Understanding Predictors of Lifelong Initiation and Follow-up Treatment for adolescents and youth living with HIV (UPLIFT): an integrated prospective cohort in Eastern Cape, South Africa

Purpose
Adolescents living with HIV (ALHIV) are a priority population for achieving global HIV prevention and treatment targets but experience poorer outcomes than adults. Long-term follow-up is essential to understand their transition into adulthood. By linking self-reported survey data with routine laboratory records, we established a social science clinical cohort of ALHIV South Africa’s Eastern Cape to explore factors shaping their long-term health and well-being.

Participants
Eligible participants were adolescents who were part of a three-wave quantitative cohort of ALHIV and not living with HIV (2014–2018) and had consented (adolescent and caregiver) to having their self-reported interviews linked with routine health records (n=1563). Adolescents were recruited into the existing three-wave cohort through clinic and community-based methods (97% enrolment, >90% retention over three waves). Between 2019 and 2022, we abstracted laboratory test records from the National Health Laboratory Services database for all eligible participants, with matching based on demographic variables. Individuals with at least one HIV-related record form our ‘lifelong social science cohort’, a total of 956 ALHIV (852 of 1107 ALHIV and 104 of 456 HIV-uninfected).

Findings to date
A total of 32 886 laboratory test records from 2004 to 2023 were matched through three rounds of data extraction, using iteratively refined record-linking searches. Most records were viral load (8864) and CD4 count (6801) results, with a median of 10 (IQR: 7–14) and 8 (IQR: 5–11) tests per matched adolescent, respectively. Overall, 956 of 1563 adolescents (61%) were successfully linked to laboratory data, including 852 of 1107 (77%) ALHIV. Analysis of the matched cohort survey-laboratory data provided several insights. Self-reported antiretroviral therapy adherence was strongly associated with viral suppression, even after adjusting for covariates. The strongest predictors of suppression were not reporting missed doses in the past 3 days, past week and not missing clinic appointments in the past year. Among adolescent girls and young women living with HIV, access to safe and affordable facilities, and kind and respectful staff were associated with a higher likelihood of multiple improved HIV-related outcomes, including viral suppression. Exposure to sexual and intimate partner violence predicted worse viral load outcomes among adolescents.

Future plans
This integrated prospective cohort provides an opportunity to characterise long-term HIV treatment outcomes among ALHIV in Africa. We will investigate how individual, familial, community and healthcare experiences in childhood, and adolescence shape these outcomes. Since the COVID-19 pandemic happened during the period of matched data, we will also investigate the potential effect of the COVID-19 pandemic on adolescent HIV treatment outcomes, with potential subgroup analyses for individuals with available COVID-19-related results.

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Evaluating an intervention to promote access to mental healthcare for low language proficient migrants and refugees across Europe (MentalHealth4All): study protocol for a pretest-post-test cross-national survey study

Background
Migrants and refugees with low language proficiency (LLP) in the dominant language of their host country have a higher risk of suffering from certain mental health disorders compared with non-migrant populations. They are also more likely to experience a lack of access to mental healthcare due to language-related and culture-related barriers. As part of the MentalHealth4All project, a digital multilingual communication and information platform was developed to promote access to mental healthcare for LLP migrants and refugees across Europe. This paper describes the study protocol for evaluating the platform in practice, among both health and/or social care providers (HSCPs) and LLP migrants and refugees.

Methods and analysis
We will conduct a pretest–post-test cross-national survey study to evaluate the platform’s effect evaluation (primary objective) and process evaluation (secondary objective). The primary outcomes (measured at T0, T2 and T3) are four dimensions of access to mental healthcare services: availability, approachability, acceptability and appropriateness of mental healthcare. Secondary outcomes (measured at T2) are: actual usage of the platform (ie, tracking data), perceived ease of use, usefulness of content, comprehensibility of information, attractiveness of content and emotional support. Participants will be recruited from nine European countries: Belgium, Germany, Italy, Lithuania, the Netherlands, Poland, Slovakia, Spain and the UK. Using convenience sampling through professional networks/organisations and key figures, we aim to include at least 52 HSCPs (ie, 6–10 per country) and 260 LLP migrants (ie, 30–35 per country). After completing a pretest questionnaire (T0), participants will be requested to use the platform, and HSCPs will participate in an additional personalised training (T1). Next, participants will fill out a post-test questionnaire (T2) and will be requested to participate in a second post-test questionnaire (T3, about 6–8 weeks after T2) to answer additional questions on their experiences through a brief phone interview (T3 is optional for migrants/refugees).

Ethics and dissemination
For all nine countries, the ethical review board of the participating university (hospital) has assessed and approved the protocol. If successful, the MentalHealth4All platform will be made publicly available to help improve access to mental healthcare services, as well as HSCPs’ cultural competencies in delivering such services, for any LLP migrants and refugees across Europe (and beyond). Findings will also be disseminated through peer-reviewed journals and conferences.

Registration details
The ‘MHealth4All project’ was prospectively registered on Open Science Framework, DOI: 10.17605/OSF.IO/U4XSM.

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Patients experience of self-testing measuring total white cell count and C reactive protein during treatment at home with antibiotics: a qualitative study

Objective
To explore patients’ experiences and preferences of self-testing using white cell count point-of-care test (POCT) and C reactive protein POCT during antibiotic treatment at home.

Setting
A University Hospital in the Region of Zealand (DK).

Participants
10 inpatients treated with antibiotics who were discharged from hospital to continue antibiotic treatment at home. They were trained in the hospital supervised by research personnel before self-testing at home.

Design
An explorative qualitative study using thematic analysis.

Results
The participants considered the self-testing beneficial, mainly due to not having to travel to get a blood test drawn, the rapid test time and the ability to closely monitor their treatment. The participants perceived that self-testing at home would make them feel more in control of their disease and would give them the ability to live a more normal life. Moreover, self-testing at home showed to be feasible for some patients but with barriers to overcome, such as the ability to use technology and cognitive challenges.

Conclusions
Our study showed that self-testing at home was feasible for some patients, provided they received thorough training at the hospital ensuring that participants were able to conduct the self-testing and use the smartphone technology before transitioning to their home. This could help reduce barriers to home self-testing by highlighting its benefits and emphasising the need for adequate patient guidance and support.

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Associations between optimism and mental health in postradiotherapy cancer survivors: a cross-sectional survey study

Objectives
Cancer patients often experience psychological distress, while optimism has been identified as a protective factor. However, the mental health of postradiotherapy cancer survivors and its association with optimism remain largely unexplored. This study assesses the mental health status and optimism levels of postradiotherapy cancer survivors and evaluates their associations.

Design
Cross-sectional survey study.

Participants
114 Hong Kong cancer survivors who (1) were aged 18 years or above and (2) had received radiotherapy for their cancer treatment and finished the radiotherapy within the previous 3 years (2021–2024).

Outcome measures
Mental health was assessed using the Chinese Depression, Anxiety and Stress Scale, and optimism was measured using the Revised Life Orientation Test. Correlation and regression analyses were used to examine the associations between these measures.

Results
Participants reported overall low optimism with mild to moderate depression, anxiety and stress. Strong negative correlations were identified between optimism and depression (r=–0.833, p

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Duration of COVID-19 symptoms in children: a longitudinal study in a Rio de Janeiro favela, Brazil

Objectives
COVID-19 in children is generally of short duration, but some may take longer to recover. This study investigated the time to symptom resolution following SARS-CoV-2 infection among children in a community setting on the outskirts of an urban centre in Brazil.

Design
Prospective cohort study.

Setting
This is a community-based cohort of children living in Manguinhos, a favela in Rio de Janeiro. The cohort was followed through home visits and telephone monitoring of symptoms. The analysis focused on symptomatic children from this cohort with confirmed SARS-CoV-2 infection. Recovery time was defined as the interval between the first date with symptoms and the first date without symptoms following a positive SARS-CoV-2 test.

Participants
A total of 1276 children (boys and girls aged 2–

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Association between left atrial appendage volume and atrial fibrillation recurrence after catheter ablation: a systematic review and meta-analysis

Objectives
To evaluate the association between left atrial appendage volume (LAAV) and atrial fibrillation (AF) recurrence after catheter ablation (CA) and explore the potential mechanism.

Design
Systematic review and meta-analysis.

Data sources
PubMed, EMBASE, Web of Science and Cochrane Library databases were searched systematically from inception through 28 September 2024 to identify relevant studies.

Eligibility criteria
Observational studies that estimated the association between LAAV and AF recurrence.

Data extraction and synthesis
Two independent investigators screened studies for inclusion and extracted data. Statistical heterogeneity was assessed using the Cochrane Q-test and I², with p 50% indicating significant heterogeneity. This study used a random-effects model to account for potential heterogeneity. The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS), Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I tool) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Publication bias was examined through funnel plots and Egger’s test.

Result
Seventeen studies (3078 patients) were included. Meta-analysis of 11 studies suggested that LAAV was significantly associated with the risk of AF recurrence in both univariate (HR 1.06, 95%CI 1.04 to 1.08, p

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Determinants of enrolment rate in 397 clinical trials for healing diabetic foot ulcers: a systematic review

Objectives
Diabetes mellitus (DM) affects over 422 million individuals globally. Diabetic foot ulcers (DFUs) stand out as a challenging complication of DM, affecting up to 34% of individuals with DM. Despite the prevalence of DFUs, clinical trials for DFUs often face slow and insufficient patient recruitment. We aimed to identify key determinants that impact subject recruitment rates in DFU clinical trials.

Design
Systematic review.

Data sources
ClinicalTrials.gov and PubMed were searched to identify DFU clinical studies published from 1 January 1990 to 9 April 2025.

Eligibility criteria
We included English-language publications of clinical trials aimed at healing DFUs that reported enrolment numbers, duration of enrolment and number of study centres.

Data extraction and synthesis
Records were extracted and subjected to two independent rounds of review by five authors (LZ, SP, RN, HL-T, and RK). Data were pooled and analysed using negative binomial regression, Kaplan-Meier methods and Cox proportional hazards models. Study enrolment and site enrolment rates, as well as time to complete study enrolment, were analysed. Between-study heterogeneity was assessed using the likelihood ratio test.

Results
397 trials involving 31 955 participants were included. On average, DFU studies enrolled 4.24 patients per month (median: 1.65). US-based studies had slower recruitment than non-US studies, with a mean enrolment rate of 1.51 patients per site per month (median: 0.58). The average time to complete enrolment was 1.28 years. Studies that employed a higher number of study sites, were conducted outside the USA, studied behavioural or dietary supplement interventions, and began enrolment more recently, were more likely to have a higher enrolment rate. Longer time to complete enrolment was associated with a larger number of study sites, trials involving at least one US site, earlier starting enrolment year, and longer follow-up duration.

Conclusions
These findings have potential practical implications for the design and conduct of future DFU trials.

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Investigating the eye in Down syndrome as a window to Alzheimers disease: the REVEAL protocol – a clinical cross-sectional study

Introduction
There is a need for early, non-invasive and inexpensive biomarkers for Alzheimer’s disease (AD), which could serve as a proxy measure in prevention and intervention trials that might eventually be suitable for mass screening. People with Down syndrome (DS) are the largest patient group whose condition is associated with a genetically determined increased risk of AD. The REVEAL study aims to examine changes in the structure and function of the eye in individuals with DS compared with those with mild cognitive impairment (MCI) and cognitively healthy control (HC) individuals. REVEAL will also explore whether these changes are connected to inflammatory markers previously associated with AD.

Methods and analysis
The protocol describes a cross-sectional, non-interventional, single-centre study recruiting three cohorts, including (1) participants with DS (target n=50; age range, 6–60 years), (2) participants with MCI (target n=50; age range, 50–80 years) and (3) HC participants (target n=50; age range, 50–80 years). The primary research objective is to profile retinal, choroidal and lenticular status using a variety of eye imaging modalities and retinal functional testing to determine potential associations with cognitive status. The REVEAL study will also measure and compare established blood markers for AD and proteomic and transcriptomic marker profiles between DS, MCI and HC groups. Between-group differences will be assessed with an independent sample t-test and 2 tests for normally distributed or binary measures, respectively. Multivariate regression analysis will be used to analyse parameters across all three cohorts. Data collection began in October 2023 and is expected to end in October 2025.

Ethics and dissemination
The study gained a favourable opinion from Health and Social Care Research Ethics Committee A (REC reference 22/NI/0158; approved on 2 December 2022; Amendment 22/0064 Amend 1, 5 April 2023; Amendment 22/0064 Amend 2; 23 May 2024; Amendment 22/0064 Amend 3; 25 June 2024; Amendment 22/0064 Amend 4; 16 January 2025; Amendment 22.0064 Amend 5; 9 May 2025; Amendment 22.0064 Amend 6; 9 June 2025). The study has also been reviewed and approved by the School of Biomedical Sciences Research Ethics Filter Committee within Ulster University. Findings from the REVEAL study will be presented to academic audiences at international conferences and peer-reviewed publications in targeted high-impact journals after data collection and analysis are complete. Dissemination activities will also include presentations at public events.

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Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model

Objective
To predict the level at a specified time and design personalised dosing, we proposed a method (Method 1) for estimating coagulation factor VIII (FVIII) pharmacokinetic (PK) parameters using 4 levels within 48 hours after administering a test dose.

Design
A retrospective study based on virtual populations and real patients.

Setting
A comprehensive hospital in China.

Participants
Virtual populations generated by Monte Carlo simulations and retrospectively collected real patient data.

Methods
PK profiles of FVIII after dosing in the virtual populations were generated from a published population PK model coupled with Monte Carlo simulation. The simulated coagulation factor levels were considered as the reference (Cref). FVIII levels at six sampling points after dosing were estimated with Method 1 and the method proposed by Lisheng Cai (Method 2) and compared with Cref. PK data from three patients with severe haemophilia A were retrospectively collected to further validate the accuracy of the two methods.

Results
In the adult group, the maximum mean deviations for Methods 1 and 2 were 0.43% (±0.35%) and –36.31% (±6.67%), with corresponding maximum root mean square errors (RMSE) of 0.12% and 28.44%, respectively. For the paediatric group, the maximum mean deviations for Methods 1 and 2 were 0.13% (±0.25%) and –34.27% (±6.74%), with maximum RMSEs of 0.05% and 25.33%, respectively. In three actual patients, mean deviations using Method 1 were 0.32%, 1.34% and 0.24%. Mean deviations using Method 2 were 13.37%, –16.86% and 56.66%.

Conclusion
The proposed method for estimating FVIII PK parameters and levels demonstrates high accuracy and has the potential for precision dosing.

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Assessment of social cognition in patients with amyotrophic lateral sclerosis: protocol for a cross-sectional comparative study at Angers University Hospita

Introduction
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting motor neurons. In addition to motor impairments, ALS frequently involves cognitive and behavioural disturbances, including deficits in social cognition, which can impact interpersonal interactions and decision-making. Despite increasing recognition of these impairments, existing assessment tools often rely on static stimuli, limiting their ecological validity.

Methods and analysis
This cross-sectional, single-centre study aims to assess social cognition abilities in patients with ALS compared with healthy controls using a combination of dynamic and static neuropsychological tools. The primary outcome measure will be performance on the Movie for the Assessment of Social Cognition, an ecologically valid test evaluating theory of mind. Secondary outcomes will include emotion recognition (static and dynamic tasks: Ekman Faces and French Emotion Evaluation Test), mood assessments (Hospital Anxiety and Depression Scale) and clinical variables such as disease severity (ALS Functional Rating Scale-Revised), cognitive function (Edinburgh Cognitive and Behavioural Screen, Mini–Mental State Examination) and disease staging (King’s ALS Clinical Staging System). A total of 74 participants (37 patients with ALS and 37 matched healthy controls) will be recruited. Group differences will be analysed using analysis of variance, while regression models will explore associations between social cognitive deficits and clinical markers of ALS progression.

Ethics and dissemination
This study has been approved by the French Ethics Committee (CPP) Ouest I under reference 2020-A01213-36. Data collection and processing comply with French and European data protection regulations (GDPR, Loi Informatique et Libertés). Findings will be disseminated through peer-reviewed journals and scientific conferences and will contribute to improving neuropsychological assessment methods for ALS.

Trial registration number
NCT04406675.

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Effects of febuxostat on heart failure patients with asymptomatic hyperuricaemia: a retrospective cohort study

Objectives
To investigate the effects of uric-acid-lowering therapy with febuxostat in asymptomatic hyperuricaemic patients with heart failure.

Methods
In this retrospective cohort analysis, we included consecutive hospitalised patients with heart failure and concomitant asymptomatic hyperuricaemia in Yangzhong People’s Hospital from 1 April 2018 through 1 April 2022. Febuxostat was used to lower serum uric acid. The primary endpoint was defined as a composite of cardiovascular death, recurrent hospitalisation and emergency room visit for cardiovascular (CV) reasons. Additional endpoints included changes in echocardiography measures, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and 6-minute walk test (6MWT) distance from baseline to the most recent clinic visit. Cox analysis was used to determine HR between febuxostat and the control group after adjustment for age, sex, body mass index, serum creatinine, atrial fibrillation and coronary heart disease and the Kaplan-Meier curve was used to describe survival.

Results
979 patients were included in the final analysis (505 in the febuxostat group vs 474 in the control group). In a follow-up duration of 16±9 months, uric acid was significantly lower in the febuxostat group compared with the control group (p

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Follow-up observation of eye movements in multiple system atrophy and Parkinsons disease: a cohort study

Objectives
We aimed to explore the changes in oculomotor deficiencies during the follow-up of patients with multiple system atrophy (MSA) and Parkinson’s disease (PD), and to investigate the value of dynamic eye movement examination in their differential diagnosis.

Design
This was a cohort study conducted from 2017 to 2023.

Setting
The Movement Disorders Clinic at a tertiary hospital in Beijing, China.

Participants
56 patients with PD and 13 patients with MSA from an initial cohort of over 1100 with parkinsonism were included in the final longitudinal analysis.

Outcome measures
Multisystem evaluations were performed at baseline. Videonystagmography (VNG) was repeated to assess oculomotor dysfunction at baseline and during follow-up. Abnormalities in the fixation and gaze-holding test, without-fixation test, reflexive and memory-guided saccade tests, smooth pursuit test and optokinetic test were qualitatively and quantitatively recorded and statistically analysed.

Results
The median follow-up time of MSA (16 months) was significantly shorter than that of PD (27 months). In MSA, the incidence of abnormalities in fixation and gaze-holding tests (0% vs 30.8%, p=0.030), reflexive saccade tests (46.2% vs 84.6%, p=0.039, with slow saccades increasing from 7.7% to 46.2%, p=0.027) and smooth pursuit tests (38.5% vs 76.9%, p=0.047) increased significantly from baseline to the end of follow-up. In PD, no significant changes were revealed during follow-up.

Conclusions
MSA exhibited more rapid and prominent changes in fixation and gaze-holding tests, reflexive saccades and smooth pursuit tests than PD. Dynamic observation of oculomotor function may aid in the differential diagnosis of Parkinson’s syndrome.

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Efficacy of cashew nut protein immunotherapy: protocol for a single-centre randomised controlled trial in a Polish paediatric population

Introduction
The prevalence of food allergies, particularly IgE-mediated allergies, is rising in developed countries, with cashew nut allergy emerging as a significant public health concern due to its potential for severe anaphylaxis and frequent association with atopic disorders. Cashew nuts are among the most common allergens in Europe and Australia, often involving cosensitisation with pistachios, hazelnuts and other allergens. Diagnosis relies on clinical history, measurement of specific IgE (sIgE) levels, skin prick tests (SPT) and oral food challenges (OFCs). Current management strategies focus on allergen avoidance and emergency interventions, whereas oral immunotherapy (OIT) represents a promising approach to desensitisation. Recent studies, including the NUT CRACKER trial, have reported high desensitisation rates with cashew OIT, although these are associated with a risk of adverse events. This study introduces a novel randomised controlled trial aimed at evaluating the efficacy and safety of cashew immunotherapy in children.

Methods and analysis
This randomised, open-label, parallel-group trial, with a 2:1 allocation ratio, will be conducted at the Department of Paediatric Pneumology and Allergology, Medical University of Warsaw, Poland. Thirty-nine children, aged 4–17 years, with confirmed IgE-mediated cashew allergy via open OFC will be enrolled. Participants in the experimental group will undergo OIT, which involves gradually increasing doses of cashew protein up to a maintenance dose of 1200 mg. The duration of OIT will range from 12 to 60 weeks, depending on individual baseline tolerance. The control group will receive standard management, including strict cashew avoidance and emergency response strategies to accidental exposure, for 1 year.
The primary endpoint is to determine the proportion of participants tolerating a 4043 mg dose of cashew protein at the study’s end in the OIT group compared with the control group. Secondary outcomes include evaluating the safety profile of OIT, assessing changes in laboratory markers such as sIgE and IgG4 levels for cashew and the major cashew allergen Ana o 3, analysing basophil activation test responses and measuring changes in SPT wheal diameter at baseline and study completion.

Ethics and dissemination
The study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/267/2023). Study findings will be published in peer-reviewed journals and presented at international conferences.

Trial registration number
NCT06328504.

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Time to Study Implementation of AI-Generated Discharge Summaries

Discharge summaries are a form of communication between hospital-based and outpatient clinicians. In addition to providing an overview of the hospital course, discharge summaries frequently include information such as abnormal test results, necessary follow-up testing, and medication changes—critical information for ensuring safe continuity of care. Although discharge summaries are a recognized patient safety tool, they are also time-consuming to generate and contribute to the substantial administrative burden placed on clinicians—2 factors strongly associated with the national physician burnout crisis. Enter large language models (LLMs).

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Optimal Data Sources for Studies of Incident Dementia

In JAMA Internal Medicine, Luchsinger et al describe the results of a prespecified secondary analysis of the GRADE clinical trial on cognitive performance. The GRADE trial randomized 3721 patients with type 2 diabetes using metformin at baseline to add either a long-acting insulin, a sulfonylurea, a glucagon-like peptide-1 (GLP-1) agonist, or a dipeptidyl peptidase-4 inhibitor. At 4 years following randomization, cognitive performance was not different between treatment groups across 3 validated cognitive tests. However, worsened glycemic control was associated with modestly lower cognitive test scores. These findings provide important data for clinicians, particularly in light of recent lay press and scientific enthusiasm about GLP-1 agonists for dementia prevention.

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