To evaluate the cost-effectiveness of implementing a penicillin allergy assessment pathway (PAAP) versus usual care within the NHS.

A decision tree analysis over a 5-year time-period, informed by a randomised controlled trial (RCT) of PAAP and systematic review. Value of information analysis was also conducted to estimate the value of conducting a new trial.

Model inputs were informed by the ALABAMA RCT participants included in the primary analysis, 811 adults with penicillin allergy labels and recent antibiotic prescriptions, and data from published literature.

Participants in the ALABAMA trial included in the primary analysis: PAAP (n=401) and usual care (n=410).

Costs are presented in GBP (£) at 2022–2023 prices, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, incremental net monetary benefit (INMB), the probability of cost-effectiveness at the £20,000 and £30,000 per QALY threshold, and the cost effectiveness of a new follow-on trial.

PAAP had incremental costs of £–83 (probability of cost saving 47.5%) and incremental QALYs of 0.036 (probability of positive benefits 47.5%). The INMBs (probability of cost-effectiveness) were £806 (48%) and £1167 (48%) under the decision thresholds of £20,000 and £30,000 per QALY, respectively. PAAP was more cost-effective among females, people aged >65 years, and more frequent antibiotic users. A new follow-on trial involving 1267 participants was estimated to cost £2.4 million and, by reducing uncertainty in the evidence, would avoid £19.6 million in costs of incorrect management decisions for eligible patients over the next 10 years.

The PAAP was considered cost-effective, but significant uncertainty remained. Future trials with adequate power and longer follow-up are needed to determine the most cost-effective models for penicillin allergy testing.

ISRCTN20579216.

Predicting the progression to severe dengue remains a critical yet challenging aspect of patient management. This umbrella review aims to identify biomarkers associated with the development of severe dengue. The primary objective is to determine which biomarkers can predict progression to severe disease in dengue-infected patients. Secondary objectives include identifying (a) early biomarkers (detected on days 1–3 of illness), (b) late biomarkers (detected after day 3), (c) biomarkers requiring further investigation and (d) differences in predictive biomarkers between patients aged

The review questions were formulated based on the Population, Concept and Context (PCC) framework. This review will follow the Joanna Briggs Institute methodology for umbrella reviews and be reported in accordance with the Preferred Reporting Items for Overviews of Systematic Reviews guidelines. The protocol has been registered in PROSPERO (CRD420251058284). MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis and DARE databases will be searched from 1/1/1990 to 1/6/2025. The findings are expected to support early risk stratification and guide future biomarker research in dengue infection. The systematic reviews included in this umbrella review may define severe dengue according to either the WHO 1997 or 2009 guidelines.

Ethical approval is not required since the work involves published documents. The review findings will be communicated to relevant stakeholders through conference presentations and publication in an open-access journal.

PROSPERO 2025 CRD420251058284. Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251058284.

Atrial fibrillation is a common arrhythmia in patients with ischaemic heart disease. New-onset atrial fibrillation after coronary revascularisation is associated with adverse cardiovascular outcomes. This study aimed to determine the long-term cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery.

A prospective observational cohort study in a real-world population setting, conducted at three tertiary centres, on new-onset atrial fibrillation incidence after percutaneous coronary intervention (N=123) or coronary artery bypass grafting (N=123). Heart rhythm was monitored the first 30 days in hospital by telemetry and on discharge using a handheld thumb ECG device three times a day, and thereafter for 2-week periods at 3, 12 and 24 months. The primary endpoint was the cumulative incidence of new-onset atrial fibrillation 24 months after the index procedure. Secondary objectives were to describe the incidence of cerebral ischaemic stroke and bleeding, myocardial infarction and major bleeding events during 24 months follow-up.

Mean age was 67 years, and male sex was more prevalent. At 30 days, the cumulative incidence of atrial fibrillation was 56% (69/123) in the coronary artery bypass graft group and 2% (3/123) in the percutaneous coronary intervention group. At 24 months, the cumulative incidence of atrial fibrillation was 58% (71/123) in the coronary artery bypass graft group and 6% (7/123) in the percutaneous coronary intervention group. Stroke, myocardial infarction and major bleeding were infrequent during follow-up.

Over 24 months of follow-up, incident new-onset atrial fibrillation mainly occurred during the first 30 days after coronary artery bypass grafting but was more evenly distributed during 24 months after percutaneous coronary intervention.

NCT04307225.

The objective of this study was to explore medical practitioners’ understanding of antimicrobial resistance (AMR) and its aspects, such as its causes, possible outcomes and how doctors can contribute to its prevention.

This qualitative study was conducted in Sri Lankan healthcare settings.

Using convenience sampling, the study included allopathic medical practitioners aged 18–60 years, excluding intern-medical officers, until data saturation.

One-on-one interviews were conducted online or in person, depending on each participant’s preference. A structured questionnaire was used to triangulate the information.

Data were categorised into four: (1) understanding, awareness and identifying AMR as an issue among medical practitioners, (2) knowledge and understanding of factors that contribute to AMR development among medical practitioners, (3) knowledge and understanding of the outcome of AMR and (4) knowledge and understanding of preventive measures against AMR among medical officers. Interviewees showed an awareness of AMR; however, their knowledge was not up to date. Key reasons for inappropriate antibiotic use included unavailability and poor quality of antibiotics and unawareness of updated guidelines, especially in the government sector. In the private sector, patient pressure, the need to attract patients and the high cost of investigations contributed to misuse. Additionally, low patient literacy about AMR was a significant factor.

This study revealed that although medical practitioners in Sri Lanka are aware of AMR, their knowledge remains limited in certain areas. Several challenges contributed to inappropriate antibiotic use, including the availability and quality of antibiotics, external pressures from patients and financial constraints. The findings of this study highlight the urgent need for continuous medical education and public awareness campaigns to improve both practitioner and patient understanding of AMR. Addressing these issues is essential for effectively preventing and managing AMR in healthcare settings in Sri Lanka.

Black and Asian women experience significantly higher rates of mortality and morbidity perinatally compared with white women and are more likely to lose their babies. These groups are also under-represented in clinical research, resulting in evidence that may not be generalisable. Tools have been developed to facilitate the inclusion of ethnic minority groups, but it is unknown to what extent representation and inclusion are considered in maternity trials.

To provide an overview of how ethnically diverse recruitment is considered and reported in maternity trials in the UK.

A scoping review was conducted, undertaking a systematic search to identify published trial protocols and their subsequent results papers, conducted within the UK, recruiting women during pregnancy or within 6 weeks postnatally between 2004 and 2024.

Data was extracted from protocols on whether representation of participants was considered in the study design and if specific recruitment and retention strategies were planned for ethnic minority groups.

Data extracted from results papers identified whether representation of participants was discussed and if recruitment strategies were discussed; these were compared against the protocol.

A total of 96 published protocols met the inclusion criteria; 8 mentioned specific recruitment strategies and 5 mentioned specific retention strategies. Only two included both recruitment and retention strategies. The most common strategies included providing different types of language support and adapting interventions to be culturally appropriate. Strategies were not evaluated.

67 results papers were available. Ethnicity was reported in 57 papers, with heterogeneity of categories between papers. Only 32 papers discussed representativeness of participants.

Few maternity trials report considerations on how they ensure they are recruiting and retaining ethnically representative participants. Minimal discussion is undertaken around the extent to which trial participants reflect the population to which findings will be applied.

Further work is needed to support implementation and evaluation of inclusive research guidance. Failing to ensure those from ethnic minority groups are included in research can exacerbate inequalities.

To assess awareness of colorectal cancer (CRC) symptoms and risk factors among adults attending Sri Lanka’s largest tertiary care hospital, and to identify sociodemographic predictors of awareness.

Descriptive cross-sectional study.

Outpatient clinics at the National Hospital of Sri Lanka (NHSL), the country’s largest tertiary care centre.

A total of 506 adults (≥18 years) recruited via convenience sampling. Data were collected from May 2022 to May 2023 at the outpatient clinics of the NHSL, the country’s largest tertiary care centre. Eligible participants included clinic attendees as well as accompanying persons of attendees, provided they met inclusion criteria. Individuals with known gastrointestinal conditions or malignancies were excluded.

Primary outcomes: awareness scores of CRC symptoms and risk factors using a culturally adapted Bowel Cancer Awareness Measure questionnaire.

Secondary outcomes: predictors of awareness based on sociodemographic variables.

58.7% (n=297) of participants could not name any CRC symptoms unprompted; blood in stools (n=93, 18.4%) was the most identified symptom unprompted. Prompted awareness improved markedly, with 75.3% (n=381) identifying blood in stools when provided with a list. Similarly, 44.3% (n=224) could not identify any CRC risk factors unprompted; excessive alcohol intake (n=368, 72.7%) and low fibre intake (n=324, 64.0%) were the most commonly recognised risk factors when prompted. The mean symptom awareness score was 5.63 (SD=2.55), corresponding to ‘fair’ awareness, and the mean risk factor awareness score was 5.47 (SD=2.63), also indicating ‘fair’ awareness. Female gender (B=0.669, p=0.008; n=237) and older age (B=0.023, p=0.034) were significantly associated with higher symptom awareness. Awareness was significantly lower among participants with lower education (B = –0.104, p=0.018; n=219) and among the unemployed (B = –0.175, p=0.045; n=152).

Unprompted awareness of CRC symptoms and risk factors was suboptimal in this population, with marked gaps in spontaneous recall. Public health campaigns should prioritise men, younger adults and individuals with lower education to enhance CRC literacy and promote earlier detection.

In patients with post-acute sequelae of COVID-19 (PASC), depression has been associated with symptom severity, the duration since infection and ongoing functional impairment. However, the interconnections between these factors remain inadequately understood.

This study aimed to explore the roles of depressive symptoms in moderating and mediating the relationships between post-COVID-19 conditions and functional capacity.

The PERCEIVE study recruited 1794 participants from Victoria and Tasmania through online advertisements based on possible PASC for a cross-sectional study. Of these, 461 participated in the longitudinal study. Post-COVID-19 duration and symptoms were recorded, and depressive symptoms and functional capacity were self-reported using the 9-item Patient Health Questionnaire and the Duke Activity Status Index (DASI), respectively. The association of depression with functional capacity was explored using ordinary least squares (OLS) regression, with companion OLS models, Sobel-Goodman tests and 1000 bootstrap iterations to assess mediation. Longitudinal data were analysed to assess changes in functional capacity and depressive symptoms over time, with mediation analysis using mixed models to explore depression as a mediator.

Participants had a mean DASI score of 35 (SD 21). Fatigue (18%), shortness of breath (11%) and chest pain (6%) were common symptoms, with severe depression linked to fatigue (93%) and shortness of breath (66%). The severity of post-COVID-19 symptoms was associated with severe depression (β=6.31, 95% CI 5.42 to 7.21) and reduced functional capacity (β=–6.40, 95% CI –9.20 to –3.61), with depression mediating 36% of the association between post-COVID-19 symptom severity and functional capacity. PASC was associated with higher depression scores (β=2.06, 95% CI 1.15 to 2.97) and lower functional capacity (β=–3.99, 95% CI –6.21 to –1.77), with depression mediating 51% of the association between PASC and reduced functional capacity. The longitudinal analysis suggested that depression is associated with the relationship between PASC and changes in functional capacity over time (unstandardised estimate=–5.16, p

Depression plays a key role in exacerbating post-COVID-19 functional impairment. This observation underscores the need for targeted physical and mental health interventions to enhance long-term recovery for those with severe conditions.

Optimal nutrition during early childhood is crucial for psychosomatic development and for preventing diet-related diseases. However, evidence from Poland highlights significant deviations from recommended dietary practices. The previous Polish Infants and Toddler Nutritional Study conducted in 2016 (PITNUTS 2016) revealed imbalances in nutrient intake among children aged 5–36 months. The aim of this study (PITNUTS 2024) is to assess the diet and nutritional status of infants and children aged 5–72 months, providing a broader understanding of eating behaviours across critical stages of growth and development and allowing evaluation of how dietary practices changed in recent years.

This cross-sectional study will recruit a nationally representative sample of Polish infants and children aged 5 to 72 months using stratified random sampling. Survey interviews will be conducted with parents or legal guardians as proxy reporters for the children. Dietary practices will be evaluated through validated qualitative and quantitative dietary assessments, ensuring a comprehensive evaluation of food consumption and energy and nutrient intake. Dietary data will be collected using the 3 day food record and the survey questionnaire, including a food frequency questionnaire (FFQ). Daily energy and nutrient intake will be compared with national dietary standards and WHO guidelines. Dietary patterns will be derived based on the FFQ data. Nutritional status will be assessed based on measured anthropometric parameters. Energy, macro- and micronutrient intake as well as dietary patterns identified among children will be associated with nutritional status, including body mass index z-score and body weight status.

The study has been approved by the ethics board of the Institute of Mother and Child. Written informed consent was obtained from all participants’ parents or legal guardians before the interviews began. The results from this study will be presented at scientific conferences and published in peer-reviewed journals, contributing to nutrition policies in Poland and informing educational materials and dietary consultation services.

NCT06417151, results.

Psychiatrists’ first exposure to patient suicide often occurs during residency training. Previous research shows that experiencing a patient’s death by suicide during residency can have significant impacts on trainees’ well-being, self-esteem and approach to practice. However, existing research on this topic is mostly limited to survey-based data, which does not facilitate nuanced exploration. This study will use a qualitative approach to gain an in-depth understanding of Canadian psychiatry residents’ experiences of a patient’s death by suicide and the types of supports that may help trainees to process this loss and integrate this experience into their professional identity formation.

This study will conduct 15–25 semistructured qualitative interviews with psychiatry resident physicians across Canada to explore their experiences of patient loss by suicide during training. Interview data will be transcribed verbatim and analysed using the principles of Constructivist Grounded Theory.

The study findings will be reported and accessible to residency training programmes, the academic community, the media and the public.

This study was approved by the Research Ethics Board of the Centre for Addiction and Mental Health (Protocol Identifying Number 2024/125).

The aim of this study was to explore why patients with hard-to-heal ulcers are treated without an aetiological diagnosis, using a grounded theory approach.

The study employed a qualitative semistructured interview design to gain in-depth insights. Data were collected in 2024, and an explanatory model was formed in accordance with grounded theory analysis.

Interviews were conducted with healthcare staff across primary, community and specialist care units in Sweden, encompassing both public and private sectors and representing a wide geographical spread.

The study involved 23 healthcare professionals, including nurses (n=18), assistant nurses (n=2) and physicians (n=3), from 22 healthcare units that participated in a preceding national mapping study. Participants were selected purposively to represent various professional roles and healthcare levels.

The analysis resulted in a theoretical model based on two categories: Healthcare traditions and clinical practices and Clinical governance. The lack of an aetiological diagnosis can be attributed to a traditional division of tasks, where ulcer care falls within the nurses’ domain. As a result, patients often receive treatment without a physician’s involvement, especially in home healthcare. Barriers and enablers for a diagnosis are present on different levels; issues close to the patient as well as structural matters. The results illustrate how healthcare units can be positioned along a scale, from traditional work distribution to evidence-based guidelines.

This study can be used to get a deeper understanding of the challenges of current wound management, where clinical governance can support or undermine the movement from a traditional work distribution towards an evidence-based clinical practice. Furthermore, this study can provide a basis for discussing quality improvement, to obtain good and equal care for patients with hard-to-heal ulcers.

Dietary modification, particularly low-carbohydrate diet, and diabetes self-management education (DSME) have shown promise in improving glycaemic control among persons with type 2 diabetes mellitus (T2DM). However, real-world evidence from India is limited. This protocol describes the methods of a cluster randomised trial to determine the effectiveness and feasibility of adopting a low-carbohydrate diet among persons with T2DM.

Our cluster-randomised trial with a mixed-method process evaluation will use computer-generated block randomisation sequence to randomise Urban Primary Health Centres (UPHCs) (n=16) to either continue delivering the usual guideline-based care under the National Programme for Prevention and Control of Non-Communicable Diseases (NPNCD) or our study intervention. The study intervention will comprise a personalised nutrition counselling focusing on (i) low-carbohydrate diet (

We will include persons with T2DM, over the age of 30 years and above, irrespective of comorbidities, registered in the selected UPHC under care for diabetes for at least a month and with an glycated haemoglobin (HbA1c) level ≥6.5% during the screening test. We will collect data electronically using semistructured questionnaires and measure HbA1c, blood pressure, lipid profile, serum creatinine and body weight at baseline, 3, 6, 9 and 12 months after enrolment. We will use a difference in difference analysis, adjusted for clustering, to compare the change in HbA1c at the follow-up visits compared with baseline across the two study arms. We will conduct both intention-to-treat and per-protocol analysis, exploring reasons for differences in effect size.

The study protocol was reviewed and approved by the Scientific Advisory Committee/Institutional Human Ethics Committee of the research institution (NIE/IHEC/202302-03). The findings of this study will be disseminated through publication in peer-reviewed journals.

Clinical Trials Registry-India (CTRI/2024/02/062202).

To evaluate the patterns of abnormal estimated glomerular filtration rate (eGFR) and urine albumin–creatinine ratio (UACR) follow-up testing for the detection of chronic kidney disease (CKD) in Australian general practices.

Retrospective, population-based observational study.

2 717 966 adults who visited a MedicineInsight participating general practice between 1 January 2012 and 31 December 2020, had ≥1 serum creatinine measurement (with or without a UACR measurement) and did not have CKD at baseline.

‘Guideline-concordant follow-up’ was defined as having a record of a repeat eGFR or UACR testing (assessed separately) within 6 months following the abnormal (eGFR2; UACR≥2.5 mg/mmol in males, ≥3.5 mg/mmol in females) incident result. Multivariable logistic regression was used to identify patient factors associated with receiving appropriate follow-up testing.

A total of 220 841 and 114 889 patients with an abnormal incident eGFR and UACR result, respectively, were identified. Nearly half (45.0%) of the patients with an abnormal eGFR result and over two-thirds (69.7%) of the patients with an abnormal UACR result did not have a follow-up test within 6 months. Patient factors associated with a higher likelihood of follow-up eGFR testing included indicators of poorer baseline health and greater CKD risk, such as comorbid diabetes (adjusted OR 1.36, 95% CI 1.32 to 1.40) or more severe incident eGFR (adjusted ORs for eGFR categories 30–44, 15–29 and

In this large, population-based study, we observed substantial gaps in the follow-up of abnormal eGFR and UACR for the detection of CKD in primary care settings. Effective strategies to optimise follow-up testing for CKD detection are needed.

Approximately, 20 million older adults undergo major elective surgery annually, yet less than 10% engage in advance care planning (ACP). This is a critical missed opportunity to optimally engage in patient-aligned medical decisions and communications in the perioperative setting. The PREPARE ACP programme (easy-to-read advance directives (ADs) and a patient-directed, online ACP programme) has been shown to increase ACP documentation and patient and clinician empowerment to discuss ACP. Yet, a gap remains in extending PREPARE’s use to surgical populations. We hypothesise that by delivering PREPARE in a patient-facing electronic health record (EHR) centric presurgery workflow for older adults, supported by automated patient reminders and outreach from a healthcare navigator (HCN), we can enable patients and/or surgical teams to engage in ACP discussions.

This is a three-site, single-blinded, pragmatic randomised trial comparing increasing intensity of ACP-focused, patient-facing EHR messaging and HCN support. The outreach occurs prior to a new presurgical clinic visit. We will enrol 6000 patients (2000 each site) aged 65 and older and randomise them equally to the following study arms: (Arm 1) ACP-related cover letter and PREPARE URL information sent via patient portal and postal mail (includes cover letter, AD and PREPARE pamphlet); (Arm 2) Arm 1 plus reminder message via text or MyChart message and (Arm 3) Arm 2 plus HCN outreach and support. The primary outcome is clinically meaningful ACP documentation in the EHR (ie, surrogate designation, documented discussions and ADs) within 6 months of the new surgical visit. The rate of ACP documentation will be compared between treatment groups using generalised estimating equations. Secondary outcomes include a validated four-item ACP engagement survey, administered 2 weeks after the presurgical visit and 6 months later. All analyses will follow the intention-to-treat principle and recent Consolidated Standards of Reporting Trials guidelines.

The study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers (21 Code of Federal Regulations (CFR) 50), Institutional Review Boards (21 CFR 56) and Obligations of Clinical Investigators (21 CFR 312). The protocol and consent form were reviewed and approved by Advarra, an National Insitutes of Health (NIH)-approved, commercial, centralised Institutional Review Board (IRB). The IRB/Independent Ethics Committee of each participating centre reviewed and approved the protocol and consent and obtained reliance agreements with Advarra prior to study initiation. The study is guided by input from patient and clinical advisory boards and a data safety monitoring board. The results of the study will be disseminated to both academic and community stakeholders, complying with all applicable privacy laws.

ClinicalTrials.gov ID: NCT06090552.

Advarra Pro 00070994.

23-38948.

Protocol Date: 24 October 2024. Protocol Version: 4.

Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis, health outcomes have improved. This paper evaluates the health system costs and the health-related quality of life implications of these guidelines.

A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015.

Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months.

Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS) and the EuroQoL; healthcare costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life Years (QALYs) were calculated from the EQ-5D utility scores. Cost–utility analysis was performed using the NHS and Social Care perspective.

A total of 49 patients were included; 35 were treated within 48 hours, ‘early’ (median (IQR) 8.25 [3.7–20.5]) and 14 were treated after 48 hours ‘delayed’ (median (IQR) 93.9 [66.7–100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0–3) compared with 4 (29%) in the delayed group. According to GOS, 10 (29%) had a good recovery in the early treatment group, but only 1 (7%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p

This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.

Ages of attainment for early gross motor milestones have been widely studied, but definitions and measurement methods have varied greatly. Since delays in motor milestones have been used extensively as one of the earliest indicators of atypical development, it is imperative to establish a universal understanding of the methods and results reported on motor milestones in typically developing children. Therefore, the primary aim of this scoping review is to provide an overview of recent studies reporting ages of onset for independent sitting and walking in typically developing children worldwide; this will be achieved by summarising how these milestones have been operationalised and evaluated, the samples from whom these data have been drawn, and the reported ages of acquisition.

To meet inclusion criteria, articles must: be original research papers published in any language since 2003, contain a sample of typically developing children and report actual ages of onset for independent sitting and/or walking. To conduct this scoping review, the Joanna Briggs Institute methodological framework will be used. Search terms will include variations of the following concepts: acquisition of motor milestone (independent sitting and/or walking), age of onset, infancy. Six databases (CINAHL Plus, Embase, PsycNet: PsycINFO & PsycArticles, PubMed, Scopus, Web of Science: Core Collection) will be searched. Records from these databases will be screened for eligibility. Two people will independently review each record during title and abstract screening, and three people will independently screen full texts and extract data. Results will be displayed in tables, graphs and narrative summaries in the scoping review.

As the review will only include previously published data, ethics approval is not required. Findings will be shared at scientific conferences and in a peer-reviewed journal.

Childhood cancer accounts for a significant proportion of global childhood mortality, especially in low-income and middle-income countries (LMICs). Unlike many adult malignancies, primary prevention of childhood cancers is not possible. Improving survival requires a two-pronged strategy: earlier diagnosis and effective treatment. Our study aims to establish the feasibility, clinical and implementation effectiveness of an adapted early warning signs and symptoms (EWSS) intervention in Cameroon and Kenya. It will equip healthcare workers, Ministry of Health (MOH) representatives and National Cancer Institute leaders with evidence-informed guidance on implementing context-adapted interventions to improve the early detection and referral of childhood cancers in these countries.

The study is a quasi-experimental, hybrid type 2 implementation effectiveness study based on a Ghanaian adaptation of the ‘Saint Siluan’ EWSS campaign. Our protocol proposes context-specific adaptation and evidence-based implementation of the EWSS intervention through iterative engagement with country-level implementation teams to train healthcare workers and improve referral pathways for earlier childhood cancer diagnoses in each study country. Training effectiveness will be measured through pretraining and post-training tests of knowledge and application, as well as training satisfaction surveys. Clinical effectiveness will be assessed by using a REDCap database to track the number of newly diagnosed childhood cancer cases in the study regions and counties, healthcare timelines and paths to diagnosis, and the stage and proportion of metastatic disease at diagnosis. Implementation effectiveness will be evaluated through interviews with senior and mid-level health system partners and clinicians, tracking fidelity to the implementation process as laid out in The Implementation Roadmap Workbook, and analysis of meeting minutes from monthly local implementation team meetings.

This study has received ethical approval from The Hospital for Sick Children (REB # 1000080092) and all participating sites. We have received National Ethical Clearance from the Cameroon Ethical Board (#1699) and Regional Administrative Authorizations from our piloting regions (Centre and West). We have also received ethical clearance from Kenyatta National Hospital (KNH) (ERB# KNH-ERC/RR/955) and our National Commission for Science, Technology and Innovation in Kenya licence from the counties we are piloting in Kenya. As clinical data will be collected from existing health registries and patient charts, patient consent will not be required; however, we will obtain consent from all members of the leadership implementation teams and operational implementation teams for their participation in the implementation meetings and from all individuals participating in the semistructured interviews. We will disseminate findings to build awareness and share findings among various target audiences: (1) key county and regional parties (eg, clinical societies, advocacy groups, country MOHs and regional bodies such as the East African Community, Economic Community of West African States); (2) international bodies such as the WHO; and (3) the academic community.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death globally. Growing evidence links gut microbiota dysbiosis to CRC, with several reviews reporting consistent microbial alterations in CRC patients that may serve as non-invasive biomarkers. However, findings vary across studies, and consensus on key microbial taxa is lacking. This umbrella review aims to clarify: (1) the association between gut microbiome composition and CRC development/progression, (2) specific microbial taxa linked to CRC risk, (3) the role of microbiome diversity in CRC outcomes and (4) potential microbial biomarkers for diagnosis, prognosis and treatment response.

This umbrella review will follow the Joanna Briggs Institute (JBI) Umbrella Review Guidelines and adhere to the Preferred Reporting Items for Overviews of Reviews. A comprehensive search will be conducted across MEDLINE (PubMed), Embase, CINAHL and key systematic review databases, including the Cochrane Database, JBI Evidence Synthesis and Database of Abstracts of Reviews of Effects, without language restrictions. The search strategy will use a combination of Medical Subject Headings terms and free-text keywords with Boolean operators. The review questions were developed using the Population, Concept and Context framework. Only high-quality (as determined by the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses), peer-reviewed quantitative systematic reviews with or without meta-analyses will be included. Overall effect estimates extracted from systematic reviews, with the number of studies that inform the outcome, will be presented.

No ethical approval is required since the work is carried out on published documents. Findings of this review will be disseminated among relevant stakeholders through multiple scientific avenues, including presentations at both national and international forums and manuscript publication in an open-access journal.

PROSPERO 2025 CRD420251035257. Available from:

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251035257.