Pragmatic Cluster-randomized Trial Research Articles

Effect of prenatal multiple micronutrient supplementation on birth weight in Ethiopia: protocol for a pragmatic cluster-randomised trial

IntroductionThis programme effectiveness study responds to the need for evidence of the effect on birth weight of switching from iron-folic acid supplementation to multiple micronutrient supplementation as part of routine antenatal care in Ethiopia. A 2019 meta-analysis reported a mean increase of 35 g in birth weight among newborns of women who took multiple micronutrient supplements in pregnancy compared with those who took iron-folic acid. Responding to that evidence, the government of Ethiopia decided to implement a 21 district pilot of the use of multiple micronutrient supplementation in routine antenatal care and requested an evaluation of implementation outcomes, including on birth weight.Methods and analysisA pragmatic, facility-based, randomised trial is being conducted in 42 districts over five regions of Ethiopia between January 2023 and December 2024. Districts have been randomised to one of the two arms, either to retain iron-folic acid supplementation as part of routine antenatal care or switch to multiple micronutrient supplementation. During the study period, the birth weights of all eligible babies born in enrolled health facilities in these 42 districts are continuously recorded alongside data on maternal receipt and use of either multiple micronutrient or iron-folic acid supplementation. We hypothesise that newborns of women resident in the 21 multiple micronutrient supplementation districts will have higher mean birth weight than newborns of women resident in the 21 iron-folic acid supplementation districts. Facility surveys involving pregnant women and healthcare workers at baseline, midline and endline contribute to a process evaluation and cost and cost-effectiveness evaluation.Ethics and disseminationThe study received ethical approval from the review boards at the Ethiopian Public Health Institute (EPHI-IRB-455-2022) and the London School of Hygiene & Tropical Medicine (LSHTM ref 28021). Results from this pragmatic trial will be used by the government of Ethiopia in assessing success of the multiple-micronutrient supplements pilot and for decision making about subsequent scale-up. Dissemination of findings will also inform global decision making, particularly in settings where a transition from iron-folic acid to multiple micronutrient supplementation is being contemplated at scale.Trial registration numberNCT05708183.

Protocol for the economic evaluation of integrated community-based care compared with integrated facility-based care for HIV, hypertension and diabetes in Tanzania and Uganda (INTE-COMM trial)

Background The number of people living with multiple chronic conditions in sub-Saharan Africa is increasing, but health facilities are unable to meet demand. To improve health system capacity and access to care, community models of HIV care have been trialled in countries such as Tanzania and Uganda. However, no evidence exists to inform policymakers on the effectiveness and cost-effectiveness of integrated community-based models of care for HIV and chronic non-communicable conditions. This protocol outlines a within-trial economic evaluation to address this gap. Methods & analysis We will estimate the costs and cost-effectiveness of integrated community-based care for HIV, hypertension and diabetes compared with facility-based care within the INTE-COMM pragmatic cluster-randomised trial in Tanzania and Uganda. Analyses will adopt a 52-week time horizon, the duration of trial follow-up. The full enrolled trial sample will be analysed from a societal perspective, comprising provider and patient perspectives. Economic costs will be estimated, which includes valuing inputs such as donated goods or time foregone by participants because of receiving care. For provider costs, participant case report forms will inform resource use along with data from facilities and community sites. Resources will be valued using project accounts, facility spending, and locally available cost data. Patient costs will be estimated based on a care-seeking and cost questionnaire administered to participants. Estimated costs will be analysed with co-primary trial outcomes on plasma viral load suppression, glycaemia and blood pressure control to calculate incremental cost-effectiveness ratios (ICER). We will also calculate ICERs for secondary trial outcomes related to health-related quality of life and wellbeing. Cost drivers and outcomes will be varied within confidence bounds in a two-way sensitivity analysis. We will investigate equity impact by estimating the mean difference in outcomes between integrated community-based and facility-based care across household socio-economic quintiles and by measuring whether participants incurred catastrophic health expenditures. Trial registration number The ISRCTN Registry: ISRCTN15319595. Registered on 07 June 2022: https://doi.org/10.1186/ISRCTN15319595

Protocol for the economic evaluation of integrated community-based care compared with integrated facility-based care for HIV, hypertension and diabetes in Tanzania and Uganda (INTE-COMM trial)

Background The number of people living with multiple chronic conditions in sub-Saharan Africa is increasing, but health facilities are unable to meet demand. To improve health system capacity and access to care, community models of HIV care have been trialled in countries such as Tanzania and Uganda. However, no evidence exists to inform policymakers on the effectiveness and cost-effectiveness of integrated community-based models of care for HIV and chronic non-communicable conditions. This protocol outlines a within-trial economic evaluation to address this gap. Methods & analysis We will estimate the costs and cost-effectiveness of integrated community-based care for HIV, hypertension and diabetes compared with facility-based care within the INTE-COMM pragmatic cluster-randomised trial in Tanzania and Uganda. Analyses will adopt a 52-week time horizon, the duration of trial follow-up. The full enrolled trial sample will be analysed from a societal perspective, comprising provider and patient perspectives. Economic costs will be estimated, which includes valuing inputs such as donated goods or time foregone by participants because of receiving care. For provider costs, participant case report forms will inform resource use along with data from facilities and community sites. Resources will be valued using project accounts, facility spending, and locally available cost data. Patient costs will be estimated based on a care-seeking and cost questionnaire administered to participants. Estimated costs will be analysed with co-primary trial outcomes on plasma viral load suppression, glycaemia and blood pressure control to calculate incremental cost-effectiveness ratios (ICER). We will also calculate ICERs for secondary trial outcomes related to health-related quality of life and wellbeing. Cost drivers and outcomes will be varied within confidence bounds in a two-way sensitivity analysis. We will investigate equity impact by estimating the mean difference in outcomes between integrated community-based and facility-based care across household socio-economic quintiles and by measuring whether participants incurred catastrophic health expenditures. Trial registration number The ISRCTN Registry: ISRCTN15319595. Registered on 07 June 2022: https://doi.org/10.1186/ISRCTN15319595

Effect of Community-Based Integrated Care for Patients With Diabetes and Depression (CIC-PDD) in China: A Pragmatic Cluster-Randomized Trial.

To develop a care model for patients with both diabetes and depression and assess the model's effectiveness. In this pragmatic cluster randomized trial, we allocated eight community health centers into two groups: the enhanced usual care group and the intervention group. A comprehensive care plan was developed for the intervention group based on the integrated care model. We recruited individuals aged ≥18 years with type 2 diabetes and depression (Patient Health Questionnaire-9 score ≥10). The primary outcome was the between-group difference in the percentage of patients who had at least a 50% reduction in depressive symptoms and a reduction of at least 0.5 percentage points in HbA1c. The outcome analysis was conducted within the intention-to-treat population; missing data were multiply imputed. We enrolled 630 participants, with 275 in the intervention group and 355 in the control group. A significantly greater percentage of patients in the intervention group met the primary outcome at 12 months (for depressive symptoms: risk difference [RD] 31.03% [62.06% vs. 31.02%, respectively; 95% CI 21.85-40.21]; for HbA1c: RD 19.16% [32.41% vs. 13.25%, respectively; 95% CI 11.35-26.97]). The patients in the intervention group showed significant enhancements in mental quality of life (mean difference [MD] 6.74 [46.57 vs. 39.83, respectively; 95% CI 3.75-9.74]), diabetes self-care activities (MD 0.69 [3.46 vs. 2.78, respectively; 95% CI 0.52-0.86]), medication adherence (MD 0.72 [6.49 vs. 5.78, respectively; 95% CI 0.37-1.07]), and experience of care (MD 0.89 [3.84 vs. 2.95, respectively; 95% CI 0.65-1.12]) at 12 months. Rural participants benefited more from the intervention. The implementation strategy can serve as a valuable blueprint for the identification and treatment of patients with physical and mental multimorbidity in primary health care settings.

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

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

Impact of a multicomponent strategy including decentralized molecular testing for tuberculosis on mortality: planned analysis of a cluster-randomized trial in Uganda

Rapid diagnosis of tuberculosis (TB) is important for improving outcomes and reducing transmission. Previous studies assessing the impact of Xpert MTB/RIF (Xpert), a molecular assay that provides results within 2h, on mortality have been inconclusive. In this planned analysis of a pragmatic cluster-randomized trial in Uganda, we assessed whether a multicomponent strategy, including decentralized Xpert testing, decreased mortality among adults evaluated for TB. Ten community health centers were randomized, using a computer-generated randomization sequence, to the XPEL-TB intervention (on-site Xpert testing plus implementation supports) and ten to routine TB care without any modifications (on-site smear microscopy and referral-based Xpert testing for selected patients). The trial included all adults ( 18 years of age) undergoing evaluation for presumptive TB at each trial health center. All-cause mortality was a secondary outcome of the trial. For this analysis, the primary outcome was the mortality rate (censored at 18 months), and the secondary outcome was the six-month mortality risk. We compared the outcomes between trial arms using cluster-level analyses to account for stratified randomization and patient-level covariates. The trial was registered with the US National Institutes of Health (identifier: NCT03044158) and the Pan African Clinical Trials Registry (identifier: PACTR201610001763265). Vital status was ascertained for 8413 of 9563 (88%) XPEL-TB trial participants who presented at the health centers from October 22, 2018 through February 29, 2020. The adjusted rate ratio (aRR) was 0.77 (95% CI: 0.47-1.28), comparing the intervention (145 deaths/3655 person-years) to routine care (154 deaths/3015 person-years). In sub-group analyses, point estimates for mortality were lower in the intervention arm among people without HIV (aRR=0.50, 95% CI: 0.26-0.96) and among females (aRR=0.64, 95% CI: 0.33-1.23). The mortality risk analysis yielded similar results. Consistent point estimates favoring the intervention in our trial and previous ones suggest that Xpert testing may have an impact on mortality at community health centers. However, the magnitude of effect is small, and statistically significant results are unlikely to be attained within a single trial. Future trials of novel TB diagnostics at community health centers should focus on more proximal outcomes including TB detection and treatment initiation. This work was supported by the National Heart, Lung, and Blood Institute of the US National Institutes of Health under award number R01HL130192.

Sex-specific clinical outcomes and healthcare resource utilization in the 5 years following hospitalization for heart failure

Abstract Background Heart failure (HF) a leading cause of hospitalization, and sex differences in care have been described. Purpose We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF. Methods This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals enrolled in the Patient-Centred Care Transitions in HF pragmatic cluster-randomized trial. Primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Results The 4441 patients (50.7% female) had high event rates. At 5 years of follow-up, 63.6% male and 65.5% of male and female patients, respectively, had died (p=0.19); 85.4% and 84.4% of male and female patients, respectively, were readmitted with no sex differences in mean [SD] all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p=0.54) or HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p=0.80) per person. The mean (SD) annual total healthcare costs per patient was $80334 (116762) for males and $81010 (112625) for females, with no sex difference (p=0.90); however, there were sex differences in cost breakdown: males incurred greater costs from specialist, hemodialysis, and day surgical care, and females incurred greater costs from home visits and long-term care. Conclusions Males and females were at similarly high risk of mortality and readmissions, and had similar total healthcare costs following hospitalized for HF. Notwithstanding similar risks, males received relatively more specialist and invasive care, and females received relatively more supportive care.

Effectiveness of a task-sharing collaborative care model for the detection and management of depression among adults receiving antiretroviral therapy in primary care facilities in South Africa: A pragmatic cluster randomised controlled trial

BackgroundHIV is characterised by high rates of comorbidity with mental health conditions including depression, as such, the detection and treatment of comorbid depression is critical to achieve viral load suppression. This study evaluated the effectiveness of a collaborative care intervention for depression among adults with comorbid depression symptoms receiving ART in primary health care (PHC) facilities. MethodsWe conducted a pragmatic cluster-randomised trial in 40 clinics in the North West province of South Africa. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Participants were ≥ 18 years, receiving ART, and had depression symptoms indicated by Patient Health Questionnaire-9 (PHQ-9) score ≥ 9. Intervention clinics received: i) supplementary mental health training and clinical communication skills for PHC nurses; ii) workshops for PHC doctors on treating depression; and iii) lay counselling services. Using mixed effects regression models, we assessed co-primary outcomes of PHQ-9 response at 6 months (≥50 % reduction in baseline PHQ-9 score) and viral load suppression at 12 months (viral load<1000 copies/mL). ResultsThe intervention had no effect in PHQ-9 response (49 % vs 57 %, risk difference (RD) = −0.08, 95 % CI = −0.19; 0.03, p = 0.184) or viral load suppression (85 % vs 84 %, RD = 0.02, 95 % CI = −0.01; 0.04, p = 0.125). Nurses referred 4298 clinic patients to counsellors, however, only 66/1008 (7 %) of intervention arm participants were referred to counsellors at any point during the study. LimitationsThe highly pragmatic approach of this trial limited exposure to the counselling component of the intervention and referral to doctors for initiation of antidepressant treatment was extremely low. ConclusionThe trial showed no effect of a district-based intervention to strengthen collaborative care for depression. The trial revealed the extent of the treatment gap in the context of scaling up mental health services. Trial registrationClinicalTrials.gov (NCT02407691); Pan African Clinical Trials Registry (201504001078347).

Implementation strategies to improve adoption of unmet social needs screening and referrals in care management using enabling technologies: study protocol for a cluster randomized trial.

Adverse social determinants of health contribute to health inequities. Practice guidelines now recommend incorporating patient unmet social needs into patient care, and payors increasingly reimburse for screening and providing related referrals to community organizations. Emergent electronic health record (EHR)-based tools can enable clinical-community linkages, but their adoption commonly faces workflow and infrastructure barriers. Targeted implementation support such as training, championship, practice facilitation, and audit and feedback, can enhance such tools' adoption, but no prior research has assessed such strategies' impact on the adoption of 'enabling technologies' supporting clinical-community linkages. This study will test whether providing targeted implementation support to safety-net primary care health center care management teams improves the sustained adoption of EHR-based enabling technologies used to 1) screen for social needs and 2) link patients to community organizations. Formative evaluation of barriers and facilitators to adopting EHR-enabled social needs referrals and ascertainment of services received will include semi-structured interviews and a 'guided tour' of enabling technology used by care managers serving patients with complex health and/or social needs. A modified Delphi process conducted with care management staff and subject matter experts will then inform the development of an intervention targeting adoption of social risk EHR-enabled tools. The intervention will be piloted in three health centers, refined, then tested in a pragmatic stepped-wedge cluster-randomized trial in 20 health centers (five wedges of four health centers) that provide care management to high-risk patients with social needs. This study is among the first to evaluate an intervention designed to support care management teams' adoption of enabling technologies to increase clinical-community linkages. It was funded in September 2023 by the National Institute of Nursing Research. Formative activities will take place from January to June 2024, the intervention will be developed in July-December 2024, the pilot study will be conducted from January-March 2025, and the cluster-randomized trial will occur from July 2025 -September 2026. Study data will be analyzed and results disseminated in 2027-2028. Study results have the potential to improve clinical-community linkages and in so doing to advance health equity. Clinicaltrials.gov registration # NCT06489002. Registered July 5, 2024, https//clinicaltrials.gov/study/NCT06489002?term=NCT06489002&rank=1.

Population-level effects on crime of recovering firearms from armed prohibited persons: intention-to-treat analysis of a pragmatic cluster-randomised trial in California cities

Population-level effects on crime of recovering firearms from armed prohibited persons: intention-to-treat analysis of a pragmatic cluster-randomised trial in California cities

Health dialogue intervention versus opportunistic screening in primary care for type 2 diabetes and cardiovascular disease prevention in settings with low socioeconomic status (DETECT): study protocol for a pragmatic cluster-randomized trial

BackgroundMeta-analyses of randomized trials suggest that health checks and health promotion interventions targeting behavior change in primary care do not prevent cardiovascular morbidity and mortality in the general population. However, whether such interventions are more effective in high-risk populations, such as people living in low socioeconomic settings, remains unclear, as they have been poorly represented in previous trials. Therefore, we aim to evaluate the effectiveness, cost-effectiveness, and implementation of systematic screening followed by an individually oriented, lifestyle-focused, health dialogue intervention for prevention of type 2 diabetes and cardiovascular disease, as compared to opportunistic screening, in primary care in socioeconomically disadvantaged areas.MethodsUsing an overall pragmatic approach and a cluster-randomized design with two arms, we aim to enroll 3000 participants aged 50–59 years from 30 primary care centers (PCCs) with an above-average level of Care Need Index in Stockholm Region, Sweden. PCCs will be randomized (1:1) either to a health dialogue intervention, which includes inviting enlisted patients to a systematic screening of risk factors followed by an individually oriented lifestyle-focused health dialogue, or to opportunistic screening, which includes screening patients for a smaller set of risk factors during an appointment at their PCC taking place for other reasons. The main outcome will be change in systolic blood pressure during 6- and 12-month follow-ups. Additional short-term outcomes will be changes in other biological risk factors, health-related quality-of-life, and lifestyle habits, as well as process and implementation outcomes, and unintended side effects. The long-term effect on type 2 diabetes and cardiovascular disease incidence and mortality will be examined using regional and nationwide registers. Changes in systolic blood pressure and other health outcomes will be analyzed using mixed-effect generalized linear modeling and mixed-effect Cox regression to capture variability between and within PCCs. A health economic evaluation will assess resource use and costs in the short- and long-term.DiscussionThis trial of lifestyle-focused health dialogues and opportunistic screening in primary care in socioeconomically disadvantaged areas in the largest region of Sweden has the potential to yield valuable insights that could support evidence-based policymaking.Trial registrationClinicalTrials.gov (NCT06067178). Prospectively registered September 27, 2023.

Population-level effects on crime of recovering firearms from armed prohibited persons: intention-to-treat analysis of a pragmatic cluster-randomised trial in California cities

BackgroundToo little is known about the effectiveness of efforts to prevent firearm violence. We evaluated California’s Armed and Prohibited Persons System (APPS), which identifies legal purchasers of firearms who have...

Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial

IntroductionAcute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers...

Health Literacy Directed Weight Loss Intervention in Primary Care Clinics.

Low income and low health literacy are associated with poorer health knowledge, health behaviors and poor health outcomes. The effectiveness of health literacy-directed weight loss treatment interventions in primary care clinics is lacking. The aim of this study was to conduct a pragmatic cluster-randomized trial (PROmoting Successful Weight Loss in Primary CarE in Louisiana ([PROPEL]) to test the effectiveness of a 24-month, patient-centered, literacy-directed obesity treatment program delivered within primary care in an underserved population. This study reports the association between health literacy and program effectiveness, examining potential correlates of weight loss related to patient adherence to the program. We randomly assigned 18 clinics to usual care (UC) or a health literacy-directed lifestyle intervention (HLI). The primary outcome was percent weight loss at 24 months. Of 803 adult participants (84% women; 67% Black), 31% had limited health literacy. Patients in UC lost an average of 0.44%of their enrollment weight after 24 months. Those with adequate literacy lost 0.57% and those with limited literacy lost 0.30%, which was not significantly different. The HLI patient group lost an average of 4.9% of their enrollment weight. Those with adequate literacy lost 5.2% and those with limited literacy, 4.7%, which was not significantly different. The advantage of adequate health literacy was consistent across the 24-month study period, though not significant. Patients in the HLI group with adequate health literacy had greater percent weight loss by a margin of 0.50 ± 0.75 (p = .50), while the UC margin was 0.27 ± 0.84 (p = .74). The percent weight loss difference between HLI and UC groups was 4.6 ± 0.8 (p < .001) among patients with adequate health literacy and 4.4 ± 1.0 (p < .001) among patients with limited health literacy. The difference in percent weight loss between the HLI and UC groups was 0.2 ± 1.1 (p = .84) higher for adequate literacy patients. A health literacy directed health coaching intervention in community clinics led to significant weight loss over 24 months but did not vary by level of patient health literacy. [HLRP: Health Literacy Research and Practice. 2024;8(4):e204-e211.].

Integrated community-based management of HIV, diabetes, and hypertension in Tanzania and Uganda: protocol for a cluster-randomized trial

Background In response to the growing burden of chronic diseases in sub-Saharan Africa, where innovative and cost-effective health solutions are imperative, this study outlines a protocol for a cluster-randomized trial that compares integrated community-based care with integrated facility-based care to improve access and outcomes for patients with HIV, diabetes, or hypertension. Methods &amp; analysis We will conduct a pragmatic cluster-randomized trial comparing integrated community care with integrated facility care in Tanzania and Uganda. Patients living with HIV, diabetes, or hypertension, stable on treatment in health facilities, will be organised into groups of approximately 8–14 persons and randomly assigned to integrated community or facility-based care. The study has two co-primary endpoints: a composite endpoint of glycemia and blood pressure control among individuals with diabetes and/or hypertension and suppression of plasma viral load among people living with HIV. Participants will receive their drugs, adherence support, and monitoring at a community venue in the integrated community arm. Those randomised to the control arm will receive integrated facility-based care. All study participants will be followed up for 12 months. A sample size of 116 groups will provide over 80% power to detect an absolute difference in blood pressure and blood glucose control of 10% at the 5% two-sided significance level. For HIV viral suppression, the trial will have over 80% power to show non-inferiority with a delta margin = 8.5%, 7.5%, and 5.5% assuming viral suppression is 85%, 90% and 95% respectively. To allow for loss to follow-up, our target for enrolment is 124 groups, each comprising an average of 14 participants. An economic evaluation within the trial will be conducted to estimate the cost and cost-effectiveness of integrated community care compared with integrated facility care. This will be complemented by a built-in social science process evaluation. Ethics and dissemination Ethical approval was granted by the Research Ethics Committees of the University College London (UCL), the National Institute of Medical Research (Tanzania), and the Uganda Virus Research Institute (Uganda). The findings will be disseminated through journal publications and meetings with key stakeholders. Trial registration number ISRCTN Registry: ISRCTN15319595, registration date: 07 June 2022.

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.