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Tuberculosis death prediction calculator for prospective use at diagnosis in resource-constrained programme settings: a statewide cohort study

Por: Shanmugasundaram · S. · Shewade · H. D. · Srinivasan · R. · Frederick · A. · Sabarinathan · R. · Harish · P. · Balu · D. · Melfha · J. M. · Gayathri · K. · Vijayaprabha · R. · Jeyakumar · A. · Kabir · D. · Eraivan · M. · Bhatnagar · T. · Murhekar · M. V.
Objectives

To develop predictive models for early and overall tuberculosis (TB) deaths for prospective use at TB diagnosis in resource-constrained TB programme settings.

Design

Statewide cohort study using routinely captured secondary data.

Setting

With the majority of TB deaths being early (within 2 months), India’s TB programme’s information management system (Ni-kshay)-dependent death prediction models (using age, gender, TB site, previous treatment, microbiological confirmation, HIV, diabetes and bank account availability) are not feasible for prospective use, as few variables are captured at diagnosis. Utilising routinely captured triage variables for severe illness at diagnosis (body mass index, pedal oedema, respiratory rate, oxygen saturation and ability to stand without support) from an ongoing statewide and state-specific differentiated TB care initiative to reduce TB deaths in Tamil Nadu state (southern India, 80 million population with 0.1 million annual notifications), robust models for prospective use were developed.

Participants

Adults (aged ≥15 years) with TB (not known to be drug-resistant at diagnosis) that were notified from public facilities of Tamil Nadu from July 2022 to June 2023.

Outcome measures

Early and overall (within 12 months of notification) TB deaths. Area under the receiver operating characteristic curve (AUC) was used to assess accuracy of models built using modified Poisson regression.

Results

Among 55 971 adults, the overall death rate was 7.4%, and 67.9% of the deaths were early. In predicting overall deaths, accuracy of the model using all Ni-kshay variables (AUC 0.716 (95% CI 0.707 to 0.725)) was as good as the model using triage variables for severe illness only (AUC 0.701 (95% CI 0.691 to 0.711)). To the latter, adding potentially capturable Ni-kshay variables at diagnosis (age, gender, TB site, previous treatment and microbiological confirmation) significantly improved model accuracy (AUC 0.754 (95% CI 0.745 to 0.763)). Further addition of remaining Ni-kshay variables did not improve accuracy significantly. Death prediction equations were generated for these models.

Conclusion

Simple and easily measurable triage variables for severe illness should be routinely captured at TB diagnosis. A death prediction calculator (http://44.208.93.99/) based on these variables (specifically triage variables for severe illness combined with age, gender, TB site, previous treatment and microbiological confirmation) may be used by Indian states and high TB burden countries seeking scalable, data-driven interventions to reduce TB deaths.

Toward a fully wireless endovascular neural interface: Evaluating power transfer efficacy

by Yi-De Tai, Joel Villalobos, Nima Wickramasinghe, Bryce Widdicombe, Ranjith R. Unnithan, David B. Grayden, Sam E. John

Background

Endovascular neural interfaces (ENIs) offer a minimally invasive approach for neural stimulation and recording without the need for open brain surgery. However, current generation devices have long transvascular wires from the implant site to the chest. Eliminating these wires will unlock clinical usability, including lowering infection risk from transvascular wires, reducing the risk of thrombosis from altered hemodynamics, and improving mechanical reliability. However, removing these transvascular wires would require efficient power transfer across the skull and tissue while meeting specific absorption rate (SAR) limits, which is a significant challenge in the field.

Objective

This work designed and evaluated endovascular receiver (Rx) and transmitter (Tx) coils within endovascular geometric and biological constraints to maximize wireless power transfer.

Methods

This study evaluated the optimal operating frequencies, quantified coupling, coil quality factors, power transfer efficiency, and SAR using computational modeling, benchtop, and in-vivo testing. The study also assessed the tolerance to coil misalignment and load mismatch. We evaluated each case with and without ferrites with measurements in air, sheep tissue, and in vivo in sheep.

Results

The results showed that inductive power transfer delivered power to endovascular geometry devices at clinically relevant depths. The maximum power transfer efficiency (PTE) reached 11% at 15 mm and 2% at 30 mm, with up to 72 mW delivered at 30 mm under SAR safety limits. The rectangular planar coil pair performed best at ≤15 mm, whereas the ferrite-core flux-pipe Tx with a helical Rx outperformed beyond ~20 mm and was more tolerant to misalignment.

Conclusion

This study demonstrated the feasibility of wirelessly powering multichannel ENIs using coils that can be placed inside a blood vessel and powered inductively. Making an endovascular neural interface fully wireless has the potential to transform the technology by improving both safety and reliability.

Effects of local heat on metabolic health, frailty risk, and exercise adaptations in pre-diabetic older adults: Protocol for the Heat and Exercise in Aging as Therapy (HEAT) clinical trial

by Hui-Ying Luk, Casey R. Appell, Fangyuan Zhang, Jarrod Blinch, K. Sreekumaran Nair, Chwan-Li Shen, Danielle E. Levitt

Introduction

Glycemic dysregulation is a hallmark of type 2 diabetes (T2D) and contributes to skeletal muscle (SKM) loss and frailty risk, especially in older adults. Glycemic control and physical function are supported by SKM capillarization and mitochondrial function, and their impairment contributes to T2D development. While high-intensity interval training (HIIT) is a promising intervention, adherence and effectiveness remain concerns for prescribing HIIT among older adults at risk for T2D. Local heat therapy (LHT) may be a more practical initial strategy to improve SKM architectural factors and precondition SKM, enhancing physiological adaptations to exercise in this population.

Methods and analysis

Heat and Exercise in Aging as Therapy (HEAT) is a two-phase, randomized, sham-controlled clinical trial investigating the efficacy of LHT to improve glycemic control and decrease frailty risk via improved SKM architecture among older adults with prediabetes. LHT is tested as a standalone intervention and as a means to precondition SKM for subsequent HIIT, improving exercise adaptations. In Phase 1, LHT and sham (CON) groups apply heat pads for 90 minutes/day, 6 days/week, for 12 weeks. A separate HIIT group completes 4x4-minute cycling intervals at 90–95% VO₂peak, 3 days/week. In Phase 2, LHT and CON groups begin HIIT. Participants (≥50 years) have impaired fasting glucose (100–125 mg/dL) and/or HbA1c (5.7–6.4%). Biospecimen collection and clinical assessments occur at baseline (T1), after Phase 1 (T2), and Phase 2 (T3). To our knowledge, this is the first study to determine the use of local heat pad on pre-diabetic older population. If successful, LHT may be a practical, scalable, non-invasive intervention to improve glycemic control and reduce frailty risk in older adults with prediabetes, preventing progression to T2D.

Add-on tocilizumab versus placebo for resistant major depression in psychiatric outpatients with low-grade inflammation in a tertiary public hospital in Southern Brazil: randomised triple-blind clinical trial protocol

Por: Portal · P. H. G. · Peixoto · G. N. · de Matos · M. R. · da Silva · L. C. N. · Alexandrino · G. B. · Dutra · P. H. G. · Carniel · B. P. · da Rocha · N. S.
Introduction

Emerging evidence supports a role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in the pathogenesis of treatment-resistant major depressive disorder (TRD). However, interventional studies targeting IL-6 in this population remain scarce. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 signalling and is approved for the treatment of autoimmune conditions such as rheumatoid arthritis. The primary objective of this study is to examine whether IL-6 inhibition via tocilizumab can impact depressive symptoms, inflammation-related biomarkers and cognition in patients with TRD. A secondary objective is to compare the biological profiles of patients with TRD with elevated inflammation to those of healthy controls.

Methods and analysis

This is a proof-of-concept, randomised, parallel-group, triple-blind, placebo-controlled clinical trial. 22 adult outpatients diagnosed with TRD and evidence of low-grade inflammation (serum C reactive protein≥3 mg/L) will be randomised (1:1) to receive either one intravenous infusion of tocilizumab (8 mg/kg; maximum 800 mg) or normal saline, administered as an add-on to their ongoing treatment. Psychiatric, cognitive and biomarker assessments will be performed at baseline and at follow-up visits on days 7, 14 and 28 post-infusion. Additionally, 10 healthy controls with no psychiatric history will undergo the same baseline assessments for biomarker comparison.

Ethics and dissemination

The study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (Project number: 2025-0245, CAAE: 88904825.7.0000.5327). Findings will be disseminated through peer-reviewed publications, scientific meetings and, on request, lay summaries for participants.

Trial registration number

NCT07052058.

Effect of a culturally adapted heart-healthy diet with phytosterols and/or krill oil on lipid-related outcomes in familial hypercholesterolaemia: protocol for a multicentre randomised controlled trial in Brazil

Introduction

An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.

Methods and analysis

The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.

Ethics and dissemination

This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.

Trial registration number

NCT06331195.

Association of 24-hour movement guideline adherence with mental health symptoms among Colombian university students: a cross-sectional study

Objective

This study aimed to determine the associations between adherence to the 24-hour movement guidelines and symptoms of anxiety and depression among Colombian university students.

Study design

Cross-sectional study.

Participants

1125 individuals (mean age 20.2±2.5 years; 56.7% female).

Setting

Students sampled from a single public university.

Primary and secondary outcome measures

Participants completed validated self-report instruments: the International Physical Activity Questionnaire-Short Form to assess physical activity (PA), sedentary behaviour (SB) and the Pittsburgh Sleep Quality Index to assess sleep duration. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale, with a score of ≥11 used to classify elevated symptoms. Binary logistic regression models were used to estimate associations between adherence to the 24-hour movement guidelines (meeting all three, two, one or none) and mental health outcomes, adjusting for potential confounders.

Results

Only 15.5% of students met all three components of the 24-hour movement guidelines. Meeting a greater number of components was significantly associated with lower odds of depressive and anxiety symptoms. In fully adjusted analyses, students who met all three guidelines were less likely to report anxiety symptoms (OR=0.26; 95%CI 0.13 to 0.54) and depressive symptoms (OR=0.42; 95%CI 0.22 to 0.79) compared with those who met none. Among individual behaviours, sufficient PA and adequate sleep were independently associated with lower odds of both outcomes, whereas high SB was associated with higher odds of elevated symptoms.

Conclusions

In this cross-sectional study, adherence to a greater number of 24-hour movement guideline components was associated with lower levels of anxiety and depressive symptoms in a graded manner. However, the cross-sectional design precludes inference regarding directionality or causality, and bidirectional associations or residual confounding remain possible. Longitudinal and interventional studies are needed to determine whether integrated daily movement behaviours influence mental health outcomes in young adults, particularly in Latin American populations.

Enhancing screening, early diagnosis and treatment initiation of oral, breast and cervical cancer in selected districts of India: an implementation research protocol

Por: Kankaria · A. · Shukla · P. · Vijayakumar · M. · Sachdeva · A. · Subramanian · M. J. · Borah · P. K. · Sahoo · S. S. · Nirgude · A. · Prusty · R. K. · T S · S. · Asuri · K. · Verma · P. · Sharma · J. · Dhaliwal · R. S. · Begum · S. · Kaur · T. · ICMR-NHRP Cancer Screening Group · Bhatla
Introduction

Despite implementation of the National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD), screening coverage for oral, breast and cervical cancers remains below 2%. Screening quality is inadequately addressed and delays in diagnosis and treatment initiation continue to persist. This multisite implementation research aims to improve district-level coverage and quality of screening, early diagnosis and timeliness of treatment initiation through a model co-developed within the NP-NCD context.

Methods and analysis

The study will be conducted in three phases across seven districts in diverse regions of India. In phase I (formative), the current status, barriers and facilitators of cancer screening, diagnosis and treatment initiation under NP-NCD will be assessed. In phase II (optimisation), a model (package of implementation strategies) will be co-developed and iteratively optimised with multistakeholder engagement at the subdistrict level to improve screening coverage and quality and strengthen the referral system for early diagnosis and treatment initiation. In phase III (scale-up and evaluation), the model will be implemented at the district level and evaluated for improvements in screening, early diagnosis and treatment initiation. A convergent mixed-methods design will be used, incorporating household surveys, facility assessments and stakeholder interviews. Implementation Research Logic Model will guide planning, execution and evaluation in the present study. Determinants of screening coverage and quality, early diagnosis and treatment initiation will be assessed using the Consolidated Framework for Implementation Research. Implementation strategies for the model will be finalised using the Expert Recommendations for Implementing Change framework. Implementation and service outcomes will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework.

Ethics and dissemination

Ethical approval has been obtained from all study sites. The study findings will be disseminated at the state, national and global levels through meetings and conferences and submitted to a peer-reviewed journal for publication.

Trial registration number

CTRI/2025/08/092672.

Accuracy of ophthalmic referral diagnoses by non-ophthalmologists in acute eye care: protocol for a systematic review and meta-analysis

Por: Cunha Gil · L. · Powis · A. · Wilson · H. · Thampy · R. · Kousha · O. · Dhawahir-Scala · F.
Introduction

Ophthalmic complaints account for a substantial proportion of presentations to emergency and acute eye care services, yet initial assessment or referral is frequently performed by non-ophthalmologist healthcare professionals. Previous single-centre studies suggest that one-third of referrals are incorrectly diagnosed, potentially delaying appropriate management of vision-threatening conditions. However, the overall magnitude of diagnostic error and patterns of misdiagnosis across healthcare settings remain unclear. This study aims to systematically review and synthesise the evidence on the diagnostic concordance of ophthalmic referral diagnoses made by non-ophthalmologists in acute eye care.

Methods and analysis

A systematic review and meta-analysis will be conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidance and registered with PROSPERO. MEDLINE (Ovid), Embase (Ovid) and the Cochrane CENTRAL database will be searched from inception to April 2025. Studies evaluating the diagnostic accuracy of referrals made by non-ophthalmologist healthcare professionals in emergency or acute eye care settings will be included. Two reviewers will independently screen studies, extract data and assess risk of bias using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) framework adapted for referral-diagnosis studies. The primary outcome will be diagnostic concordance between referral and final ophthalmologist diagnosis. Where appropriate, pooled concordance proportions will be synthesised using a random-effects meta-analysis. Condition-specific 2x2 diagnostic accuracy analyses will only be undertaken where valid binary target conditions and sufficient denominators are reported. Heterogeneity will be assessed using Cochran’s Q test and the I² statistic with subgroup analyses exploring differences by referring clinician type and anatomical location of ophthalmic pathology.

Ethics and dissemination

Ethical approval is not required for this study as it will synthesise data from previously published studies; findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant academic conferences.

PROSPERO registration number

CRD420261352717.

DREAMSPHEN: a randomised controlled study comparing dose reduction of antipsychotics vs maintenance treatment in schizophrenia spectrum disorder after stratification based on patients psychotic phenotype - study protocol of a personalised medicine approac

Por: Berna · F. · Horowitz · M. A. · Javelot · H. · Meyer · N. · Foucher · J. R.
Introduction

The DREAMSPHEN study (Dose REduction of Antipsychotics vs. Maintenance treatment in schizophrenia after Stratification based on psychotic PHENotype) aims to compare the benefits and risks of a hyperbolic tapering method for antipsychotics to the maintenance of antipsychotics in a sample of clinically stabilised patients with schizophrenia spectrum disorder.

Methods and analysis

A sample of 288 patients will be recruited from 12 centres in France. Inclusion criteria are: diagnosis of schizophrenia spectrum disorder (according to the 5th version of the Diagnostic and Statistical Manual of mental disorders, DSM-5), minimum of 3 months remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine and long-acting antipsychotic injection). First, the psychotic phenotype of the patients (cycloid psychosis vs other psychotic phenotype) will be assessed. Then, patients will be randomised either to the maintenance of treatment (MT) or to the antipsychotics dose reduction (DR) arm. DR will follow a hyperbolic schema according to Horowitz protocol. Patients will be assessed at baseline, and every 2 months until 24 months follow-up regarding social functioning, psychotic and negative symptoms, side effects of antipsychotic medication, cognitive functioning, patient satisfaction, substance and alcohol use, and quality of life. The primary outcome will be a good social functioning after 24 months defined as a score at the Personal and Social Performance Scale >70. Secondary outcome measures will include: psychotic and negative symptoms, hospitalisation for psychotic episode, antipsychotic dose, antipsychotic side effects, withdrawal symptoms, cognitive functioning, patient’s well-being and quality of life. Safety measures will include death, admissions to psychiatric hospital, psychotic relapses and severe self-harm.

Ethics and dissemination

The DREAMSPHEN trial aims to better identify patients with psychotic disorders who are most likely to benefit from antipsychotic tapering with an aim to inform future clinical treatment guidelines for antipsychotic treatment. DREAMSPHEN V2.0 of the 14 May 2025 has received ethical approval from Comité de protection des personnes Ile de France IV (N° 2023-509558-80-00) on 17 July 2025.

Trial registration number

EU Clinical Trials Register – EudraCT no. 2023-509558-80-00. Clinical trials: NCT07152184. Registered on 9 August 2025.

Surgery or radiotherapy for early-stage cancer study protocol for an emulated target trial of radical radiotherapy versus radical cystectomy, with either following neoadjuvant chemotherapy, for organ-confined muscle-invasive bladder cancer

Por: Kagenaar · E. · Lugo-Palacios · D. G. · Bromley · H. · Aggarwal · A. · Hutchings · A. · ONeill · S. · Rachet · B. · Cresswell · J. · Choudhury · A. · Grieve · R.
Introduction

Neoadjuvant chemotherapy (NAC) followed by definitive treatment consisting of either radical radiotherapy or radical cystectomy is the recommended treatment for patients with organ-confined muscle-invasive bladder cancer (OC-MIBC). A randomised controlled trial (RCT) aimed to compare the effectiveness of radical radiotherapy and radical cystectomy but failed to recruit. Radical radiotherapy is non-invasive and organ-preserving, and observational studies have suggested this treatment may be associated with similar outcomes compared with radical cystectomy. However, in these observational studies, the risk of confounding was high, and they did not consider the receipt of NAC. The surgery or radiotherapy (SORT) for the early-stage cancer study will assess the comparative effectiveness and cost-effectiveness of either radical cystectomy or radical radiotherapy, both after NAC for OC-MIBC. We will use a target trial emulation approach to reduce the risk of bias when assessing comparative effectiveness from observational data.

Methods and analysis

The SORT study will use UK’s National Cancer Registry to identify individuals diagnosed with urothelial OC-MIBC (T2-4aN0M0) between 1 January 2015 and 31 December 2021 who received either radical radiotherapy or radical cystectomy after NAC. The data will be linked to Hospital Episode Statistics (HES), National Radiotherapy Data Set (RTDS) and Systemic Anti-Cancer Therapy (SACT) data sets to gather information on clinical, tumour and socio-demographic characteristics and receipt of treatment. Using the target trial emulation framework, we will define the eligibility criteria and radical radiotherapy and radical cystectomy receipt. To reduce the risk of confounding, we will use advanced statistical approaches to allow for differences in measured baseline characteristics between the comparison groups.

The primary outcome is 3-year all-cause mortality after radical treatment receipt. Secondary outcomes will include all-cause and bladder-cancer-associated mortality at 3 and 5 years, time to death, incremental costs and incremental cost-effectiveness reported according to net health benefits.

Ethics and dissemination

The study was approved by the London School of Hygiene and Tropical Medicine Ethics Committee (Reference number 29717 - 1). Results will be communicated in open-access journals and conferences to clinicians, researchers, patients and policymakers.

Effect of supplemental hydrocortisone during stress in prednisolone-induced adrenal insufficiency: a study protocol for a multicentre, randomised, double-blinded, placebo-controlled clinical trial on health-related quality of life in patients with polymya

Por: Borresen · S. W. · Hansen · S. B. · Al-Jorani · H. · Tei · R. · Dreyer · A. F. · Boesen · V. B. · Bislev · L. S. · Jorgensen · N. T. · Jensen · R. C. · Bjergstrom · M. L. L. · Christensen · L. L. · Frederiksen · J. S. S. · Glintborg · D. · Bjorner · J. B. · Feldt-Rasmussen · U. · Jor
Introduction

Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone.

Methods and analysis

A multicentre, randomised, double-blinded, placebo-controlled, clinical trial including patients with PMR/GCA receiving ongoing prednisolone ≤5 mg/day. Eligible patients undergo an adrenocorticotropic hormone (ACTH) test, and 250 patients with a stimulated cortisol

Ethics and dissemination

The study is approved by the Ethics Committee of the Capital Region of Denmark and the Danish Medicines Agency. Recruitment began June 2022. The last patient’s last visit is expected in 2026. Results will be disseminated via peer-reviewed publication and conference presentations.

Trial registration numbers

EudraCT:2021-002528-18, CTIS:2024-518272-30-00, NCT05435781.

Effects of Erbium:YAG laser combined with vaginal estriol therapy in postmenopausal women with Genitourinary Syndrome of Menopause: protocol for a randomised, double-blind, controlled trial

Introduction

Genitourinary syndrome of menopause (GSM) is a chronic, oestrogen-deficient condition that is frequently underdiagnosed and undertreated. Although low-dose vaginal estriol improves epithelial trophism and microbial balance, a substantial proportion of women report persistent symptoms. High-quality randomised evidence evaluating combined therapeutic strategies remains scarce. Energy-based modalities, including the erbium:YAG (Er:YAG) laser (=2940 nm), have been proposed as adjunctive treatments. This trial aims to assess the efficacy of Er:YAG laser therapy combined with vaginal estriol compared with estriol alone in postmenopausal women with GSM.

Methods and analysis

This is a single-centre, randomised, double-blind, controlled clinical trial. Postmenopausal women aged 45–70 years with vaginal pH ≥5.0 and at least one moderate GSM symptom (Visual Analogue Scale ≥4) will be eligible. Exclusion criteria include current systemic or local hormone therapy, previous vaginal energy-based treatment, abnormal cervical cytology and body mass index ≥35 kg/m2. All participants will receive vaginal estriol cream (0.5 mg per dose) daily for 14 days, followed by twice-weekly administration for 16 weeks. Participants will be randomised (1:1) to receive either estriol plus sham Er:YAG laser or estriol plus active Er:YAG laser. Three laser sessions will be delivered at approximately 4-week intervals. Assessments will occur at baseline, monthly during treatment and 4 months after the final session. The primary outcome is the Vulvovaginal Health Index, with the primary endpoint defined as the change from baseline to 4 months post-treatment, reflecting sustained effect. Secondary outcomes include GSM symptom severity, vaginal microbiome composition (16S rRNA sequencing), quality of life (Menopause Rating Scale) and sexual function (Female Sexual Function Index). Data will be analysed using repeated-measures analysis of variance or appropriate non-parametric tests, with significance set at p

Ethics and dissemination

Ethical approval has been obtained from the Human Research Ethics Committee of UNINOVE. Written informed consent will be obtained. Findings will be disseminated via peer-reviewed journals and scientific meetings.

Trial registration number

NCT06873971.

Cost analysis of the use of digital rectoscopy versus flexible sigmoidoscopy in rectal cancer patients undergoing watch and wait

Por: Sekhon Inderjit Singh · H. K. · Harper · H. · Butnari · V. · Beni · R. · Lozano · E. · Goede · A.
Introduction and objective

Organ preservation strategies for rectal cancer following neoadjuvant treatment require intensive endoscopic monitoring to detect early luminal recurrence. This is termed 'Watch and Wait' (WAW). Standard protocols commonly mandate flexible sigmoidoscopy every 3–4 months for 2 years. Digital proctoscopy with the LumenEye device has been shown to be a safe alternative that can be performed in an outpatient setting without the need for sedation and with less staffing requirements. The study objective is to evaluate the economic implications of using digital proctoscopy compared with flexible sigmoidoscopy for patients with rectal cancer managed under a WAW protocol.

Setting and design

The study was conducted in a secondary care National Health Service (NHS) setting. A cost comparison analysis was performed over a 2 year time horizon (seven procedures per patient). 177 procedures on rectal cancer patients undergoing WAW with digital proctoscopy between August 2023 and November 2024 were included. The control group, that is, flexible sigmoidoscopy was modelled. The base case was flexible sigmoidoscopy without sedation. Scenarios using sedation were also evaluated. Costs were categorised into fixed and variable costs. A one-way sensitivity analysis, probabilistic sensitivity analysis and What-If scenarios were also performed.

Outcome measures and results

The primary outcome was the minimum cost difference between the two procedures. The secondary outcome measure was the robustness of the cost differences. Over 2 years, the total cost per patient was £768.92 (95% CI £656.6 to £900.7) for digital proctoscopy compared with £1,588.15 (95% CI £1458.1 to £1725.2) for flexible sigmoidoscopy without sedation. The absolute minimum cost saving per patient is £820.23 (95% CI £648.7 to £985.1). Cost savings increased to £848.94 (95% CI £677.20 to £1013.83) to £935.62 (95% CI £761.02 to £1103.08) when sedation was used in flexible sigmoidoscopy procedures. Personnel costs during the procedure and recovery phase were the dominant cost drivers for flexible sigmoidoscopy. Probabilistic sensitivity analysis and What-If scenarios confirmed the robustness of the findings, with flexible sigmoidoscopy remaining more costly.

Conclusion

Digital proctoscopy with the LumenEye device is a cost-saving alternative to flexible sigmoidoscopy for patients with rectal cancer on a WAW protocol. Our findings support the integration of digital proctoscopy into WAW pathways as a cost-efficient alternative within resource-constrained healthcare systems. Endoscopy service pressures are also likely to be alleviated.

Lived experiences, challenges and coping strategies of patients with spinal cord injury using intermittent catheterisation in Riyadh, Saudi Arabia: a qualitative study

Por: Abuzied · Y. · Al-Amer · R. · Abdul Halain · A. · Japar · S.
Objectives

This study explored the lived experiences, challenges and coping strategies of Arab male patients with spinal cord injury (SCI) who rely on intermittent catheterisation (IC) to manage neurogenic bladder.

Design

A descriptive qualitative approach was employed, with data analysed using a phenomenological framework.

Setting

Rehabilitation Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

Participants

Male patients with SCI undergoing rehabilitation and performing IC were included in the study. Although both male and female patients were approached to participate, all eligible female patients declined participation. During the recruitment process, some female patients informally expressed privacy concerns and discomfort related to discussing bladder management issues and genital care, which may have contributed to their decision to decline participation.

Results

10 male participants with SCI were recruited after eligible female patients declined participation. Three main themes, each with associated subthemes, emerged to reflect the participants’ experiences. Theme 1: Frequent use of IC in daily life, comprised four subthemes: (1) frequency of practice, (2) environmental and health-related challenges, (3) privacy during IC and (4) fluid intake and output. Theme 2: Cleanliness and general care included two subthemes: (1) catheter cleaning and (2) incontinence. Theme 3 focused on body image and sexuality. Cultural and social norms, including privacy concerns and sensitivities surrounding intimate care in the local context, played a significant role in shaping participants’ experiences and coping strategies.

Conclusions

IC was associated with challenges affecting multiple aspects of daily life among patients with SCI, including social interactions and body image. Participants described various coping strategies used to manage the physical and psychological demands associated with IC. These experiences appeared to be influenced by cultural considerations, including privacy, modesty and sensitivity surrounding urinary care within the local Saudi context.

Identifying social determinants of health subgroups and their associations with health outcomes in a prospective US adult COVID-19 cohort: an analysis of the INSPIRE registry

Por: Burrola-Mendez · Y. · Lin · E. · Parrish · C. · Hsu · C. · Hill · M. J. · Gottlieb · M. · Rising · K. L. · Wisk · L. E. · Gentile · N. L. · Geyer · R. E. · Weinstein · R. A. · Santangelo · M. · Gatling · K. · Dyal · J. W. · Elmore · J. G. · Rodriguez · R. M. · Watts · P. · Chen · J. · Diao
Objective

To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

Design

Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

Setting

Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and Seattle).

Participants

Adults aged ≥18 years, fluent in English or Spanish, with self-reported acute COVID-19 symptoms and a confirmed positive SARS-CoV-2 test within 42 days before enrolment (9 December 2020 to 12 August 2022), and access to an internet-connected device. Exclusions included incarceration, inability to provide informed consent, lack of confirmed SARS-CoV-2 infection or no internet access. Of 3791 eligible participants with complete baseline data, 2897 (76.4%) completed the 3-month follow-up and 2666 (70.3%) completed the 6-month follow-up; most were aged 18–49 years (74–75%), female (66–67%), white (86.6–87.5%) and non-Hispanic (86.6–87.5%).

Outcome measures

Prespecified primary outcomes were physical and mental health (Patient-Reported Outcomes Measurement Information System (PROMIS)-29 V.2.1 T-scores for depression, anxiety, fatigue, sleep disturbance, pain interference, physical function and social participation), cognitive function (PROMIS Cognitive Function Short Form 8 T-scores) and missed workdays due to illness (binary: >1 week vs ≤1 week, from a single-item survey). All measures were self-reported and collected at baseline, 3 months and 6 months; no changes from protocol.

Results

LCA identified a 4-class model as optimal (lowest Bayesian Information Criterion (BIC) after evaluating 1–7 class models; significant demographic differences (2 p

Conclusions

In this US prospective cohort, SDOH-based subgroups showed persistent disparities in health outcomes post-SARS-CoV-2 infection. Findings highlight the urgent need for intersectional approaches to address systemic inequities in post-COVID-19 recovery.

Trial registration number

NCT04610515.

Randomised multiple centre trial of conservative versus liberal fluid administration for children receiving a kidney transplant (LIMITS): clinical trial protocol

Por: Calder · N. D. M. · Kaloyirou · F. · Griffiths · J. · Brown · R. · Hudson · C. · Sharma · R. · Hardwick · H. · Oni · L. · Callaghan · C. · Stevenson · M. · Shenoy · M. · Reynolds · B. · Marks · S. · Wray · J. · Thomas · H. · Peters · M. J. · Hayes · W.
Introduction

In current practice, fluid volumes administered to children following kidney transplant vary widely. Up to 52% of children experience fluid overload-related complications. Current fluid guidelines are not evidence-based and the optimal amount of fluid for children after transplant is not known. The aim of Randomised multiple centre trial of conservative versus LIberal fluid adMInisTration for children receiving a kidney tranSplant (LIMITS) is to determine whether relative limitation of fluid volume administered to children receiving kidney transplants is superior to liberal fluid volume administration.

Methods and analysis

LIMITS is a pragmatic, open-label, UK-based, multicentre randomised controlled trial, with an internal pilot phase and integrated economic evaluation. A total of 140 children receiving kidney transplants will be randomised to receive either conservative postoperative fluid administration (maximum of 150 mL/m2/hour for no longer than 18 hours, followed by a fixed daily target of maximum 1.5 L/m2/day thereafter) versus the comparator of liberal postoperative fluid administration (fluid volume administered to replace urine output and insensible losses for at least 48 hours with target urine output >2 mL/kg/hour). The primary outcome is mean days at home in the first 30 days after kidney transplant. The primary outcome will be analysed using a mixed linear regression model adjusted for donor type (living vs deceased donor) and participant weight (

Ethics and dissemination

The trial received Health Research Authority approval on 20 August 2025 (REC reference: 25/EE/0161, IRAS project ID: 354370). Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain.

Trial registration number

ISRCTN21516608.

Driving factors and barriers to irrational antibiotic prescribing in Pakistan: a qualitative study of physicians, pharmacists and nurses perspectives in public and private hospitals

Por: Khan · M. E. · Jamil · E. · Abubakar · M. · Javed · A. · Abbas · D. · Nawaz · E. · Atiq · B. · Razi · B. H. · Saeed · A. R. · Rasool · H. · Zubair · M. · Rasool · H. · Khan · S. W. · Shoul · A. · Batool · A. · Khan · M. U. · Ullah · M.
Background

Irrational prescribing is a major global health concern, contributing significantly to increased morbidity, mortality and antimicrobial resistance (AMR). Despite existing knowledge and awareness, irrational antibiotic use remains prevalent among healthcare professionals.

Objectives

This qualitative study aimed to explore the contributing factors to irrational antibiotic prescribing, understand healthcare professionals’ perceptions, identify barriers to rational use and gather suggestions for improving rational antibiotic use.

Study design and participants

A qualitative study using semi-structured interviews was conducted with participants. A total of 60 healthcare professionals (20 physicians, 20 pharmacists and 20 nurses) participated after providing verbal consent.

Methodology

Semi-structured interviews were conducted with healthcare professionals across various clinical settings in Pakistan until data saturation was reached. The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was used to ensure transparent reporting. An inductive thematic analysis approach was employed and themes and subthemes were developed from the data.

Results

The findings revealed a generally good understanding of irrational prescribing. Contributing factors included prescriber-related issues, patient expectations, weak regulatory oversight and underutilisation of pharmacists. Key barriers identified were financial constraints, lack of awareness and insufficient resources. Suggestions for improvement included regular audits, public awareness campaigns, an integrated healthcare system, interprofessional collaboration, drug utilisation reviews, adverse drug reaction reporting, standardising hospital policies and strengthening regulatory frameworks.

Conclusion

This study highlights critical factors and barriers contributing to irrational antibiotic prescribing and presents practical suggestions to improve rational use. Implementing evidence-based approaches, updating clinical guidelines, and promoting awareness among healthcare professionals are essential steps toward improving prescribing practices and combating AMR.

Completeness of the COVID-19 vaccination schedule and associated factors among persons experiencing homelessness in Brazil: a national cross-sectional study

Por: Soares Tenorio de Araujo · J. · Berra · T. Z. · Tartaro · A. F. · Rosa · R. J. · Tavares · R. B. V. · Alves · Y. M. · Pelodan · M. E. P. · Moura · H. S. D. · Ferezin · L. P. · Ramos · A. C. V. · do Nascimento · M. C. · Lima de Freitas · G. · Arcencio · R. A.
Objectives

To analyse the completeness of the COVID-19 vaccination schedule and identify factors associated with vaccine uptake.

Design

Cross-sectional study.

Setting

Data were collected through face-to-face interviews conducted in all 26 Brazilian state capitals and the Federal District between 2022 and 2023, using a sequential sampling approach.

Participants

A total of 1392 individuals aged 18 years or older experiencing homelessness for at least 6 months were included.

Primary and secondary outcome measures

The primary outcome was the completeness of the COVID-19 vaccination schedule (complete vs incomplete), based on self-reported vaccination status. Secondary analyses examined sociodemographic, institutional and behavioural factors associated with vaccine uptake using binary logistic regression.

Results

Completion of the vaccination schedule was positively associated with receiving government aid (OR: 1.58; 95% CI 1.09 to 2.30), visits from street clinic health agents (OR: 3.19; 95% CI 1.95 to 5.36), prior COVID-19 diagnosis (OR: 5.77; 95% CI 3.17 to 11.15), support for mandatory vaccination (OR: 3.76; 95% CI 2.48 to 5.76), trust in vaccine efficacy (OR: 3.92; 95% CI 2.63 to 5.89), seeking information from community sources (OR: 1.91; 95% CI 1.01 to 3.88) and trust in federal authorities (OR: 1.57; 95% CI 1.06 to 2.31).

Conclusions

This study identified structural, social and individual factors associated with complete COVID-19 vaccination among people experiencing homelessness in Brazil. Although overall coverage was substantial, gaps in vaccination completeness persisted. Social support, healthcare outreach and trust in vaccines were associated with higher uptake, highlighting important barriers and facilitators to vaccination in socially vulnerable populations.

Integrating Dental Healthcare into Primary Health Care through an implementation model in two districts of Karnataka in India: An implementation research study protocol

Por: Chilgod · L. · Krishna B M · R. · Raveendran · R. · B Hebbar · P.
Introduction

Despite progress in primary care, access to oral health remains limited in India. Integrating oral health into primary care can improve oral health outcomes for communities, especially in rural areas. This study aims to develop an implementation model for integrating dental healthcare into primary healthcare systems in Chamarajanagar and Mysuru districts of Karnataka.

Methods and analysis

A mixed-methods implementation research approach will be adopted for this study, comprising three phases: formative, pilot and implementation and evaluation.

A mixed-methods study at the district level will be conducted to capture diverse perspectives and characterise inequalities in oral healthcare access and literacy levels across urban, rural and tribal areas. Oral health literacy surveys, facility preparedness checklists and in-depth interviews will be conducted. With a consultative approach involving stakeholders, we ensure their input in the design and pilot the integrated interventions to build a replicable model for integrating dental health services into primary healthcare.

Through this structured approach, the study seeks to improve overall oral health outcomes and achieve sustainable improvements in oral health at both community and system levels.

Ethics and dissemination

This study has been approved by the Institutional Ethics Committee at the Institute of Public Health Bengaluru (IPH/23-24/E/374). Findings will be disseminated through workshops, presentations and publications in peer-reviewed journals.

Comparative efficacy and acceptability of treatment options for depressive disorders in children and adolescents: protocol of a network meta-analysis

Por: Guo · J. · Lu · Z. · Zhang · Y. · Sun · Y. · Kang · Z. · Sun · J. · Zhao · G. · Feng · X. · Yuan · R. · Zhu · Y. · Yu · T. · Yang · Y. · Chen · H. · Yue · W.
Introduction

The incidence of depression among children and adolescents has been increasing in recent years, posing significant challenges to public health and clinical care. A variety of treatments, including pharmacotherapy, psychotherapy and physical interventions, are widely used in clinical practice. However, a comprehensive synthesis of the evidence on the efficacy and acceptability of all these treatment modalities is currently lacking. This study aims to use network meta-analysis (NMA) to compare the efficacy and acceptability of all available treatments for depression in children and adolescents, offering valuable insights to inform clinical decision-making and guide future research in this critical area.

Methods and analysis

We will include randomised controlled trials evaluating active interventions for depressive disorders in children and adolescents. Seven electronic databases (PubMed, Embase, the Cochrane Library, Web of Science, PsycINFO, Scopus and ClinicalTrials.gov) were searched from inception to 2 July 2024 and updated on 2 November 2025. Two of four investigators will independently screen studies, extract data from eligible articles and assess the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome will be the change in depressive symptoms. Secondary outcomes will include acceptability (all-cause discontinuation), response rate, remission rate and overall functioning. Pairwise and Bayesian NMA will be conducted. Small-study effects and publication bias will be assessed. The certainty of the evidence will be evaluated according to the Confidence in Network Meta-Analysis approach.

Ethics and dissemination

As this review involves secondary analysis of previously published studies, ethical approval is not required. The findings will be disseminated through publication in peer-reviewed journals.

PROSPERO registration number

PROSPERO-ID CRD42024557384.

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