Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.

This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.

Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.

Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT06100978.

Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.

This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.

Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, ³Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.

This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.

Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.

Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

An estimated population of approximately 3 million individuals residing in Xizang.

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

The estimated basic reproduction number (R₀ ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

The standard treatment for high-grade squamous intraepithelial lesions is excisional involving the uterine cervix, while surveillance is an acceptable approach for low-grade squamous intraepithelial lesions. There is controversy about excisional treatment on pregnancy outcomes. The objective of this study was to determine pregnancy outcomes in women living with and without HIV who underwent excisional treatment for high-grade cervical intraepithelial lesions.

This retrospective cohort study compared the pregnancy outcomes of women with and without HIV who were or were not treated for cervical intraepithelial lesions. A cohort of 488 women with and without HIV infection who did or did not receive excisional treatment for cervical intraepithelial lesions between 2009 and 2022 was enrolled. Adverse pregnancy outcomes (preterm delivery and pregnancy loss) in women with and without HIV, untreated or treated for cervical dysplasia, were recorded and analysed. The significance of the obtained results was judged at the 5% level.

The study was conducted at all Academic Model Providing Access to Healthcare-Kenya satellite sites, which offer cervical cancer screening and treatment for cervical dysplasia in western Kenya. The Moi Teaching and Referral Hospital was also included.

A cohort of 488 women aged between 20 years and 49 years, with and without HIV, diagnosed and treated for high-grade cervical intraepithelial neoplasia, and those followed up for low-grade cervical intraepithelial neoplasia between 2009 and 2022, were included.

The study was interested in adverse pregnancy outcomes, particularly pregnancy loss and preterm delivery following cervical excision treatment for high-grade cervical intraepithelial lesions.

After adjustment for confounding factors, excisional treatment involving the uterine cervix—particularly cold knife conisation—was associated with higher odds of adverse pregnancy outcomes (OR 13.1; 95% CI 1.1 to 137.1; p=0.032). A prior history of adverse pregnancy outcomes was also strongly associated with subsequent adverse outcomes after treatment (OR 37.7; 95% CI 13.8 to 102.7; p

Adverse pregnancy outcomes after excisional treatment of the uterine cervix for high-grade squamous intraepithelial lesions are multifactorial and were associated with cold knife conisation and prior adverse pregnancy outcomes, while maternal HIV infection was not independently associated with adverse outcomes.

To investigate the trajectories of swallowing function recovery and associated influencing factors in adult patients following orotracheal extubation in the intensive care unit (ICU).

Prospective cohort study.

Emergency ICU of a tertiary hospital in Shenyang, China.

A total of 182 adult patients who underwent orotracheal intubation were enrolled between December 2023 and December 2024 using convenience sampling. Among them, 168 patients completed all follow-up assessments, with a loss-to-follow-up rate of 10.1%.

Swallowing function was assessed using the Standardised Swallowing Assessment (SSA) at 2, 4, 6, 8, 24 and 48 hours after extubation. Latent class growth modelling (LCGM) was used to identify distinct swallowing function trajectories. Unordered multinomial logistic regression was performed to examine factors associated with different trajectory classes.

Among the 168 patients who completed all six assessments, no significant differences in baseline characteristics were observed between patients who completed follow-up and those lost to follow-up (all p>0.05). LCGM identified three distinct swallowing function trajectories: a low-risk group (46.1%), characterised by consistently low SSA scores below the dysfunction threshold (26 points); a rapid recovery group (24.6%), in which SSA scores declined to below 26 points within 24 hours after extubation and a high-risk group (29.3%), characterised by persistently elevated SSA scores above 26 points. Multinomial logistic regression analysis showed that age ≤50 years, absence of spinal cord injury or rib fractures, APACHE II score

Distinct trajectories of swallowing function recovery were observed in adult ICU patients after orotracheal extubation. Several clinical factors were associated with more favourable recovery patterns. These findings may help improve the understanding of heterogeneity in postextubation swallowing function and inform future risk stratification and individualised management strategies.

Ethics approval and consent to participate in the trial were approved by the Institutional Research Ethics Committee of General Hospital of Northern Theatre, Shenyang, Liaoning province, PR China (Project Number: Y (2023)232). Written informed consent was obtained from all participants. All procedures were conducted in accordance with relevant guidelines and regulations and the Declaration of Helsinki.

While diabetes prevention programmes (DPPs) effectively reduce the risk of type 2 diabetes, optimising referral to these programmes is challenging. Our prior research (a qualitative study on the pilot of the National Diabetes Prevention Programme (NDPP) and a systematic review) identified a range of barriers and facilitators to referral from healthcare workers’ perspectives. This study aims to gain consensus on the main factors influencing referral to a newly established NDPP and using the Behaviour Change Wheel (BCW) to select behaviour change techniques (BCTs) for an implementation strategy to improve referral to the programme in the future.

A two-round modified online Delphi survey prioritised 17 barriers and facilitators of the referral process, followed by a mapping exercise with the BCW, which guided the identification of techniques to change referral behaviour from general practice.

The survey took place online with healthcare professionals working in the primary care setting in Ireland (April to June 2024). The NDPP was in the pilot phase and was not available in all areas. This study sought to learn from this pilot phase to inform the referral process, which was not yet fully established.

Healthcare professionals eligible to refer or involved in referral to the NDPP in Ireland (general practitioners, practice nurses and dietitians delivering the NDPP) took part in the Delphi survey. Recruitment was through a number of gatekeepers, a health service manager and professional groups who shared invitations to participate with eligible healthcare professionals.

In the Delphi survey round 1, respondents were asked to rate the importance of 17 factors (nine facilitators and eight barriers) influencing referral on a 5-point Likert scale (not important to very high importance) and an open text box captured other suggested important factors. Barriers included limited practical information about the availability of the programme, concerns about workload, competing priorities and concern about patient motivation, the time commitment for patients and referral delays. Facilitators included electronic referral and feedback, promotion of the programme by healthcare professionals and consultation with patients before referral. Consensus was defined as agreement of ≥70% for each factor in the combined categories of high importance/very high importance, low/moderate importance or not important. Factors not reaching consensus after the first round were included in round 2 with any new factors from round 1. Factors that did not reach consensus or reached consensus as not important or of low/moderate importance were excluded. Only factors reaching consensus as being of high importance/very high importance across the two rounds were included in the final prioritised list.

The Delphi survey had 37 responses to round 1 and 23 (62%) responses to round 2. 12 factors reached consensus as being of high/very high importance to improve referral. The 12 factors are mapped to seven intervention functions in the BCW and to nine key BCTs (feedback on the outcome of the behaviour, social support, instruction on how to perform a behaviour, information about the health consequences, information about social and environmental consequences, demonstration of the behaviour, prompts/cues, credible source and restructuring the physical environment). The strategy to improve referrals should include education delivered by educators to referrers, educational materials on the DPP and practical support to facilitate referrals. The health service should continue to provide electronic referrals and electronic prompts to refer could be considered as part of the electronic health record.

This study systematically prioritises factors perceived to influence referral and identifies BCTs to improve referral to an NDPP. The BCTs are a starting point for a strategy to improve referral to DPPs. Further consultation with stakeholders is recommended to discuss the acceptability, feasibility and operationalisation of the BCTs in the Irish setting.

To evaluate the feasibility of conducting a full-scale randomised controlled trial to assess the clinical and cost-effectiveness of the MAINTAIN intervention, designed to support recovery and independence following a fall among people living with dementia.

Pilot cluster randomised controlled trial (c-RCT).

Community-based healthcare services across six UK sites representing primary and secondary care settings.

31 participant-carer dyads were recruited. Eligibility criteria included a diagnosis of dementia and a recent fall. Exclusion criteria included severe comorbidity precluding participation. The consent rate was 84%, and retention at follow-up was 81%.

The MAINTAIN intervention comprised tailored, home-based therapy sessions delivered by trained professionals, focusing on functional recovery, confidence and re-engagement in daily activities, compared with usual care. The intervention was delivered over 12 weeks with booster sessions up to week 24, with the full trial period lasting 28 weeks.

Feasibility outcomes included recruitment and retention rates, intervention adherence and data completeness for outcome and economic measures. Exploratory outcomes assessed functional performance and quality of life. Feasibility outcomes were assessed at baseline, 12 weeks and 28 weeks.

Recruitment occurred over an 8-month period (September 2023–April 2024) across six UK sites. Most intervention participants (89%) attended at least 60% of planned sessions. Completion rates for outcome and economic data were high, indicating strong acceptability and feasibility of both the intervention and trial procedures.

The pilot c-RCT demonstrated that recruitment, retention and intervention delivery were feasible and well accepted. Findings support progression to a definitive trial to evaluate the effectiveness and cost-effectiveness of the MAINTAIN intervention.

ISRCTN16413728 (International Standard Randomised Controlled Trial Number registry).

Young children and children living with HIV are at high risk of progressing to tuberculosis (TB) disease following Mycobacterium tuberculosis (Mtb) exposure and infection, and also of developing severe forms of disease and TB-related mortality. Identifying children who have very early (sub-clinical) TB disease, prior to progression to clinically apparent TB, would mean that TB preventive treatment (TPT) could be more efficiently targeted to this group. Identifying biomarker changes on drug therapy in children with Mtb infection or very early disease could pave the way for the development of tests that can identify which children have viable bacilli and are therefore at increased risk of disease progression.

The INTREPID study will use already collected samples taken from well-phenotyped paediatric cohorts in three clinical studies conducted in South Africa in children Mtb exposure to disease and from children treated for Mtb infection and early TB disease, as well as targeted Mtb antibody analysis. Data on viral co-infections and relevant clinical and epidemiological parameters will be integrated and evaluated to identify the optimal biosignatures that can predict future progression to clinically overt disease in children below 5 years of age, including those living with HIV.

The study protocol received ethical approval from the Stellenbosch University Health Research Ethics Committee (N23/03/025). The study findings will be disseminated through peer-reviewed publications, scientific conferences and formal presentations to healthcare professionals and to local communities, in collaboration with the Desmond Tutu TB Centre Community Advisory Board.

More than 300 million major surgical procedures are carried out under general anaesthesia each year worldwide, and advanced airway management remains one of the leading daily challenges for clinicians. Data from large international prospective cohort studies on adverse events such as cardiovascular collapse, cardiac arrest and severe hypoxaemia during advanced airway management to facilitate anaesthesia are lacking.

The International obServational sTudy on AiRway manaGement in operAting room and non-operaTing room anaEsthesia (STARGATE) study will be an international prospective observational cohort study describing the incidence of major adverse events associated with advanced airway management (tracheal intubation or supraglottic airway device placement) for general anaesthesia in the operating and non-operating room for surgery and medical procedures. The secondary aim will be to describe the practice of airway management in a large international cohort. Critically ill patients will be excluded from this study. Data on patients’ characteristics, type of procedure and the adopted airway management strategy, post-procedure adverse events, operator characteristics and in-hospital mortality will be prospectively collected. The study aims to enrol 10 500 patients.

The study has been approved by the Ethics Committee of the coordinating centre (Comitato Etico Interaziendale AOU San Luigi Gonzaga, N° 25/2023). Each of the participating centres will then seek approval of their local Ethics Committee before enrolment. Data will be disseminated to the scientific community by original articles submitted to international peer-reviewed journals.

NCT05759299.

Involuntary sterilisation, the non-consensual medical control of an individual’s fertility, is recognised by the WHO, United Nations High Commissioner for Refugees and UN Women as a serious human rights violation and form of gender-based violence. Survivors of involuntary sterilisation who can prove they were sterilised in their countries of origin have a legal path to asylum in the USA. This study aims to describe the experiences of women seeking asylum in the USA who were subjected to involuntary sterilisation in their countries of origin.

Semistructured, first-person interviews.

A New York City-based medical human rights programme.

14 adult women who experienced involuntary sterilisation at an average age of 27 years old in their countries of origin (79% from Honduras, 14% from Guatemala, 7% from Mexico) before applying for protected immigration status in the USA.

Inductive qualitative analysis identified common themes across participants including shared experiences of discrimination due to race/ethnicity, exposure to lifelong violence in women’s home countries, involuntary sterilisation during antepartum and intrapartum care, lack of informed consent, psychological symptoms, delayed discovery, an appreciation for more responsive healthcare in the USA and a desire to have additional children. Of note, only 43% of participants were aware that they had been sterilised and were therefore eligible for asylum when they entered the USA. 71% of participants had been granted protected status in the USA at the time of interview; 29% were engaged in the asylum process.

The results of the study can inform clinicians about the impact of involuntary sterilisation, heighten awareness of this violation in the context of gender-based violence as a nexus for asylum and advance advocacy in healthcare and policy. Results suggest women would benefit from more comprehensive screening for involuntary sterilisation before and during the asylum process, as well as culturally-responsive and trauma-informed support.