Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients’ viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions.

We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation.

We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions.

No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice.

This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls.

Meta-epidemiological study.

Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018.

Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis.

Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up.

Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p

Placebo control trials of surgery have similar recruitment issues but higher attrition compared with non-operative (non-placebo) control trials. Study design should incorporate strategies such as increased timepoints for given follow-up duration to mitigate losses to follow-up and dropout.

CRD42019117364.

Hip osteoarthritis (OA) is a major cause of pain and disability worldwide. Lack of effective therapies may reflect poor knowledge on its aetiology and risk factors, and result in the management of end-stage hip OA with costly joint replacement. The Worldwide Collaboration on OsteoArthritis prediCtion for the Hip (World COACH) consortium was established to pool and harmonise individual participant data from prospective cohort studies. The consortium aims to better understand determinants and risk factors for the development and progression of hip OA, to optimise and automate methods for (imaging) analysis, and to develop a personalised prediction model for hip OA.

World COACH aimed to include participants of prospective cohort studies with ≥200 participants, that have hip imaging data available from at least 2 time points at least 4 years apart. All individual participant data, including clinical data, imaging (data), biochemical markers, questionnaires and genetic data, were collected and pooled into a single, individual-level database.

World COACH currently consists of 9 cohorts, with 38 021 participants aged 18–80 years at baseline. Overall, 71% of the participants were women and mean baseline age was 65.3±8.6 years. Over 34 000 participants had baseline pelvic radiographs available, and over 22 000 had an additional pelvic radiograph after 8–12 years of follow-up. Even longer radiographic follow-up (15–25 years) is available for over 6000 of these participants.

The World COACH consortium offers unique opportunities for studies on the relationship between determinants/risk factors and the development or progression of hip OA, by using harmonised data on clinical findings, imaging, biomarkers, genetics and lifestyle. This provides a unique opportunity to develop a personalised hip OA risk prediction model and to optimise methods for imaging analysis of the hip.

Potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.

Scoping review.

PubMed, CINAHL, Embase, Cochrane Central and Google Scholar (1 January 2000 to 31 May 2022).

Studies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilisation in healthcare settings.

Using Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilisation.

From 7818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the USA (35.3%), with randomised controlled trial as the most common design (55.9%). Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%) but were rarely (14.9%) guided by an implementation model, framework or theory. Academic detailing, clinical decision support or electronic medical record interventions, performance reports and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients’ age (55.8%), history of gastrointestinal disorders (47.1%), or history of kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter (OTC) NSAIDs in addition to prescription. The majority of studies (76.2%) reported a reduction in the utilisation of potentially harmful NSAIDs. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation.

Many varied interventions to de-implement potentially harmful NSAIDs have been applied in healthcare settings worldwide. Based on these findings and identified knowledge gaps, further efforts to comprehensively evaluate the effectiveness of interventions and the combination of intervention characteristics associated with effective de-implementation are needed. In addition, future work should be guided by de-implementation theory, focus on OTC NSAIDs and incorporate patient-focused strategies and outcomes, including the evaluation of unintended consequences of the intervention.

Breast cancer stands as the most prevalent type of cancer affecting women globally, and chemotherapy plays a pivotal role in its treatment by diminishing tumour recurrence and enhancing the survival rates of patients. However, chemotherapy-related cognitive impairment (CRCI) often occurs in patients undergoing treatment. Although multiple clinical trials have indicated that exercise therapy can improve CRCI in patients with breast cancer, there are variations in the types of exercise interventions and their effectiveness. We aim to perform a pioneering network meta-analysis (NMA) to assess and prioritise the effectiveness of various exercise interventions in enhancing cognitive function in patients with breast cancer undergoing chemotherapy.

We will search multiple databases, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Sinomed databases, from their inception to May 2023. The main outcome is the cognitive function changes in patients with breast cancer, including subjective and objective results. We will specifically include randomised controlled trials reported in English and Chinese languages, whose primary outcome consists of an assessment of the cognitive function of patients with breast cancer using standardised and validated assessment tools, encompassing both subjective and objective outcomes. The quality of all the trials included will be evaluated based on ‘Version 2 of the Cochrane tool for assessing the risk of bias in randomized controlled trials (RoB2)’. We will conduct a Bayesian NMA to thoroughly evaluate and compare the effectiveness of different exercise interventions. We will use cumulative ranking probability plots to estimate the ranking of the best interventions for various exercises. Network plots and funnel plots will be employed to display the study sizes and participants of each exercise intervention, as well as potential publication biases.

The study findings will be shared via peer-reviewed journals to ensure the highest quality and credibility of the research. As the reporting will not include any private patient data, there are no ethical considerations associated with this protocol.

CRD42023406597.

Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%–94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD.

A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.

Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child’s treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability.

The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).

Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials.

NCT04968522.

Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not.

Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities.

This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

Supervised exercise training is among the first-line therapies for patients with peripheral artery disease (PAD). Current recommendations for exercise include guidance focusing on claudication pain, programme and session duration, and frequency. However, no guidance is offered regarding exercise training intensity. This study aims to compare the effects of 12-week-long supervised walking exercise training (high-intensity interval training (HIIT) vs moderate-intensity exercise (MOD)) in patients with chronic symptomatic PAD.

This study is a monocentric, interventional, non-blinded randomised controlled trial. 60 patients (30 in each group) will be randomly allocated (by using the random permuted blocks) to 12 weeks (three times a week) of HIIT or MOD. For HIIT, exercise sessions will consist of alternating brief high-intensity (≥85% of the peak heart rate (HR_peak)) periods (≤60 s) of work with periods of passive rest. Patients will be asked to complete 1 and then 2 sets of 5–7 (progressing to 10–15x60 s) walking intervals. For the MOD group, exercise training sessions will consist of an alternation of periods of work performed at moderate intensity (≤76% HR_peak) and periods of passive rest. Interventions will be matched by training load. The primary outcome will be the maximal walking distance. Secondary outcomes will include functional performance, functional capacity, heath-related quality of life, self-perceived walking abilities, physical activity and haemodynamic parameters.

The Angiof-HIIT Study was approved by the Human Research Ethics Committee of the Canton de Vaud (study number: 2022-01752). Written consent is mandatory prior to enrolment and randomisation. The results will be disseminated via national and international scientific meetings, scientific peer-reviewed journals and social media.

NCT05612945.

Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.

Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.

IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.

This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.

Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.

ISRCTN96296121.

Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities.

We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction).

We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings—namely, workplace and healthcare facilities.

Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04–3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58–87% for countries with off-site self-testing (outside the workplace, for example, home) and 15–50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29–35%) versus off-site self-testing (7–27%).

Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.

To compare vaccination willingness before rollout and 1 year post-rollout uptake among the general population and under-resourced communities in high-income countries.

A realist review.

Embase, PubMed, Dimensions ai and Google Scholar.

High-income countries.

We defined vaccination willingness as the proportion of participants willing or intending to receive vaccines prior to availability. We defined vaccine uptake as the real proportion of the population with complete vaccination as reported by each country until November 2021.

We included data from 62 studies and 18 high-income countries. For studies conducted among general populations, the proportion of vaccination willingness was 67% (95% CI 62% to 72%). In real-world settings, the overall proportion of vaccine uptake among those countries was 73% (95% CI 69% to 76%). 17 studies reported pre-rollout willingness for under-resourced communities. The summary proportion of vaccination willingness from studies reporting results among people from under-resourced communities was 52% (95% CI 0.46% to 0.57%). Real-world evidence about vaccine uptake after rollout among under-resourced communities was limited.

Our review emphasises the importance of realist reviews for assessing vaccine acceptance. Limited real-world evidence about vaccine uptake among under-resourced communities in high-income countries is a call to context-specific actions and reporting.

Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation.

The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation.

The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III—PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences.

NCT04273360.

Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder.

We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11–13 weeks’ gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at

Ethical approval for the study was obtained from the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2021.406) in Hong Kong and the Ethics Committee of each participating hospital in Mainland China. The study is registered at ClinicalTrials.gov. The results of the AVERT trial will be disseminated at international academic conferences and published in high-impact factor journals.

NCT05580523.

Patients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses.

Registry-based cohort study.

CHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis.

Cancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)—of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis—13.0 years (IQR 2.9–30.0) in CHD versus 24.6 years (IQR 8.6–35.1) in controls. Median age at death was 15.1 years (IQR 3.6–30.7) in CHD patients versus 18.5 years (IQR 6.1–32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies.

Cancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.