Survival status and predictors of mortality among patients with breast cancer in Ethiopia: a systematic review and meta-analysis

Objectives
This study aimed to evaluate survival outcomes and identify key mortality predictors among patients with breast cancer in Ethiopia.

Study design
A systematic review and meta-analysis.

Study participants
The study used 11 primary studies, involving a total of 4131 participants.

Data sources
We searched PubMed, Embase, Web of Science, Scopus and Google Scholar until 7 March 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Eligibility criteria for selecting studies
All observational studies that had reported the survival status and/or at least one predictor of mortality of women patients with breast cancer were considered.

Data extraction and synthesis
Three independent reviewers (HA, HKN and DGA) used a structured data extraction form to extract the data. To compute the pooled survival and mortality rates, the survival rates at different observation periods and the mortality rates reported in the included studies were extracted.

Results
Eleven studies were analysed. All studies were of good quality based on Newcastle-Ottawa Scale. However, heterogeneity was high (I² = 98.2%, p=0.00). Funnel plots showed significant publication bias. The Grading of Recommendations, Assessment, Development, and Evaluations assessment indicated moderate certainty for mortality rates and predictors, limited by heterogeneity and regional data gaps. The pooled mortality rate was 36% (95% CI: 25% to 46%). The survival rates at 1, 3 and 5 years were 85% (95% CI: 75% to 96%), 66% (95% CI: 48% to 84%) and 22% (95% CI: 1% to 43%), respectively. Key mortality predictors included advanced clinical stage (Adjusted Hazard Ratio (AHR): 4.14; CI: 2.53 to 6.78), rural residence (AHR: 1.65; 95% CI: 1.27 to 2.14), positive lymph node status (AHR: 2.85; 95% CI: 1.50 to 5.44), no hormonal therapy (AHR: 2.02; 95% CI: 1.59 to 2.56), histologic grade III (AHR: 1.76; 95% CI: 1.29 to 2.41), hormone receptor negativity (AHR: 1.54; 95% CI: 1.05 to 2.25) and comorbidities (AHR: 2.24; 95% CI: 1.41 to 3.56).

Conclusion
Breast cancer in Ethiopia poses a high mortality rate primarily due to late-stage diagnosis, rural residency, histologic grade III, positive lymph node status and comorbidities. To improve survival outcomes, it is crucial to expand access to early screening, particularly in rural areas, implement comprehensive treatment protocols and strengthen healthcare infrastructure to address these critical factors.

PROSPERO registration number
CRD42024575074.

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Breaking prolonged sitting with high-intensity interval training to improve cognitive and brain health in middle-aged and older adults: a protocol for the pilot feasibility HIIT2SITLess trial

Introduction
Excessive sedentary time (ST) is linked to dementia risk, poorer attentional control and episodic memory. These cognitive decrements have been associated with decreased functional connectivity (FC) in the frontoparietal network (FPN) and default mode networks (DMN) with ageing. Physical activity (PA) interventions can enhance FC in these networks, but these interventions are not designed to decrease ST among older adults. Prolonged sitting (ie, sitting continuously for ≥20 min) can acutely reduce frontoparietal brain function and attentional control, while a single PA bout lasting at least 20 min can enhance them. It has been theorised that stimulation of the cerebral norepinephrine release through peripheral increase in catecholamines may explain this effect. In contrast, the effects of shorter (

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Machine learning model for differentiating malignant from benign thyroid nodules based on the thyroid function data

Objectives
To develop and validate a machine learning (ML) model to differentiate malignant from benign thyroid nodules (TNs) based on the routine data and provide diagnostic assistance for medical professionals.

Setting
A qualified panel of 1649 patients with TNs from one hospital were stratified by gender, age, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAB).

Participants
Thyroid function (TF) data of 1649 patients with TNs were collected in a single centre from January 2018 to June 2022, with a total of 273 males and 1376 females, respectively.

Measures
Seven popular ML models (Random Forest, Decision Tree, Logistic Regression (LR), K-Neighbours, Gaussian Naive Bayes, Multilayer Perception and Gradient Boosting) were developed to predict malignant and benign TNs, whose performance indicators included area under the curve (AUC), accuracy, recall, precision and F1 score.

Results
A total of 1649 patients were enrolled in this study, with the median age of 45.15±13.41 years, and the male to female ratio was 1:5.055. In the multivariate LR analysis, statistically significant differences existed between the TNs group and thyroid cancer group in gender, age, free triiodothyronine (FT3), free thyroxine (FT4) and TPOAB. Among the seven tested ML models, the best performance was achieved in the Gradient Boosting model in terms of precision, AUC, accuracy, recall and F1 score, with the AUC of 0.82, accuracy of 79.4% and precision of 0.814 after experimental verification. FT4, TPOAB and FT3 were validated as the top three features in the Gradient Boosting model.

Conclusions
This study innovatively developed a predictive model for benign and malignant TNs based on the Gradient Boosting Decision Tree algorithm. For the first time, it validated the clinical predictive value of TF parameters (FT4, FT3) and TPOAB as key biomarkers.

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Redefining QUAIDE: paving the way for better AI in preclinical endoscopy

We read with great interest the recent article by Antonelli et al1 on the quality assessment for artificial intelligence in digestive endoscopy (QUAIDE) framework, which enhances the quality and reproducibility of artificial intelligence (AI)-based gastrointestinal endoscopy research. While QUAIDE provides a solid foundation for pre-clinical research design, we see opportunities for further improvement in several key areas. First, preclinical endoscopy AI research often involves sensitive patient data, requiring strict adherence to data privacy and ethical standards.2 Currently, the QUAIDE framework does not adequately address data privacy protection, particularly in terms of anonymisation, de-identification, data-sharing agreements and informed consent. Including these standards is crucial for ensuring patient data safety, especially in multicentre collaborations, where varying anonymisation practices across centres increase the risk of data breaches.3 Establishing unified data management protocols would ensure consistency across centres, reduce legal and ethical risks and safeguard data confidentiality…

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SPHINX, a Guardian of Wisdom

We thank Ramchandani et al for their letter on the SPHINX trial and appreciate the opportunity to address their points.1 2 Sample size The SPHINX trial aimed to assess whether endoscopic sphincterotomy (ES) could reduce post-ERCP pancreatitis (PEP). However, quantifying this effect proved difficult due to conflicting results from previous, heterogeneous randomised controlled trials (RCTs), which differed in sample size, patient populations and stent types.3–5 The trial by Zhou et al (2012) reported a 69% relative risk reduction in PEP after ES, which served as reference for our sample size calculation.3 However, since the other trials did not show this benefit, we considered this effect overestimated.4 5 The SPHINX trial was designed to detect a 50% relative risk reduction in PEP in patients with suspected distal malignant biliary obstruction (MBO). Based on…

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Global health inequalities in the burden of gastrointestinal cancers from 1990 to 2021

We read with great interest the study by Danpanichkul et al,1 which assessed the global burden of gastrointestinal cancers, including oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers, from 2000 to 2021. The study revealed that the burden of all types of cancers varies across geographical and socioeconomic levels. The incidence rates of some types of gastrointestinal cancer in higher sociodemographic index (SDI) countries tend to decrease or increase at a slower rate compared with the more significant rise observed in lower SDI countries. Another study on global gastrointestinal cancer also noted that the incidence tends to be concentrated in countries with higher SDI.2 In this global context, quantifying the inequalities in the burden of gastrointestinal cancers across countries is crucial for informing targeted strategies and optimising future efforts to reduce the global disparities in cancer burden. We use the SDI to represent the…

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Carbon footprinting and environmental impact of gastrointestinal endoscopy procedures at a tertiary care institution: a prospective multi-dimensional assessment

Background
Given the imperative to combat climate change, reducing the healthcare sector’s implications on the environment is crucial.

Objective
This study aims to offer a comprehensive assessment of the environmental impact of gastrointestinal endoscopy (GIE) procedures, specifically focusing on greenhouse gas (GHG) emissions and waste generation.

Design
A prospective study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from 29 May to 10 June 2023, including all consecutive GIE procedures. Carbon emissions for various variables involved were calculated with specific emission factors using ‘The GHG Protocol’.

Results
Based on data from 3244 consecutive patients undergoing 3873 procedures, the study revealed a total carbon footprint of 148 947.32 kg CO2e or 38.45 kg CO2e per procedure. Excluding patient travel, the emissions were 6.50 kg CO2e per procedure. The total waste generated was 1952.50 kg, averaging 0.504 kg per procedure, far less than 2–3 kg per procedure in the West. The waste disposal breakdown was 9.5% direct landfilling, 64.8% incineration, then landfilling and 25.7% recycling, which saved 380 kg CO2e. India effectively recycles 25.7% of hospital-related waste, which undergoes landfilling in the West. The primary contributors to GHG emissions were patient travel (83.09%), electricity consumption (10.42%), medical gas transport and usage (3.63%) and water consumption (1.86%). Diagnostic procedures generate less waste and lower carbon footprint than therapeutic procedures.

Conclusion
This study highlights the significant environmental footprint of GIE procedures, emphasising the importance of optimising practices to reduce patient travel and repeat procedures, alongside improving electricity and water management for sustainable healthcare.

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Detection of large flat colorectal lesions by artificial intelligence: a persistent weakness and blind spot

Message Computer-aided detection (CADe) has increased adenoma detection in randomised trials. However, unlike other detection adjuncts, CADe is lesion specific, that is, it is trained on a specific set of lesions. If the training does not include sufficient examples of precancerous lesion subsets, CADe may not perform adequately for lesions in that subset. In a prospective assessment of a second-generation CADe programme in 165 colonoscopies, we identified 26 flat lesions ≥10 mm in 17 patients. The endoscopist identified 22 of 26 lesions before the CADe programme. In 13 lesions, the CADe either generated no detection signal or only a signal over part of the lesion after colonoscope position or luminal inflation adjustment. Thus, the second-generation CADe algorithm, like the first generation, frequently fails to effectively detect large flat colorectal lesions, which are likely very important lesions that a CADe programme should identify. Details The first CADe…

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Are histamine-2 receptor antagonists a reasonable comparator: comparing apples and apples?

We recently read with great interest the article by Devin Abrahami et al.1 We would like to raise some concerns that warrant further discussion. The association between proton pump inhibitors (PPIs) and the risk of inflammatory bowel disease (IBD) remains a debate, the authors mostly focus on the protopathic bias introduced by study design. However, in this study, the authors used histamine-2 receptor antagonists (H2RAs) as an active comparator. While this partially balanced the bias introduced by indications, it may have masked the potential impact of PPIs on the incidence of IBD. In the general population, the age-standardised and sex-standardised incidence of IBD is 10.9 per 100 000 person-years.2 Bin Xia et al through the NHS and UK Biobank cohorts, investigated the association between PPIs and the risk of IBD, reporting incidence rates of 12.8 and 34.6 per 100 000 person-years for non-regular PPI users, respectively.

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Sphincterotomy with FCSEMS (SPHINX): a monumental answer or the beginning of new mysteries?

We read with interest the recently published randomised controlled trial (RCT) ‘SPHINX’,1 addressing the role of endoscopic sphincterotomy (ES) with fully covered s metal stent (FCSEMS) placement in preventing post-ERCP pancreatitis (PEP). Although this is the largest RCT on the topic, several concerns warrant discussion. Published data report variable rates of PEP after SEMS ranging from 0% to 26.8%,2–4 with lot of heterogeneity regarding the PEP preventive measures. Nevertheless severe pancreatitis remains rare. To assess the impact of ES a larger sample size will be required. The SPHINX trial sample estimation was based on two studies by Tol et al,5 which reported 18% PEP with FCSEMS placement in the preoperative biliary drainage setting, and Zhou et al,6 31.7% PEP in the non-ES group, which is way higher than the presumed 16% in the SPHINX trial. Furthermore, it…

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Reparative immunological consequences of stem cell transplantation as a cellular therapy for refractory Crohns disease

Background
Treatment strategies for Crohn’s disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.

Objective
The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs).

Design
Adults with CD with active clinical and endoscopic disease who failed available medical therapies were enrolled in a phase II study of SCT for refractory CD (n=19). Blood and intestinal samples were collected longitudinally and analysed using CyTOF and scRNA-seq. Stem cell autografts were functionally assayed in mouse xenograft models.

Results
scRNA-seq and CyTOF analyses reveal that SCT predominantly affected the intestinal myeloid lineage with loss of inflammatory populations and return of macrophages capable of supporting mucosal healing. Xenograft models using patient HSCs suggested that HSCs support the early reconstitution of the myeloid lineage and reveal an impairment of short and long-term HSC engraftment that may determine SCT outcomes.

Conclusions
This study suggests SCT functions as a myeloid-directed cellular therapy reinforcing the critical role of macrophages in refractory CD pathophysiology and as a target for cellular therapies. Furthermore, we report an unrecognised functional heterogeneity among HSC subpopulations in CD that may be relevant to our understanding of CD treatment and pathophysiology.

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Rapid cycle, randomised testing of precision feedback to improve engagement with a process measure dashboard amongst urologists: study protocol for a hybrid trial

Introduction
Rapid-cycle randomised testing holds high potential to enhance quality improvement practice but remains under-utilised because it requires significant resource commitment. However, infrastructure for learning networks, such as collaborative quality initiatives and large-scale quality improvement consortia, holds potential to support rapid-cycle testing at low cost and with minimal effort. For example, rapid-cycle randomised testing could be used to optimise ‘precision feedback’, which prioritises highly motivating tailored content to improve engagement with audit and feedback. We combined these concepts (rapid cycle, randomised testing and precision feedback) with a low-resource emphasis in conceiving this trial.

Methods and analysis
A stepped wedge randomised controlled trial will deliver an intervention consisting of precision feedback and modifications to audit and feedback communication to 100 urologists performing ureteroscopy within the Michigan Urological Surgery Improvement Collaborative (MUSIC) and will be compared with a control consisting of standard ‘one-size-fits-all’ audit and feedback. The study’s primary endpoint is online dashboard engagement, measured as the clickthrough rate through the tracking of embedded links in emails. The stent rate following pre-stented ureteroscopy will also be measured. The primary hypothesis is that precision feedback will increase engagement with an audit and feedback dashboard and decrease rates of stenting following pre-stented ureteroscopy. Endpoints will be analysed by linear modelling accounting for repeated measures within individuals, exploring the primary hypothesis through a main effect by the study arm.

Ethics and dissemination
Ethics and regulatory approval have been obtained from the Institutional Review Board of the University of Michigan (HUM#00248876). The findings will be disseminated in peer-reviewed journals and conferences.

Trial registration number
ClinicalTrials.gov registration number: NCT06465667. Registered 6/20/2024.

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Middle meningeal artery (MMA) embolisation for chronic subdural haematomas: rationale and design for the STOp Recurrence of MMA Bleeding (STORMM) randomised control trial–a study protocol

Introduction
Chronic subdural haematomas (cSDH) are common and can result in neurological impairment and reduced consciousness. Surgery is typically performed once neurological symptoms develop. Recent studies suggest that arteries nourished by the middle meningeal artery (MMA) may be responsible for haematoma progression and that MMA embolisation is clinically useful. There is less evidence that MMA embolisation can be an option for individuals without surgical treatment. We propose a multicentre study to investigate the efficacy of MMA embolisation to reduce cSDH recurrence and to improve outcomes.

Methods and analysis
cSDH patients with surgical indication will be randomised between the conventional management group (ie, surgery alone without MMA embolisation, Arm 1) and the surgery followed by MMA embolisation group (Arm 2) at multiple centres within Switzerland and Europe. The primary outcome will be the recurrence rate of cSDH. For that purpose, we estimate a minimum enrolment of 156 patients (alpha=0.05, power of 80%). Other major outcomes will include radiological parameters (volume, haematoma size, unilateral/bilateral presence) as well as clinical outcome scales and readmission rates. Outcomes will be recorded at admission and 6 weeks’ and 6 months’ follow-ups. Embolisation alone will be proposed to unoperated patients (surgical contraindication or refusal of surgery); the group of patients accepting and receiving embolisation (Arm 3) will additionally be compared with the group of untreated patients (Arm 4).

Ethics and dissemination
While it has been suggested that MMA embolisation reduces recurrence, no high-level evidence exists. As low risks exist with neuro-interventional procedures, there is equipoise for randomising patients to evaluate the potential benefits of MMA embolisation and to determine if these clearly outweigh the risks and costs. Peer-reviewed publications and presentations of the results at international meetings are planned.

Trial registration number
The protocol is approved by the Geneva and Ticino Ethics Commission for Research (2023-00848) and is recorded on clinicaltrials.gov (NCT06163547).

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Codevelopment of a complex intervention to reduce inequalities in paediatric diabetes secondary care outcomes for children with type 1 diabetes from underserved groups

Objectives
To codevelop (with children and young people with diabetes (CYPD)) an intervention to improve diabetes control and future health outcomes of CYPD from ‘underserved’ groups, to reduce treatment outcome inequalities between different socioeconomic and ethnic groups. To follow Medical Research Council guidance for complex interventions and the COM-B (Capability, Opportunity, Motivation, Behaviour) model for behaviour change intervention development.

Design
In phase 1 (previously reported), we established the evidence base, conducted literature reviews and analysed data from semistructured interviews with CYPD and their carers. In phase 2 (this report), we applied the COM-B framework to identify intervention components; in phase 3 (this report), we evaluated these components, including focus groups with CYPD, their carers’ and healthcare practitioner (HCP) surveys, using the Acceptability, Practicability, Effectiveness, Affordability, Spill-Over Effects, Equity criteria.

Setting
Secondary care; children, young people and their carers’ were approached from two large paediatric diabetes services in England, both with socioeconomically and ethnically diverse underserved populations; paediatric diabetes HCPs were surveyed across four English regions.

Participants
N=69 underserved CYPD (aged 5–19 years) and/or family members took part in interviews; N=48 paediatric diabetes HCP survey respondents (survey 1); N=34 paediatric diabetes HCP survey respondents (survey 2); N=3 young people’s advisory group participants; N=17 underserved CYPD/carers focus group participants; N=9 wider stakeholder participants.

Results
The codevelopment process and integration of COM-B established four elements for an intervention package: (1) an enhanced peer support/mentoring programme; (2) provision of a health and well-being coach to CYPD/families; (3) family/community support to address social and community issues and (4) training for HCPs, including cultural competence, poverty proofing and to emphasise the need for increased sensitivity and better supported communication in work with CYPD from underserved groups.

Conclusions
The Diversity in Diabetes codevelopment work informed an intervention to improve diabetes care in underserved groups, reflecting sociocultural contexts and plausible support options at the individual, community and clinical levels. The ‘Diversity in Diabetes’ programme will next test feasibility and further refine the intervention package in two more paediatric diabetes centres in England.

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Comparing effectiveness of conservative policy to craniofacial surgery in children with metopic synostosis: protocol for an observational cohort study on clinical outcomes, psychosocial well-being and costs in a Dutch academic hospital

Introduction
Traditionally, surgical intervention has been the standard treatment for children with metopic synostosis, assuming that it reduces the risk of raised intracranial pressure, thereby preventing vision and cognitive impairment, and also restores the abnormal head shape. However, recent research suggests a sporadic occurrence of raised intracranial pressure in patients with metopic synostosis. In addition, following surgery, an overall tendency to have worse cognitive and behavioral outcomes and more refractive errors compared to healthy peers is observed. Research on conservative (non-surgical) treatment in metopic synostosis is limited and lacks a comparative design. The purpose of this study is to compare the (cost-)effectiveness of conservative and surgical treatment in patients with metopic synostosis.

Methods and analysis
This is the protocol for an observational cohort study with a duration of 8 years. A total of 450 patients with metopic synostosis will be included. The primary outcome is head growth as a predictor for increased intracranial pressure. Non-inferiority with regard to head growth from 0 to 8 years (yearly difference in SD) is determined using a linear mixed model adjusted for potential confounders. Secondary outcomes include papilledema, orthoptic outcomes; forehead shape; cognitive, behavioural and psychological outcomes; and societal costs. A cost-effectiveness analysis will be performed.

Ethics and dissemination
The study has been reviewed and approved by the Medical Research Ethics Committee of the Erasmus MC, University Medical Center Rotterdam (MEC-2022-0142). Written informed consent will be obtained from both parents of each participant. The results will be disseminated by publication in international peer-reviewed journals.

Trial registration number
ClinicalTrials.gov NCT06069479.

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Protocol for an observational study to assess the impact of pharmacogenetics on outcomes in vascular surgery (PROSPER)

Introduction
Patients with chronic limb-threatening ischaemia (CLTI) are often prescribed clopidogrel in order to reduce their risk of major adverse limb and cardiovascular events. Clopidogrel is metabolised by the CYP2C19 enzyme and genetic variations in CYP2C19 are common. These variants can influence an individual’s ability to metabolise clopidogrel to its active metabolite. Few studies have investigated the relationship between patient genotype and outcomes in vascular surgery. This work aims to establish the relationship between patient genotype and outcomes after revascularisation in patients with CLTI who are prescribed clopidogrel. It will consider whether pharmacogenetics can be used to ensure patients are prescribed effective medications to optimise their outcomes.

Methods and analysis
This is an observational cohort study of patients undergoing lower limb surgical, endovascular or hybrid revascularisation for CLTI at Manchester University NHS Foundation Trust. Patients taking clopidogrel post-procedure, as well as those prescribed a non-clopidogrel based medication regimen, will be recruited prior to or shortly after revascularisation. Patients will undergo CYP2C19 genotyping and will be followed up using online records. The study has 90% power to detect 114 amputations with a target sample size of 483 participants. The primary outcomes are risk of amputation at 1 year and a composite endpoint for the risk of major adverse limb events (MALE) or death from any cause at 1 year. Secondary outcomes are risk of MALE at 1 year, risk of major adverse cardiovascular events (MACE) or death from any cause at 1 year, death within 30 days of revascularisation, minor re-interventions at 1 year, total number of re-interventions at 1 year and rate of systemic or gastrointestinal bleed at 1 year.
Risk of amputation, MALE and MACE will be analysed using Cox models. All remaining outcomes will be analysed using negative binomial models. Potential competing events for the risk of amputation will be investigated as part of a sensitivity analysis. Patients given a non-clopidogrel-based medication will be compared as an additional analysis.

Ethics and dissemination
Manchester University Research Ethics Committee approval obtained as part of the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial process (IRAS 305751). The results of the study will be published in a peer-reviewed journal and presented at international conferences.

Registration
This work is a sub-protocol for the IPTIP study which is registered as ISRCTN14050335.

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