Complier Average Causal Effect Research Articles

Comparison of diclofenac with tramadol, tizanidine or placebo in the treatment of acute low back pain and sciatica: multi-center randomized controlled trial.

Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50mg, tizanidine 2mg, or placebo every 6hours for 2weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. Two hundred and ninety-one patients were analyzed with the mean age of 47.4years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

Estimating the Complier Average Causal Effect with Non-Ignorable Missing Outcomes Using Likelihood Analysis

Missing data problems arise in randomized trials, which complicates the inference of causal effects if the missing mechanism is non-ignorable. We tackle the challenge of identifying and estimating the complier average causal effect parameters under non-ignorable missingness by increasing the covariates to mitigate the sensitivity to the violation of specific identification assumptions. The missing data mechanism is assumed to follow a logistic model, wherein the absence of the outcome is explained by the outcome itself, the treatment received, and the covariates. We establish the identifiability of the models under mild conditions by assuming that the outcome follows a normal distribution. We develop a computational method to estimate model parameters through a two-step likelihood estimation approach, employing subgroup analysis. The bootstrap method is employed for variance estimation, and the effectiveness of our approach is confirmed through simulation. We applied the proposed method to analyze the household income dataset from the Chinese Household Income Project Survey 2013.

Power Analyses for Estimation of Complier Average Causal Effects Under Random Encouragement Designs in Education Research: Theory and Guidance

Random encouragement designs evaluate treatments that aim to increase participation in a program or activity. These randomized controlled trials (RCTs) can also assess the mediated effects of participation itself on longer term outcomes using a complier average causal effect (CACE) estimation framework. This article considers power analysis methods for such CACE analyses for a range of RCT designs, including nonclustered, clustered, and random block designs. The focus is on behavioral encouragements to promote action, such as text messaging, that are increasingly being tested in education trials. We derive asymptotic distributions of the CACE estimators using generalized estimating equations theory, which underlie the power formulas. We incorporate noncompliance from both the actual receipt of the encouragement and participation itself. An illustrative power analysis provides sample size guidance using an available Shiny R dashboard.

Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK

Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief. Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611). Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study. Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management. Wellcome Trust and Bliss.

Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer

Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late local toxic effects after breast irradiation. Strong evidence of effectiveness is lacking. To assess effectiveness of HBOT for late local toxic effects in women who received adjuvant radiotherapy for breast cancer. This was a hospital-based, pragmatic, 2-arm, randomized clinical trial nested within the prospective UMBRELLA cohort following the trials within cohorts design in the Netherlands. Participants included 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction 12 months or longer after breast irradiation. Data analysis was performed from May to September 2023. Receipt of 30 to 40 HBOT sessions over a period of 6 to 8 consecutive weeks. Breast, chest wall, and/or shoulder pain 6 months postrandomization measured by the European Organization for Research and Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were patient-reported fibrosis, edema, movement restriction, and overall quality of life. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles. Between November 2019 and August 2022, 125 women (median [range] age at randomization, 56 [37-85] years) with late local toxic effects were offered to undergo HBOT (intervention arm), and 61 women (median [range] age at randomization, 60 [36-80] years) were randomized to the control arm. Of those offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity. In ITT, moderate or severe pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI, 0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75% (9.7 of 12.9) among control participants expected to complete HBOT if offered (adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49 (51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no significant differences in breast edema, movement restriction, and quality of life between groups in ITT and CACE. In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller than anticipated proportion of women with late local toxic effects was prepared to undergo HBOT. ClinicalTrials.gov Identifier: NCT04193722.

Impact of a post-partum family planning intervention on contraception and fertility in Tanzania: two-year follow-up of a cluster-randomised controlled trial

Purpose We evaluate contraceptive use and pregnancy two years following an intervention in Tanzania, which provided antenatal post-partum family planning counselling and post-partum intrauterine device (PPIUD) services following delivery. Methods We analyse data from five hospitals in Tanzania using a difference-in-difference cluster randomised design, with randomisation at the hospital level. We use women-level data collected at the index birth and a follow-up survey two years later among 6,410 women. Outcomes (overall modern contraceptive use, contraceptive type, pregnancy) are modelled with an intent-to-treat (ITT) approach using linear regression. We compare with the complier average causal effect (CACE) of the intervention among those counselled. Results The intervention increased long-term PPIUD use by 5.8 percentage points (95% CI: 0.7–11.2%) through substitution away from other modern methods. There was no impact on overall modern contraceptive prevalence or pregnancy. Only 29% of women reported receiving PPIUD counselling. When accounting for this in the CACE analysis we saw a larger impact with 25.7% percentage point increase in PPIUD use (95% CI: 22.7–28.6%). Conclusion The intervention provided women an additional contraceptive choice, resulting in higher use of PPIUD over two years. Increase in PPIUD use was brought about by shifting methods, not creating new modern contraceptive users.

Clinical and cost-effectiveness of an adapted intervention for preschoolers with moderate to severe intellectual disabilities displaying behaviours that challenge: the EPICC-ID RCT.

Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship. To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities. A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n = 155) or treatment as usual arm (n = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle. Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic. The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge. We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p = 0.014) and -11.53 (95% CI -26.97 to 3.91, p = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively (p = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention. There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention. Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks. Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes. This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1). This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information.

A Randomized Controlled Trial of the Effectiveness and Mechanisms of Change in a School-Based Intervention Combining Universal and Indicated Prevention for Preschoolers’ Behavior Problems

ABSTRACT The Social-Emotional Prevention Program (SEP) is a multi-focused intervention combining universal and indicated intervention strategies delivered face-to-face and through the use of technology. The study’s objectives were to assess comparatively SEP effectiveness as a function of preschoolers’ baseline risk of externalizing problems and to evaluate its hypothesized mechanisms of action. A randomized controlled trial (RCT) was conducted with five schools assigned to either the intervention or to a comparison condition (wait-list control). Structural equation models (SEM) and complier average causal effects (CACE) were conducted to evaluate program effectiveness and mechanisms of change. Research Findings: SEP participation was associated with improved social-emotional competence irrespective of baseline risk and at-risk preschoolers were more likely to exhibit reductions in externalizing problems. However, perceptions about which risk group benefited more varied as a function of rater. Patterns for SEP mechanisms of action suggest that these were similar across risk status with both child emotion regulation and parental emotion socialization practices emerging as paths to improved social-emotional competencies. Practice and Policy: The present findings add to the extant evidence suggesting that multi-focused programs combining universal and indicated prevention strategies could be successfully delivered in schools to promote social-emotional learning.

Instrumental variables for implementation science: exploring context-dependent causal pathways between implementation strategies and evidence-based interventions

BackgroundThe impact of both implementation strategies (IS) and evidence-based interventions (EBI) can vary across contexts, and a better understanding of how and why this occurs presents fundamental but challenging questions that implementation science as a field will need to grapple with. We use causal epidemiologic methods to explore the mechanisms of why sharp distinctions between implementation strategies (IS) and efficacy of an evidence-based intervention (EBI) may fail to recognize that the effect of an EBI can be deeply intertwined and dependent on the context of the IS leading to its uptake.MethodsWe explore the use of instrumental variable (IV) analyses as a critical tool for implementation science methods to isolate three relevant quantities within the same intervention context when exposure to an implementation strategy is random: (1) the effect of an IS on implementation outcomes (e.g., uptake), (2) effect of EBI uptake on patient outcomes, and (3) overall effectiveness of the IS (i.e., ~ implementation*efficacy). We discuss the mechanisms by which an implementation strategy can alter the context, and therefore effect, of an EBI using the underlying IV assumptions. We illustrate these concepts using examples of the implementation of new ART initiation guidelines in Zambia and community-based masking programs in Bangladesh.ResultsCausal questions relevant to implementation science are answered at each stage of an IV analysis. The first stage assesses the effect of the IS (e.g., new guidelines) on EBI uptake (e.g., same-day treatment initiation). The second stage leverages the IS as an IV to estimate the complier average causal effect (CACE) of the EBI on patient outcomes (e.g., effect of same-day treatment initiation on viral suppression). The underlying assumptions of CACE formalize that the causal effect of EBI may differ in the context of a different IS because (1) the mechanisms by which individuals uptake an intervention may differ and (2) the subgroup of individuals who take up an EBI may differ. IV methods thus provide a conceptual framework for how IS and EBIs are linked and that the IS itself needs to be considered a critical contextual determinant. Moreover, it also provides rigorous methodologic tools to isolate the effect of an IS, EBI, and combined effect of the IS and EBI.DiscussionLeveraging IV methods when exposure to an implementation strategy is random helps to conceptualize the context-dependent nature of implementation strategies, EBIs, and patient outcomes. IV methods formalize that the causal effect of an EBI may be specific to the context of the implementation strategy used to promote uptake. This integration of implementation science concepts and theory with rigorous causal epidemiologic methods yields novel insights and provides important tools for exploring the next generation of questions related to mechanisms and context in implementation science.

Effects of Compliance to a Training Intervention for High School Students with ADHD

ABSTRACT Objective We evaluated the effects of treatment compliance with the Challenging Horizons Program (CHP) for high school aged adolescents with attention-deficit hyperactivity disorder (ADHD). Method Participants were 185 high school aged adolescents (65% non-Hispanic White; 79% male) with a diagnosis of ADHD who were randomly assigned to either CHP or community control. Outcomes included parent-rated academic functioning, parent- and self-rated social-emotional functioning, and GPA. The complier average causal effect (CACE) was estimated using propensity-weighted models for youth engaging in ≥ 30 CHP individual sessions (15–20 min) across the academic year. Results Most (78%) CHP participants engaged in≥30 CHP sessions. CACE analyses using latent growth curve modeling revealed significant treatment effects among treatment compliers across ratings of academic and social outcomes relative to similar control participants. For most outcomes, CACE estimates were larger than those found in intent-to-treat analyses, especially at 6-months follow-up. Conclusions Compliance with 30 or more individual CHP sessions appeared to be an attainable threshold associated with incremental gains across several academic and social outcomes. Effects of compliance were amplified at 6-months follow-up, supporting the hypothesized theory of change of training interventions. Future work should focus on facilitators of treatment engagement and feasibility of the CHP as delivered by high school personnel.

A preoperative supervised exercise program potentially improves long-term survival after elective abdominal aortic aneurysm repair

ObjectiveA preoperative supervised exercise program (SEP) improves cardiorespiratory fitness and perioperative outcomes for patients undergoing elective abdominal aortic aneurysm (AAA) repair. The aim of this study was to assess the effect of a preoperative SEP on long-term survival of these patients. A secondary aim was to consider long-term changes in cardiorespiratory fitness and quality of life. MethodsPatients scheduled for open or endovascular AAA repair were previously randomized to either a 6-week preoperative SEP or standard management, and a significant improvement in a composite outcome of cardiac, pulmonary, and renal complications was seen following SEP. For the current analysis, patients were followed up to 5 years post-surgery. The primary outcome for this analysis was all-cause mortality. Data were analyzed on an intention to treat (ITT) and per protocol (PP) basis, with the latter meaning that patients randomized to SEP who did not attend any sessions were excluded. The PP analysis was further interrogated using a complier average causal effect (CACE) analysis on an all or nothing scale, which adjusts for compliance. Additionally, patients who agreed to follow-up attended the research center for cardiopulmonary exercise testing and/or provided quality of life measures. ResultsITT analysis demonstrated that the primary endpoint occurred in 24 of the 124 participants at 5 years, with eight in the SEP group and 16 in the control group (P = .08). The PP analysis demonstrated a significant survival benefit associated with SEP attendance (4 vs 16 deaths; P = .01). CACE analysis confirmed a significant intervention effect (hazard ratio, 0.36; 95% confidence interval, 0.16-0.90; P = .02). There was no difference between groups for cardiorespiratory fitness measures and most quality of life measures. ConclusionsThese novel findings suggest a long-term mortality benefit for patients attending a SEP prior to elective AAA repair. The underlying mechanism remains unknown, and this merits further investigation.

Cost-Effectiveness a Parenting Skills Program Implemented in Public PreK Schools in Disadvantaged Urban Communities.

Little is known about the cost-effectiveness of parent training programs when offered universally in U.S. elementary schools in disadvantaged urban communities. To estimate the cost-effectiveness of a universal school-based implementation study of the Chicago Parent Program (CPP). CPP was offered universally from 2014 to 2017 to parents of PreK students in 12 Baltimore City Title 1 schools (n = 380; 61.1% Black/African American, 24.1% Hispanic). CPP program implementation and operating costs were estimated using microcosting methods and data drawn from study records. A Complier Average Causal Effects (CACE) framework was used to estimate an Incremental Cost Effectiveness Ratio (ICER) for CPP's average cost per child per 1% decrease in conduct problem prevalence at follow-up. This ICER was then compared with comparable ICERs for four parenting interventions that have been implemented and evaluated in Europe: Connect, Incredible Years, COPE, and Comet. CPP cost $937.51 per child (95% CI: $902.09 to $971.92). Adjusted CACE estimates indicated that CPP resulted in a 31.4% reduction (95% CI: -39.7% to -23.9%) in conduct problem prevalence at follow-up among children whose parents attended CPP. The mean ICER for CPP was $29.86 per each 1% reduction in prevalence (95% CI: $21.05 to $50.71). CPP's ICER was similar to ICERs for Connect ($25.50) and COPE ($29.72), and less than ICERs for Incredible Years ($50.36) and Comet ($59.69). School-based CPP offered universally to parents of children transitioning to Kindergarten in extremely disadvantaged U.S. urban communities was found to offer relatively good value compared with similar parenting programs that are widely used in Europe.

Sensitivity of estimands in clinical trials with imperfect compliance.

In clinical trials that are subject to noncompliance, the commonly used intention-to-treat estimand is valid as a causal effect of treatment assignment but is sensitive to the level of compliance. An alternative estimand, the complier average causal effect (CACE), measures the average effect of treatment received in the latent subset of subjects who would comply with either assigned treatment. Because the principal stratum of compliers can vary with the circumstances of the trial, CACE too depends on the compliance fraction. We propose a model in which an underlying latent proto-compliance interacts with trial characteristics to determine a subject's compliance behavior. When the latent compliance is independent of the individual treatment effect, the average causal effect is constant across compliance classes, and CACE is robust across trials and equal to the population average causal effect. We demonstrate the potential degree of sensitivity of CACE in a simulation study, an analysis of data from a trial of vitamin A supplementation in children, and a meta-analysis of trials of epidural analgesia in labor.

Impact of the WHO Safe Childbirth Checklist on safety culture among health workers: A randomized controlled trial in Aceh, Indonesia.

The World Health Organization (WHO) developed the Safe Childbirth Checklist (SCC) to increase the application of essential birth practices to ultimately reduce perinatal and maternal deaths. We study the effects of the SCC on health workers safety culture, in the framework of a cluster-randomized controlled trial (16 treatment facilities/16 control facilities). We introduced the SCC in combination with a medium intensity coaching in health facilities which already offered at minimum basic emergency obstetric and newborn care (BEMonC). We assess the effects of using the SCC on 14 outcome variables measuring self-perceived information access, information transmission, frequency of errors, workload and access to resources at the facility level. We apply Ordinary Least Square regressions to identify an Intention to Treat Effect (ITT) and Instrumental Variable regressions to determine a Complier Average Causal Effect (CACE). The results suggest that the treatment significantly improved self-assessed attitudes regarding the probability of calling attention to problems with patient care (ITT 0.6945 standard deviations) and the frequency of errors in times of excessive workload (ITT -0.6318 standard deviations). Moreover, self-assessed resource access increased (ITT 0.6150 standard deviations). The other eleven outcomes were unaffected. The findings suggest that checklists can contribute to an improvement in some dimensions of safety culture among health workers. However, the complier analysis also highlights that achieving adherence remains a key challenge to make checklists effective.

Effect of pelvic floor muscle training on reports of urinary incontinence in obese women undergoing a low-calorie diet before bariatric surgery — protocol of a randomized controlled trial

BackgroundObesity represents a growing threat to health with multiple negative impacts including urinary incontinence. Pelvic floor muscle training (PFMT) is the first line of treatment for urinary incontinence. Both surgical and conservative weight loss results in improvement of urinary incontinence reports in obese women and we hypothesize that a low-calorie diet in combination with PFMT would result in additional beneficial effects to urinary symptoms in women with UI compared would with weight loss alone.ObjectiveTo assess the effect of a low-calorie diet plus PFMT protocol in obese women’s urinary incontinence reports.MethodsThis is a protocol for a randomized controlled trial that will include obese women reporting UI and being able to contract their pelvic floor muscles. The participants will be randomly allocated in two groups: group 1 will participate in a 12-week protocol of low-calorie diet delivered by a multi-professional team at a tertiary hospital; group II will receive the same low-calorie diet protocol during 12 weeks and will additionally participate in 6 group sessions of supervised PFMT delivered by a physiotherapist. The primary outcome of the study is self-reported UI, and severity and impact of UI on women’s quality of life will be assessed by the ICIQ-SF score. The secondary outcomes will be adherence to the protocols assessed using a home diary, pelvic floor muscle function assessed by bidigital vaginal palpation and the modified Oxford grading scale, and women’s self-perception of their PFM contraction using a questionnaire. Satisfaction with treatments will be assessed using a visual analog scale. The statistical analysis will be performed by intention to treat and multivariate analysis of mixed effects will be used to compare outcomes. The complier average causal effects (CACE) method will be used to assess adherence. There is an urgent need for a high-quality RCT to investigate if the association of a low-calorie diet and PFMT can provide a larger effect in the improvement of urinary incontinence reports in women with obesity.Trial registrationClinical Trials NCT04159467. Registered on 08/28/2021.

Assessing the effectiveness and the mechanisms of the Social-Emotional Prevention Program for Preschoolers: Findings from a universal school-based intervention

The Social-Emotional Prevention Program (SEP) encompasses a multifaceted approach (classroom curriculum, with teacher and parent training) intended to increase preschool children's social adjustment, as well as to reduce risk of emotional and behavioral problems. The present study's focus was on implementing the technology-assisted SEP version and was aimed at (a) investigating the program's effectiveness on children's social-emotional competencies and parental practices, as well as (b) testing the program's conceptual framework, with an emphasis on children's emotion regulation (ER) skills and parental emotion socialization practices as explanatory intervention mechanisms. A randomized-controlled trial (RCT) was conducted with five schools assigned to either the intervention or to a comparison condition (wait-list control). Structural equation models (SEM) and complier average causal effects (CACE) were conducted to evaluate SEP effectiveness on teacher- and parent-rated child outcomes (primary outcomes) and parenting behaviors (secondary outcomes). Findings from the present study indicated that (a) SEP fosters increased social-emotional competencies and increased use of adaptive ER strategies, with teacher and parent ratings converging to support these outcomes; (b) parental participation in the program increased the use of reappraisal and emotion coaching strategies; and (c) children's ER mediated the intervention's effect on social competence, whereas parental coaching and parental ER mediated SEP effects on children's ER. This study's findings suggest that the SEP may be an effective universal intervention for promoting preschoolers' social-emotional competence and may provide emerging evidence to support the program's hypothesized mechanisms of change.

The Effectiveness of a Parents as Teachers Home Visitation Program on School Readiness: An Application of Complier Average Causal Effect Analysis

ABSTRACT Purpose The purpose of this study is to evaluate an encouragement trial of a Parents as Teachers (PAT) home visitation intervention on the school readiness of preschool children using an innovative analysis to address issues of selective enrollment. Method Families were given the opportunity to enroll in a PAT program through a randomized lottery. The PAT program is assessed using standardized measures of school readiness before and after the two-year program. A comparison of three different analyses is used to evaluate the program – Average Treatment Effect (ATE) analysis, Intent-to-Treat (ITT) analysis, and Complier Average Causal Effect (CACE) analysis. CACE is an innovative analysis developed specifically to diagnose bias arising from selective enrollment in the context of an encouragement trial. Result All three analyses (ATE, ITT, and CACE) provide statistically significant evidence of an effective PAT program. However, the effect sizes for the CACE analysis are over twice as large as the other two analyses. The Cohen’s D for CACE is .934 compared to .424 for ATE and .381 for ITT. Conclusion This study provides evidence of an effective PAT program. The comparison of ATE, ITT, and CACE analyses reveals the potential for meaningful under-reporting of the program’s impact if selective enrollment is ignored. CACE analysis demonstrates how selective enrollment can bias evaluations of home visitation interventions in general.

Estimating complier average causal effects for clustered RCTs when the treatment affects the service population

Abstract Randomized controlled trials (RCTs) sometimes test interventions that aim to improve existing services targeted to a subset of individuals identified after randomization. Accordingly, the treatment could affect the composition of service recipients and the offered services. With such bias, intention-to-treat estimates using data on service recipients and nonrecipients may be difficult to interpret. This article develops causal estimands and inverse probability weighting (IPW) estimators for complier populations in these settings, using a generalized estimating equation approach that adjusts the standard errors for estimation error in the IPW weights. While our focus is on more general clustered RCTs, the methods also apply (reduce) to nonclustered RCTs. Simulations show that the estimators achieve nominal confidence interval coverage under the assumed identification conditions. An empirical application demonstrates the methods using data from a large-scale RCT testing the effects of early childhood services on children’s cognitive development scores. An R program for estimation is available for download.

Effects of Cross-Age Peer Mentoring Program within a Randomized Controlled Trial

This paper summarizes results from an impact study that employed a randomized controlled trial to estimate the efficacy of a cross-age peer mentor program designed to prevent school dropout during the transition from middle to high school. We present findings from the intent-to-treat (ITT) analyses, which included 1,351 ninth-grade students, alongside those of two different methods that estimate the complier average causal effect (CACE) of participating in the program. Although the confirmatory study, which investigated impact on attendance and credit accrual in ninth grade, was null, ITT analyses on exploratory outcomes indicate modest, yet potentially meaningful program impact on ninth-grade outcomes of discipline, school attachment, and expectations of degree attainment across varying dosage levels. CACE estimates also suggest that a threshold level of program participation broadens the program’s impact on additional exploratory academic achievement and social and emotional learning outcomes. Given the adverse effects of the transition to high school, this promising evidence indicates that the cross-age peer mentoring intervention could be an effective strategy for high schools to implement that leverages existing staff and students.

Family-based improvement for health literacy among the Yi nationality (FAMILY) in Liangshan: protocol of an open cohort stepped wedge cluster randomized controlled trial

BackgroundImprovement of health literacy constitutes a cornerstone to improving public health. However, the overall health literacy of Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) in the southwest Sichuan Province of China has kept extremely low for a long time. How to improve health literacy of the Yi nationality residents is key to be urgently solved. Notably, Family Branch System is a distinctive patrilineal bloodline organization of Yi nationality, which plays an important role in the daily life of Yi nationality. Meanwhile, Contracted Family Doctor Services is conducted in Liangshan Prefecture. Therefore, this study proposes an intervention model of health education based on Family Branch System and Contracted Family Doctor Services, which is a Family-based Improvement for Health Literacy among the Yi nationality (FAMILY) in Liangshan, when improving traditional Innovative Care for Chronic Conditions Framework (ICCC) framework.MethodsAn open cohort stepped wedge cluster randomized trial design is used to implement health literacy education interventions including project preparation, core group building, promotion within family branch and competition between family branches while using Contracted Family Doctor Services as control measure. The study will be conducted among Yi nationality residents in Meigu County and Yanyuan County, with health literacy level of residents as the primary outcome. Finally, mixed-effects model and causal inference method will be used to evaluate intervention effect.DiscussionThis study highlights family, using the unique Family Branch System and Contracted Family Doctor Services in Liangshan Prefecture to design intervention among improved ICCC framework, and combines the mixed-effects model with complier average causal effects (CACE) to estimate the intervention effect under non-compliance for the first time. Besides, other key technologies to be adopted include construction of electronic questionnaire quality control system, with quality control based on artificial intelligence. This trial contributes to exploring an effective way to improve health literacy of Yi nationality residents in Liangshan Prefecture, which will provide reference for other areas, especially poor areas, to improve residents’ health literacy.Trial registrationISRCTN11299863 on June 1, 2022; https://www.isrctn.com/.