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☐ ☆ ✇ PLOS ONE Medicine&Health

Environment and weight class linked to skin microbiome structure of juvenile Eastern hellbenders (<i>Cryptobranchus alleganiensis alleganiensis</i>) in human care

by Andrea C. Aplasca, Peter B. Johantgen, Christopher Madden, Kilmer Soares, Randall E. Junge, Vanessa L. Hale, Mark Flint

Amphibian skin is integral to promoting normal physiological processes in the body and promotes both innate and adaptive immunity against pathogens. The amphibian skin microbiota is comprised of a complex assemblage of microbes and is shaped by internal host characteristics and external influences. Skin disease is a significant source of morbidity and mortality in amphibians, and increasing research has shown that the amphibian skin microbiota is an important component in host health. The Eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a giant salamander declining in many parts of its range, and captive-rearing programs are important to hellbender recovery efforts. Survival rates of juvenile hellbenders in captive-rearing programs are highly variable, and mortality rates are overall poorly understood. Deceased juvenile hellbenders often present with low body condition and skin abnormalities. To investigate potential links between the skin microbiota and body condition, we collected skin swab samples from 116 juvenile hellbenders and water samples from two holding tanks in a captive-rearing program. We used 16s rRNA gene sequencing to characterize the skin and water microbiota and observed significant differences in the skin microbiota by weight class and tank. The skin microbiota of hellbenders that were housed in tanks in close proximity were generally more similar than those housed physically distant. A single taxa, Parcubacteria, was differentially abundant by weight class only and observed in higher abundance in low weight hellbenders. These results suggest a specific association between this taxa and Low weight hellbenders. Additional research is needed to investigate how husbandry factors and potential pathogenic organisms, such as Parcubacteria, impact the skin microbiota of hellbenders and ultimately morbidity and mortality in the species.
☐ ☆ ✇ PLOS ONE Medicine&Health

A new program for systematically enhancing cognitive reserve in healthy adults: A pilot randomized active-controlled clinical trial

Por: Carol Kotliar · Lisandro Olmos · Martín Koretzky · Ricardo Jauregui · Tomás Delía · Oscar Cingolani — Octubre 1st 2025 at 16:00

by Carol Kotliar, Lisandro Olmos, Martín Koretzky, Ricardo Jauregui, Tomás Delía, Oscar Cingolani

Objective

To evaluate the effectiveness of the Mental Training Tech 24.5 (MTT24.5) cognitive stimulation program, designed to enhance cognitive performance and neuroplasticity in healthy adults.

Background

Cognitive decline is a significant concern in aging populations, with research suggesting that neuroplasticity and cognitive reserve can be enhanced through targeted cognitive training. The MTT24.5 program aims to stimulate brain function through a combination of new knowledge acquisition (DATA) and learning techniques (TECHS), organized into a systematic algorithm. This approach may offer a novel way to prevent or mitigate age-related cognitive decline.

Design

Pilot clinical study, active-controlled, open randomization.

Setting

Adults from the general population with no clinical cognitive deterioration, recruited from three sites within the Autonomous City of Buenos Aires and its metropolitan area.

Participants

120 volunteers were enrolled, of which 76 participants (56 in the intervention group, 20 in the control group) met the study requirements and selected a site closest to their residence.

Methods

The MTT24.5 program consists of 12 weekly in-person sessions (totaling 24.5 hours), during which participants learned 40 knowledge units (DATA) and 100 learning techniques (TECHS). These were organized into binomials, where each unit of DATA was paired with 3–4 TECHS. Pre- and post-intervention assessments included medical history, lifestyle factors, cognitive reserve scale, Addenbrooke’s Cognitive Examination-Revised (ACE-R), and Mini-Mental State Examination (MMSE).

Results

The mean age was 59 years for both groups. Baseline ACE-R scores were comparable (91.3). The global cognitive score increased by 4.6 points (5%) in the intervention group compared to a decrease of 0.5 points in the control group (p  Conclusions

The MTT24.5 program, based on a systematic algorithm for acquiring new knowledge and skills, significantly enhances cognitive reserve and overall cognitive performance, particularly in individuals with lower baseline cognitive scores. These findings suggest that structured cognitive stimulation could play a critical role in preventing cognitive decline and promoting cognitive health in healthy adults. Given the promising results, future studies involving larger populations and long-term follow-up are essential to validate these effects and explore the potential for mitigating age-related cognitive decline and enhancing quality of life.

Registration

The study was registered in accordance with local regulations at the National Council for Scientific and Technological Research (CONICET) – Institute of Biomedical Research (BIOMED), and also in the National Ethics Committee, and at clinicaltrials.gov (NCT06549517).

☐ ☆ ✇ PLOS ONE Medicine&Health

Continuous or discrete magnitudes? A comparative study between cats, dogs and humans

Por: Mireia Solé Pi · Luz A. Espino · Péter Szenczi · Marcos Rosetti · Oxána Bánszegi — Octubre 1st 2025 at 16:00

by Mireia Solé Pi, Luz A. Espino, Péter Szenczi, Marcos Rosetti, Oxána Bánszegi

A long-standing question in the study of quantity discrimination is what stimulus properties are controlling choice. While some species have been found to do it based on the total amount of stimuli and without using numerical information, others prefer numeric rather than any continuous magnitude. Here, we tested cats, dogs, and humans using a simple two-way spontaneous choice paradigm (involving food for the first two, images for the latter) to see whether numerosity or total surface area has a greater influence on their decision. We found that cats showed preference for the larger amount of food when the ratio between the stimuli was 0.5, but not when it was 0.67; dogs did not differentiate between stimuli presenting the two options (smaller vs. larger amount of food) regardless of the ratio between them, but humans did so almost perfectly. When faced with two stimuli of the same area but different shapes, dogs and humans exhibited a preference for certain shapes, particularly the circle, while cats’ choices seemed to be at chance level. Furthermore, cats’ and dogs’ reaction times were equal across conditions, while humans were quicker when choosing between stimuli in trials where the shape was the same, but the surface area was different, and even more so when asked to choose between two differently sized circle shapes. Results suggest that there is no universal rule regarding how to process quantity, but rather that quantity estimation seems to be tied to the ecological context of each species. Future work should focus on testing quantity estimation in different contexts and different sources of motivation.
☐ ☆ ✇ PLOS ONE Medicine&Health

LncRNA RP11-818O24.3 regulates proliferation and differentiation of hair follicle stem cells by targeting FGF2/PI3K/AKT pathway

Por: Linlin Bao · Haibo Zhao · Haiyue Ren · Chong Wang · Su Fang — Octubre 1st 2025 at 16:00

by Linlin Bao, Haibo Zhao, Haiyue Ren, Chong Wang, Su Fang

Hair follicle stem cells (HFSCs) play critical roles in adult hair regeneration, owing to its self-renewal and multipotent differentiation properties. Emerging evidence has shown that long noncoding RNAs (LncRNAs) are implicated in biological processes such as proliferation, differentiation and apoptosis. However, the specific role of LncRNA RP11-818O24.3 in regulating HFSCs remains unclear. To explore the effect of LncRNA RP11-818O24.3 on HFSCs, stable LncRNA RP11-818O24.3 overexpression and knockdown HFSCs were established using a lentivirus vector system. The effect of LncRNA RP11-818O24.3 on proliferation was evaluated by Cell Counting Kit-8 (CCK8) and EdU incorporation experiments. The differentiation of HFSCs into neurons and keratinocyte stem cells was detected by immunofluorescence staining. We showed that LncRNA RP11-818O24.3 overexpression promoted the proliferation and inhibited cell apoptosis in HFSCs. High levels of LncRNA RP11-818O24.3 promoted the differentiation of HFSCs into CD34+K15+ keratinocyte progenitors and CD34+Nestin+neuron-specific enolase (NSE)+ neural stem cells. Additionally, LncRNA RP11-818O24.3 increased fibroblast growth factor 2 (FGF2) expression and the subsequent activation of the PI3K/AKT signaling pathway. These data demonstrated that LncRNA RP11-818O24.3 promotes self-renewal, differentiation, and the capability to inhibit apoptosis of HFSCs via FGF2 mediated PI3K/AKT signaling pathway, highlighting its potential role as a therapeutic strategy for treating hair loss diseases.
☐ ☆ ✇ BMJ Open

Understanding structured medication reviews delivered by clinical pharmacists in primary care in England: a national cross-sectional survey

Por: Agwunobi · A. J. · Seeley · A. E. · Tucker · K. L. · Bateman · P. A. · Clark · C. E. · Clegg · A. · Ford · G. · Gadhia · S. · Hobbs · F. D. R. · Khunti · K. · Lip · G. Y. H. · de Lusignan · S. · Mant · J. · McCahon · D. · Payne · R. A. · Perera · R. · Seidu · S. · Sheppard · J. P. · Willia — Octubre 1st 2025 at 08:29
Objectives

This study explored how Structured Medication Reviews (SMRs) are being undertaken and the challenges to their successful implementation and sustainability.

Design

A cross-sectional mixed methods online survey.

Setting

Primary care in England.

Participants

120 clinical pharmacists with experience in conducting SMRs in primary care.

Results

Survey responses were received from clinical pharmacists working in 15 different regions. The majority were independent prescribers (62%, n=74), and most were employed by Primary Care Networks (65%, n=78), delivering SMRs for one or more general practices. 61% (n=73) had completed, or were currently enrolled in, the approved training pathway. Patient selection was largely driven by the primary care contract specification: care home residents, patients with polypharmacy, patients on medicines commonly associated with medication errors, patients with severe frailty and/or patients using potentially addictive pain management medication. Only 26% (n=36) of respondents reported providing patients with information in advance. The majority of SMRs were undertaken remotely by telephone and were 21–30 min in length. Much variation was reported in approaches to conducting SMRs, with SMRs in care homes being deemed the most challenging due to additional complexities involved. Challenges included not having sufficient time to prepare adequately, address complex polypharmacy and complete follow-up work generated by SMRs, issues relating to organisational support, competing national priorities and lack of ‘buy-in’ from some patients and General Practitioners.

Conclusions

These results offer insights into the role being played by the clinical pharmacy workforce in a new country-wide initiative to improve the quality and safety of care for patients taking multiple medicines. Better patient preparation and trust, alongside continuing professional development, more support and oversight for clinical pharmacists conducting SMRs, could lead to more efficient medication reviews. However, a formal evaluation of the potential of SMRs to optimise safe medicines use for patients in England is now warranted.

☐ ☆ ✇ BMJ Open

Time to first optimal glycaemic control and associated factors among adult patients with diabetes at the University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia: a retrospective cohort study

Por: Getahun · A. D. · Ayele · E. M. · Tsega · T. D. · Anberbr · S. S. · Geremew · G. W. · Biyazin · A. A. · Taye · B. M. · Mekonnen · G. A. — Octubre 1st 2025 at 08:29
Objective

To assess the time to first optimal glycaemic control and its predictors among adult patients with type 1 and type 2 diabetes at the University of Gondar Comprehensive Specialized Hospital in Ethiopia.

Design

A retrospective cohort study.

Setting

University of Gondar Comprehensive Specialized Hospital, northwest, Ethiopia.

Participants

We recruited 423 adult diabetic patients who were diagnosed between 1 January 2018 and 30 December 2022 at the University of Gondar Comprehensive Specialized Hospital.

Outcome measures

The primary outcome was the time from diagnosis to the achievement of the first optimal glycaemic control, measured in months. A Cox proportional hazards regression model was fitted to identify predictors of time to first optimal glycaemic control. Data were collected with KoboToolbox from patient medical charts and exported to Stata V.17. The log-rank test was used to determine the survival difference between subgroups of participants.

Results

Median time to first optimal glycaemic control was 10.6 months. Among 423 adult diabetic patients, 301 (71.16%) achieved the first optimal glycaemic control during the study period. Age category (middle age (adjusted HR (AHR)=0.56, 95% CI 0.41 to 0.76), older age (AHR=0.52, 95% CI 0.33 to 0.82)), comorbidity (AHR=0.52, 95% CI 0.35 to 0.76), therapeutic inertia (AHR=0.20, 95% CI 0.13 to 0.30) and medication non-compliance (AHR=0.49, 95% CI 0.27 to 0.89) were significant predictors of time to optimal glycaemic control.

Conclusion

The median time to first optimal glycaemic control was prolonged. Diabetic care should focus on controlling the identified predictors to achieve optimal glycaemic control early after diagnosis.

☐ ☆ ✇ BMJ Open

New regimens of benznidazole for the treatment of chronic Chagas disease in adult participants in indeterminate form or with mild cardiac progression (NuestroBen study): protocol for a phase III randomised, multicentre non-inferiority clinical trial

Por: Marques · T. · Forsyth · C. · Barreira · F. · Lombas · C. · Blum de Oliveira · B. · Laserna · M. · Molina · I. · Bangher · M. d. C. · Javier Fernandez · R. · Lloveras · S. · Fernandez · M. L. · Scapellato · P. · Patterson · P. · Garcia · W. · Ortiz · L. · Schijman · A. · Moreira · O. C. — Septiembre 30th 2025 at 09:49
Introduction

Chagas disease (CD) is one of the most neglected diseases in the world. In Latin America, CD is endemic in 21 countries, with an estimated 70 million people at risk of infection. Current treatments are limited to two nitroheterocyclic compounds: nifurtimox and benznidazole (BZN). Each has significant limitations, including long duration and safety concerns. However, data from recently completed studies suggest that reduced-duration regimens may be equally effective while enhancing safety.

Methods and analysis

NuestroBen is a phase III, randomised, multicentre clinical trial designed to assess whether shorter (2- and 4-week) regimens of BZN are non-inferior to the standard 8-week treatment. A total of 540 adult participants with no evidence of organ damage (the indeterminate form) or with mild cardiac progression (mild electrocardiographic alterations and without systolic dysfunction or symptoms), all in the chronic phase of CD, will be recruited at six study sites in Argentina and two study sites in Bolivia. Participants will be randomised to receive one of the two shortened regimens of BZN (300 mg per day for 2 or 4 weeks) or standard treatment (300 mg per day for 8 weeks). The primary endpoint is sustained elimination of parasitaemia from the end of treatment through 12 months of follow-up. Secondary endpoints will assess sustained clearance of parasitaemia at 1, 4, 6 and 8 months of follow-up from the end of treatment, drug tolerability and adherence to treatment. NuestroBen will also evaluate whether two shortened regimens of BZN improve drug tolerability and treatment adherence compared with the current standard treatment while maintaining efficacy in participants with the indeterminate form of CD or with mild cardiac involvement.

Ethics and dissemination

In Argentina, this study was approved by Fundación de Estudios Farmacológicos y Medicamentos ‘Luis M. Zieher’ for its conduct at the Instituto de Cardiología de Corrientes ‘Juana Francisca Cabral’ (reference: NuestroBen-2020/2021) and the Instituto Nacional de Parasitología ‘Dr. Mario Fatala Chaben’ (reference: NuestroBen-2020/2021) by Comité Institucional de Ética de Investigación en Salud for the Centro de Chagas y Patología Regional de Santiago del Estero (reference: NuestroBen-2020-088/2021), by Comité de Ética en Investigación for the Hospital de Infecciosas F.J. Muñiz (reference: NuestroBen-2020–4037) and the Hospital General de Agudos D.F. Santojanni (reference: NuestroBen-2020–4039) and by Comité de Bioética for the Fundación Huésped (reference: NuestroBen-2020/2021). In Bolivia, it was approved by Comité de Ética en Investigación en Salud from the Universidad Autónoma Juan Misael Saracho (reference: NuestroBen-2020/2025). All participants are asked to provide written informed consent to participate. Recruitment processes started in July 2023, and as of 15 June 2025, 140 participants have been recruited. Findings will be shared with Argentinian and Bolivian public health officials and with the Chagas and tropical medicine communities via international conferences. Findings will also be published in medical journals.

Trial registration number

NCT04897516.

☐ ☆ ✇ BMJ Open

Mindsets and menses: decoding young womens attitudes towards menstrual leave - an observational study from South India

Por: George · N. · Mahendran · P. · Kulothungan · K. · Dharmaraj · R. B. · Muniyapillai · T. · Subramanian · T. · Muthu Ranga Babu · A. · Arumugam · A. · Subramanian · S. · Shabash Khan · S. · Selvam · S. · Veeraragavan Suresh Babu · A. — Septiembre 30th 2025 at 09:49
Objective

The primary objective of this study is to investigate the perceived need and attitudinal perspectives regarding menstrual leave policies among young women in rural South India. The secondary objective was to determine the socio-demographic, menstrual and workplace-related factors associated with attitudes towards menstrual leave among young women.

Design

An analytical cross-sectional study was performed from May 2023 to August 2023.

Setting

In a rural district of Tamil Nadu, South India.

Participants

The study encompassed 955 young female students above 18 years of age enrolled in educational institutions in a rural district of Tamil Nadu, India. Participants were pursuing diverse professional programmes including medical, dental, allied health sciences, pharmacy and engineering courses.

Outcome measures

The primary outcomes included assessment of basic menstrual characteristics (age of menarche, regularity, product usage and pain experiences), pain evaluation using the WaLIDD scale (which measured working ability, anatomical pain location, pain intensity via Wong Baker scale and pain duration) and attitude assessment through a 10-dimension Likert scale. The attitude assessment explored both supportive factors (pain management, environmental considerations, medical leave allocation, menstruation normalisation and performance impact) and potential concerns (medicalisation, perceptions of fragility, stigma, disclosure issues and abnormal leave usage). Secondary outcome measures encompassed the analysis of factors influencing these attitudes, followed by a multivariable linear regression model to identify significant predictors.

Results

Among 955 female students (mean age 19.56±1.33 years), the majority supported menstrual leave for maintaining hygiene (82.3%) and managing dysmenorrhoea (75.8%). A substantial proportion (64.4%) viewed it as a means of normalising menstruation discourse, while 61.6% believed it could enhance workplace performance. However, concerns existed about medicalising menstruation (47.9%) and reinforcing gender stereotypes (43.4%). Multivariate analysis revealed that medical students (B=0.67, 95% CI: 1.34 to 2.00), those with graduate-educated fathers (B=1.64, 95% CI: 0.31 to 2.97), earlier age at menarche (B=–0.23, 95% CI: –0.45 to –0.01) and participants reporting menstrual interference with daily activities (B=0.96, 95% CI: 0.02 to 0.89) held significantly more positive attitudes.

Conclusion

While young women generally support menstrual leave policies, particularly for hygiene and pain management, there are significant concerns about workplace stigmatisation and gender stereotyping. Educational background, parental education and personal menstrual experiences significantly influence attitudes toward menstrual leave. These findings suggest the need for carefully structured menstrual leave policies that balance biological needs with workplace/student place equality concerns.

☐ ☆ ✇ BMJ Open

Risk and resilience factors associated with the progression of influenza to severe disease outcomes: umbrella review protocol

Por: Park · J. Y. · Dowell · A. · Turner · N. · Albrecht · S. · Hills · I. · Marsh · S. — Septiembre 30th 2025 at 09:49
Introduction

Influenza is a major global health concern, responsible for up to 650 000 respiratory-related deaths annually. Although influenza is often perceived as mild in healthy adults, it can cause severe outcomes in high-risk groups, such as older adults, young children, pregnant women and those with underlying medical conditions. Various clinical, sociodemographic and environmental factors influence the progression to severe outcomes, whereas resilience factors, such as vaccination, may reduce risks. Despite growing research, the evidence base regarding risk and resilience is spread across many different aspects of the literature. This umbrella review will synthesise evidence from existing systematic reviews and meta-analyses to identify key risk and resilience factors associated with the progression of influenza to severe outcomes in the general population.

Methods and analysis

This umbrella review follows the Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include systematic reviews and meta-analyses reporting host-related risk or resilience factors for severe influenza outcomes. Four databases (EMBASE, Scopus, Medline and CINAHL) will be searched for English-language publications. Study quality will be assessed using AMSTAR 2, and the body of evidence will be evaluated using Grading of Recommendations Assessment, Development and Evaluation. Due to heterogeneity, findings will be analysed narratively. Risk and resilience factors will be grouped into demographic, clinical, behavioural, social and psychological domains.

Ethics and disseminations

No ethical approval is required. The completed review will be shared through peer-reviewed journals and conference presentations.

PROSPERO registration number

CRD420250644475.

☐ ☆ ✇ BMJ Open

Australian research priorities for inherited retinal diseases: a James Lind Alliance priority setting partnership

Por: Robertson · E. G. · Hetherington · K. · Prain · M. · Ma · A. · Ayton · L. N. · Jamieson · R. V. · Shepard · E. · Boyd · L. · Hall · J. · Boyd · R. · Karandrews · S. · Feller · H. · Simunovic · M. P. · Grigg · J. R. · Yamamoto · K. · Wakefield · C. E. · Gonzalez-Cordero · A. — Septiembre 30th 2025 at 09:49
Objectives

Inherited retinal diseases (IRDs) are a broad range of diseases associated with abnormalities/degeneration of retinal cells. We aimed to identify the top 10 Australian research priorities for IRDs to ultimately facilitate more meaningful and potentially cost-effective research.

Design

We conducted a James Lind Alliance priority setting partnership that involved two Australian-wide surveys and online workshops.

Setting

Australia-wide.

Participants

Individuals aged 16 years or older were eligible to participate if they had an IRD, were caregivers of an individual with an IRD or were health professionals providing care to this community.

Outcome measure

In Survey 1, we gathered participants’ unanswered questions about IRDs. We grouped these into summary questions and undertook a literature review to verify if they were truly unanswered (ie, evidence uncertainties). In Survey 2, participants voted for the uncertainties that they considered a priority. Top-ranked uncertainties progressed for discussion and final prioritisation in two workshops.

Results

In Survey 1, we collected 223 questions from 69 participants. We grouped these into 42 summary questions and confirmed 41 as evidence uncertainties. In Survey 2, 151 participants voted, with the 16 uncertainties progressing to final prioritisation. The top 10 priorities, set by the 24 workshop participants, represented (1) treatment/cure; (2) symptoms and disease progression; (3) psychosocial well-being and (4) health service delivery. The #1 priority was for treatment to prevent, slow down or stop vision loss, followed by the #2 priority to address the psychological impact of having an IRD.

Conclusion

The top 10 research priorities highlight the need for IRD research that takes a whole-person, systems approach. Collaborations to progress priorities will accelerate the translation of research into real-world benefits.

☐ ☆ ✇ BMJ Open

Quadrivalent HPV Vaccine Evaluation Study with Addition of the Nonavalent Vaccine (QUEST-ADVANCE): protocol of an observational cohort study

Por: Middeldorp · M. · Donken · R. · Nirmal · A. · Smith · B. · Citlali Marquez · A. · Bettinger · J. A. · Brisson · M. · Burchell · A. N. · Dobson · S. R. · Dawar · M. · Franco · E. L. · Grennan · T. · Krajden · M. · Mayrand · M.-H. · McNeil · S. · Naus · M. · Sauvageau · C. · Singer · J. · Sm — Septiembre 30th 2025 at 09:49
Introduction

The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE.

Methods and analysis

QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1–3 doses of the quadrivalent or nonavalent HPV vaccine at 9–14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9–14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4–5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20–27-year-old females vaccinated at 9–14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16–26 years of age up to 12 years postvaccination.

Ethics and dissemination

QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children’s and Women’s Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.

☐ ☆ ✇ BMJ Open

ColoCap: determining the diagnostic accuracy of colon capsule endoscopy compared with standard colonoscopy in patients at risk of colorectal disease - a study protocol

Por: Ibrahim · H. · Haritakis · M. · Ballantine · L. · McCormack · K. · Cotton · S. · Hudson · J. · Atkin · K. · Rogers · S. · Nixon · L. S. · Verghese · A. · Holmes · H. · Treweek · S. · MacLennan · G. · Dolwani · S. · Gardner · G. · Hurt · C. · Watson · A. · Turvill · J. — Septiembre 30th 2025 at 09:49
Background

Lower gastrointestinal symptoms attributed to colorectal disease are common. Early diagnosis of serious colorectal disease such as colorectal cancer (CRC), precancerous growths (polyps) and inflammation is important to ensure the best possible outcomes for a patient. The current ‘gold standard’ diagnostic test is colonoscopy. Colonoscopy is an invasive procedure. Some people struggle to cope with it and require intravenous sedation and/or analgesia. It is also resource-intensive, needing to be performed in specialist endoscopy units by a trained team. Across the UK, the demand for colonoscopy is outstripping capacity and the diagnosis of colorectal disease is being delayed. A colon capsule endoscope (CCE) is an alternative colorectal diagnostic. It is a ‘camera in a pill’ that can be swallowed and which passes through the gastrointestinal tract, obtaining visual images on the colon. There is now established experience of CCE in the UK. CCE might provide a less invasive method to diagnose colorectal disease if found to be accurate and effective and provide a means by which to increase the National Health Service (NHS) diagnostic capacity.

Aims and objectives

The aim of this study is to determine the diagnostic accuracy of CCE when compared with colonoscopy in representative and clinically meaningful cohorts of patients. An evaluation of the experiences of CCE for the patient and clinical team and an assessment of cost effectiveness will be undertaken.

Methods

We will undertake three research workstreams (WS). In WS1, we shall perform a paired (back-to-back) study. Each participant will swallow the CCE and then later on the same day they will have a colonoscopy. The study has been designed in collaboration with our Patient Advisory Group and as closely mirrors standard care as is possible. 973 participants will be recruited from three representative clinical contexts; suspected CRC, suspected inflammatory bowel disease and postpolypectomy surveillance. Up to 30 sites across the UK will be involved to maximise inclusivity. Measures of diagnostic accuracy will be reported along with CCE completion rates, number of colonoscopy procedures potentially prevented and adverse events, such as capsule retention. A nested substudy of intraobserver and interobserver agreement will be performed. WS2 will develop models of cost-effectiveness and WS3 will evaluate the patient and clinician experience, with reference to acceptability and choice.

Anticipated impact

The study findings will provide the evidence base to inform future colorectal diagnostic services.

Ethics and dissemination

The study has approval from the North East—Tyne and Wear South research ethics committee (REC reference 24/NE/0178, IRAS 331349). The findings will be disseminated to the NHS, National Institute for Health and Care Excellence, other clinical stakeholders and participants, patients and the public.

Trial registration number

ISRCTN16126290.

☐ ☆ ✇ BMJ Open

Nutritional status and its influencing factors among elderly patients with malignant tumours: a retrospective study from a tertiary hospital in Chengdu, China

Por: Duan · R. · Wang · F. · Zhang · T. · Feng · T. · Ren · T. — Septiembre 30th 2025 at 09:49
Objective

To investigate the nutritional status and its influencing factors in elderly patients aged 60 years and above with malignant tumours.

Design

A retrospective observational study.

Setting

The First Affiliated Hospital of Chengdu Medical College, a tertiary care hospital in Chengdu, China.

Participants

A total of 450 elderly patients with cancer (aged ≥60 years) admitted between January 1, 2022, and January 1, 2023. Patients were selected based on their clinical records, excluding those with communication disorders, mental illness or incomplete data.

Primary outcome measures

Nutritional status was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Participants were categorised based on the presence or absence of malnutrition. Multivariate logistic regression was used to identify independent risk factors for malnutrition.

Results

Of the 450 patients included, 63.7% were male and 36.3% female, with a median age of 69 years. The prevalence of severe malnutrition was 46.4%. Univariate analysis showed significant associations between malnutrition and factors such as older age (p

Conclusions

Malnutrition is highly prevalent in elderly patients with cancer and is significantly associated with age, BMI, albumin levels and self-care ability. Early identification and targeted nutritional interventions may improve outcomes and quality of life in this population.

☐ ☆ ✇ BMJ Open

Hospitalisation and mortality trends in ANCA-associated vasculitis in Mexico: results from a nationwide retrospective registry analysis

Por: Etchegaray-Morales · I. · Mendoza-Pinto · C. · Barrera-Hernandez · S. · Martinez-Barragan · Y. M. · Munguia-Realpozo · P. · Pelaez-Ballestas · I. · Berra-Romani · R. · Ramirez-Lara · E. · Ayon-Aguilar · J. · Mendez-Martinez · S. — Septiembre 29th 2025 at 07:52
Objective

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) entails substantial morbidity and mortality, yet no epidemiologic evidence exists on its outcomes in Mexico. This study assessed national hospitalisations (2005–2022) and mortality (2000–2022) related to AAV using data from the General Board of Health Information.

Design

Retrospective, population-based time-trend analysis on administrative health data.

Setting

Mexico’s national hospital discharge and mortality registries, covering 1 January 2000 through 31 December 2022.

Participants

All individuals aged ≥ 15 years with a primary or secondary International Classification of Diseases, 10th revision, diagnosis of AAV recorded during hospitalisation or on death certificates nationwide.

Outcome measures

The study’s primary outcomes were the age-standardised hospitalisation and mortality rates for AAV (expressed per 100 000 population, overall and by sex), with temporal trends in both rates quantified using Joinpoint regression to calculate annual percent change (APC) and average APC (AAPC).

Results

We identified 2804 hospitalisations and 599 deaths. Females accounted for 49.7% of hospitalisations, while males represented 48.7% of deaths. Although the overall age-standardised hospitalisation rate (ASHR) and mortality rate (ASMR) AAPCs were not statistically significant, relevant trends emerged. From 2010 to 2022, ASHR declined significantly (APC: –5.2%; 95% CI –9.7, –0.5; p=0.03), whereas mortality rates remained stable from 2000 to 2022 (AAPC: +3%; 95% CI –4.6, 11.3; p=0.45). Nevertheless, mortality increased among males (APC: +6.4%; 95% CI 0.9, 12.2; p=0.02) and individuals over 45 years (APC: +8.6%; 95% CI 1.7, 16.0; p=0.02) from 2008 onwards.

Conclusions

Overall, these findings indicate no major changes in national rates but reveal a decline in hospitalisations since 2010 and a rise in mortality for specific subgroups since 2008. Targeted interventions, particularly for older adults and men, appear warranted to address this evolving disease burden. Future research should explore underlying risk factors and evaluate tailored strategies to improve clinical outcomes in AAV across Mexico.

☐ ☆ ✇ BMJ Open

Transformative learning through communal documentary viewing: a mixed methods study on kidney transplantation and organ donation in medical education

Por: McCaffrey · D. · Corr · M. · Fergie · R. · Courtney · A. · Brown · T. · Gormley · G. — Septiembre 29th 2025 at 07:52
Objectives

To explore how learner transformation manifests in a communal arts and humanities (AH) educational activity for medical students.

Design

Mixed methods explorative study.

Setting

UK-based medical school that follows a 5-year case-based learning curricular model.

Interventions

A group of 105 first-year medical students attended a group viewing of a TV documentary titled, ‘Life on the List’ as part of their core curriculum. The documentary explores the humanistic aspects of kidney disease, organ donation and transplantation by portraying the personal stories of transplant recipients, donors and healthcare professionals. Following the screening, attendees engaged in a question-and-answer session with an expert panel.

Main outcome measures

Perceived transformation of learning was measured using a quantitative Likert-scale paired pre-screening and post-screening questionnaire. Additionally, the qualitative study used facilitated focus groups (FGs) to explore how learners may or may not have transformed their learning based on the AH educational activity.

Participants

Inclusion criteria were: (a) first-year medical students and (b) those who attended the screening. Those not meeting these criteria were excluded. The quantitative questionnaire was completed by 94 participants, while 19 attended FG interviews.

Results

Paired t-tests were conducted to compare pre-screening and post-screening responses across five questions. All results demonstrated statistical significance (phow learning was transformed: (1) an absorbing experience; (2) confronting and challenging: different ways of seeing the world; (3) collective reflection: the power and safety of the crowd; (4) ‘everything just came into perspective’: accepting the world in a new way; and (5) willing to change the world: advocacy and agency. By this collective experience focusing on real patient stories and providing an opportunity for discussion and reflection, participants were offered a holistic view on kidney medicine and transplantation. Overwhelmingly, participants were inspired to strive for person-centred care, with many being motivated to explore kidney medicine and transplantation as career options.

Conclusion

Couched in pedagogy, an AH educational activity for medical students can leverage learner transformation and promote person-centred care. With respect to kidney medicine, organ donation and transplantation, such activities can provide early career exposure to these fields. Students may be inspired to act as positive ambassadors for organ donation and transplantation and further explore these areas as future career options. Further research should investigate AH interventions in diverse groups from a longitudinal perspective to consider long-term effects in promoting holistic and empathetic patient care.

☐ ☆ ✇ BMJ Open

Minimum effective dose of betamethasone for incisional local infiltration for the prevention of postoperative pain after spine surgery: study protocol for a randomised controlled trial

Por: Wang · Y. · Han · B. · Zhao · C. · Ren · H. · Jia · W. · Luo · F. — Septiembre 29th 2025 at 07:52
Introduction

Postoperative pain is particularly pronounced in spinal surgery. Inadequate management of acute postoperative pain not only reduces patient satisfaction and delays recovery but also increases the risk of developing chronic pain. Local infiltration analgesia (LIA) is a widely used technique for perioperative pain management. However, even with the use of long-acting local anaesthetics, such as ropivacaine, postoperative analgesia often remains insufficient. Preliminary evidence suggests that combining diprospan, a mixture of betamethasone disodium phosphate and betamethasone dipropionate, with ropivacaine can significantly reduce analgesic requirements in the immediate postoperative period. However, concerns about steroid-related complications, including hyperglycaemia and surgical site infections, highlight the need to identify the minimum diprospan concentration to achieve a balance between efficacy and safety. This randomised, controlled, evaluator-blinded trial aims to investigate the dose-response relationship of diprospan as an adjunct to ropivacaine for LIA in spinal surgery to determine the minimum effective dose for effective and safe pain management.

Methods and analysis

This is a single-centre, randomised, evaluator-blinded, controlled, dose-mapping study in which subjects will be randomised in a 1:1:1:1:1 ratio to the control group or to receive diprospan at concentrations of 0.003%, 0.006%, 0.009% or 0.012%. Patients will receive either 0.5% ropivacaine alone or a corresponding dose of diprospan combined with 0.5% ropivacaine for LIA. All participants will be followed for a duration of 3 months. The primary outcome measure will be cumulative sufentanil consumption within the first 48 hours postsurgery. Secondary outcomes will include additional assessments of analgesia, steroid-related adverse events and other complications within the 3-month follow-up period.

Ethics and dissemination

This study protocol was approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2024-365-02-1). Written informed consent will be obtained from all participants. The results will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT06785350.

☐ ☆ ✇ BMJ Open

Psychosis and self-harm in prison: a population-based case-control study

Por: Chowdhury · N. Z. · Hwang · Y. I. · Spike · E. · Kariminia · A. · Dean · K. · Adily · A. · Ellis · A. · Greenberg · D. M. · Grant · L. · Allnutt · S. · Butler · T. — Septiembre 29th 2025 at 07:52
Background

Self-harm and suicide are common among prison inmates, but less is known about these phenomena in those with psychosis.

Objectives

The aim of this study was to examine self-harm behaviour in New South Wales (NSW) prisons in Australia among inmates diagnosed with psychosis. This study also examined self-harm-related alerts applied by Corrective Services to assist staff with the management of the security and well-being of inmates.

Design and setting

A retrospective case-control data-linkage study was conducted using administrative data collections in NSW, Australia.

Participants

The study included all individuals diagnosed with psychosis and incarcerated between 2001 and 2020 in NSW as cases and an age and sex matched control group with no such diagnosis with a record of incarceration in the same time period.

Primary and secondary outcome measures

The primary outcome measure was self-harm among the cases and controls. The secondary outcome measure was the application of alerts by Corrective Services in relation to self-harm incidents.

Results

Multivariate regression analysis was used to examine predictors of self-harm in prison. Prisoners with psychosis (n=14 900) were more likely to self-harm than controls (n=2713), with 15.0% versus 3.6% engaging in self-harm (highest odds of self-harm observed in those with schizophrenia and related psychoses, aOR=4.84, 95% CI: 3.93 to 5.98). Those of Aboriginal heritage had an increased risk of self-harm (aOR=1.58, 95% CI: 1.43 to 1.75). Factors associated with a lower risk of self-harm were male sex and older age (≥25 years) at the time of their first incarceration. 35.6% of those released from prison with a prior psychosis diagnosis had at least one alert applied during incarceration compared with 10.1% of prisoners without a diagnosis of psychosis. Overall, 35 individuals with psychosis and 1 individual from the control group died while in prison between 2001 and 2020. 17 prison suicides were recorded from the study population; all occurred in the psychosis group.

Conclusions

Given the heightened risk of self-harm in those with histories of psychosis, consideration should be given to sharing mental health information between agencies to improve the care and management of this group during incarceration. Prison alerts may be a useful tool to help staff manage inmates’ well-being if used appropriately.

☐ ☆ ✇ BMJ Open

Comparative Efficacy and Safety of Pharmacological Agents for Chronic Low Back Pain: A Systematic Review and Bivariate Bayesian Network Meta-analysis Protocol

Por: Aremu · O. · Ogunlade · O. · Mata · T. — Septiembre 29th 2025 at 07:52
Introduction

Non-specific chronic low back pain is a leading cause of disability-adjusted life-years (DALYs) with a lifetime prevalence of 80%–85%. Although many modalities of treating chronic low back pain are available, pharmacotherapy remains a very important treatment modality, according to many recognised guidelines. Each of these pharmacological agents has evidence supporting its efficacy in treating chronic low back pain, and each of them is associated with side effects. At present, no study has unified these two outcomes or ranked them from the most effective to the least effective. Thus, this study aims to identify pharmacological agents that rank best by conducting multivariate bivariate network meta-analysis.

Methods

Four databases (Medline/Pubmed, Cochrane Central Register for Controlled Trials, Cochrane Database for Systematic Reviews and CINAHL) will be systematically searched from their inception to 31 July 2024 for randomised control trials that meet the inclusion criteria. Appropriate data will be extracted from the relevant studies, including the two outcomes of interest: the pain intensity score and the proportion of patients who withdrew from the study because of adverse events. A bivariate Bayesian network meta-analysis will be used to combine the two outcomes of interest to form a single probability that will rank the pharmacotherapy agents from the most effective and safe to the least. The studies will be assessed for risk of bias, and their evidence will be graded using the Grading of Recommendations Assessment, Development, and Evaluation assessment tool. Inconsistency, which is a key assumption of network meta-analysis, will be assessed using both local and global methods.

Ethics and Dissemination

This systematic review is based on already published data, so it does not require ethical approval. The findings from the review, after completion, will be disseminated via peer-reviewed publications.

PROSPERO registration number

CRD42024569192.

☐ ☆ ✇ BMJ Open

Protocol for an observational cohort study integrating real-world data and microsimulation to assess imaging surveillance strategies in stage I-IIIA NSCLC patients in OneFlorida+

Por: Braithwaite · D. · Karanth · S. D. · Bian · J. · Meza · R. · Jeon · J. · Tammemagi · M. · Wheeler · M. · Cao · P. · Rackauskas · M. · Shrestha · P. · Yoon · H.-S. · Borondy Kitts · A. · Verma · H. · Blair · M. C. · Chen · A. · Das · D. · Lou · X. · Wu · Y. · Han · S. · Hochhegger · B. · Guo · Y — Septiembre 29th 2025 at 07:52
Introduction

Although lung cancer remains the leading cause of cancer deaths in the US, recent advances in early detection and treatment have led to improvements in survival. However, there is a considerable risk of recurrence or second primary lung cancer (SPLC) following curative-intent treatment in patients with early-stage non-small cell lung cancer (NSCLC). Professional societies recommend routine surveillance with CT to optimise the detection of potential recurrence and SPLC at a localised stage. However, no definitive evidence demonstrates the effect of imaging surveillance on survival in patients with NSCLC. To close these research gaps, the Advancing Precision Lung Cancer Surveillance and Outcomes in Diverse Populations (PLuS2) study will leverage real-world electronic health records (EHRs) data to evaluate surveillance outcomes among patients with and without guideline-adherent surveillance. The overarching goal of the PLuS2 study is to assess the long-term effectiveness of surveillance strategies in real-world settings.

Methods and analysis

PLuS2 is an observational study designed to assemble a cohort of patients with incident pathologically confirmed stage I/II/IIIA NSCLC who have completed curative-intent therapy. Patients undergoing imaging surveillance will be followed from 2012 to 2026 by linking EHRs with tumour registry data in the OneFlorida+ Clinical Research Consortium. Data will be consolidated into a unified repository to achieve three primary aims: (1) Examine the utilisation and determinants of CT imaging surveillance by race/ethnicity and socioeconomic status, (2) Compare clinical endpoints, including recurrence, SPLCs and survival of patients who undergo semiannual versus annual CT imaging and (3) Use the observational data in conjunction with validated microsimulation models to simulate imaging surveillance outcomes within the US population. To our knowledge, this study represents the first attempt to integrate real-world data and microsimulation models to assess the long-term impact and effectiveness of imaging surveillance strategies.

Ethics and dissemination

This study involves human participants and was approved by the University of Florida Institutional Review Board (IRB), University of Florida IRB 01, under approval number IRB202300782. The results will be disseminated through publications and presentations at national and international conferences. Safety considerations encompass ensuring the confidentiality of patient information. All disseminated data will be de-identified and summarised.

☐ ☆ ✇ BMJ Open

Cohort profile: trajectory of knee health in runners with and without heightened osteoarthritis risk (TRAIL) in Australia--prospective cohort study

Por: De Oliveira Silva · D. · Mentiplay · B. F. · Girdwood · M. · Haberfield · M. J. · Bruder · A. M. · Culvenor · A. G. · West · T. J. · Hill · J. P. · Carey · D. L. · Johnston · R. T. R. · Crossley · K. M. — Septiembre 29th 2025 at 07:52
Purpose

The TRAjectory of knee heaLth in runners (TRAIL) study is a prospective cohort study investigating the long-term knee health trajectories of runners with and without a heightened osteoarthritis risk. This study aims to describe the recruitment results and baseline characteristics of the TRAIL cohort.

Participants

Runners aged 18–50 years and running ≥3 times and ≥10 km per week on average in the past 6 months were eligible. Participants were recruited via running podcasts, running clubs and social media between July 2020 and August 2023. Data were collected at study enrolment and at a face-to-face baseline testing session, which occurred a median of 33 weeks (IQR 18 to 86 weeks) after enrolment. Follow-up data collection is ongoing.

Findings to date

Out of 462 runners who completed an online registration form, 268 runners enrolled, of which 135 had a history of knee surgery (46% females) and 133 were non-surgical controls (50% females). 60% of the surgery group had undergone anterior cruciate ligament reconstruction, 33% meniscus and/or cartilage surgery, and 7% other knee surgery. 54 participants previously enrolled were unable to continue in the study before attending baseline data collection. Of the 214 runners who remained in the study and attended baseline data collection, 108 had a history of knee surgery (49% females) and 106 did not have a history of knee surgery (51% females).

Future plans

Participants will be followed for 10 years through ongoing patient-reported outcomes and continuous monitoring of training loads using wearable devices. At baseline, 4- and 10-year follow-up, knee MRI and knee-health patient-reported outcomes will be collected to evaluate structural and symptomatic knee osteoarthritis progression. Data will inform guidelines for safe running practices and rehabilitation post-knee surgery.

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