by Tadgh Connery, Sofija Kukulite, Conor Farrell, Rosa Horgan, Karen Barry, Megan Doyle, Annalisa Setti, Mike Murphy
BackgroundDeath anxiety is fast becoming recognised as a transdiagnostic construct across myriad mental health conditions. Though existing clinical treatments of death anxiety, such as Cognitive Behaviour Therapy type interventions, have been shown to be effective, Terror Management Theory (TMT) proposes self-esteem as a protective factor against death anxiety by endowing individuals with a feeling of significance in life and helping them to process the nature of death and its inevitability. Despite the centrality of self-esteem to TMT, however, extant research examining its relationship with death anxiety has yet to be synthesised. The current study aims to systematically review peer-reviewed, quantitative research examining the association between death anxiety and self-esteem and, where possible, to test the strength of these associations through meta-analysis.
MethodA systematic search of quantitative and mixed-methods studies will be conducted across six databases: MEDLINE; PsycINFO; PubMed; Web of Science; CINAHL and; EMBASE. Google Scholar will also be searched and the first 200 records by relevance will be screened for eligibility. Searches will be conducted by TC, and records will be screened by TC, SK, CF, RH and KB, so that each record is screened for eligibility by at least two authors. Data extraction and quality assessment, using the Joanna Briggs Inventory Risk of Bias tools, will be performed by TC, SK, CF, RH and KB, so that each record is assessed by at least two authors, with doubts and discrepancies being resolved through discussion with AS and MM. A narrative synthesis of relevant data will be presented and, where sufficient data are available, meta-analysis will be conducted using the MAJOR extension for Jamovi to establish an overall effect size for the association between death anxiety and self-esteem. Should sufficient data be available, demographic factors, such as gender and age, and clinical population status (clinical vs. non-clinical population) will be examined as moderators of the effect. This protocol was developed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and has been registered in PROSPERO (CRD42024591775).
DiscussionThe current review will systematically examine the relationship between death anxiety and self-esteem. Should sufficient data be available, an overall effect size of the relationship will be generated. By better understanding how death anxiety is related to self-esteem, and by establishing the size and significance of the relationship will aid firstly in systematically validating TMT and, secondly, identify whether self-esteem may be targeted in future death anxiety interventions to reduce death anxiety and improve individuals’ overall mental health.
Chronic diseases require sustained medication adherence, yet nonadherence remains common, leading to poor outcomes and increased healthcare costs. Digital self-management technologies such as mobile health (mHealth) apps, SMS reminders, and web-based platforms offer scalable ways to support adherence, but evidence on their overall effectiveness across diverse contexts is fragmented.
To systematically review and meta-analyze the effectiveness of self-management technologies in improving medication adherence among adults with chronic diseases and to examine potential moderators of intervention impact.
Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, CINAHL, and JMIR for peer-reviewed studies (January 2010–June 2025) evaluating digital self-management interventions with adherence outcomes and comparator groups. Eligible designs included RCTs, quasi-experimental, and controlled before-after studies in adults with chronic disease. Random-effects meta-analysis estimated pooled effect sizes (Cohen's d). Heterogeneity (I 2), subgroup analyses, and publication bias (Egger's, Begg's, trim-and-fill) were assessed.
Fifty-two studies were included, spanning 2015–2025. Early interventions (2015–2019) focused on feasibility, using SMS and basic web tools; later years (2021–2025) showed technological maturity, dominated by mHealth apps integrating monitoring, reminders, and education. The pooled random-effects effect size was d = 0.268 (95% CI 0.123–0.414, p = 0.0003), indicating a small-to-moderate benefit. Heterogeneity was high (I 2 = 89%). Medium-duration (10.8–24 weeks) interventions had the largest effect (d = 0.50), and effects varied markedly by country (e.g., Iran d = 2.29; Taiwan d = −0.94). Begg's test suggested possible publication bias; trim-and-fill adjustment increased the pooled effect to d = 0.366.
Digital self-management technologies yield a statistically significant, small-to-moderate improvement in medication adherence across chronic diseases, with potential underestimation due to selective reporting. Effectiveness is moderated by temporal trends, geography, intervention duration, and study design, underscoring the need for context-specific adaptation and methodological rigor. Future research should prioritize large, well-controlled trials, pre-registration, and exploration of cultural and systemic determinants to optimize intervention impact.
This study aims to explore the history of prior abortions and the factors influencing them among young women seeking abortion services in Foshan, Guangdong, China.
This is a retrospective, cross-sectional study of young women seeking abortion care.
Gynaecological outpatient clinics at the Department of Gynaecology, Foshan Women and Children Hospital Affiliated to Guangdong Medical University, Foshan, Guangdong, China, between 2013 and 2023.
A total of 7361 young women aged 12–25 years seeking abortion services.
Data on abortion history, sociodemographic factors, contraceptive use and postabortion contraceptive choices were collected and analysed, with special emphasis on the incidence of repeat abortions and the factors associated with them.
Of the 7361 participants, 34.2% reported at least one previous abortion, underscoring a notable public health concern. The mean age of the participants was 22.30 years (SD=2.13). Women with a history of abortion were significantly older than those without (22.57 vs 22.08 years, p
This study underscores the need for targeted interventions to address the multifaceted factors leading to repeat abortions among young women in China. The results offer valuable insights for improving reproductive health outcomes in this vulnerable population and highlight the importance of expanding access to contraceptive education and services in China.
To describe prescription patterns, dosing and persistence of guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction in Singapore, and to identify factors associated with the use of quadruple therapy (ACE inhibitor (ACEi)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitor).
Retrospective, observational cohort study.
Secondary and tertiary care settings across seven public hospitals in Singapore.
3999 adults hospitalised from 2020 to 2022 with a first heart failure-related admission and left ventricular ejection fraction ≤40%. Patients with absolute contraindications to specific GDMT classes were excluded from eligibility calculations.
Primary outcomes were the proportions of eligible patients prescribed each GDMT class and quadruple therapy at discharge. Secondary outcomes were 6-month prescription patterns, dose attainment and predictors of quadruple therapy use.
Among eligible patients, 80%–99% met criteria for each GDMT drug class, yet only 29% received quadruple therapy at discharge in 2022. Prescription rates for ACEi/ARB/ARNI (67%), beta-blockers (89%), MRAs (40%), and SGLT2 inhibitors (46%) remained suboptimal despite high eligibility. At discharge, over 90% of patients on ACEi/ARB/ARNI and beta-blockers received ≤50% of target doses. By 6 months, prescription rates declined by 16% for ACEi/ARB/ARNI, 26% for beta-blockers and 7% for MRAs, while SGLT2 inhibitor use increased. Older age (OR 0.97, 95% CI 0.96 to 0.98) and chronic kidney disease stage 3a–4 (OR 0.65 to 0.04) were associated with lower odds of receiving quadruple therapy, while significant institutional variation was observed.
Despite high eligibility, uptake and optimisation of GDMT remain poor in Singapore, with substantial treatment gaps driven by underprescription, inadequate dosing and discontinuation. Interventions targeting clinician awareness, postdischarge support and institutional practice variation may improve adherence to guideline-recommended therapy.
An alarmingly low number of children meet public health guidelines for physical activity and dietary behaviours and, therefore, are at increased risk of developing lifestyle-related diseases. This paper describes the protocol of the B-Challenged project, which aims to co-create systemic actions to promote active outdoor play and healthy dietary behaviours before, during or after their outdoor play together with children themselves.
In five European countries, child-centred Participatory Action Research (PAR)—combined with systems dynamics methods—was conducted with 15–20 child co-researchers (aged 9–12 years) and 15–20 adult actors (eg, youth workers, local policy makers). In the first phase, the main drivers of children’s active outdoor play and related dietary behaviours were mapped by (1) analysing existing cohort data, and (2) conducting child-centred PAR. In the second phase, systemic actions targeting the local physical and social environments will be co-created and implemented by child co-researchers and adult actors to promote children’s active outdoor play and related healthy dietary behaviours. A mixed-methods design will be used to evaluate (1) if actions positively contributed to systems change and 6- to 12-year-olds’ outdoor play and related dietary behaviours (140 children per country); (2) the process of conducting multi-actor, child-centred PAR and implementing the co-created actions and (3) if the child-centred PAR positively contributed to child co-researchers’ feelings of empowerment.
Ethics approval for the mapping phase was obtained and approval for implementation and evaluation will be obtained from the five local research institutions. Participating children, one of their parents/caregivers and adult actors had given informed consent before participating in the project. Throughout the project, child-friendly methods, materials and language will be applied, and ethical challenges and potential solutions will be discussed. Project results will be disseminated locally and internationally through various channels and activities among the scientific community, professionals—for example, in health and policy making, children and other citizens.
by Ratikorn Chaisiwamongkol, Rattapon Uppala, Phanthila Sitthikarnkha, Leelawadee Techasatian, Suchaorn Saengnipanthkul, Pope Kosalaraksa, Kaewjai Thepsuthammarat, Sirapoom Niamsanit
Background and aimsDiabetic ketoacidosis (DKA) remains a major cause of pediatric morbidity and death. This study examined national trends in DKA hospitalizations and factors associated with in-hospital mortality among Thai children.
Materials and methodsA nationwide, retrospective cohort study was conducted using data from the National Health Security Office (NHSO) during 2015–2023. Children aged 1 month to under 18 years hospitalized with DKA were identified using International Classification of Diseases, 10th Revision, Thai Modification (ICD-10-TM) codes. Prevalence and mortality were described by year and region. Factors associated with death were assessed with multivariable logistic regression; model discrimination used area under the curve (AUC).
ResultsAmong 10,669 admissions, national DKA prevalence increased from 4.5 to 11.8 per 10,000 pediatric hospitalizations, with Bangkok showing the highest rates. The overall intubation rate was 10.2%, peaking in infants and older adolescents. Although national mortality declined from 2.2% to 0.6%, regional and age-specific fluctuations persisted. Independent associations with mortality included malignancy (Adjusted odds ratio [AOR] 5.25, 95% CI: 1.63-16.92; p=0.005), septic shock (AOR 2.93, 95% CI: 1.71-5.03; p Conclusion
DKA hospitalizations are increasing in Thailand, with regional variation and persistent mortality risk, particularly among patients with critical complications and vulnerable groups. Although declining mortality trends and lower mortality in recurrent cases suggests improved protocol-based treatment, targeted prevention strategies remain essential for high-risk populations.
by Hemant Mahajan, Poppy Alice Carson Mallinson, Judith Lieber, Santhi Bhogadi, Santosh Kumar Banjara, Anoop Shah, Vipin Gupta, Gagandeep Kaur Walia, Bharati Kulkarni, Sanjay Kinra
Background and AimCardiovascular diseases (CVDs) represent a growing public-health challenge in India, where nearly one in four deaths is CVD-related. Accurate risk stratification underpins targeted prevention, yet laboratory-dependent tools are often impractical in resource-limited settings. The World Health Organization (WHO) and GLOBORISK initiatives both offer non-laboratory-based 10-year CVD risk algorithms alongside their laboratory-based counterparts. We aimed to compare laboratory- and non-laboratory-based WHO and GLOBORISK CVD risk scores, assess their concordance, and examine relationships with sub-clinical atherosclerosis in a rural Indian cohort.
Materials and MethodsWe conducted a cross-sectional analysis of 2,465 adults (1,184 men, 1,281 women) aged 40−74 years from the third wave (2010−12) of the Andhra Pradesh Children and Parents Study (APCAPS). Participants with prior CVD were excluded. Ten-year CVD risk was calculated using sex-specific WHO (South Asia) and India-calibrated GLOBORISK models, both laboratory-based (age, sex, smoking, systolic blood pressure, diabetes, total cholesterol) and non-laboratory-based (age, sex, smoking, systolic blood pressure, BMI) algorithms. Categorical agreement was quantified via percentage agreement and quadratic weighted kappa (κ); continuous agreement by Bland-Altman analysis. We also evaluated linear associations between each risk score (categorical and continuous) and three sub-clinical atherosclerosis markers: carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and augmentation index (AIx), through sex-stratified multi-level linear regression with random intercept at the household level, adjusting for multiple testing (p Results
Median WHO-CVD-risk was 6.0% (IQR 4% − 9%) in men and 3.0% (2% − 4%) in women for both lab and non-lab models; median GLOBORISK-CVD-risk was 12.0% (9% − 16%) for lab-model vs. 15.0% (10% − 16%) for non-lab-model in men and 5.0% (3% − 9%) for lab-model vs. 5.0% (3% − 9%) for non-lab-model in women. Categorical agreement was substantial to almost perfect: WHO κ = 0.82 (overall), GLOBORISK κ = 0.72. Bland-Altman analyses demonstrated mean differences Conclusion
Non-laboratory-based WHO and GLOBORISK CVD risk scores exhibit high overall agreement with laboratory-based models and correlate strongly with subclinical atherosclerosis in rural India. However, modest underestimation in high-risk subgroups (diabetics, hypercholesterolemia) warrants cautious interpretation. These findings support the feasibility of non-lab risk assessment in resource-constrained settings, while underscoring the need for prospective validation against hard cardiovascular outcomes prior to large-scale implementation.
To comprehensively analyse the life expectancy at birth of people with intellectual disability, including people with Down syndrome, to inform health equity and service planning.
Retrospective cohort study.
Residents of New South Wales (NSW), Australia, with intellectual disability from birth onwards between 1 January 2001 and 31 December 2018.
Our study sample comprised 100 089 individuals with intellectual disability in the dataset, spanning from birth onwards, between 1 January 2001 and 31 December 2018.
All cause mortality. Life expectancy was estimated using ordinary and abridged life table methods, based on age-specific population count, and compared with the general NSW population.
Life expectancy at birth of people with intellectual disability was 67 years, 16 years shorter than the NSW average. Males and females with intellectual disability had a similar life expectancy. Individuals with Down syndrome had a life expectancy of 54 years, significantly shorter than those without Down syndrome. The life expectancy gap for people with intellectual disability narrowed with increasing age.
People with intellectual disability in Australia experience a substantial life expectancy gap, with greater disparities for those with Down syndrome. These findings underscore the need for targeted health and social interventions to address systemic inequities and improve health outcomes across the lifespan.
Suboptimal feeding practices in children under five remain a critical concern, particularly in low- and middle-income countries. Integrated Supplementary Feeding programmes (SFPs) combined with Social and Behaviour Change Communication (SBCC) interventions have shown potential, yet global evidence on their design and effectiveness remains scattered across diverse settings and varies widely in scope and quality. This review aims to map global evidence on integrated SFP and SBCC interventions for children aged 6–59 months, assessing their impact on anthropometric, biochemical, nutritional, health, developmental, functional, microbiological and infant and young child feeding (IYCF) outcomes, and to identify contextual factors, evidence gaps and successful strategies. The review will also aim to document cost effectiveness and economic outcomes of this integrated intervention.
The review will follow Joanna Briggs Institute (JBI) methodology, applying the Population–Concept–Context framework and the review title has been registered in Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/ZJ5BG). Eligible studies published between 2000 and 2025 will include community-based interventions for children under five that combine SFP and SBCC. The review will focus on SFP interventions delivered through community-based or public health platforms, including but not limited to take home ration, hot cooked meal, micronutrient powders, coupled with SBCC modalities such as home visits, mobile health and mass media campaigns. Comprehensive searches will be conducted in MEDLINE (PubMed), Cochrane CENTRAL, Google Scholar and organisational websites. Two independent reviewers will screen, extract and appraise studies using Covidence and JBI tools. Data will be analysed using descriptive statistics to summarise study characteristics, intervention types and reported outcomes, helping understand patterns across time and settings. Qualitative findings will be synthesised through descriptive content analysis involving coding and theme development. Expected outcomes include a range of study designs from different settings across the globe, covering diverse delivery models of integrated SFP and SBCC with reported outcomes including dietary indicators, anthropometry, nutritional biomarkers, caregiver practices and cost-effectiveness.
This review is part of a larger cluster randomised controlled trial (NECCTAR) which has received ethical approval from the independent institutional ethics committee of all the participating institutes. The current review will involve only publicly available literature and does not have a separate institutional ethics committee approval. Findings will be disseminated through academic conferences and publications in peer-reviewed journals.
The review title has been registered in OSF (https://doi.org/10.17605/OSF.IO/ZJ5BG).
Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM.
This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18–55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control.
The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings.
by Chanavee Toh, Kedsiree Sanit, Pimsiri Sripongpun, Naichaya Chamroonkul, Suthat Liangpunsakul, Teerha Piratvisuth, Apichat Kaewdech
Background and aimsChronic hepatitis B virus (HBV) infection remains a major global health burden and a leading cause of hepatocellular carcinoma (HCC). While cirrhosis is a well-established risk factor, the contributions of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic risk factors (CMRFs) are less clearly defined. This study aimed to evaluate the impact of MASLD and CMRFs on HCC risk in patients with chronic hepatitis B (CHB).
MethodsWe conducted a retrospective cohort study of CHB patients at Songklanagarind Hospital between 2011 and 2021, excluding those diagnosed with HCC within six months of follow-up. Clinical and imaging data were analyzed. Cumulative HCC incidence was estimated using Nelson-Aalen plots. Multivariable Cox regression was used to identify independent predictors. The aMAP score was evaluated in subgroups with obesity, CMRFs, and MASLD.
ResultsAmong 4,944 patients, 151 (3.1%) developed HCC. Cirrhosis (adjusted hazard ratio [aHR] 7.22), obesity (aHR 1.85), and male sex (aHR 1.78) were independent risk factors. Statin use (aHR 0.43), higher platelet count (aHR 0.62), and higher albumin (aHR 0.64) were protective. Diabetes and hypertension showed nonsignificant trends, and steatosis and dyslipidemia without statins were not significantly associated with HCC. Risk increased with the number of CMRFs. The aMAP score showed good discrimination in patients with obesity (C-index 0.82), CMRFs (0.79), MASLD (0.74), and in the non-cirrhotic MASLD and non-MASLD (0.69 and 0.71, respectively).
ConclusionsCirrhosis, male sex, and obesity were key HCC risk factors. The aMAP score effectively stratified HCC risk among metabolically at-risk CHB patients.
by Panawit Hanpinitsak, Tatpong Katanyukul, Norrawit Tonmitr, Chanon Suntra, Sora-at Tanusilp, Arthit Phuphaphud
Monitoring cattle behavior plays an important role in improving farm productivity, maintaining animal welfare, and supporting efficient management practices. This study presents a multi-view behavior recognition system that uses synchronized top-view and front-view CCTV footage, combined with deep learning techniques. The system includes four main components: cow identification, behavior classification, identity-behavior association using Intersection-over-Union (IoU), and a decision-level ensemble to combine information from both views. YOLOv8 models are applied separately to each camera angle to detect individual cows and classify six key behaviors: drinking, eating, standing, lying, riding, and chin resting, with the latter two being relevant for estrus detection. The system matches cow identities to their behaviors within each view and then integrates the results to produce a final activity label for each cow.Acute lower limb ischaemia (ALI) is a life- and limb-threatening vascular emergency requiring urgent intervention. Despite advancements in therapeutic strategies, outcome reporting for ALI remains inconsistent, limiting evidence synthesis and guideline development. The CORE-ALI study aims to develop a Core Outcome Set (COS) to standardise outcome reporting and ensure the inclusion of both clinical and patient-centred metrics.
CORE-ALI will use a structured, multi-phase methodology guided by the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Core Outcome Set-STAndards for Reporting (COS-STAR) guidelines. Phase 1 involves stakeholder engagement through semi-structured interviews with patients, clinicians and policymakers from diverse European healthcare systems. Qualitative data will be analysed using thematic analysis to generate a preliminary list of outcomes. In Phase 2, a multi-round Delphi survey (anticipated two to three rounds) will prioritise and refine outcomes through consensus building, with quantitative data analysed using descriptive and non-parametric statistical methods. Phase 3 will culminate in a consensus meeting to finalise the COS. Multilingual accommodations will ensure inclusivity, and General Data Protection Regulation (GDPR)-compliant platforms will secure data handling.
The study has received ethics approval from the Ethics Committee of the Medical University of Innsbruck (EK Nr: 1082/2025) on 20/05/2025. Additional local ethics approvals are required and will be obtained at all participating sites prior to the initiation of recruitment. The final Core outcome set will be disseminated through peer-reviewed publications, presentations at international conferences and engagement with professional societies and patient organisations.
COMET initiative (Registration No. 3346).
To assess diagnostic concordance and reclassification following an India-led, multinational virtual multidisciplinary discussion (V-MDD) platform for interstitial lung disease (ILD).
Prospective, multicentre service-evaluation study.
Twenty-four Indian referral centres connected through a secure virtual platform, with international faculty participation from the UK, Greece and Sri Lanka.
A total of 127 anonymised ILD cases discussed across 29 V-MDD sessions (February 2024–February 2025). Each panel included ≥4 pulmonologists, two pulmonary pathologists, one of three rotating thoracic radiologists and one of two rheumatologists, along with international experts.
The cohort (mean age 52.6±16.1 years; 53.5% female (68/127)) most frequently presented with dyspnoea (82.6%) and cough (73.2%). Pre-V-MDD diagnoses included hypersensitivity pneumonitis (HP) and sarcoidosis as distinct disease entities, and usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) as radiological patterns, along with connective tissue disease (CTD)-ILD and other ILDs. Concordance between pre- and post-V-MDD CT diagnoses was substantial (=0.658; 95% CI 0.562 to 0.754; p
The India-led, multinational V-MDD model demonstrated substantial diagnostic concordance and refined nearly one-quarter of ILD diagnoses. This virtual, scalable framework expands access to subspecialty expertise and offers a practical blueprint for standardising ILD care in resource-limited and cross-border settings.
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). While etrasimod demonstrated efficacy in randomised controlled trials, understanding its effectiveness in an observational setting is crucial.
EFFECT-UC is a prospective, multinational, non-interventional study to evaluate the real-world effectiveness of etrasimod in adults with moderately to severely active UC. The study consists of a 52-week treatment period and a 28-day safety follow-up period and aims to enrol ~300 patients per cohort. Eligible patients (18–64 years) are advanced therapy naïve or experienced and are initiating etrasimod in a real-world clinical setting. Treatment will be guided independently by the clinician’s judgement. Patient-reported outcomes will be collected electronically throughout the study and daily for the first 2 weeks. Exploratory data, including faecal calprotectin, endoscopy and intestinal ultrasound, will be collected at predefined visits or during standard care. Primary endpoints are symptomatic remission at week 12 and week 52. Secondary endpoints include patient-reported outcome 2 (combined rectal bleeding and stool frequency subscores) response at week 12 and week 52 and corticosteroid-free symptomatic remission at week 52.
Ethics approval was obtained for all sites. Recruitment is underway for cohort 1, comprising patients from the UK, Germany and Canada. Interim results for this cohort are expected in 2026 and final results in 2028; these will be submitted for publication in peer-reviewed journals and presented at appropriate congresses.
This study aimed to determine the prevalence of cervical high-risk human papillomavirus (hrHPV) in a community-based setting and its risk factors association in women living in hard-to-reach areas in Bangladesh.
A cross-sectional study
The study was carried out in six subdistricts, located in hard-to-reach and climate-impacted regions of Bangladesh.
A total of 8000 married women aged 30–60 years were invited for screening. Women who were unable to give consent, were pregnant or had a hysterectomy with removal of the cervix, previous screening less than 5 years, or treatment of the cervix or had symptoms of potential cervical cancer were excluded.
A community-based hrHPV self-collected screening for cervical cancer was conducted from June 2022 to July 2023.
Prevalence of cervical hrHPV and risk factor association.
11 127 women were eligible for screening; 7850 women submitted hrHPV self-swabs, 7828 valid HPV test results were reported and 164 women (2.1%) tested hrHPV positive. Women living in the North were 2.1 times more likely to be hrHPV positive compared with women living in the South (adjusted OR (AOR)=2.1, 95% CI: 1.5 to 3.8, p=0.023) and widowed women were 3.0 times more likely to be hrHPV positive than married women (AOR=3.0, 95% CI: 1.7 to 5.3, p=0.001). Another risk factor associated with testing hrHPV positive was the use of hormonal contraceptives for 5 years and above (AOR=7.0, 95% CI: 2.0 to 24.4, p=0.002).
The study identified a low overall prevalence of hrHPV infection (2.1%) among women in hard-to-reach areas in Bangladesh, with some regional variations. Higher prevalence was observed in widowed compared with married women and among women reporting more than 5 years of hormonal contraceptive use. This study shows no evidence of particularly high-risk groups in hard-to-reach areas in Bangladesh. The findings support the feasibility of implementing a nationwide hr-HPV-based self-sampling strategy as a viable approach to reach WHO targets for reducing the burden of cervical cancer. Recommendation for policymakers to support future research to identify hrHPV prevalence among women in comparable groups in other geographically remote areas in Bangladesh.
by Natthakul Akarapredee, Chalirmporn Atasilp, Chonlaphat Sukasem, Pimonpan Jinda, Rattanaporn Sukprasong, Jiraporn Jensuriyarkun, Soravit Wongjitjanyong, Patompong Satapornpong, Natchaya Vanwong
IntroductionIrinotecan is a chemotherapy agent commonly prescribed for metastatic colorectal cancer but often leads to neutropenia. Variations in genes encoding drug-metabolizing enzymes and transporters may affect the toxicity and effectiveness of irinotecan. This study aimed to examine the impact of these genetic polymorphisms on irinotecan outcomes in Thai colorectal cancer patients.
MethodsThe study retrospectively analyzed 41 metastatic colorectal cancer patients treated with irinotecan-based chemotherapy. Genotyping was conducted for 23 single nucleotide polymorphisms in genes including UGT1A1, CYP3A4, CYP3A5, CES1, ABCB1, ABCC2, ABCC5, ABCG1, ABCG2, and SLCO1B1.Toxicity and efficacy were assessed, with statistical significance set at a Bonferroni-corrected P value Results
In terms of toxicity, UGT1A1*6 was significantly associated with both all-grade and severe neutropenia in the first cycle (p p p ABCC2 -24C > T variant was linked to all-grade neutropenia in the second cycle (p = 0.001). For efficacy, patients with the wild-type UGT1A1*6 had longer progression-free survival (PFS) (p SLCO1B1 521T > C variant was associated with improved PFS (p Conclusion
UGT1A1*6 and ABCC2 -24C > T variants emerge as potential predictors of irinotecan-induced neutropenia, while UGT1A1*6 and SLCO1B1 521T > C may serve as markers of prolonged PFS in Thai patients. Validation through larger prospective studies is essential to confirm and refine these genetic associations.
by Moe Thi Thi Han, Tay Zar Myo Oo, Busayamas Chewaskulyong, Sakorn Pornprasert, Kanyamas Choocheep, Khanittha Punturee, Warunee Kumsaiyai, Yupanun Wuttiin, Sawitree Chiampanichayakul, Ratchada Cressey
Non-smoking-related lung cancer is increasingly associated with environmental factors such as particulate matter (PM) exposure. Using deep small RNA sequencing, we identified distinct miRNA expression patterns in lung cancer patients compared to non-cancer controls, stratified by smoking status. Notably, hsa-miR-125b-5p and hsa-miR-100-5p were significantly downregulated in non-smoking lung cancer patients. Pathway enrichment analysis revealed smoking amplifies pathways related to glycan biosynthesis, signal transduction, and transcriptional regulation, while non-smoking lung cancer is characterized by immune dysfunction and metabolic alterations, including oxidative phosphorylation and natural killer cell cytotoxicity. Validation in a larger cohort using quantitative RT-PCR confirmed the suppression of miR-125b-5p and miR-100-5p in non-smoking lung cancer patients. Additionally, miR-203a and miR-199a-3p were identified as potential biomarkers for lung cancer, independent of smoking status. Chronic PM exposure in primary bronchial/tracheal epithelial cells initially elevated miR-125b-5p and miR-100-5p expression, but prolonged exposure suppressed these miRNAs while increasing their target genes, TXNRD1 and HOXA1, suggesting stress-induced dysregulation. Functional studies using miRNA mimics demonstrated that miR-125b-5p and miR-100-5p suppress PM-induced cancer cell mobility and colony formation, with miR-125b-5p exhibiting broader effects. These findings underscore the critical roles of miR-125b-5p and miR-100-5p in PM-associated lung cancer progression and their potential as biomarkers and therapeutic targets. This study highlights distinct mechanisms of lung carcinogenesis in smokers and non-smokers, providing a foundation for targeted interventions in PM-associated lung cancer.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.