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.

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.

Recent research has highlighted non-operative management (NOM) as a viable alternative for frail older adults with hip fractures in the final phase of life. This study aims to guide Dutch physicians and hospitals nationwide in a standardised implementation of shared decision-making regarding surgery or NOM in selected frail older adults with a hip fracture.

The patient population for implementation includes frail older adults aged ≥70 years with an acute proximal femoral fracture, nursing home care or a similar level of care elsewhere and at least one additional criterion (ie, malnutrition, severe mobility impairment or ASA≥4). The 2-year implementation study will be conducted in four phases. In phases 1 and 2, barriers and facilitators for implementation will be identified and an implementation protocol, educational materials and patient information will be developed. Phase 3 will involve an implementation pilot in 14 hospitals across the Netherlands. The protocol and educational material will be improved based on healthcare provider and patient experiences gathered through interviews. Phase 4 will focus on upscaling to nationwide implementation and the effect of the implementation on NOM rate will be measured using data from the Dutch Hip Fracture Audit.

The study was exempted by the local Medical Research Ethics Committee (MEC-2023-0270, 10 May 2023) and Medical Ethics Committee United (W23.083, 26 April 2023). The study’s results will be submitted to an open access international peer-reviewed journal. Its protocols, tools and results will be presented at several national and international academic conferences of relevant orthogeriatric (scientific) associations.

NCT06079905 .

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.

Exploring clinical information-seeking behaviour (CISB) and its associated factors contributes to its theoretical advancement and offers a valuable framework for addressing physicians’ information needs. This study delved into the dimensions, interactions, strategies and determinants of CISB among physicians at the point of care.

A grounded theory study was developed based on Strauss and Corbin’s approach. Data were collected by semistructured interviews and then analysed through open, axial and selective coding.

The study was conducted at academic centres affiliated with Isfahan University of Medical Sciences.

This investigation involved recruiting 21 specialists and subspecialists from the academic centres.

The findings revealed that physicians’ CISB encompassed multiple dimensions when addressing clinical inquiries. Seven principal themes emerged from the analysis: ‘clinical information needs’, ‘clinical question characteristics’, ‘clinical information resources’, ‘information usability’, ‘factors influencing information seeking’, ‘action/interaction encountering clinical questions’ and ‘consequences of CISB’. The core category identified in this study was ‘focused attention’.

The theoretical explanation demonstrated that the CISB process was interactive and dynamic. Various stimuli, including causal, contextual and intervening conditions, guide physicians in adopting information-seeking strategies and focusing on resolving clinical challenges. However, insufficient stimuli may hinder physicians’ engagement in CISB. Understanding CISB helps managers, policy-makers, clinical librarians and information system designers optimally implement several interventions, such as suitable training methods, reviewing monitoring and evaluating information systems, improving clinical decision support systems, electronic medical records and electronic health records, as well as monitoring and evaluating these systems. Such measures facilitate focused attention on clinical issues and promote CISB among physicians.

Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement.

We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors.

No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online.

CRD42022347881.

Globally, cardiovascular disease (CVD) remains the leading cause of death, warranting effective management and prevention measures. Risk prediction tools are indispensable for directing primary and secondary prevention strategies for CVD and are critical for estimating CVD risk. Machine learning (ML) methodologies have experienced significant advancements across numerous practical domains in recent years. Several ML and statistical models predicting CVD time-to-event outcomes have been developed. However, it is not known as to which of the two model types—ML and statistical models—have higher discrimination and calibration in this regard. Hence, this planned work aims to systematically review studies that compare ML with statistical methods in terms of their predictive abilities in the case of time-to-event data with censoring.

Original research articles published as prognostic prediction studies, which involved the development and/or validation of a prognostic model, within a peer-reviewed journal, using cohort or experimental design with at least a 12-month follow-up period will be systematically reviewed. The review process will adhere to the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist.

Ethical approval is not required for this review, as it will exclusively use data from published studies. The findings of this study will be published in an open-access journal and disseminated at scientific conferences.

CRD42023484178.

International trials can be challenging to operationalise due to incompatibilities between country-specific policies and infrastructures. The aim of this systematic review was to identify the operational complexities of conducting international trials and identify potential solutions for overcoming them.

Systematic review.

Medline, Embase and Health Management Information Consortium were searched from 2006 to 30 January 2023.

All studies reporting operational challenges (eg, site selection, trial management, intervention management, data management) of conducting international trials were included.

Search results were independently screened by at least two reviewers and data were extracted into a proforma.

38 studies (35 RCTs, 2 reports and 1 qualitative study) fulfilled the inclusion criteria. The median sample size was 1202 (IQR 332–4056) and median number of sites was 40 (IQR 13–78). 88.6% of studies had an academic sponsor and 80% were funded through government sources. Operational complexities were particularly reported during trial set-up due to lack of harmonisation in regulatory approvals and in relation to sponsorship structure, with associated budgetary impacts. Additional challenges included site selection, staff training, lengthy contract negotiations, site monitoring, communication, trial oversight, recruitment, data management, drug procurement and distribution, pharmacy involvement and biospecimen processing and transport.

International collaborative trials are valuable in cases where recruitment may be difficult, diversifying participation and applicability. However, multiple operational and regulatory challenges are encountered when implementing a trial in multiple countries. Careful planning and communication between trials units and investigators, with an emphasis on establishing adequately resourced cross-border sponsorship structures and regulatory approvals, may help to overcome these barriers and realise the benefits of the approach.

osf-registrations-yvtjb-v1.

The study aims to investigate the perceptions of patients with thyroid cancer on the potential impact of diagnosis and treatment delays during the COVID-19 pandemic.

This study involved qualitative semi-structured telephone interviews. The interviews were transcribed verbatim, analysed using the thematic framework analysis method and reported using the Consolidated Criteria for Reporting Qualitative Research.

Participants in the study were treated and/or managed at hospital sites across New South Wales and Victoria, Australia.

17 patients with thyroid cancer were interviewed and included in the analysis (14 females and 3 males).

The delays experienced by patients ranged from 12 months. The patients reported about delays to diagnostic tests, delays to surgery and radioactive iodine treatment, perceived disease progression and, for some, the financial burden of choosing to go through private treatment to minimise the delay. Most patients also reported not wanting to experience delays any longer than they did, due to unease and anxiety.

This study highlights an increased psychological burden in patients with thyroid cancer who experienced delayed diagnosis and/or treatment during COVID-19. The impacts experienced by patients during this time may be similar in the case of other unexpected delays and highlight the need for regular clinical review during delays to diagnosis or treatment.

An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution.

A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms.

The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients.

NCT04624737

Intensive care units (ICUs) admit the most severely ill patients. Once these patients are discharged from the ICU to a step-down ward, they continue to have their vital signs monitored by nursing staff, with Early Warning Score (EWS) systems being used to identify those at risk of deterioration.

We report the development and validation of an enhanced continuous scoring system for predicting adverse events, which combines vital signs measured routinely on acute care wards (as used by most EWS systems) with a risk score of a future adverse event calculated on discharge from the ICU.

A modified Delphi process identified candidate variables commonly available in electronic records as the basis for a ‘static’ score of the patient’s condition immediately after discharge from the ICU. L1-regularised logistic regression was used to estimate the in-hospital risk of future adverse event. We then constructed a model of physiological normality using vital sign data from the day of hospital discharge. This is combined with the static score and used continuously to quantify and update the patient’s risk of deterioration throughout their hospital stay.

Data from two National Health Service Foundation Trusts (UK) were used to develop and (externally) validate the model.

A total of 12 394 vital sign measurements were acquired from 273 patients after ICU discharge for the development set, and 4831 from 136 patients in the validation cohort.

Outcome validation of our model yielded an area under the receiver operating characteristic curve of 0.724 for predicting ICU readmission or in-hospital death within 24 hours. It showed an improved performance with respect to other competitive risk scoring systems, including the National EWS (0.653).

We showed that a scoring system incorporating data from a patient’s stay in the ICU has better performance than commonly used EWS systems based on vital signs alone.

ISRCTN32008295.