Pragmatic Cluster-randomized Trial Research Articles

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

School-based caries prevention using silver diamine fluoride: A pragmatic randomized trial in low-income rural children.

Dental caries is the world's most prevalent noncommunicable disease, disproportionately affecting children from low-income families and rural geographic areas. The CariedAway 3.0 study was a cluster-randomized pragmatic non-inferiority trial comparing silver diamine fluoride (SDF) to sealants and atraumatic restorations (ART) for the prevention and control of dental caries. All participants also received fluoride varnish. Analysis consisted of mixed-effects logistic regression for caries prevalence and weighted least squares and mixed-effects negative binomial regression for caries incidence. A non-inferiority margin of 10% for the difference between groups was used. Dental caries was defined as an ICDAS score of four or greater. A total of 3345 children were enrolled across 35 schools; however there was a large proportion of children who were noncompliant and received external dental care over the course of the trial. In adjusted analyses of compliant participants (n=1083; 543 in the SDF group and 540 in the sealant and ART group), there was no difference in the weighted risk difference between treatment groups (B=0.003, 95% CI = -0.0001, 0.0008). The odds of caries prevalence was elevated in the SDF group in longitudinal analyses (OR = 1.35, 95% CI = 0.86, 2.11) but was not significant and was below the non-inferiority margin. There were no significant differences between groups for caries incidence in adjusted models (IRR = 1.19, 95% CI = 0.81, 1.74). Results for intent to treat analyses were similar to that of per-protocol. In this school-based clinical trial, the prevalence of dental caries in children treated with SDF and fluoride varnish was non-inferior compared to those treated with sealants, ART, and fluoride varnish, although the overall risk was slightly higher. Unfortunately, a high rate of dropout and participant noncompliance was observed, likely due to the impacts of COVID-19 on study procedures. As a result, observed effects may be unreliable beyond the short-term. NCT03448107.

Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial.

The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30mL/kg crystalloid fluid for hypotension or lactate ≥ 4mmol/L, remains controversial. We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2mmol/L were eligible. The intervention was theimplementation of the 1-h sepsis bundle.The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24h, acute heart failure at 24h, SOFA score at 72h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40min in the intervention group vs 113min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.

Behavioral economic interventions to embed early palliative care in community oncology (BE-EPiC): A pragmatic cluster-randomized trial.

Behavioral economic interventions to embed early palliative care in community oncology (BE-EPiC): A pragmatic cluster-randomized trial.

Abstract PO2-12-09: Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer

Abstract Background: SPPADE symptoms (Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression/distress, and Energy deficits/fatigue) may result from cancer and its treatment. The aim of this analysis was to characterize SPPADE symptoms in patients with breast cancer. Methods. SPPADE data were drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a stepped-wedge pragmatic cluster-randomized trial designed to evaluate a symptom management intervention in routine practice (NCT03892967). Symptom severity was measured on a 0-10 scale via a survey administered by patient portal, in-clinic tablet, or interactive voice response system (by phone) prior to, during, or soon after an outpatient oncology encounter. Scores of 4-6 were categorized as “moderate” and ≥7 as “severe.” In this analysis, only the data from each patient’s initial survey were included. Results. A total of 9,651 patients with breast cancer completed an initial E2C2 survey between March 2019 and January 2023. The proportion of patients with moderate or severe SPPADE symptoms were as follows: 22% moderate and 10% severe for insomnia; 18% moderate and 7% severe for pain; 17% moderate and 7% severe for anxiety; 15% moderate and 5% severe for emotional distress; 25% moderate and 12% severe for fatigue; and 22% moderate and 8% severe for impaired physical function. Table 1 presents score means and standard deviations by demographic subgroup. Conclusions. SPPADE symptoms are common in patients with breast cancer. These observations warrant routine implementation of symptom surveillance and management in breast oncology. Funding acknowledgement: The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium is a Cancer Moonshot Research Initiative under the authorization of the 2016 United States 21st Century Cures Act. This research was supported by the National Cancer Institute of the NIH, UM1CA233033 (Mayo Clinic, Rochester, MN). Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer Citation Format: Kathryn Ruddy, Veronica Grzegorczyk, Deirdre Pachman, Sandra Mitchell, Bolun Liu, Deanne Smith, Ciara O'Sullivan, Shawna Ehlers, Jeph Herrin, Parvez Rahman, Andrea Cheville. Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-09.

Noninferiority of Silver Diamine Fluoride vs Sealants for Reducing Dental Caries Prevalence and Incidence

Dental caries is the world's most prevalent noncommunicable disease and a source of health inequity; school dental sealant programs are a common preventive measure. Silver diamine fluoride (SDF) may provide an alternative therapy to prevent and control caries if shown to be noninferior to sealant treatment. To determine whether school-based application of SDF is noninferior to dental sealants and atraumatic restorative treatment (ART) in the prevalence of dental caries. The Silver Diamine Fluoride Versus Therapeutic Sealants for the Arrest and Prevention of Dental Caries in Low-Income Minority Children (CariedAway) study was a pragmatic noninferiority cluster-randomized clinical trial conducted from February 2018 to June 2023 to compare silver diamine fluoride vs therapeutic sealants for the arrest and prevention of dental caries. Children at primary schools in New York, New York, with at least 50% of the student population reporting as Black or Hispanic and at least 80% receiving free or reduced lunch were included. This population was selected as they are at the highest risk of caries in New York. Students were randomized to receive either SDF or sealant with ART; those aged 5 to 13 years were included in the analysis. Treatment was provided at every visit based on need, and the number of visits varied by child. Schools with preexisting oral health programs were excluded, as were children who did not speak English. Of 17 741 students assessed for eligibility, 7418 were randomized, and 4100 completed follow-up and were included in the final analysis. Participants were randomized at the school level to receive either a 38% concentration SDF solution or glass ionomer sealants and ART. Each participant also received fluoride varnish. Primary study outcomes were the prevalence and incidence of dental caries. A total of 7418 children (mean [SD] age, 7.58 [1.90] years; 4006 [54.0%] female; 125 [1.7%] Asian, 1246 [16.8%] Black, 3648 [49.2%] Hispanic, 153 [2.1%] White, 114 [1.5%] multiple races or ethnicities, 90 [1.2%] other [unspecified], 2042 [27.5%] unreported) were enrolled and randomized to receive either SDF (n = 3739) or sealants with ART (n = 3679). After initial treatment, 4100 participants (55.0%) completed at least 1 follow-up observation. The overall baseline prevalence of dental caries was approximately 27.2% (95% CI, 25.7-28.6). The odds of decay prevalence decreased longitudinally (odds ratio [OR], 0.79; 95% CI, 0.75-0.83) and SDF was noninferior compared to sealants and ART (OR, 0.94; 95% CI, 0.80-1.11). The crude incidence of dental caries in children treated with SDF was 10.2 per 1000 tooth-years vs 9.8 per 1000 tooth-years in children treated with sealants and ART (rate ratio, 1.05; 95% CI, 0.97-1.12). In this school-based pragmatic randomized clinical trial, application of SDF resulted in nearly identical caries incidence compared to dental sealants and ART and was noninferior in the longitudinal prevalence of caries. These findings suggest that SDF may provide an effective alternative for use in school caries prevention. ClinicalTrials.gov Identifier: NCT03442309.

Decentralising chronic disease management in sub-Saharan Africa: a protocol for the qualitative process evaluation of community-based integrated management of HIV, diabetes and hypertension in Tanzania and Uganda

IntroductionSub-Saharan Africa continues to experience a syndemic of HIV and non-communicable diseases (NCDs). Vertical (stand-alone) HIV programming has provided high-quality care in the region, with almost 80% of people living...

PLUS-IS-LESS project: Procalcitonin and Lung UltraSonography-based antibiotherapy in patients with Lower rESpiratory tract infection in Swiss Emergency Departments: study protocol for a pragmatic stepped-wedge cluster-randomized trial

BackgroundLower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED).MethodsThe PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning.DiscussionThe PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful.The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance.Trial registrationThis study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406.Trial statusRecruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.

Symptom burden in patients with early-onset colorectal cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial.

31 Background: Incidence of early-onset colorectal cancer (eoCRC, <50 years of age at diagnosis) is increasing globally. However, little is known regarding symptom burden in this sub-population. We compared symptoms in patients with eoCRC to those of patients with average-onset CRC (aoCRC, diagnosed at age ≥ 50). Methods: E2C2 is a stepped-wedge, cluster-randomized pragmatic trial evaluating a collaborative care model for the assessment and management of six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, emotional Distress, and Energy deficit (SPPADE)]. Patients were asked to complete assessments rating each of these symptoms on an 11-point numerical rating scale. Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of patients with CRC, comparing SPPADE symptoms on an initial survey, regardless of timing in treatment course, between patients with eoCRC and aoCRC. Results: Patients with CRC (n=4281) completed a survey between March 2019 and December 2022. Patient demographics and SPPADE symptoms are reported in the table. Patients with eoCRC were more likely to report severe sleep disturbance ( p<0.0001), pain ( p=0.03485), anxiety ( p<0.0001), emotional distress ( p<0.0001), and fatigue ( p=0.01083). In patients with eoCRC, women were more likely to report severe pain (12.6% vs 6.9%, p=0.0069), anxiety (16.1% vs 10.0%, p=0.012), emotional distress (12.1% vs 5.4%, p=0.00066), fatigue (18.9% vs 13.4%, p=0.038), and physical function impairment (10.1% vs 5.8%, p=0.026) compared to men. Conclusions: Patients with eoCRC reported higher symptom severity than patients with aoCRC. This suggests unique needs for symptom management in patients with eoCRC. Additional research is needed to evaluate how time since diagnosis, disease characteristics, cancer-directed treatment patterns, and co-occurring symptoms are associated with specific symptoms in this population. [Table: see text]

Deintensification of potentially inappropriate medications amongst older frail people with type 2 diabetes: Protocol for a cluster randomised controlled trial (D-MED study)

AimsAmongst elderly people with type 2 diabetes (T2D) over prescribing can result in emergency ambulance call-outs, falls and fractures and increased mortality, particularly in frail patients. Current clinical guidelines, however, remain focused on medication intensification rather than deintensification where appropriate. This study aims to evaluate the effectiveness of an electronic decision-support system and training for the deintensification of potentially inappropriate medications amongst older frail people with T2D, when compared to ‘usual’ care at 12-months. MethodsThis study is an open-label, multi-site, two-armed pragmatic cluster-randomised trial. GP practices randomised to the ‘enhanced care’ group have an electronic decision support system installed and receive training on the tool and de-intensification of diabetes medications. The system flags eligible patients for possible deintensification of diabetes medications, linking the health care professional to a clinical algorithm. The primary outcome will be the number of patients at 12-months who have had potentially inappropriate diabetes medications de-intensified. ResultsStudy recruitment commenced in June 2022. Data collection commenced in January 2023. Baseline data have been extracted from 40 practices (3145 patients). ConclusionsDigital technology, involving computer decision systems, may have the potential to reduce inappropriate medications and aid the process of de-intensification. Trial registrationInternational Standard Randomised Controlled Trial Number: ISRCTN53221378. Available at: https://www.isrctn.com/ISRCTN53221378.

MEDICATION DE-ESCALATION AND GLYCATED HEMOGLOBIN AMONG OLDER ADULTS WITH DIABETES AND DEMENTIA

Abstract Patients with co-occurring diabetes and dementia and low (< 7.0) glycated hemoglobin (HbA1c) are at risk for adverse events and may require antihyperglycemic medication de-escalation. Whether de-escalation leads to a desired HbA1c is unknown. We assessed the relationship between antihyperglycemic de-escalation and attainment of a desired HbA1c. We selected older adults with diabetes and dementia with low HbA1c enrolled in the Enhanced Quality in Primary Care for Elders with Diabetes and Dementia, a multicenter cluster-randomized pragmatic trial. We determined whether antihyperglycemic medications were de-escalated during the twenty-four-month intervention. We classified a positive outcome as a subsequent desired HbA1c range for those who entered the study with HbA1cs < 7.0. We controlled for age, sex, race/ethnicity, Charlson comorbidity index, antihyperglycemic medications, and the COVID-19 pandemic. We performed a multivariable generalized linear binomial regression analysis and report the likelihood (adjusted risk ratio; aRR) (plus 95% confidence interval (CI)) of achieving the desired range HbA1c. The predominant population was older adults 85 years and older (42%), females (60%), and non-Hispanic Whites (64%). A tenth of the population had de-escalation and 19% of the population achieved the desired HbA1c range at the end of the study period. Metformin was the most frequently retained medication after de-escalation (66.7%). After adjusting for potential confounders, de-escalation was associated with 2.2 times the likelihood of attaining the desired HbA1c range (aRR: 2.20; 95% CI: 1.34 – 3.55). In conclusion, antihyperglycemic medication de-escalation improves the glycemic control of older adults with DM/ADRD.

PRAGMATIC IMPLEMENTATION OF AN ADVANCE CARE PLANNING INTERVENTION: FINDINGS FROM SHARING CHOICES

Abstract Advance care planning (ACP) is defined as a key task in ambulatory care for patients to share values, goals, and preferences for future medical care. Ideally ACP is revisited throughout the course of serious illness and engages family in discussions with clinicians. Most interventions, however, have not targeted primary care as a setting for ACP but have instead targeted a specific illness, conversation or setting such as the inpatient hospital or nursing home. Additionally, family is often not included in ACP discussions. This symposium will discuss critical components of the SHARING Choices cluster-randomized pragmatic trial, including the setup, monitoring, and analysis of this intervention within two primary care health systems located in the Baltimore-Washington DC metropolitan corridor. Each presenter will discuss key efforts conducted during the trial that highlight challenges, lessons learned, and novel approaches of embedding an evidence-based intervention within usual care settings targeting older adults 65 years of age and older. Preliminary analyses indicate that the ACP intervention was highly effective for increasing the likelihood of having advance directives in the patients’ electronic health records within 1-year of intervention initiation (odds ratio = 2.88, p < 0.001). Attendees of this symposium will take away relevant insights for implementing effective ACP and communication interventions within primary care settings as well as supporting outcome data. Our discussant will provide thoughts on the implications of these results for current primary care organizations and in the field of ACP and communication for older adults including those with dementia.

Design and implementation of the hospital airway resuscitation trial

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials—alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.

Integrating Community Health Workers' Dual Clinic-Community Role in Safety-Net Primary Care: Implementation Lessons from a Pragmatic Diabetes-Prevention Trial.

Over a third of US adults carry a diagnosis of prediabetes, 70% of whom may progress to type 2 diabetes mellitus ("diabetes"). Community health workers (CHWs) can help patients undertake healthy behavior to prevent diabetes. However, there is limited guidance to integrate CHWs in primary care, specifically to address CHWs' dual clinic-based and community-oriented role. Using evidence from CHWs' adaptations of a diabetes-prevention intervention in safety-net hospitals in New York City, we examine the nature, intent, and possible consequences of CHWs' actions on program fidelity. We propose strategies for integrating CHWs in primary care. Case study drawing on the Model for Adaptation Design and Impact (MADI) to analyze CHWs' actions during implementation of CHORD (Community Health Outreach to Reduce Diabetes), a cluster-randomized pragmatic trial (2017-2022) at Manhattan VA and Bellevue Hospital. CHWs and clinicians in the CHORD study, with a focus in this analysis on CHWs. Semi-structured interviews and focus group discussion with CHWs (n=4); semi-structured interviews with clinicians (n=17). Interpretivist approach to explain CHWs' adaptations using a mix of inductive and deductive analysis. CHWs' adaptations extended the intervention in three ways: by extending social assistance, healthcare access, and operational tasks. The adaptations were intended to improve fit, reach, and retention, but likely had ripple effects on implementation outcomes. CHWs' focus on patients' complex social needs could divert them from judiciously managing their caseload. CHWs' community knowledge can support patient engagement, but overextension of social assistance may detract from protocolized health-coaching goals. CHW programs in primary care should explicitly delineate CHWs' non-health support to patients, include multiprofessional teams or partnerships with community-based organizations, establish formal communication between CHWs and clinicians, and institute mechanisms to review and iterate CHWs' work to resolve challenges in their community-oriented role.

Multi-center, pragmatic, cluster-randomized, controlled trial of standardized peritoneal dialysis (PD) training versus usual care on PD-related infections (the TEACH-PD trial): trial protocol

BackgroundPeritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices.MethodsThe TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.DiscussionTEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections.Trial registrationClinicalTrials.gov NCT03816111. Registered on 24 January 2019.

Evaluation of the impact of letters to GP practices to promote asthma prescription uptake in school-age children during summer (TRAINS study): a pragmatic cluster-randomised controlled trial

BackgroundAsthma exacerbations peak in school-aged children after the return to school in September. Previous studies have shown a decline in collections of asthma prescriptions during August. The PLEASANT trial demonstrated that sending a reminder letter to parents increased prescription uptake; reduced unscheduled care, and was cost saving to the health service. We aimed to assess whether informing general practitioner (GP) practices about the PLEASANT trial and its results could lead to its implementation in routine practice. MethodsThe trial to assess implementation of new research in a primary care setting (TRAINS) was a pragmatic cluster-randomised (1:1) trial conducted in England involving GP practices contributing to the Clinical Practice Research Datalink (CPRD). The intervention was a letter informing the GP practice of the PLEASANT trial results with recommendations for implementation. GP practices in the control group continued with usual care without receiving any letters about PLEASANT trial. The intervention was distributed via CPRD by both mail and email in June 2021. The trial received both University of Sheffield Ethics approval and Independent Scientific Advisory Committee (ISAC) approval. The primary outcome was the proportion of children with asthma (aged 4–15 years) who had a prescription for a preventer between Aug 1 and Sept 30, 2021. This trial is registered with ClinicalTrials.gov, NCT05226091. FindingsA total of 1326 GP practices, including 90 583 children with asthma, were included in the study. These practices were randomly allocated to the intervention group (664 practices, 44 708 children) or the control group (662 practices, 45 875 children). In assessing the impact of the intervention on the proportion of children collecting a preventer prescription, 15 716 (35·3%) of 44 708 children from the intervention group and 16 001 (35·1%) of 45 559 children from the control group picked up a prescription. There was no statistically significant difference observed (odds ratio [OR] 1·01, 95% CI 0·97–1·05), indicating that the intervention had no effect. InterpretationThe study findings suggest that passive intervention of providing a letter to GPs did not achieve the intended outcomes. To bridge the gap between evidence and practice, alternative, more proactive strategies could be explored to address the identified issues. FundingJazan University.

Effects of the Million Hearts Model on Myocardial Infarctions, Strokes, and Medicare Spending

The Million Hearts Model paid health care organizations to assess and reduce cardiovascular disease (CVD) risk. Model effects on long-term outcomes are unknown. To estimate model effects on first-time myocardial infarctions (MIs) and strokes and Medicare spending over a period up to 5 years. This pragmatic cluster-randomized trial ran from 2017 to 2021, with organizations assigned to a model intervention group or standard care control group. Randomized organizations included 516 US-based primary care and specialty practices, health centers, and hospital-based outpatient clinics participating voluntarily. Of these organizations, 342 entered patients into the study population, which included Medicare fee-for-service beneficiaries aged 40 to 79 years with no previous MI or stroke and with high or medium CVD risk (a 10-year predicted probability of MI or stroke [ie, CVD risk score] ≥15%) in 2017-2018. Organizations agreed to perform guideline-concordant care, including routine CVD risk assessment and cardiovascular care management for high-risk patients. The Centers for Medicare & Medicaid Services paid organizations to calculate CVD risk scores for Medicare fee-for-service beneficiaries. CMS further rewarded organizations for reducing risk among high-risk beneficiaries (CVD risk score ≥30%). Outcomes included first-time CVD events (MIs, strokes, and transient ischemic attacks) identified in Medicare claims, combined first-time CVD events from claims and CVD deaths (coronary heart disease or cerebrovascular disease deaths) identified using the National Death Index, and Medicare Parts A and B spending for CVD events and overall. Outcomes were measured through 2021. High- and medium-risk model intervention beneficiaries (n = 130 578) and standard care control beneficiaries (n = 88 286) were similar in age (median age, 72-73 y), sex (58%-59% men), race (7%-8% Black), and baseline CVD risk score (median, 24%). The probability of a first-time CVD event within 5 years was 0.3 percentage points lower for intervention beneficiaries than control beneficiaries (3.3% relative effect; adjusted hazard ratio [HR], 0.97 [90% CI, 0.93-1.00]; P = .09). The 5-year probability of combined first-time CVD events and CVD deaths was 0.4 percentage points lower in the intervention group (4.2% relative effect; HR, 0.96 [90% CI, 0.93-0.99]; P = .02). Medicare spending for CVD events was similar between the groups (effect estimate, -$1.83 per beneficiary per month [90% CI, -$3.97 to -$0.30]; P = .16), as was overall Medicare spending including model payments (effect estimate, $2.11 per beneficiary per month [90% CI, -$16.66 to $20.89]; P = .85). The Million Hearts Model, which encouraged and paid for CVD risk assessment and reduction, reduced first-time MIs and strokes. Results support guidelines to use risk scores for CVD primary prevention. ClinicalTrials.gov Identifier: NCT04047147.

The implementation and effectiveness of multi-tasked, paid community health workers on maternal and child health: A cluster-randomized pragmatic trial and qualitative process evaluation in Tanzania.

Community health worker programs have proliferated worldwide based on evidence that they help prevent mortality, particularly among children. However, there is limited evidence from randomized studies on the processes and effectiveness of implementing community health worker programs through public health systems. This paper describes the results of a cluster-randomized pragmatic implementation trial (registration number ISRCTN96819844) and qualitative process evaluation of a community health worker program in Tanzania that was implemented from 2011-2015. Program effects on maternal, newborn and child health service utilization, childhood morbidity and sick childcare seeking were evaluated using difference-in-difference regression analysis with outcomes measured through pre- and post-intervention household surveys in intervention and comparison trial arms. A qualitative process evaluation was conducted between 2012 and 2014 and comprised of in-depth interviews and focus group discussions with community health workers, community members, facility-based health workers and staff of district health management teams. The community health worker program reduced incidence of illness and improved access to timely and appropriate curative care for children under five; however, there was no effect on facility-based maternal and newborn health service utilization. The positive outcomes occurred because of high levels of acceptability of community health workers within communities, as well as the durability of community health workers' motivation and confidence. Implementation factors that generated these effects were the engagement of communities in program startup; the training, remuneration and supervision of the community health workers from the local health system and community. The lack of program effects on maternal and newborn health service utilization at facilities were attributed to lapses in the availability of needed care at facilities. Strategies that strengthen and align communities' and health systems core capacities, and their ability to learn, adapt and integrate evidence-based interventions, are needed to maximize the health impact of community health workers.

Agreement of Antipsychotic Use between Nursing Home Electronic Records and Minimum Data Set

ObjectivesNursing home (NH) Minimum Data Set (MDS) have frequently been used to measure medication use in epidemiologic studies, but there is little evidence on the accuracy of MDS-based medication records. We compared antipsychotic use estimated using 2 data sources—MDS and NH electronic medication administration records (eMAR). DesignCross-sectional comparison. Setting and ParticipantsThis analysis was based on MDS and linked eMAR data of 604 NH residents with dementia at 54 NHs in 10 states, participating in a cluster-randomized pragmatic trial (METRIcAL), from June 2019 to February 2020. MethodsOne admission, quarterly, or annual MDS assessment was chosen for each participant. The MDS assessment recorded the number of antipsychotic treatment days during a 7-day window. We then identified antipsychotic administrations during the corresponding window in the eMAR. We used Cohen kappa to assess agreement in the proportion of participants on antipsychotics during the week and used intraclass correlation coefficient (ICC) to assess the agreement of treatment days. We further used the eMAR data as a reference to calculate validity parameters. ResultsA total of 29.5% of study participants were identified as antipsychotic users based on the MDS vs 28.3% based on the eMAR data (kappa value: 0.96). MDS-based average treatment duration was estimated to be 2.0, consistent with eMAR-based estimate (1.8 days, ICC: 0.96). The sensitivity was 98.8% (95% CI 95.8%-99.9%), the specificity was 97.9% (95% CI 96.1%-99.1%), the positive predictive value was 94.9% (95% CI 90.8%-97.3%), and the negative predictive value was 99.5% (95% CI 98.2%-99.9%). Conclusions and ImplicationsAgreement between the MDS and eMAR in antipsychotic use is high, suggesting that the MDS is a valid tool to measure antipsychotic use in epidemiologic studies. Further studies with large and diverse populations are warranted to confirm our findings.

Dietary intake during a pragmatic cluster-randomized weight loss trial in an underserved population in primary care

BackgroundCurrently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals.MethodsPatients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status.ResultsA total of 803 patients were recruited. 84.4% were female, 67.2% African American, 26.1% received Medicaid, and 65.5% made less than $40,000. No differences in F/V intake were seen between the ILI and UC groups at months 6, 12, or 24. The ILI group reduced percent fat at months 6, 12, and 24 compared to UC. Change in F/V intake was negatively correlated with weight change at month 6 whereas change in fat intake was positively associated with weight change at months 6, 12, and 24 for the ILI group.ConclusionsThe pragmatic weight loss intervention in primary care did not increase F/V intake but did reduce fat intake in an underserved population with obesity. F/V intake was negatively associated with weight loss at month 6 whereas percent fat was positively correlated with weight loss throughout the intervention. Future efforts better targeting both increasing F/V intake and reducing fat intake may promote greater weight loss in similar populations.Trial registrationNCT Registration: NCT02561221