The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.

REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.

All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to – Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.

NCT03374800.

Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk.

In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain–body interactions in the context of cardiovascular health.

Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.

NCT03841669.

The burden of cardiovascular risk factors is increasing in India, which, in turn, can adversely impact cognition. Our objective was to examine the effect of cardiovascular risk factors measured by Framingham Risk Score (FRS) on cognitive performance among a cohort of healthy, ageing individuals (n=3609) aged ≥45 years from rural India.

A cross-sectional analysis.

A rural community setting in southern India.

Healthy, ageing, dementia-free participants, aged 45 years and above, belonging to the villages of Srinivaspura (a rural community located around 100 km from Bangalore, India), were recruited.

Using a locally adapted, validated, computerised cognitive test battery, we assessed cognitive performance across multiple cognitive domains: attention, memory, language, executive functioning and visuospatial ability.

The median (IQR) age of the sample was 57 (50.65) and 50.5% were women. Multiple linear regression analysis showed that participants with higher FRS performed poorly in attention (visual attention (β=–0.018, p=0.041)), executive functioning (categorical fluency (β=–0.064, p

Increased cardiovascular risk as evidenced by FRS was associated with poorer cognitive performance in all cognitive domains among dementia-free middle-aged and older rural Indians. It is imperative to design and implement appropriate interventions (pharmacological and lifestyle-based) for cardiovascular risk reduction and thereby, prevent or mitigate accelerated cognitive impairment in ageing individuals.

Children with congenital heart disease (CHD) are at risk for executive functions (EF) impairments. To date, interventions have limited effects on EF in children and adolescents with complex CHD. Therefore, we developed a new multimodal and personalised EF intervention (E-Fit). This study aims to test the feasibility of this intervention called ‘E-Fit’ for children with complex CHD and EF impairments.

This is a single-centre, single-blinded, randomised controlled feasibility study exploring the E-Fit intervention. We aim to enrol 40 children with CHD aged 10–12 years who underwent infant cardiopulmonary bypass surgery and show clinically relevant EF impairments (T-score ≥60 on any Behaviour Rating Inventory for Executive Function questionnaire summary scale). The multimodal intervention was developed with focus groups and the Delphi method involving children and adolescents with CHD, their parents and teachers, and health professionals. The intervention is composed of three elements: computer-based EF training using CogniFit Inc 2022, performed three times a week at home; weekly EF remote strategy coaching and analogue games. The content of the computer and strategy training is personalised to the child’s EF difficulties. The control group follows their daily routines as before and completes a diary about their everyday activities four times a week. Participants will be randomised in a 1:1 ratio. Feasibility is measured by the participants’ and providers’ ratings of the participants’ adherence and exposure to the intervention, recruitment rates and the evaluation of the intended effects of the programme.

Local ethics committee approval was obtained for the study (BASEC-Nr: 2021-02413). Parents provide written informed consent. Key outputs from the trial will be disseminated through presentations at conferences, peer-reviewed publications and directly to participating families. Furthermore, these results will inform the decision whether to proceed to a randomised controlled trial to investigate effectiveness.

NCT05198583.

The COVID-19 pandemic prompted planning for clinical surges and associated resource shortages, particularly of equipment such as ventilators. We sought to examine the experience of the healthcare professionals who created policies for crisis standards of care, and allocation of ventilators in the event of shortage.

To that end, we conducted semistructured interviews with healthcare professionals in the USA involved in institutional planning for resource shortages in the setting of the COVID-19 pandemic.

USA.

We conducted 25 interviews between May and July 2021. Half of the respondents were female (48%), many from Northeastern institutions (52%), and most practised in academic institutions (92%).

Many (64%) respondents reported that their institution had an approved policy to guide ventilator allocation in the event of a shortage. We identified one overarching theme: the work of planning for resource shortages imposed a psychological burden on many planners. We identified four subthemes that influenced that burden: impact of leadership, institutional variation in process and policies, faith in the policies and future directions.

Improved leadership strategies and cross-institutional collaboration can reduce the psychological burden of planning and facilitate updating plans in anticipation of future shortages.

The WHO has stated that vaccine hesitancy is a serious threat to overcoming COVID-19. Vaccine hesitancy among underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution. In Canada, governments of each province or territory manage their own healthcare system, providing an opportunity to compare and contrast distribution strategies. The overarching objective of this study is to identify effective vaccine distribution approaches and advance knowledge on how to design and implement various strategies to meet the different needs of underserved communities.

Multiple case studies in seven Canadian provinces will be conducted using a mixed-methods design. The study will be informed by Experience-Based CoDesign techniques and theoretically guided by the Socio-Ecological Model and the Vaccine Hesitancy Matrix frameworks. Phase 1 will involve a policy document review to systematically explore the vaccine distribution strategy over time in each jurisdiction. This will inform the second phase, which will involve (2a) semistructured, in-depth interviews with policymakers, public health officials, researchers, providers, groups representing patients, researchers and stakeholders and (2b) an analysis of population-based administrative health data of vaccine administration. Integration of qualitative and quantitative data will inform the identification of effective vaccine distribution approaches for various populations. Informed by this evidence, phase 3 of the study will involve conducting focus groups with multiple stakeholders to codesign recommendations for the design and implementation of effective vaccine delivery strategies for equity-deserving and at-risk populations.

This study is approved by the University of Toronto’s Health Sciences Research Ethics Board (#42643), University of British Columbia Behavioural Research Ethics Board (#H22-01750-A002), Research Ethics Board of the Nova Scotia Health Authority (#48272), Newfoundland and Labrador Health Research Ethics Board (#2022.126), Conjoint Health Research Ethics Board, University of Calgary (REB22-0207), and University of Manitoba Health Research Board (H2022-239). The outcome of this study will be to produce a series of recommendations for implementing future vaccine distribution approaches from the perspective of various stakeholders, including equity-deserving and at-risk populations.

Child eye health is a serious public health issue in Ethiopia, where children under the age of 15 account for over half of the population. Our aim was to review Ethiopian health policy and practice to reveal approaches and commitment to promotion and delivery of child eye health services.

We conducted a mixed-methods situational analysis employing documentary analysis and key informant interview methods. Government publications touching on any element of child eye health were included. Key informants were eligible if they were leaders, authorities, researchers or clinicians involved in child health. Data was combined and analysed by narrative synthesis, using an adaptation of the Eye Care Situation Analysis Tool as a framework.

Eleven documents developed by the Ministries of Health and Education were included and interviews with 14 key informants were conducted. A focus on child eye health was lacking in key health policy documents, demonstrated by limited allocation of funds, a shortage of human resources, and a subpar referral system across all levels of child eye care.

The study identified several gaps and limitations in child eye health in Ethiopia. There is a need for health policies that strengthen ownership, finance and partnerships for improved coordination, and collaboration with line ministries and other stakeholders to improve child eye health services in Ethiopia.

Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.

A systematic review of the literature.

We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO ‘COVID-19 Global literature on coronavirus disease’ database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control.

Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels.

At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies.

In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7–5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%–12%); n=101), with the highest estimates in areas following widespread local transmission.

The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

Nearly 30 000 Mexican women develop breast cancer annually, frequently presenting unmet supportive care needs. In high-income countries, incorporating electronic patient-reported outcomes (ePROs) into cancer care has demonstrated potential for increasing patient-centred care and reducing unmet needs. No such ePRO interventions have been implemented in Mexico. This paper presents the study protocol for designing and evaluating an ePRO digital health application combined with proactive follow-up by nurses.

We designed a two-component intervention for women receiving breast cancer treatment: a responsive web application for monitoring ePROs and clinical algorithms guiding proactive follow-up by nurses. We will conduct a pilot test of the intervention with 50 patients with breast cancer for 6 weeks to assess feasibility and adjust the application. We will conduct a parallel arm randomised controlled trial assigning 205 patients each to intervention and control in one of Mexico’s largest public oncology hospitals. The intervention will be provided for 6 months, with additional 3 months of post-intervention observation. The control group will receive usual healthcare and a list of breast cancer information sources. Women diagnosed with stages I, II or III breast cancer who initiate chemotherapy and/or radiotherapy will be invited to participate. The primary study outcome will be supportive care needs; secondary outcomes include global quality of life and breast symptoms. Information on the outcomes will be obtained through web-based self-administered questionnaires collected at baseline, 1, 3, 6 and 9 months.

The National Research and Ethics Committees of the Mexican Institute of Social Security approved the study (R-2021-785-059). Participants will sign an informed consent form prior to their inclusion. Findings will be disseminated through a policy brief to the local authorities, a webinar for patients, publications in peer-reviewed journals and presentations at national and international conferences.

NCT05925257.

Current treatment decision-making in high-grade soft-tissue sarcoma (STS) care is not informed by individualised risks for different treatment options and patients’ preferences. Risk prediction tools may provide patients and professionals insight in personalised risks and benefits for different treatment options and thereby potentially increase patients’ knowledge and reduce decisional conflict. The VALUE-PERSARC study aims to assess the (cost-)effectiveness of a personalised risk assessment tool (PERSARC) to increase patients’ knowledge about risks and benefits of treatment options and to reduce decisional conflict in comparison with usual care in high-grade extremity STS patients.

The VALUE-PERSARC study is a parallel cluster randomised control trial that aims to include at least 120 primarily diagnosed high-grade extremity STS patients in 6 Dutch hospitals. Eligible patients (≥18 years) are those without a treatment plan and treated with curative intent. Patients with sarcoma subtypes or treatment options not mentioned in PERSARC are unable to participate. Hospitals will be randomised between usual care (control) or care with the use of PERSARC (intervention). In the intervention condition, PERSARC will be used by STS professionals in multidisciplinary tumour boards to guide treatment advice and in patient consultations, where the oncological/orthopaedic surgeon informs the patient about his/her diagnosis and discusses benefits and harms of all relevant treatment options. The primary outcomes are patients’ knowledge about risks and benefits of treatment options and decisional conflict (Decisional Conflict Scale) 1 week after the treatment decision has been made. Secondary outcomes will be evaluated using questionnaires, 1 week and 3, 6 and 12 months after the treatment decision. Data will be analysed following an intention-to-treat approach using a linear mixed model and taking into account clustering of patients within hospitals.

The Medical Ethical Committee Leiden-Den Haag-Delft (METC-LDD) approved this protocol (NL76563.058.21). The results of this study will be reported in a peer-review journal.

NL9160, NCT05741944.