Cluster-randomized Clinical Trial Research Articles

Protocol for a cluster randomized clinical trial of a mastery-climate motor skills intervention, Children's Health Activity and Motor Program (CHAMP), on self-regulation in preschoolers.

Self-regulation (SR) is critical to healthy development in children, and intervention approaches (i.e., professional training, classroom-based curricula, parent-focused intervention) have shown to support or enhance SR. However, to our knowledge, none have tested whether changes in children's SR across an intervention relate to changes in children's health behavior and outcomes. This study, the Promoting Activity and Trajectories of Health (PATH) for Children-SR Study uses a cluster-randomized control trial to examine the immediate effects of a mastery-climate motor skills intervention on SR. Secondly, this study examines the associations between changes in SR and changes in children's health behaviors (i.e., motor competence, physical activity, and perceived competence) and outcomes (i.e., body mass index and waist circumference) (ClinicalTrials.gov Identifier, NCT03189862). The PATH-SR study will be a cluster-randomized clinical trial. A total of 120 children between the ages of 3.5 to 5 years of age will be randomized to a mastery-climate motor skills intervention (n = 70) or control (n = 50) condition. SR will be assessed using measures that evaluate cognitive SR (cognitive flexibility and working memory), behavioral SR (behavioral inhibition), and emotional SR (emotional regulation). Health behaviors will be assessed with motor skills, physical activity, and perceived competence (motor and physical) and health outcomes will be waist circumference and body mass index. SR, health behaviors, and health outcomes will be assessed before and after the intervention (pre-test and post-test). Given the randomization design, 70 children in the intervention group and 50 in the control group, we have 80% power to detect an effect size of 0.52, at a Type I error level of 0.05. With the data collected, we will test the intervention effect on SR with a two-sample t-test comparing the intervention group and the control group. We will further evaluate the associations between changes in SR and changes in children's health behaviors and health outcomes, using mixed effect regression models, with a random effect to account for within-subject correlations. The PATH-SR study addresses gaps in pediatric exercise science and child development research. Findings hold the potential to help shape public health and educational policies and interventions that support healthy development during the early years. Ethical approval for this study was obtained through the Health Sciences and Behavioral Sciences Institutional Review Board, University of Michigan (HUM00133319). The PATH-SR study is funded by the National Institutes of Health Common Fund. Findings will be disseminated via print, online media, dissemination events and practitioner and/or research journals. ClinicalTrials.gov Identifier, NCT03189862.

A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial

BackgroundAntimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+).MethodsePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design.DiscussionThis trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences.Trial registrationThe qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN (ISRCTN 13429325) on 24 March 2022

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalised with COVID-19 (COVASP): a pragmatic, cluster-randomised, non-inferiority trial

The COVID-19 pandemic has been associated with increased antimicrobial use despite low rates of bacterial co-infection. Prospective audit and feedback is recommended to optimise antibiotic prescribing, but high-quality evidence supporting its use for COVID-19 is absent. We aimed to study the efficacy and safety of prospective audit and feedback in patients admitted to hospital for the treatment of COVID-19. COVASP was a prospective, pragmatic, non-inferiority, small-unit, cluster-randomised trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, AB, Canada, with COVID-19 pneumonia. All patients aged at least 18 years who were admitted from the community to a designated study bed with microbiologically confirmed SARS-CoV-2 infection in the preceding 14 days were included if they had an oxygen saturation of 94% or lower on room air, required supplemental oxygen, or had chest-imaging findings compatible with COVID-19 pneumonia. Patients were excluded if they were transferred in from another acute care centre, enrolled in another clinical trial that involved antibiotic therapy, expected to progress to palliative care or death within 48 h of hospital admission, or managed by any member of the research team within 30 days of enrolment. COVID-19 unit and critical care unit beds were stratified and randomly assigned (1:1) to the prospective audit and feedback plus standard of care group or the standard of care group. Patients were masked to their bed assignment but the attending physician and study team were not. The primary outcome was clinical status on postadmission day 15, measured using a seven-point ordinal scale. We used a non-inferiority margin of 0·5. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT04896866, and is now closed. Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0-5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0-3·0] vs 2·0 [IQR 2·0-4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population. None.

Sickle Cell Trevor Thompson Transition Project (ST3P-UP) protocol for managing care transitions: Methods and rationale

BackgroundEmerging adults with sickle cell disease (EASCD) experience significant challenges transitioning from pediatric to adult care. Acute care utilization increases, quality of life (QOL) declines, with an increased risk of mortality. Currently, there are no practice standards to guide emerging adults through the transition process. We are creating a structured transition education (STE) based program for EASCD by customizing the Six Core Elements (6 CE) of Health Care Transition model and are evaluating the effectiveness of adding peer mentoring (PM). MethodsThe Sickle Cell Trevor Thompson Transition Project (ST3P-UP) is an ongoing multi-site, cluster randomized clinical trial with a target enrollment of 537 EASCD aged 16 to 25 years in pediatric care. Each site (n = 14) comprises a pediatric clinic, adult clinic, and a sickle cell disease (SCD) community-based organization (CBO). Sites are randomized 1:1 to either STE or STE + PM. EASCDs are followed prospectively for 24 months. Rapid cycle plan-do-study-act quality improvement (QI) methods are used to implement the STE. The primary objective is to compare the effectiveness of STE + PM versus STE only at decreasing the number of acute care visits per year over 24 months. The secondary objectives are to compare overall healthcare utilization and patient-reported QOL outcomes at 24 months. ConclusionWe aim to demonstrate the feasibility of using a QI approach to implement 6 CE-based practice standards at 14 disparate SCD clinical programs to guide EASCD through the transition process. We hypothesize that adding PM to the STE program will improve acute care reliance, QOL, and satisfaction with transition outcomes.

Effects of a School-Based Nutrition, Gardening, and Cooking Intervention on Metabolic Parameters in High-risk Youth

Although school-based gardening programs for children have consistently been shown to improve dietary behaviors, no cluster randomized clinical trial (RCT) has evaluated the effects of a school-based gardening intervention on metabolic outcomes. To evaluate the effects of a school-based gardening, nutrition, and cooking intervention (Texas Sprouts) on changes in metabolic outcomes in elementary schoolchildren. This study was a secondary analysis of a cluster RCT, conducted over 3 years from 2016 to 2019, at low-income elementary schools with majority Hispanic students in the greater Austin, Texas, area. Data were analyzed from January to August 2022. Texas Sprouts was 1 school year long (9 months) and consisted of (1) Garden Leadership Committee formation; (2) a 0.25-acre outdoor teaching garden; (3) 18 student gardening, nutrition, and cooking lessons taught by trained educators throughout the school year; and (4) 9 monthly parent lessons. The delayed intervention was implemented the following academic year and received an identical intervention. The following measures were obtained at baseline and postintervention (9 months): demographics via survey; measured height, weight, and body mass index parameters; and glucose, insulin, homeostatic model assessment of insulin resistance, and a lipid panel via an optional fasting blood draw. Sixteen elementary schools were randomly assigned to either Texas Sprouts intervention (8 schools) or to delayed intervention (control, 8 schools). A total of 3302 children (aged 7-12 years) were enrolled in Texas Sprouts, and fasting blood samples were obtained from 1104 children (or 33% of those enrolled) at baseline. The final analytic sample included 695 children (307 boys [44.17%]; mean [SE] age, 9.28 [0.04] years; 480 Hispanic children [69.02%]; 452 [65.03%] eligible for free or reduced lunch) with complete demographic data and baseline and postintervention (9-month) fasting blood draws. Compared with control schools, children from Texas Sprouts schools had a 0.02% reduction in mean hemoglobin A1c (95% CI, 0.03%-0.14%; P = .005) and a 6.40 mg/dL reduction in mean low-density lipoprotein cholesterol (95% CI, 3.82-8.97 mg/dL; P = .048). There were no intervention effects on glucose, insulin, homeostatic model assessment of insulin resistance, or other lipid parameters. In this cluster RCT, Texas Sprouts improved glucose control and reduced low-density lipoprotein cholesterol in high-risk youth. These findings suggest that elementary schools should incorporate garden-based interventions as a way to improve metabolic parameters in children. ClinicalTrials.gov Identifier: NCT02668744.

Efficacy of a Primary Care-Based Mobile Application to Increase Hepatitis C Screening Among Asian Americans: A Secondary Analysis of a Randomized Clinical Trial.

Hepatitis C virus (HCV) screening remains suboptimal. We assessed the efficacy of a mobile application and provider alert in enhancing HCV screening among Asian Americans. A secondary analysis of a cluster-randomized clinical trial was performed during the birth cohort screening era to assess the efficacy of a Hepatitis App (intervention), a multilingual mobile application delivering interactive video education on viral hepatitis and creating a Provider Alert printout, at primary care clinics within 2 healthcare systems in San Francisco from 2015 to 2017. A comparison group received usual care and a similar intervention on nutrition and physical activity. The outcome was electronic health record (EHR) documentation of HCV screening along with patient-provider communication about testing and test ordering. Four hundred fifty-two participants (mean age 57 years, 36% male, 80% foreign-born) were randomized by provider clusters to the intervention (n = 270) or comparison groups (n = 182). At 3-month follow up, the intervention group was more likely than the comparison group to be aware of HCV (75% vs 59%, P = .006), to discuss HCV testing with their providers (63% vs 13%, P < .001), to have HCV testing ordered (39% vs 10%, P < .001), and to have EHR-verified HCV testing (30% vs 6%, P < .001). Within the intervention group, being born between 1945 and 1965 (odds ratio, 3.15; 95% confidence interval, 1.35-7.32) was associated with increased HCV testing. The Hepatitis App delivered in primary care settings was effective in increasing HCV screening in a socioeconomically diverse Asian American cohort. This highlights the importance of mobile technology as a patient-centered strategy to address gaps in HCV care.

Comparing the effect of parental education via both lecture and film upon vaccination uptake for children under one year of age: A cluster randomized clinical trial

Background and AimVaccination is the most cost-effective action in preventing infectious diseases. Despite Iran's success in high vaccination coverage, in some areas there is a delay in vaccination. The aim of this study was to determine and compare the effect of education on immunization via lecture and film upon parental delay in vaccination uptake for children under 12 months of age. MethodsA multicentre cluster-randomized clinical trial with comprehensive urban health centres (CUHCs) in Shooshtar city, Khuzestan province, Iran as the unit of randomization was conducted. Overall, 8 CUHCs were randomized to receive education either via film (n = 165) or lecture (n = 164). In order to assign CUHCs to two groups, a simple random sampling method of coin tossing was used. Parents with children under 12 months and with a history of delayed vaccination were included in the study. Consecutive sampling was performed until the number needed for the cluster was reached. Interventions were delivered in small groups of 5–8 participants. Demographical data and clinical histories were collected from parents directly via a personal characteristic’s questionnaire. Clinical data was extracted from vaccination records, the child's vaccine card and the vaccine information registration system. Statistical analyses of intervention effects were performed as per-protocol analysis. ResultsIn terms of individual characteristics and vaccine information significant differences between the two groups were only observed in relation to the parent of the participant, the child's gender, the number of children in the family, and timely injection of the vaccine in the previous child (p < 0.05). The chance of delay in vaccination after the intervention, without and considering the effect of intervening variables was 78 % and 74 % higher in the lecture group than in the film group, respectively (OR = 1.786, CI = 1.152–2.774 vs AOR = 1.743, CI = 1.011–3.007). Overall, 37.6 % of children in the film-based education group and 51.8 % of children in the lecture-based education group received their next vaccine with a delay of more than 7 days. ConclusionEducation delivered via film can reduce the delay in vaccination more effectively. These findings, along with those of other studies conducted around the world suggest that multimedia education should be considered more widely in the field of education in children's vaccination.

Effectiveness of a game-based educational strategy e-EDUCAGUIA for implementing antimicrobial clinical practice guidelines in family medicine residents in Spain: a randomized clinical trial by cluster

BackgroundClinical practice guidelines (CPGs) have teaching potential for health professionals in training clinical reasoning and decision-making, although their use is limited. The objective was to evaluate the effectiveness of a game-based educational strategy e-EDUCAGUIA using simulated clinical scenarios to implement an antimicrobial therapy GPC compared to the usual dissemination strategies to improve the knowledge and skills on decision-making of family medicine residents. Additionally, adherence to e-EDUCAGUIA strategy was assessed.MethodsA multicentre pragmatic cluster-randomized clinical trial was conducted involving seven Teaching Units (TUs) of family medicine in Spain. TUs were randomly allocated to implement an antimicrobial therapy guideline with e-EDUCAGUIA strategy ( intervention) or passive dissemination of the guideline (control). The primary outcome was the differences in means between groups in the score test evaluated knowledge and skills on decision-making at 1 month post intervention. Analysis was made by intention-to-treat and per-protocol analysis. Secondary outcomes were the differences in mean change intrasubject (from the baseline to the 1-month) in the test score, and educational game adherence and usability. Factors associated were analysed using general linear models. Standard errors were constructed using robust methods.ResultsTwo hundred two family medicine residents participated (104 intervention group vs 98 control group). 100 medicine residents performed the post-test at 1 month (45 intervention group vs 55 control group), The between-group difference for the mean test score at 1 month was 11 ( 8.67 to 13.32) and between change intrasubject was 11,9 ( 95% CI 5,9 to 17,9). The effect sizes were 0.88 and 0.75 respectively. In multivariate analysis, for each additional evidence-based medicine training hour there was an increase of 0.28 points (95% CI 0.15–0.42) in primary outcome and in the change intrasubject each year of increase in age was associated with an improvement of 0.37 points and being a woman was associated with a 6.10-point reduction. 48 of the 104 subjects in the intervention group (46.2%, 95% CI: 36.5–55.8%) used the games during the month of the study. Only a greater number of evidence-based medicine training hours was associated with greater adherence to the educational game ( OR 1.11; CI 95% 1.02–1.21).ConclusionsThe game-based educational strategy e-EDUCAGUIA shows positive effects on the knowledge and skills on decision making about antimicrobial therapy for clinical decision-making in family medicin residents in the short term, but the dropout was high and results should be interpreted with caution. Adherence to educational games in the absence of specific incentives is moderate.Trial registrationClinicalTrials.gov Identifier: NCT02210442. Registered 6 August 2014.

Active vs Traditional Methods of Recruiting Children for a Clinical Trial in Rural Primary Care Clinics

To our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed. To evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity. This cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. Clinic eligibility criteria included at least 40% pediatric patients with Medicaid coverage and at least 100 potential participants. Eligibility criteria for children included a rural home address, age 6 to 11 years, and body mass index at or above the 85th percentile. Recruitment began February 3, 2020, and randomization of participants occurred on August 17, 2020. Data were analyzed from October 3, 2021, to April 21, 2022. Two recruitment methods were assessed: the active method, for which a list of potential participants seen within the past year at each clinic was generated through the electronic health record and consecutively approached by research staff based on visit date to the clinic, and the traditional method, for which recruitment included posters, flyers, social media, and press release. Clinics were randomized to the order in which the 2 methods were implemented in 4-week periods, followed by a 4-week catch-up period using the method found most effective in previous periods. For each recruitment method, the number and proportion of randomized children among those who were approached was calculated. A total of 104 participants were randomized (58 girls [55.8%]; mean age, 9.3 [95% CI, 9.0-9.6] years). Using the active method, 535 child-parent dyads were approached and 99 (18.5% [95% CI, 15.3%-22.1%]) were randomized. Using the traditional method, 23 caregivers expressed interest, and 5 (21.7% [95% CI, 7.5%-43.7%]) were randomized. All sites reached full enrollment using the active method and no sites achieved full enrollment using the traditional method. Mean time to full enrollment was 26.3 (range, 21.0-31.0) days. This study supports the use of the active approach with local primary care clinics to recruit children with overweight and obesity from rural communities into clinical trials. ClinicalTrials.gov Identifier: NCT04142034.

Intraclass Correlation and Variance in the Characteristics of Primary Care Patients Managing Chronic Medical and Behavioral Conditions.

Background To avoid statistical errors, researchers who recruit patients from selected medical practices and analyze them at the individual level need to account for the clustered nature of their sample. This is most often done using the intraclass correlation coefficients (ICCs), a measure of how strongly subjects recruited from the same cluster (in this case patients from a clinic) resemble each other. Aims The aim is to support the design of cluster-randomized studies by supplying estimates of variance and ICC of various measures using a population of patients from multiple primary care clinics. Materials and methods ICCs were extracted from a large cluster-randomized pragmatic clinical trial of adult primary care patients managing multiple chronic conditions, the Integrating Behavioral Health and Primary Care study (IBH-PC). IBH-PC collected demographics and patient-reported health outcomes on over 3,000 adults from 44 primary care practices in 13 states across the US. We present estimates of the standard deviation and ICC for gender, race, ethnicity, marital status, employment, income, education, social determinants of health, PROMIS-29 functional status, Duke Activity Status Index (DASI), nine-item Patient Health Questionnaire (PHQ-9) depression score, Generalized Anxiety Disorder (GAD-7) anxiety score, Asthma Symptom Utility Index, restricted activity days, medication adherence, health care visits in the past month, emergency room visits in the past year, hospital days in the past year, perception of quality and patient-centeredness of care, alcoholic drinks per month, and the GAIN substance use disorder screener. Results ICCs varied broadly with the highest values found for race and income and the lowest for short-term estimates of the GAIN. Conclusions These values can be used to inform the design, especially power estimates and sample size requirements, of future studies.

Transition to independent care for youth living with HIV: a cluster randomised clinical trial

Transitioning youth living with HIV to adult care is a crucial step in the HIV care continuum; however, tools to support transition in sub-Saharan Africa are insufficient. We assessed the effectiveness of an adolescent transition package (ATP) to improve youth readiness for transition to independent HIV care. In this hybrid type 1, multicentre, cluster randomised clinical trial, we assessed the effectiveness of an ATP (administered by routine clinic staff, which included standardised assessments and chapter books to guide discussions at scheduled clinic visits) in four counties in Kenya, with HIV clinics randomly assigned 1:1 to ATP or control (standard-of-care practice). Clinics were eligible to participate if they had at least 50 youth (aged 10-24 years) living with HIV enrolled in care. We used restricted randomisation to achieve cluster balance and an independent biostatistician used computer-generated random numbers to assign clinics. We excluded very large clinics with more than 1000 youth, clinics with fewer than 50 youth, paediatric-only clinics, clinics with logistical challenges, and the smallest clinics in Homa Bay county. Youth were eligible for the transition intervention if they were enrolled in participating clinics, were aged 15-24 years, and were aware of their positive HIV diagnosis. Study staff assessed transition readiness scores overall and by four domains (HIV literacy, self-management, communication, and support) in youth with HIV, which were then compared between groups by use of mixed-effects linear regression models. Analysis was by intention-to-treat and was adjusted for multiple comparisons. This trial is registered with ClinicalTrials.gov, NCT03574129. We identified 35 clinics in four counties; of these, ten were assigned to the intervention group and ten to the control group. Of 1066 youth with HIV enrolled between Nov 1, 2019, and March 18, 2020, 578 (54%) were in intervention and 488 (46%) in control sites. Mean baseline transition readiness score was 12·1 (SD 3·4) in ATP sites and 11·4 (3·7) in control sites. At 1 year, adjusting for baseline scores, age, and months since HIV disclosure, participants in the ATP group had significantly higher overall transition readiness scores (adjusted mean difference 1·7, 95% CI 0·3-3·1, p=0·024), and higher scores in HIV literacy domain (adjusted mean difference 1·0, 0·2-1·7, p=0·011). At 12 months, 15 serious adverse events were recorded, none of which were thought to be related to study participation. Integrating ATP approaches could enhance long-term HIV care in youth with HIV as they age into adulthood. US National Institutes of Health.

Personalized Disease Prevention (PDP): study protocol for a cluster-randomized clinical trial

BackgroundThe US Preventive Services Task Force recommends 25 primary preventive services for middle-aged adults, but it can be difficult to do them all.MethodsThe Personalized Disease Prevention (PDP) cluster-randomized clinical trial will evaluate whether patients and their providers benefit from an evidence-based decision tool to prioritize preventive services based on their potential to improve quality-adjusted life expectancy. The decision tool will be individualized for patient risk factors and available in the electronic health record. This Phase III trial seeks to enroll 60 primary care providers (clusters) and 600 patients aged 40–75 years. Half of providers will be assigned to an intervention to utilize the decision tool with approximately 10 patients each, and half will be assigned to usual care. Mixed-methods follow-up will include collection of preventive care utilization from electronic health records, patient and physician surveys, and qualitative interviews. We hypothesize that quality-adjusted life expectancy will increase by more in patients who receive the intervention, as compared with controls.DiscussionPDP will test a novel, holistic approach to help patients and providers prioritize the delivery of preventive services, based on patient risk factors in the electronic health record.Trial registrationClinicalTrials.gov NCT05463887. Registered on July 19, 2022.

StOP? II trial: cluster randomized clinical trial to test the implementation of a toolbox for structured communication in the operating room—study protocol

BackgroundSurgical care, which is performed by intensely interacting multidisciplinary teams of surgeons, anesthetists, and nurses, remains associated with significant morbidity and mortality. Intraoperative communication has been shown to be associated with surgical outcomes, but tools ensuring efficient intraoperative communication are lacking. In a previous study, we developed the StOP?-protocol that fosters structured intraoperative communication. Before the critical phases of the operation, the responsible surgeon initiates and leads one or several StOP?s. During a StOP?, the surgeon informs about the progress of the operation (status), next steps and proximal goals (objectives), and possible problems (problems) and encourages all team members to voice their observations and ask questions (?). In a before-after study performed mainly in visceral surgery, we found effects of the StOP?-protocol on mortality, length of hospital stay, and reoperation. We intend to assess the impact of the StOP?-protocol in a cluster randomized trial, in a wider variety of surgical specialties (i.e., general, visceral, thoracic, vascular surgery, surgical urology, and gynecology). The primary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces patient mortality within 30 days after the operation. The secondary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces unplanned reoperations, length of hospital stay, and unplanned hospital readmissions.MethodsThis study is designed as a multicenter, cluster-randomized parallel-group trial. Board-certified surgeons of participating clinical departments will be randomized 1:1 to the StOP? intervention group or to the standard of care (control) group. The intervention group will undergo a training to use the StOP?-protocol and receive regular feedback on their compliance with the protocol. The surgeons in the control group will communicate as usual during their operations. The unit of observation will be operations performed by cluster surgeons. Consecutive patients will be enrolled over 4 months per cluster. A total of 400 surgeons will be recruited, and we expect to collect patient outcome data for 14,000 surgical procedures.DiscussionThe StOP?-protocol was designed as a tool to structure communication during surgical procedures. Testing its effects on patient outcomes will contribute to implementing evidenced-based interventions to reduce surgical complications.Trial registrationClinicalTrials.gov NCT05356962. Registered on May 2, 2022

Bioequivalence of micronutrient powders to Corn-soy Blend on serum zinc concentration of children (6-36 months) with Moderate Acute Malnutrition in Thika urban slums, Kenya: A cluster-randomized controlled trial.

Zinc deficiency is common among children with Moderate Acute Malnutrition (MAM) and contributes to growth failure, increased morbidity and mortality. Diarrhoea and poor dietary practices are the main causes of zinc deficiency. Corn-soy Blend (CSB), the standard product in management of children with MAM has a limitation of poor micronutrient bioavailability. Micronutrient powders (MNPs) which are added at the point of consumption have a potential in improving micronutrient status however, scientific evidence on efficacy on improving the zinc status is scarce. A cluster-randomized clinical trial was designed to establish bioequivalence of MNPs to CSB on serum zinc status among children (6–36 months) with MAM in Thika informal settlements, Kenya. Sample size was calculated to show bioequivalence within ±20% limit. Twelve villages were randomized to four study groups. Three experimental groups received different formulations of MNPs added to unfortified CSB porridge as; multiple micronutrients containing zinc (CSB-MNP-A n = 84), multiple micronutrients without zinc (CSB-MNP-B n = 88) and zinc only (CSB-MNP-C n = 94). Control group (n = 80) received standard CSB fortified with multiple micronutrients. Standard amount of CSB was consumed in feeding centres for six months. Serum zinc concentration was assessed pre- and post-intervention. Data was analyzed based on treatment assignment regardless of adherence and drop-out status. Mixed effects linear regression was used to model pre-post change in serum zinc concentration, adjusting for clustering effect and baseline differences. Bioequivalence was assessed using two one-sided t-tests. At baseline, 84.4% were zinc deficient (serum zinc <65μg/dL) and zinc intake was sub-optimal (<3 mg/day) for 95.7% of children. Mean change in serum zinc concentration was significantly higher (p = 0.024) in CSB-MNP-A (18.7 ± 2.1) μg/dL compared to control group (11.8 ± 2.6 μg/dL). MNPs are not bioequivalent to CSB within the ±20% bioequivalence limit. MNPs are more effective in improving serum zinc status compared to CSB. Trials with larger sample sizes are recommended to validate the current findings.Trial registration: Pan African Clinical Trials Registry: PACTR201907492232376.

Effect of Clinical Decision Support With Audit and Feedback on Prevention of Acute Kidney Injury in Patients Undergoing Coronary Angiography

Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes. To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI. A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020. During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention. The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models. Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events. Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation. ClinicalTrials.gov Identifier: NCT03453996.

Effect of an Individualized Audit and Feedback Intervention on Rates of Musculoskeletal Diagnostic Imaging Requests by Australian General Practitioners

Audit and feedback can improve professional practice, but few trials have evaluated its effectiveness in reducing potential overuse of musculoskeletal diagnostic imaging in general practice. To evaluate the effectiveness of audit and feedback for reducing musculoskeletal imaging by high-requesting Australian general practitioners (GPs). This factorial cluster-randomized clinical trial included 2271 general practices with at least 1 GP who was in the top 20% of referrers for 11 imaging tests (of the lumbosacral or cervical spine, shoulder, hip, knee, and ankle/hind foot) and for at least 4 individual tests between January and December 2018. Only high-requesting GPs within participating practices were included. The trial was conducted between November 2019 and May 2021, with final follow-up on May 8, 2021. Eligible practices were randomized in a 1:1:1:1:1 ratio to 1 of 4 different individualized written audit and feedback interventions (n = 3055 GPs) that varied factorially by (1) frequency of feedback (once vs twice) and (2) visual display (standard vs enhanced display highlighting highly requested tests) or to a control condition of no intervention (n = 764 GPs). Participants were not masked. The primary outcome was the overall rate of requests for the 11 targeted imaging tests per 1000 patient consultations over 12 months, assessed using routinely collected administrative data. Primary analyses included all randomized GPs who had at least 1 patient consultation during the study period and were performed by statisticians masked to group allocation. A total of 3819 high-requesting GPs from 2271 practices were randomized, and 3660 GPs (95.8%; n = 727 control, n = 2933 intervention) were included in the primary analysis. Audit and feedback led to a statistically significant reduction in the overall rate of imaging requests per 1000 consultations compared with control over 12 months (adjusted mean, 27.7 [95% CI, 27.5-28.0] vs 30.4 [95% CI, 29.8-30.9], respectively; adjusted mean difference, -2.66 [95% CI, -3.24 to -2.07]; P < .001). Among Australian general practitioners known to frequently request musculoskeletal diagnostic imaging, an individualized audit and feedback intervention, compared with no intervention, significantly decreased the rate of targeted musculoskeletal imaging tests ordered over 12 months. ANZCTR Identifier: ACTRN12619001503112.

Thirteenth annual UPenn conference on statistical issues in clinical trials: Cluster-randomized clinical trials-opportunities and challenges (afternoon panel session).

Thirteenth annual UPenn conference on statistical issues in clinical trials: Cluster-randomized clinical trials-opportunities and challenges (afternoon panel session).

Assessment of Oxygen Supply-Demand Imbalance and Outcomes Among Patients With Type 2 Myocardial Infarction

Type 2 myocardial infarction occurs owing to multiple factors associated with myocardial oxygen supply-demand imbalance, which may confer different risks of adverse outcomes. To evaluate the prevalence and outcomes of different factors associated with oxygen supply-demand imbalance among patients with type 2 myocardial infarction. In this secondary analysis of a stepped-wedge, cluster randomized clinical trial conducted at 10 secondary and tertiary care hospitals in Scotland, 6096 patients with an adjudicated diagnosis of type 1 or type 2 myocardial infarction from June 10, 2013, to March 3, 2016, were identified, and the findings were reported on August 28, 2018. The trial enrolled consecutive patients with suspected acute coronary syndrome. The diagnosis of myocardial infarction was adjudicated according to the Fourth Universal Definition of Myocardial Infarction and the primary factor associated with oxygen supply-demand imbalance in type 2 myocardial infarction was defined. This secondary analysis was not prespecified. Statistical analysis was performed from July 7 to 30, 2020. Implementation of a high-sensitivity cardiac troponin I assay. All-cause death at 1 year according to the factors associated with oxygen supply-demand imbalance among patients with type 2 myocardial infarction. Of 6096 patients (2602 women [43%]; median age, 70 years [IQR, 58-80 years]), 4981 patients had type 1 myocardial infarction, and 1115 patients had type 2 myocardial infarction. The most common factor associated with oxygen supply-demand imbalance was tachyarrhythmia (616 of 1115 [55%]), followed by hypoxemia (219 of 1115 [20%]), anemia (95 of 1115 [9%]), hypotension (89 of 1115 [8%]), severe hypertension (61 of 1115 [5%]), and coronary mechanisms (35 of 1115 [3%]). At 1 year, all-cause mortality occurred for 15% of patients (720 of 4981) with type 1 myocardial infarction and 23% of patients (285 of 1115) with type 2 myocardial infarction. Compared with patients with type 1 myocardial infarction, those with type 2 myocardial infarction owing to hypoxemia (adjusted odds ratio [aOR], 2.35; 95% CI, 1.72-3.18) and anemia (aOR, 1.83; 95% CI, 1.14-2.88) were at greatest risk of death, whereas those with type 2 myocardial infarction owing to tachyarrhythmia (aOR, 0.83; 95% CI, 0.65-1.06) or coronary mechanisms (aOR, 1.07; 95% CI, 0.17-3.86) were at similar risk of death as patients with type 1 myocardial infarction. In this secondary analysis of a randomized clinical trial, mortality after type 2 myocardial infarction was associated with the underlying etiologic factor associated with oxygen supply-demand imbalance. Most type 2 myocardial infarctions were associated with tachyarrhythmia, with better prognosis, whereas hypoxemia and anemia accounted for one-third of cases, with double the mortality of type 1 myocardial infarction. These differential outcomes should be considered by clinicians when determining which cases need to be managed if patient outcomes are to improve. ClinicalTrials.gov Identifier: NCT01852123.

Weekly Iron Supplementation in 2-Year-Olds is Effective in Combating Anaemia

Introduction: Iron deficiency anaemia is a serious public health problem in developing countries, especially among children, as it is associated with serious developmental problems.&#x0D; Objective: To assess the effects of weekly ferrous sulphate supplementation on haemoglobin (Hb) levels and the prevalence of anaemia in children aged 2 to 3 years.&#x0D; Methods: A cluster-randomized clinical trial was conducted; two schools were randomly chosen. In the first school, the children received 6mg/kg of elemental iron in the form of iron sulphate once a week (intervention). In the other school, the children received a placebo (control). The intervention group had 44 participants at the end of the study, and the control group had 48 children. Blood samples were taken at baseline and at the end of the study to assess serum Hb levels and anaemia prevalence. The intervention lasted 14 weeks.&#x0D; Results: There was a mean increase in Hb of 0.85g/dL (p=0.0003) in the intervention group and a decrease of 0.74g/dL (p=0.0001) in the control group. The prevalence of anaemia significantly decreased in the weekly supplementation group with p=0.0002.&#x0D; Conclusion: Weekly iron supplementation in preschool-age children promoted a significant increase in Hb levels and a decrease in the prevalence of anaemia.

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care

SummaryBackgroundPatients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina.MethodsRegional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient–provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350.FindingsParticipants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = −0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient–provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy.InterpretationThese findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted.FundingNational Institutes of Health.