Stepped-wedge Cluster-randomised Controlled Trial Research Articles

Cost Analysis of a Hand Hygiene Improvement Strategy in Long-Term Care Facilities

ObjectivesTo evaluate whether the costs of a successful tailored multifaceted strategy to improve hand hygiene compliance outweighed the savings by reducing infection costs in Dutch long-term care facilities (LTCFs). DesignA retrospective cost analysis alongside a stepped-wedge cluster-randomized controlled trial. Setting and ParticipantsThe study included 14 LTCFs (23 wards) in the Netherlands. MethodsThe cost analysis was based on the costs of the intervention vs the savings from avoided infections and associated treatment costs. Infection-related costs of the “usual-care” period were compared with the combined infection-related costs and intervention costs from the “intervention” period and the costs in the “post-intervention period.” Multilevel analyses, with a linear model with periods as fixed effects, random effects for cluster LTCFs, and fixed effects for each step, were completed. ResultsThere are no significant differences in total costs considering the 3 periods. When adjusting for time and clustering, the mean infection-related costs per week per LTCF for all the infections combined were highest during “usual-care” before the hand hygiene intervention was performed, namely 680 euros per week. Assuming the effect of the improvement strategy would be present for 12 months, the costs per week in the “intervention” and “post-intervention” periods were 627 euros (95% CI, 383–871) and 731 euros (95% CI, 508–954), respectively. Assuming the effect of the improvement strategy will last longer than 1 year (ie, 18 and 24 months), the average cost for the “intervention period” and the “post-intervention” period decreased to 615 euros and 719 euros during the intervention and 609 euros and 715 euros after the intervention, respectively. Conclusions and ImplicationsOur multifaceted hand hygiene improvement strategy achieves cost savings. The results of our study are the first of an economic analysis of a hand hygiene improvement strategy in LTCFs. The results need to be confirmed by further economic evaluations.

Improving mental health in chronic care in general practice: study protocol for a cluster-randomised controlled trial of the Healthy Mind intervention

BackgroundMental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being.MethodsA stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices.DiscussionThe Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being.Trial registrationClinicalTrials.gov NCT05611112. Registered on October 28, 2022.

Effect of a multimodal prevention strategy on dialysis-associated infection events in outpatients receiving haemodialysis: The DIPS stepped wedge, cluster-randomized trial

ObjectivesPatients with haemodialysis catheters are susceptible to dialysis-associated infections, particularly bloodstream infections. There have been few systematic attempts to reduce this burden. Our study aimed to investigate the effect of a multimodal prevention strategy on dialysis-associated infection events (DAIE) among haemodialysis outpatients. MethodsA multicentre, stepped wedge, cluster-randomized controlled trial was done from October 2019 to September 2021. Outpatient dialysis facilities entered into the intervention phase in three randomly assigned clusters, at three predefined time points. The multimodal prevention strategy consisted of infection surveillance and hand hygiene (HH) compliance observation with active feedback and teaching aseptic procedures, and a patient flyer.The primary outcome was incidence rates of different DAIE, such as bloodstream infections, intravenous antimicrobial starts, and local access-site infections per 1000 dialysis. As secondary outcome, we analysed the HH compliance change. ResultsA total of 43 haemodialysis outpatient facilities with 11 251 patients and 1 413 457 proceeded haemodialysis were included in the DIPS-trial. Incidence rates were 0.71 DAIE per 1000 dialysis (95% CI, 0.65–0.78) in the control and 0.31 (95% CI, 0.27–0.36) in the intervention group. The univariable analysis yielded an incidence rate ratio (IRR) of 0.44 (95% CI, 0.33–0.59) for DAIE. Especially in patients with a central venous catheter, we saw a significant decrease in DAIE in the intervention group (IRR 0.4; 95% CI, 0.28–0.58). The HH observation combined with feedback and intensified training, resulted in an increase of HH compliance from 58–65%. DiscussionA multimodal prevention strategy showed a significant preventive effect on DAIE among haemodialysis outpatients. This reduction also applied to bloodstream infections, especially in patients with a central venous catheter.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection

BackgroundClostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +).MethodsWe used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research.ResultsA total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals.ConclusionsUse of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

CRADLE-5: a stepped-wedge type 2 hybrid implementation-effectiveness cluster randomised controlled trial to evaluate the real-world scale-up of the CRADLE Vital Signs Alert intervention into routine maternity care in Sierra Leone—study protocol

BackgroundThe CRADLE Vital Signs Alert intervention (an accurate easy-to-use device that measures blood pressure and pulse with inbuilt traffic-light early warning system, and focused training package) was associated with reduced rates of eclampsia and maternal death when trialled in urban areas in Sierra Leone. Subsequently, implementation was successfully piloted as evidenced by measures of fidelity, feasibility and adoption. The CRADLE-5 trial will examine whether national scale-up, including in the most rural areas, will reduce a composite outcome of maternal and fetal mortality and maternal morbidity and will evaluate how the CRADLE package can be embedded sustainably into routine clinical pathways.MethodsCRADLE-5 is a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care across eight rural districts in Sierra Leone (Bonthe, Falaba, Karene, Kailahun, Koinadugu, Kono, Moyamba, Tonkolili). Each district will cross from control to intervention at six-weekly intervals over the course of 1 year (May 2022 to June 2023). All women identified as pregnant or within six-weeks postpartum presenting for maternity care in the district are included. Primary outcome data (composite rate of maternal death, stillbirth, eclampsia and emergency hysterectomy) will be collected. A mixed-methods process and scale-up evaluation (informed by Medical Research Council guidance for complex interventions and the World Health Organization ExpandNet tools) will explore implementation outcomes of fidelity, adoption, adaptation and scale-up outcomes of reach, maintenance, sustainability and integration. Mechanisms of change and contextual factors (barriers and facilitators) will be assessed. A concurrent cost-effectiveness analysis will be undertaken.DiscussionInternational guidance recommends that all pregnant and postpartum women have regular blood pressure assessment, and healthcare staff are adequately trained to respond to abnormalities. Clinical effectiveness to improve maternal and perinatal health in more rural areas, and ease of integration and sustainability of the CRADLE intervention at scale has yet to be investigated. This trial will explore whether national scale-up of the CRADLE intervention reduces maternal and fetal mortality and severe maternal adverse outcomes and understand the strategies for adoption, integration and sustainability in low-resource settings. If successful, the aim is to develop an adaptable, evidence-based scale-up roadmap to improve maternal and infant outcomes.Trial registrationISRCTN 94429427. Registered on 20 April 2022.

Study protocol of an economic evaluation embedded in the Midwives and Obstetricians Helping Mothers to Quit Smoking (MOHMQuit) trial

BackgroundTobacco smoking during pregnancy is the most important preventable risk factor for pregnancy complications and adverse birth outcomes and can have lifelong consequences for infants. Smoking during pregnancy is associated with higher healthcare costs related to birth complications and during childhood. Psychosocial interventions to support pregnant women to quit are effective, yet provision of smoking cessation support has been inconsistent. The Midwives and Obstetricians Helping Mothers to Quit Smoking (MOHMQuit) intervention provides systems change, and leadership and clinician elements, to support clinicians to help women stop smoking in pregnancy. There have been few long-term analyses conducted of the cost-effectiveness of smoking cessation interventions for pregnant women that target healthcare providers. This protocol describes the economic evaluation of the MOHMQuit trial, a pragmatic stepped-wedge cluster-randomised controlled implementation trial in nine public maternity services in New South Wales (NSW), Australia, to ascertain whether MOHMQuit is cost-effective in supporting clinicians to help women quit smoking in pregnancy compared to usual care.MethodsTwo primary analyses will be carried out comparing MOHMQuit with usual care from an Australian health care system perspective: i) a within-trial cost-effectiveness analysis with results presented as the incremental cost per additional quitter; and ii) a lifetime cost-utility analysis using a published probabilistic decision analytic Markov model with results presented as incremental cost per quality-adjusted life-year (QALY) gained for mother and child. Patient-level data on resource use and outcomes will be used in the within-trial analysis and extrapolated and supplemented with national population statistics and published data from the literature for the lifetime analysis.DiscussionThere is increasing demand for information on the cost-effectiveness of implementing healthcare interventions to provide policy makers with critical information for the best value for money within finite budgets. Economic evaluation of the MOHMQuit trial will provide essential, policy-relevant information for decision makers on the value of evidence-based implementation of support for healthcare providers delivering services for pregnant women.Trial registrationsACTRN12622000167763, registered 2 February 2022.

Effect and Process Evaluation of an Intervention to Improve Hand Hygiene Compliance in Long-Term Care Facilities

ObjectivesThis study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change. DesignWe conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback). Setting and ParticipantsThe study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands. MethodsHand hygiene compliance was observed during 5 measurement periods using WHO's “Five Moments for Hand Hygiene.” Multilevel analyses and corresponding tests were completed on an intention-to-treat basis. ResultsThe absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P < .001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P < .002) before a clean and aseptic procedure, 18% (95% CI 10-26, P < .001) after touching a resident, 14% (95% CI 7-22, P < .003) before touching a resident, 10% (95% CI 5-15, P < .001) after contact with body fluid, and 1% (95% CI –11 to 13, P = .8) after touching a resident's surroundings.With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores. Conclusions and ImplicationsOur strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance.

The POP (Permanent Supportive Housing Overdose Prevention) Study: protocol for a hybrid type 3 stepped-wedge cluster randomized controlled trial

BackgroundPermanent supportive housing (PSH)—subsidized housing paired with support services such as case management—is a key part of national strategic plans to end homelessness. PSH tenants face high overdose risk due to a confluence of individual and environmental risk factors, yet little research has examined overdose prevention in PSH.MethodsWe describe the protocol for a hybrid type 3 stepped-wedge cluster randomized controlled trial (RCT) of overdose prevention practice implementation in PSH. We adapted evidence-based overdose prevention practices and implementation strategies for PSH using input from stakeholder focus groups. The trial will include 20 PSH buildings (with building size ranging from 20 to over 150 tenants) across New York City and New York’s Capital Region. Buildings will be randomized to one of four 6-month intervention waves during which they will receive a package of implementation support including training in using a PSH Overdose Prevention (POP) Toolkit, time-limited practice facilitation, and learning collaboratives delivered to staff and tenant implementation champions appointed by each building. The primary outcome is building-level fidelity to a defined list of overdose prevention practices. Secondary and exploratory implementation and effectiveness outcomes will be examined using PSH staff and tenant survey questionnaires, and analysis of tenant Medicaid data. We will explore factors related to implementation success, including barriers and facilitators, using qualitative interviews with key stakeholders. The project is being conducted through an academic-community partnership, and an Advisory Board including PSH tenants and other key stakeholders will be engaged in all stages of the project.DiscussionWe describe the protocol for a hybrid type 3 stepped-wedge cluster RCT of overdose prevention practice implementation in PSH. This study will be the first controlled trial of overdose prevention implementation in PSH settings. The research will make a significant impact by testing and informing future implementation strategies to prevent overdose for a population at particularly high risk for overdose mortality. Findings from this PSH-focused research are expected to be broadly applicable to other housing settings and settings serving people experiencing homelessness.Trial registrationClinicalTrials.gov, NCT05786222, registered 27 March 2023.

Feasibility of implementing a surgical patient safety checklist: prospective cross-sectional evaluation

BackgroundThe World Health Organization’s Global Patient Safety Action Plan 2021–2030 call for attention to patient and family involvement to reduce preventable patient harm. Existing evidence indicates that patients’ involvement in their own safety has positive effects on reducing hospitalisation time and readmissions. One intervention reported in the literature is the use of checklists designed for patients’ completion. Studies on such checklists are small scale, but they are linked to reduction in length of hospital stay and readmissions. We have previously developed and validated a two-part surgical patient safety checklist (PASC). This study aims to investigate the feasibility of the PASC usage and implementation prior to its use in a large-scale clinical trial.MethodsThis is a prospective cross-sectional feasibility study, set up as part of the design of a larger stepped-wedge cluster randomised controlled trial (SW-CRCT). Descriptive statistics were used to investigate patient demographics, reasons for not completing the PASC and percentage of PASC item usage. Qualitative patient interviews were used to identify barriers and drivers for implementation. Interview was analysed through content analysis.ResultsOut of 428 recruited patients, 50.2% (215/428) used both parts of PASC. A total of 24.1% (103/428) of the patients did not use it at all due to surgical or COVID-19-related cancellations. A total of 19.9% (85/428) did not consent to participate, 5.1% (22/428) lost the checklist and 0.7% (3/428) of the patients died during the study. A total of 86.5% (186/215) patients used ≥ 80% of the checklist items. Barriers and drivers for PASC implementation were grouped into the following categories: Time frame for completing the checklist, patient safety checklist design, impetus to communicate with healthcare professionals and support throughout the surgical pathway.ConclusionsElective surgical patients were willing and able to use PASC. The study further revealed a set of barriers and drivers to the implementation. A large-scale definitive clinical-implementation hybrid trial is being launched to ascertain the clinical effectiveness and scalability of PASC in improving surgical patient safety.Trial registrationClinicaltrials.gov: NCT03105713. Registered 10.04.2017

Improving rural and regional access to long-acting reversible contraception and medical abortion through nurse-led models of care, task-sharing and telehealth (ORIENT): a protocol for a stepped-wedge pragmatic cluster-randomised controlled trial in Australian general practice

IntroductionWomen living in rural and regional Australia often experience difficulties in accessing long-acting reversible contraception (LARC) and medical abortion services. Nurse-led models of care can improve access to these services...

Implementation of an evidence-based management algorithm for patients with chronic pancreatitis (COMBO trial): study protocol for a stepped-wedge cluster-randomized controlled trial

BackgroundChronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP.MethodsThe COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial.DiscussionThis is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice.Trial registrationISRCTN, ISRCTN13042622. Registered on 5 September 2020.

Short- and long-term effects of an electronic medication management system on paediatric prescribing errors

Electronic medication management (eMM) systems are designed to improve safety, but there is little evidence of their effectiveness in paediatrics. This study assesses the short-term (first 70 days of eMM use) and long-term (one-year) effectiveness of an eMM system to reduce prescribing errors, and their potential and actual harm. We use a stepped-wedge cluster randomised controlled trial (SWCRCT) at a paediatric referral hospital, with eight clusters randomised for eMM implementation. We assess long-term effects from an additional random sample of medication orders one-year post-eMM. In the SWCRCT, errors that are potential adverse drug events (ADEs) are assessed for actual harm. The study comprises 35,260 medication orders for 4821 patients. Results show no significant change in overall prescribing error rates in the first 70 days of eMM use (incident rate ratio [IRR] 1.05 [95%CI 0.92–1.21], but a 62% increase (IRR 1.62 [95%CI 1.28–2.04]) in potential ADEs suggesting immediate risks to safety. One-year post-eMM, errors decline by 36% (IRR 0.64 [95%CI 0.56–0.72]) and high-risk medication errors decrease by 33% (IRR 0.67 [95%CI 0.51–0.88]) compared to pre-eMM. In all periods, dose error rates are more than double that of other error types. Few errors are associated with actual harm, but 71% [95%CI 50–86%] of patients with harm experienced a dose error. In the short-term, eMM implementation shows no improvement in error rates, and an increase in some errors. A year after eMM error rates significantly decline suggesting long-term benefits. eMM optimisation should focus on reducing dose errors due to their high frequency and capacity to cause harm.

Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial

Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. UK National Institute for Health and Care Research.

Implementation of high-sensitivity cardiac troponin and risk of myocardial infarction or death at 5 years: a stepped-wedge cluster-randomised controlled trial

Abstract Background Implementation of a high-sensitivity cardiac troponin I assay with the sex-specific 99th centile as the diagnostic threshold identifies more patients with myocardial injury and infarction, but whether this impacts on long-term clinical outcomes is unknown. Purpose In a prespecified analysis of a stepped-wedge cluster-randomised controlled trial performed across ten hospitals in Scotland, we evaluated the impact of implementing a high-sensitivity cardiac troponin I assay on outcomes at 5 years in consecutive patients with suspected acute coronary syndrome. Methods Throughout the trial, all 48,282 patients had cardiac troponin I concentrations measured using both a contemporary (standard care) and high-sensitivity (implementation) assay. During standard care, results from the high-sensitivity assay were concealed and the contemporary assay was used to guide care. Hospitals were randomly allocated to early (n=5) or late (n=5) implementation of the high-sensitivity assay using the sex-specific 99th centile to guide care and results from the contemporary assay were concealed. Patients reclassified by the high-sensitivity assay were defined as those with cardiac troponin concentrations above the sex-specific 99th centile but below the contemporary assay diagnostic threshold. Subsequent myocardial infarction or all-cause death at 5 years was compared before and after implementation using an adjusted Cox proportional hazards model in those reclassified by the high-sensitivity assay and stratified by index diagnosis. Results Overall, 10,360 patients had cardiac troponin concentrations greater than the sex-specific 99th centile of whom 1,771 (17%) were reclassified by the high-sensitivity assay. Compared to those identified as having elevated cardiac troponin by the contemporary assay, patients reclassified by the high-sensitivity assay were more likely to have non-ischemic myocardial injury (54% versus 28%) and less likely to have type 1 myocardial infarction (33% versus 59%; P&amp;lt;0.001 for both). In those reclassified, the 5-year incidence of subsequent myocardial infarction or all-cause death was 63% (456/720) before and 54% (567/1051) after implementation of the high-sensitivity assay (adjusted hazard ratio [aHR] 0.75 [95% CI 0.57–0.98]) (Figure 1). Following implementation, subsequent myocardial infarction or all-cause death at 5 years was reduced in patients with non-ischemic myocardial injury (aHR 0.66 [0.51–0.86]) but not type 1 or type 2 myocardial infarction (aHR 0.90 [0.78–1.03] and 0.81 [0.55–1.20], respectively). Conclusions In patients with suspected acute coronary syndrome, implementation of a high-sensitivity cardiac troponin assay was associated with a lower risk of subsequent myocardial infarction or death at 5 years. Improvements in outcome were greater in those with a diagnosis of non-ischemic myocardial injury rather than infarction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Reducing malaria transmission in forest-going mobile and migrant populations in Lao PDR and Cambodia: protocol for stepped-wedge cluster-randomised controlled trial

BackgroundCountries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region.MethodsA personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package.DiscussionThis study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy.Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021

Effect of a perinatal care quality improvement package on patient satisfaction: a secondary outcome analysis of a cluster-randomised controlled trial

ObjectiveTo investigate the effect of a quality improvement (QI) package on patient satisfaction of perinatal care.DesignSecondary analysis of a stepped-wedge cluster-randomised controlled trial. Participating hospitals were randomised by size into...

Use of an electronic medication management support system in patients with polypharmacy in general practice: study protocol of a quantitative process evaluation of the AdAM trial.

Background:Interventional studies on polypharmacy often fail to significantly improve patient-relevant outcomes, or confine themselves to measuring surrogate parameters. Interventions and settings are complex, with many factors affecting results. The AdAM study’s aim is to reduce hospitalization and death by requiring general practitioners (GPs) to use a computerized decision-support system (CDSS). The study will undergo a process evaluation to identify factors for successful implementation and to assess whether the intervention was implemented as intended.Objective:To evaluate our complex intervention, based on the Medical Research Council’s guideline dimensions.Research Questions:We will assess implementation (reach, fidelity, dose, tailoring) by asking: (1) Who took part in the intervention (proportion of GPs using the CDSS, proportion of patients enrolled in them)? Information on GPs’ and patients’ characteristics will also be collected. (2) How many and which medication alerts were dealt with? (3) Was the intervention implemented as intended? (4) On what days did GPs use the intervention tool?Methods:The process evaluation is part of a stepped-wedge cluster-randomized controlled trial. Characteristics of practices, GPs and patients using the CDSS will be compared with the non-participating population. CDSS log data will be analyzed to evaluate how the number of medication alerts changed between baseline and 2 months later, and to identify the kind of alerts that were dealt with. Comparison of enrolled patients on weekdays versus weekends will shed light on GPs’ use of the CDSS in the absence or presence of patients. Outcomes will be presented using descriptive statistics, and significance tests will be used to identify associations between them. We will conduct subgroup analyses, including time effects to account for software improvements.Discussion:This study protocol is the basis for conducting analyses of the quantitative process evaluation. By providing insight into how GPs conduct medication reviews, the evaluation will provide context to the trial results and support their interpretation. The evaluation relies on the proper documentation by GPs, potentially limiting its explanatory power.

Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial

BackgroundHome care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home.MethodsThis study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs’ sense of competence in dementia care provision.DiscussionUpskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs.Trial registrationanzctr.org.au; ACTRN12619000251123. Registered on 20 February 2019.

INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial

BackgroundEarly intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH.MethodsINTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions.DiscussionAs the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.Trial registrationClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017

Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial.

PurposeOral chlorhexidine is used widely for mechanically ventilated patients to prevent pneumonia, but recent studies show an association with excess mortality. We examined whether de-adoption of chlorhexidine and parallel implementation of a standardized oral care bundle reduces intensive care unit (ICU) mortality in mechanically ventilated patients.MethodsA stepped wedge cluster-randomized controlled trial with concurrent process evaluation in 6 ICUs in Toronto, Canada. Clusters were randomized to de-adopt chlorhexidine and implement a standardized oral care bundle at 2-month intervals. The primary outcome was ICU mortality. Secondary outcomes were time to infection-related ventilator-associated complications (IVACs), oral procedural pain and oral health dysfunction. An exploratory post hoc analysis examined time to extubation in survivors.ResultsA total of 3260 patients were enrolled; 1560 control, 1700 intervention. ICU mortality for the intervention and control periods were 399 (23.5%) and 330 (21.2%), respectively (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI] 0.82 to 1.54; P = 0.46). Time to IVACs (adjusted hazard ratio [aHR], 1.06; 95% CI 0.44 to 2.57; P = 0.90), time to extubation (aHR 1.03; 95% CI 0.85 to 1.23; P = 0.79) (survivors) and oral procedural pain (aOR, 0.62; 95% CI 0.34 to 1.10; P = 0.10) were similar between control and intervention periods. However, oral health dysfunction scores (− 0.96; 95% CI − 1.75 to − 0.17; P = 0.02) improved in the intervention period.ConclusionAmong mechanically ventilated ICU patients, no benefit was observed for de-adoption of chlorhexidine and implementation of an oral care bundle on ICU mortality, IVACs, oral procedural pain, or time to extubation. The intervention may improve oral health.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-021-06475-2.