were associated with increased number of sickness absence days during the 18 months follow-up. Higher certainty of return to work within three months ([exp (B) 0.63], 95% CI 0.48–0.83) was associated with a decreased number of sickness absence days during the 18 months follow-up.ConclusionsOur study suggests that work-related factors, i.e., high job demands and impaired work ability, are associated with an increased number of days on sickness absence. Additionally, the certainty of returning to work within three months is associated with fewer days on sickness absence. The results highlight the importance of addressing specific workplace factors when designing interventions aimed at decreasing sickness absence for employees on sickness absence due to CMDs. The results could be used to inform a dialogue between healthcare personnel and employees on sickness absence due to CMDs, and to serve as basis for a structured inventory to assist healthcare personnel in addressing workplace factors.

Effectiveness of a Web-Based Self-Guided Intervention (MINDxYOU) for Reducing Stress and Promoting Mental Health Among Health Professionals: Results From a Stepped-Wedge Cluster Randomized Trial.

The high levels of sustained stress that health professionals often experience are a significant risk factor for developing mental health problems, such as anxiety, depression, and somatic symptoms, that not only affect their well-being but also have major social and organizational consequences. Different interventions, including those based on third-wave psychotherapy principles (ie, mindfulness, compassion, and acceptance), have proven to be effective in reducing stress in this population. Among them, those delivered on the web constitute a promising alternative with notable advantages in accessibility and flexibility, but some adherence inconveniences may limit their efficacy. This study aimed to evaluate the effectiveness of the MINDxYOU program, a web-based self-guided intervention based on third-wave psychotherapy principles, to reduce perceived stress and promote mental health in a sample of health professionals. In a stepped-wedge cluster randomized design, 357 health professionals from health centers in Aragon and Málaga, Spain, were recruited. They were divided into 6 clusters-3 per region-and randomly assigned to 1 of the 3 sequences, each starting with a control phase and then transitioning to the intervention phase (the MINDxYOU program) after 8, 16, or 24 weeks. This self-guided, web-based program, designed to be completed over 8 weeks, included weekly contact (via WhatsApp, call, or email) from the research team to promote adherence. Participants were assessed on the web every 8 weeks for 5 assessments. Perceived stress was the study's primary outcome, with additional measures of clinical factors (anxiety, depression, and somatization) and process variables (resilience, mindfulness, compassion, and acceptance). The program was initiated by 229 participants, 112 (48.9%) of whom were completers (ie, completed at least 3 of the 4 modules). Perceived stress demonstrated a significant reduction both when considering the entire sample (β=-1.08, SE 0.51; P=.03) and the sample of completers (β=-1.84, SE 0.62; P=.003). The proportion of participants reflecting "low stress" increased after the treatment (n=90, 46.6% vs n=100, 28.8% at baseline). Intracluster analysis revealed that pre- versus postintervention moderate effects were present in 2 clusters (Cohen d=0.46 and 0.62), and these were maintained in subsequent assessments. The linear mixed-effects models also showed that depression, anxiety, and somatization, as well as resilience, self-compassion, and some mindfulness facets, experienced significant improvements (P<.05) when comparing the intervention and control phases. The MINDxYOU program was effective in reducing perceived stress and promoting mental health, as well as increasing resilience, mindfulness facets, and self-compassion. These effects suggest that participants experienced a tangible improvement that could potentially enhance their well-being. Adherence to the intervention was moderate, while program use was notable compared to similar interventions. Finding ways to promote adherence to the intervention would contribute to increasing the effectiveness of this program. ClinicalTrials.gov NCT05436717; https://clinicaltrials.gov/study/NCT05436717. RR2-10.1186/s12912-022-01089-5.

Training and Technical Assistance Increase the Fidelity of Implementation of a Universal Prevention Initiative in Rural Schools: Results from a 3-Year Cluster-Randomized Trial.

The need for well-implemented evidence-based interventions (EBIs) for the prevention of behavioral issues among children and adolescents is substantial. In rural areas, the need often matches or surpasses that of urban areas. Schools have a wide reach for prevention-focused EBIs. However, implementation in rural schools is often hindered by limited resources and capacity. Rural School Support Strategies (RS3) are a bundle of implementation supports that address implementation challenges in rural settings. They include providing additional leadership and coaching training, individualized technical assistance (mostly virtual), and monthly meetings of a virtual learning collaborative. A cluster-randomized Hybrid Type 3 implementation-effectiveness trial tested RS3 for implementing school-wide positive behavioral interventions and supports (PBIS), a universal prevention approach to improving student behavior, academic outcomes, and school climate. Forty rural schools received a multi-day training on PBIS each summer for 3years. Half were randomized to also receive RS3 support. Linear and logistic regression models examined the effect of treatment condition and dosage of support on implementation fidelity for Tier 1 (universal) PBIS. Condition and dosage (number of hours) of support increased the odds of schools achieving the 70% threshold for adequate implementation fidelity. In the first year, the higher dosage of technical assistance events increased the likelihood of schools reaching fidelity, whereas later in the trial, the higher dosage of attendance at the virtual learning collaborative sessions yielded significant improvements in fidelity. Implications for accelerating the implementation of universal prevention initiatives in schools-particularly in rural settings-are discussed. This study was prospectively registered on ClinicalTrials.gov (NCT03736395), on November 9, 2018.

Contamination effects in cluster randomised trials of TB interventions.

<sec><title>BACKGROUND</title>Cluster randomised trials (CRTs) of TB interventions have achieved mixed results, with many lacking significant reductions in outcomes. Contamination in CRTs, resulting from short and long-term movement between clusters and the general population, may dilute the impact of measured intervention.</sec><sec><title>METHODS</title>We systematically reviewed the literature to identify CRTs that aimed to capture the population-level effects of the intervention on TB. Details of trial designs, interventions, outcomes, populations, cluster configurations, and geographic data were extracted to produce text summaries, descriptive statistics, and spatial analyses.</sec><sec><title>RESULTS</title>We screened 1,039 abstracts and included 20 reports from seven CRTs. The median number of clusters was 32 (IQR 23-61), with populations ranging from 400-50,000 individuals per cluster. Four trials reported spatial data, from which the mean distance between clusters was 12.3 km (range 3.71-35.9). Several trials acknowledged design limitations, such as small cluster sizes and population mobility, which could have led to underestimations of intervention impact. Trials used various geographic, social, and pre-existing TB measures to select and allocate study clusters. Data on the potential for contamination are inconsistent.</sec><sec><title>CONCLUSION</title>Gaps remain in the reporting of methods and results, suggesting necessary improvements to standardised reporting tools. These insights can inform recommendations for improved CRT design and reporting practices.</sec>.

Perspectives on Conducting Behavioral Intervention With Adolescents Using a Virtual Platform-A Thematic Analysis From the Viewpoint of Study Coordinators.

The COVID-19 pandemic led to widespread adoption of virtual communication platforms. Virtual study visits were implemented in the pilot cluster randomized trial (CRT) stage of Teen Adherence in KidnEy transplant Improving Tracking To Optimize Outcomes (TAKE-IT TOO). The present study aimed to understand study coordinators' perspectives on conducting a behavioral intervention with adolescent kidney transplant recipients using virtual conferencing platforms. Study coordinator participants (N = 6) completed questionnaires and participated in a semi-structured interview that probed comfort with digital technology, issues encountered, and overall perspectives on conducting virtual study visits. Qualitative thematic analysis was used to identify themes and subthemes. Participants expressed confidence with technology and ability to handle the complexities of the virtual conferencing. Some expressed that virtual study visits led to a change in work habits and higher workload due to increased technology complexity. Qualitative analyses of participant interviews revealed four themes: adaptability, accessibility, logistics (including subthemes scheduling and fluidity), and communication (including subthemes clarity, engagement, and rapport). Convenience for coordinators and the perceived comfort for adolescents were noted advantages for virtual visits. Technical issues, periodic adolescent distractions, and challenges with instructional teaching through virtual conferencing were identified as potential limitations of virtual study visits. Overall, virtual study visits were appreciated and endorsed by study coordinators. Researchers should consider the feasibility of completing study-related tasks virtually, including accessibility of visual materials on all type of electronic devices, and ensure adequate training of study personnel when deciding to implement virtual platform in CRTs.

Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9months (1+1 co-administration) or YF vaccine administered separately at age 10months (1+1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9months (3+0 separate). Blood samples were collected 28-35days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres≥1:8 were calculated with 95% confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than-10%. Forty-eight, 66, and 98 participants enrolled in 3+0 separate, 1+1 co-administration, and 1+1 separate groups respectively had NA results. Per protocol analysis of the 3+0 separate, 1+1 co-administration, 1+1 separate, and the combined 1+1 separate and 3+0 separate groups found that 81%, 85%, 92%, and 88% of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1+1 co-administration and 1+1 separate groups was -7% (95% CI, -18% to 3%). The difference between 1+1 co-administration and 3+0 separate groups was 4% (95% CI, -10% to 15%). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613.

Effects of a smartphone game to facilitate active neck movements on the incidence of neck pain among office workers: a 6-month cluster-randomised controlled trial

To evaluate the effects of a smartphone game for active neck movement exercise on perceived neck discomfort, new onset neck pain, and active cervical range of motion among high-risk office workers. A 6-month prospective cluster-randomized controlled trial was conducted. Workers were randomly assigned at the cluster level into either the intervention group (n=50), who received a smartphone game to play twice a day, or the control group (n=50), who received a placebo seat pad to use while sitting. Both groups were followed up for 6 months and outcome measures included the incidence of neck pain, perceived neck discomfort, assessed by the Borg CR-10, and active cervical range of motion. Analyses were performed using Cox proportional hazard models. The 6-month incidence of neck pain was 20% and 44% in the intervention and control groups, respectively. Hazard ratios, after adjusting for biopsychosocial factors, showed a protective effect of the smartphone game for new onset neck pain (HRadj=0.43, 95% CI 0.20 to 0.91). The between group differences in perceived neck discomfort during the follow up did not reach the minimally clinically important difference level. Mean active cervical range of motion in the intervention group were significantly greater than the control group in all directions (p<0.05). The smartphone game for active neck movement exercise is an effective intervention to prevent neck pain among high-risk office workers.

Structured lactation support for mothers of very low birthweight preterm infants and establishment of human donor milk banks in German NICUs (Neo-MILK): protocol for a hybrid type 1 effectiveness-implementation cluster-randomised controlled trial

BackgroundHuman milk, especially mother’s own milk (MOM), is vital for newborns and crucial for very low birthweight (VLBW, <1500 g) preterm infants, who face increased vulnerability. As the production of...

Safety of 3-month rifampicin-isoniazid TPT in child household contacts in a community-based intervention.

<sec><title>BACKGROUND</title>The WHO recommends shorter TB preventive treatment (TPT) regimens and decentralised delivery models to improve effectiveness. This study evaluated the safety of a 3-month rifampicin-isoniazid (3RH) regimen administered by community health workers (CHWs) in households in Cameroon and Uganda.</sec><sec><title>METHODS</title>A cluster-randomised trial was conducted among child contacts of TB patients. We compared the safety of 3RH delivered by CHWs at home (intervention) vs standard-of-care, facility-based administration of 3RH. Safety outcomes included adverse events (AEs), serious adverse events (SAEs), and adverse reactions (ARs). We described the steps from symptom identification by CHWs to classification by a clinician.</sec><sec><title>RESULTS</title>Of 1,316 children initiated on 3RH, AEs were reported in 8.7% (81/936) in the intervention arm versus 11.3% (43/380) in the standard-of-care arm, P = 0.15. Overall, 37 SAEs occurred in 36 children, all non-medication related. There were 16 ARs reported, occurring in 1.0% (9/936) of children in the intervention arm and 1.6% (6/380) in the standard-of-care arm, P = 0.22. During 4,608 follow-up visits, 21 children reporting AR symptoms were identified by CHWs, 16 were assessed by clinicians, and 4 ARs were confirmed.</sec><sec><title>CONCLUSIONS</title>The 3RH regimen was safe, including when administered by trained CHWs in community settings, supporting its use in decentralised healthcare models.</sec>.

Early detection and a treatment bundle strategy for postpartum haemorrhage: a mixed-methods process evaluation.

Postpartum haemorrhage is a leading cause of maternal mortality. A multicountry, cluster-randomised trial (E-MOTIVE) demonstrated a 60% reduction in adverse postpartum haemorrhage outcomes. The E-MOTIVE intervention included early postpartum haemorrhage detection using calibrated blood-collection drapes, followed by a postpartum haemorrhage treatment bundle (ie, uterine massage, oxytocics, tranexamic acid, intravenous fluids, examination and escalation [MOTIVE]), supported by implementation strategies. We report a mixed-methods process evaluation assessing the implementation of the E-MOTIVE intervention in Kenya, Nigeria, South Africa, and Tanzania. In this mixed-methods process evaluation, data sources were observations of health workers providing clinical care to pregnant women and pregnant people during vaginal birth and postpartum haemorrhage at intervention sites, and surveys and qualitative interviews with health workers at intervention and control sites. Intervention sites received the calibrated drapes, MOTIVE bundle, and implementation strategies and control sites used uncalibrated drapes. Primary implementation outcomes included fidelity, adoption, adaptation, acceptability, feasibility, and contamination to the calibrated drape, MOTIVE bundle, and implementation strategies. Between June 1, 2022, and Jan 31, 2023, 2578 births were observed, 295 pregnant women and people had postpartum haemorrhage, 47 qualitative interviews were done, and 889 surveys were completed. Fidelity to calibrated drape use was high (birth observations 2578 [100%] of 2578; survey 451 [98·3%] of 459). Among health workers, calibrated drape acceptability was high; however, they reported barriers to pregnant women's and people's acceptability. Fidelity to postpartum haemorrhage treatment bundle delivery was high (birth observations 286 [96·9%] of 295), with moderate to high fidelity in median time from postpartum haemorrhage diagnosis to final treatment initiation (≤15 min initiation time in 191 [66·8%] of 295 birth observations, 16-20 min in 42 [14·7%] birth observations), and high acceptability and feasibility. Research midwives participated in clinical assessments after birth and bundle delivery in some sites (mixed fidelity). This process evaluation shows generally high levels of fidelity, feasibility, and acceptability of the calibrated drape and treatment bundle across evaluation methods and countries. The E-MOTIVE intervention should be included in national policies, with consideration for health workforce, supplies, and medication issues, which might need addressing for successful implementation. The Bill and Melinda Gates Foundation and the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, a co-sponsored programme of WHO. For the Swahili translation of the abstract see Supplementary Materials section.

Knowledge, practice, and information sources regarding infectious diseases among Chinese children and adolescents: a National-Level cross-sectional study

ObjectiveTo investigate the characteristics and interrelationships between knowledge, preventive practice, and information sources of infectious diseases among Chinese children.MethodsThis study used data collected from the baseline survey of a China national multi-centered cluster-randomized controlled trial in 2013. A total of 30,287 children completed a questionnaire package that included measures for knowledge, preventive practice and information sources related to infectious diseases.ResultsThe mean scores of knowledge and prevention practices of infectious diseases were 2.35 and 12.16, respectively. Children received information about infectious diseases primarily through school, other individuals, and electronic media. Knowledge and practices among children differed significantly across gender, age, single-child, living with parents or not, residence(urban/rural), regions, parental age and parents’ education levels. Multivariable linear regression analysis showed that higher levels of knowledge(b = 0.102), and receiving information through schools(b = 0.054), electronic media(b = 0.016), and paper media(b = 0.054) were significantly associated with better preventive practice.ConclusionsChildren’s knowledge and various sources of access to information significantly predicted the prevention practice score. It might add value to future interventions and policy-making in promoting preventive measures for infectious diseases.

Cultivating evidence-based clinical reasoning and action in youth mental health care: The Reaching Families multisite randomized trial.

Despite decades of policy emphasizing the role of evidence in guiding services, few studies have sought to improve the degree to which evidence is used in supervision and treatment. This study reports supervisor and therapist outcomes from the Reaching Families multisite cluster-randomized controlled trial, which tested the effects of a coordinated knowledge system (CKS) against practice guidelines (PG) on the use of evidence in supervision and treatment targeting low treatment engagement in publicly funded youth community mental health organizations located in two geographically distinct, underresourced communities where service inequities are common. The sample included 121 mental health professionals (92.6% female; 81.0% Black, Indigenous, and people of color1) randomly assigned to a CKS or PG control condition. We recorded, transcribed, and coded 430 supervision and 208 treatment sessions involving 221 youth (Mage = 13.1 years, 46.2% female; 78.7% Black, Indigenous, and people of color) and/or their caregivers who reported engagement concerns during therapy. CKS dyads showed uniformly greater use of evidence focused on specific client needs relative to dyads in the PG condition, with large effect sizes and no differences in the effect of condition across the sites. Secondary analyses showed that tools in the CKS condition were perceived significantly more positively than those in the PG condition in terms of effort and effectiveness, and supervisory workload was the same across both conditions. In routine clinical care delivered within highly representative community settings, a strategically designed knowledge resource can improve evidence-based reasoning and action and be perceived as easy to use and useful without negatively impacting workload. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Pharmacist vs physician management of e-visit requests for COVID-19 medication: A randomized clinical trial.

Electronic visits (e-visits), defined as structured asynchronous electronic messages between patients and clinicians requiring clinical decision-making, are being increasingly used to enhance access to outpatient health care services, but the primary care physicians who typically manage them face work overflow. Pharmacists have been proposed to manage e-visits that lead to prescription requests, but scant evidence exists about the effectiveness of this approach. To compare pharmacist management of structured asynchronous e-visit requests for COVID-19 medication with physician management regarding quality of care, timeliness, and patient care experience. This cluster-randomized clinical trial included adults from 17 medical facilities of Kaiser Permanente Northern California who made e-visits requesting COVID-19 medication (nirmatrelvir-ritonavir) from October 9 to December 11, 2023. In the Pharmacist Care group, a regional team of pharmacists managed e-visits for COVID-19 medication; in the Physician Care group, pools of adult and family medicine physicians managed these visits. The primary outcome was whether a patient with 1 or more potential serious drug-drug interactions received counseling via an electronic secure message. Secondary outcomes included prescribing rates, time to the prescription, and patient perceptions of care quality. Among the 1,753 eligible patients (mean age = 52.2 [SD = 15.9] years; 57.7% female), 642 received Pharmacist Care and 1,111 received Physician Care. The percentage of patients with a potential drug-drug interaction who were sent counseling messages by the clinician did not differ between the Pharmacist Care (76 of 79 [96.2%]) and Physician Care groups (193 of 201 [96.0%]) (risk difference [RD] = 0.18%; 95% CI = -4.8% to 5.2%). The pharmacist and physician groups had similar rates of prescribing (87.4% vs 84.4%; RD = 2.9; 95% CI = -0.4 to 6.3). Pharmacist Care compared with Physician Care had faster mean time from the initial e-visit submission to the resulting prescription (1.0 vs 2.5 hours; RD = -1.5; 95% CI = -1.9 to -1.2). Pharmacist Care took more clinician time per visit than Physician Care (10.7 vs 4.2 minutes), resulting in higher estimated cost ($11.40 vs $6.70). After the study period, the pharmacist team made protocol changes to improve workflow efficiency, and a follow-up analysis 12 months later found significant reductions in per-visit time (to 5.7 minutes) and estimated cost (to $6.03) under Pharmacist Care. Patient perceptions of care did not differ significantly between groups. Pharmacist care and physician care for patient e-visits for COVID-19 medication both yielded high quality of care, with no significant group differences. Evaluation of pharmacist care may be warranted for other e-visits designed to facilitate medication prescribing. ClinicalTrials.gov NCT06096863.