This real-world study investigated the changes of lipid lowering therapy (LLT) usage in patients with high or very high cardiovascular (CV) risk in the UK and the group of all other European countries in the SANTORINI study up to 1 year from baseline and the impact this treatment had on the attainment of low-density lipoprotein cholesterol (LDL-C) risk-adjusted goals set by the National Institute for Health and Care Excellence (NICE) and those in the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines.

Secondary analysis of the SANTORINI dataset (an international, prospective, observational, non-interventional study (NCT04271280)).

Primary and secondary care centres in the UK and the group of other European countries (Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden and Switzerland).

663 UK patients with high and very high CV risk were included in this analysis and 8502 from the group of other European countries. Of these, 380 UK patients and 6830 from the group of other European countries had LDL-C information available at baseline and 1-year follow-up.

The primary objectives were to describe patients’ lipid management, LDL-C levels at 1-year follow-up and their attainment of 2023 NICE (≤2.0 mmol/L) and 2019 ESC/EAS LDL-C 2019 guideline-recommended LDL-C goals (

Over the course of 1-year follow-up, the overall proportion of UK patients on no LLT reduced from 20.4% at baseline to 7.1%, similar to that observed in the group of other European countries (baseline–20.9%, 1 year–3.0%). The proportion of UK patients receiving LLT monotherapy increased from 74.8% at baseline to 84.9%, higher at both time points than that observed for the group of other European countries (baseline: 52.0%, 1 year: 55.0%). The use of any combination therapy increased slightly from baseline to 1 year in the UK overall cohort (4.9% vs 7.1%) and overall in the group of all other European countries, the cohort increased from baseline (27.1%) to 1 year (40.2%). Overall, mean (SD) LDL-C levels in the UK were 2.5 (1.2) mmol/L at baseline and 2.1 (1.0) mmol/L at 1 year and for the group of other European countries were 2.4 (1.2) mmol/L at baseline and 2.0 (0.9) mmol/L at 1 year. The overall proportions of UK patients achieving the UK NICE treatment goal and ESC/EAS 2019 guidelines at baseline versus 1-year follow-up were 40.3% vs 52.6% and 22.9% vs 32.9%, respectively; 21.1% and 30.9% of patients in the group of other European countries achieved the ESC/EAS 2019 guidelines at baseline and 1-year follow-up, respectively.

In this UK-focused analysis of the SANTORINI study, use of LLT increased modestly over 1 year, accompanied by a reduction in average LDL-C levels. However, mean LDL-C remained above the NICE goal, and attainment of both NICE and ESC/EAS LDL-C thresholds remained suboptimal. The findings highlight continued opportunities to optimise lipid management in UK clinical practice, including the potential for broader use of combination therapies.

Inadequate emergence is a common postoperative complication in elderly patients following major abdominal surgery. This study was designed to determine its incidence, identify associated risk factors and characterise its clinical subtypes within this high-risk cohort.

This prospective single-centre cohort study was conducted at a comprehensive specialised tertiary care hospital in Northwest Ethiopia. Consecutive patients aged 65 years and older scheduled for elective major abdominal surgery under general anaesthesia were enrolled.

The primary outcome was the proportion of patients experiencing inadequate emergence.

A total of 388 patients were analysed. Inadequate emergence occurred in 21.9% of participants (95% CI 14.3% to 31.6%), with hypoactive emergence observed in 10.7% and emergence delirium in 11.2%. Multivariable logistic regression identified several independent predictors, including advanced age (adjusted OR (AOR)=1.9; 95% CI 1.5 to 8.2), preoperative anxiety (AOR=2.7; 95% CI 1.2 to 7.2), prolonged preoperative fasting (AOR=2.1; 95% CI 1.8 to 9.1), non-ketofol-based induction (AOR=3.4; 95% CI 1.6 to 6.3), absence of abdominal field block (AOR=4.2; 95% CI 4.0 to 9.6), substantial intraoperative blood loss (>1000 mL; AOR=1.9; 95% CI 1.2 to 7.6), postoperative nausea and vomiting requiring antiemetics (AOR=2.2; 95% CI 2.1 to 7.1) and presence of an indwelling urinary catheter (AOR=2.4; 95% CI 1.8 to 7.9).

Inadequate emergence occurred in approximately one in five elderly patients undergoing elective major abdominal surgery. Independent predictors included advanced age, major intraoperative blood loss, postoperative nausea/vomiting requiring antiemetics, non-ketofol-based induction, preoperative anxiety, absence of abdominal field block, presence of an indwelling urinary catheter and prolonged preoperative fasting.

Maternal human milk feedings continue an offspring’s exposure to the programming stimuli of maternal metabolism during the postnatal period. While considerable research focuses on associations between in utero environments and offspring metabolic disease, few studies have been able to specifically measure how human milk composition modifies programming of children’s growth in conjunction with comprehensive measures of maternal glycaemia during pregnancy.

The Glycemia Range and Offspring Weight and adiposity in response To Human milk (GROWTH) Study is a longitudinal cohort enrolling women with a singleton pregnancy who (1) undergo serial testing of glycaemia during pregnancy and (2) are intending to provide their breast milk through direct breastfeeding or pumped milk as the primary nutrition for their infant. Enrolment started in October 2023 and is expected to be completed in December 2026. Key procedures include virtual lactation support visits, serial human milk sampling at three time points, maternal and infant blood sampling, serial maternal and child anthropometric measurements and diet assessment. After delivery, mother–child dyads are followed until children turn 2 years of age. The primary exposure variable is maternal glycaemia obtained from a fasting, 3 hour 100 g oral glucose tolerance test performed at 24–28 weeks of gestation, and the primary outcome measure is the composite of human milk linoleic and docosahexaenoic acid concentrations in milk samples collected at 1 month postpartum.

Lurie Children’s Hospital Institutional Review Board (IRB) provides central oversight of the GROWTH Study in conjunction with each participating centre’s IRB. The GROWTH Study data has the potential to inform perinatal health and future research in lactation and human milk science by providing comprehensive measures of human milk composition and early childhood growth and body composition parameters impacted by maternal metabolism in pregnancy.

To test a theory-informed, person-centred rehabilitation intervention for older adults following a hospital admission complicated by delirium, developed in line with the Medical Research Council framework for complex interventions, to determine whether: (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible.

Multicentre, single-arm feasibility study.

19 patient (aged >65 years old) and carer pairs were recruited from six National Health Service acute hospitals across the UK.

Home-based rehabilitation programme designed to support recovery after hospital discharge, addressing cognitive, physical, physiological and psychosocial needs. Delivered by a trained team of occupational therapists, physiotherapists and rehabilitation support workers, the intervention included a comprehensive home assessment, collaborative goal setting, up to 10 personalised sessions over 12 weeks and the use of a recovery record to guide progress, education and psychosocial support.

Examined aspects of feasibility including eligibility, recruitment, data collection, attrition, acceptability of the rehabilitation intervention and potential to calculate cost-effectiveness.

In total, 419 patients were identified as having delirium and 36 met the full eligibility. 19 patient and carer pairs agreed to participate in the study (consent rate 53%; 95% CI 35% to 70%) with 13 participants going on to start the intervention (68%; 95% CI 43% to 87%) and 10 participants completing final follow-up (53%; 95% CI 29% to 76%). Baseline assessments were conducted either during hospitalisation or postdischarge, with initial assessments occurring a mean of 18 days (SD=13.0) postdischarge, and 77% completed within 14 days. Participants completed a mean of eight sessions (SD=2.9). 19 participants completed the primary outcome at baseline, while 10 participants completed it at 6-month follow-up. The economic evaluation indicated a total cost of £1249.29 per participant, covering assessments, intervention sessions and training costs.

The intervention showed feasibility among older adults recovering from delirium, as evidenced by the trial processes for participants who entered the study. However, recruitment challenges indicate a need for better strategies and further research through a definitive randomised controlled trial to demonstrate the effectiveness and cost-effectiveness of the intervention.

ISRCTN15676570

People living with HIV (PLHIV) frequently face psychological challenges, including stigma, stress and social isolation, which can negatively affect adherence to antiretroviral therapy (ART). Even in high-income countries where treatment is accessible, poor adherence can lead to drug resistance, reduced immune function and early morbidity. This systematic review aims to synthesise evidence on the relationship between psychological and mental health factors and ART adherence among PLHIV in high-income settings.

We will include studies published in any language between January 2015 and the date of the last searches. Reports of studies published in languages other than English, and which appear to be eligible for inclusion after the first level of screening, will be translated using Google Translate.

Studies will be included if they continue to meet the inclusion criteria and the quality of the translation is sufficient to extract the relevant data. PLHIV aged ≥15 years receiving ART in high-income countries. The studies to be included must assess psychological or mental health variables and ART adherence. Peer-reviewed journal articles will be the primary source of evidence. Grey literature identified from reference lists of key articles or using Google Advanced search techniques will be included. Searches for published studies will be done in OVID Medline, PsycINFO and Embase. Cochrane CENTRAL will be used to identify clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform.

Two independent reviewers will assess study quality and risk of bias using the Newcastle-Ottawa Scale, National Institutes of Health (NIH) Quality Assessment Tool and Jadad Scale. Discrepancies will be resolved by a third reviewer. Synthesis of quantitative data will be primarily descriptive. Predictors that have been examined in three or more studies will be reported in detail while those assessed in fewer studies will be presented concisely.

This study will be a review of the literature and will not involve primary collection of patients’ data. We will include amendments to the protocol in the final review. The final study will be published in a peer-reviewed journal and presented at conferences. The results of this systematic review will inform clinical practice, guide future research and support policy development that minimise mental health barriers to ART adherence.

CRD420251102248.

Data on long-term outcomes after surgical repair of pulmonary valve stenosis are limited. This study evaluated survival, clinical outcomes and quality of life (QoL) after surgery during childhood.

Single centre, longitudinal cohort study evaluating consecutive patients with pulmonary valve stenosis who underwent surgical repair between 1968–1980 and were evaluated every decade since 1990.

Of the original cohort of 89 operated patients, 11 died (12%), including 2 who died within 30 days postsurgery (2%), and 7 (8%) were lost to follow-up. Survival at 50 years follow-up was 87%, which was not significantly different from the GDP. Of the remaining 71 survivors, 32 refrained earlier from participating in this cohort study, leaving 39 eligible, of whom 34 (87%) participated again (50% male, median age 48 years) with a median follow-up of 45 (range 40–52) years. Event-free survival was 50%, with supraventricular tachycardia (14%) and reintervention (13%) being the most frequent events, although less frequently in the last 10 years. At last follow-up, biventricular function was preserved in most patients. Reduced right and left ventricular ejection fraction (EF) was found in 33% and 13%, respectively. Exercise capacity and maximum rate of oxygen consumption were mildly impaired in 14% and 32% of patients. Patients who underwent an infundibulectomy during initial surgery were significantly more likely to undergo reintervention (HR=8.32, p=0.003). Patient-reported QoL scores remained stable over time and consistently exceeded those of the age-matched GDP.

Fifty-year survival after surgery for pulmonary valve stenosis was excellent and comparable to the GDP. Most patients maintained preserved ventricular function, functional capacity and excellent QoL. Routine lifelong follow-up may not be necessary for all patients, but should be considered for those who underwent an infundibulectomy or have residual lesions.

Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy.

This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers.

The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences.

NCT06885736.

Irritability represents one of the most common causes of referral to child and adolescent mental health services. Conceptually, tonic irritability (i.e., persistent grumpy mood) can be distinguished from phasic irritability (i.e., temper outbursts). The objective of this research project is to develop a fine-grained, ecologically valid and multimodal characterisation of tonic and phasic irritability to better understand the differential role of the two components in developmental psychopathology.

The study has a longitudinal observational and experimental design and involves two sites: (a) the Division of Child and Adolescent Psychiatry at the University Hospital of Lausanne and (b) the Division of Youth Mental Health at the Faculty of Psychology at the University of Basel. 220 help-seeking and healthy youths aged 8–14 years and their families will participate in the study consisting of a baseline assessment (i.e., self-report, interviews, cognitive assessments, autonomic measures, as well as in-situ experiments), an ecological momentary assessment (EMA) phase (over 2 weeks, including experience sampling method, cognitive assessment and passive monitoring) and a 1-year follow-up. Statistical analyses will include multilevel regression (e.g., linear mixed modelling).

We obtained ethical approval from the local ethics committees (Cantonal Research Ethics Commission on Human Beings, CER-VD, #2023-01846) and data collection began in January 2025. The results of the present study will be published in peer-reviewed scientific journals and will be presented at key conferences in the field of child and adolescent mental health, as well as at conferences focusing on EMA. Additionally, findings will be disseminated to practitioners, the educational sector and associations working with youths. We further intend to make the findings accessible to the general public through social media, for instance.

Tuberculosis (TB) remains a major global health challenge, with an estimated 10.8 million new cases and 1.25 million deaths in 2023. Despite advances in molecular detection of Mycobacterium TB (MTB), significant diagnostic gaps remain: in 2023, only 48% of newly diagnosed TB cases received rapid diagnostic testing, far below the 100% target. These challenges are intensified in high-burden settings, where sputum collection and distinguishing TB from other illnesses are difficult. The Xpert MTB Host Response (Xpert-HR) assay measures host immune gene expression from blood, shows promise but variable accuracy across studies. Hence, this study will perform an Individual Patient Data Meta-Analysis (IPDMA) to evaluate the diagnostic accuracy, subgroup performance, predictive values and clinical benefit of Xpert-HR compared with conventional sputum-based testing.

This systematic review and IPDMA will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Diagnostic Test Accuracy guidelines. Prospective studies including adolescents (>12 years) or adults with presumed TB tested using the Xpert MTB Host-Response assay will be identified through PubMed, Embase and Web of Science. Study quality will be assessed using an adapted diagnostic accuracy tool. Diagnostic accuracy will be pooled using random-effects models, with subgroup analyses where applicable. Decision curve analysis will evaluate clinical utility. Predictive values will be estimated across TB prevalences of 1-10%. Both one-stage and two-stage IPDMA approaches will be explored, and the proportion of unevaluable samples will be reported.

The review will be based on deidentified individual patient data to be obtained upon request from the corresponding authors of studies fulfilling all the data sharing agreement. Ethical approval has been obtained from the Ethical Committee of the Medical Faculty of Heidelberg University (Approval No. S-043/2026). The results will be disseminated through publication in a peer-reviewed journal, and through presentations at academic conferences.

CRD420251071857.

Chronic central serous chorioretinopathy (CSC) can cause progressive and permanent vision loss. Although photodynamic therapy (PDT) is a primary treatment option globally, it is not approved for CSC worldwide, limiting therapeutic access. The REPLAY trial is a phase III, investigator-initiated trial to evaluate the efficacy and safety of reduced-fluence PDT (rf-PDT) for chronic CSC to seek the first regulatory approval globally.

This study comprises two cohorts. The ‘untreated cohort’ is a multicentre, randomised, placebo-controlled, double-masked trial involving 60 patients with untreated, fovea-involving chronic CSC, randomised 2:1 to receive a single rf-PDT or placebo treatment. The ‘previously treated cohort’ is a single-arm, open-label trial for up to 10 patients with recurrent CSC after PDT. The primary endpoint for both cohorts is the proportion of eyes with a complete resolution of subfoveal fluid at 12 weeks post-treatment, assessed by optical coherence tomography. Secondary endpoints include changes in best-corrected visual acuity, central choroidal thickness, recurrence rates and incidence of adverse events over a 48 week follow-up.

The study protocol was approved by the Kyoto University Hospital Institutional Review Board, IRB of Chiba University Hospital, Tokyo Women’s Medical University Institutional Review Board and Institutional Review Board of Kansai Medical University Hospital. Written informed consent is obtained from all participants. The results will be disseminated through publication in a peer-reviewed journal and presentations at scientific conferences.

jRCT2051230156 (URL: https://jrct.mhlw.go.jp/latest-detail/jRCT2051230156).

To examine HIV care attrition patterns and risk factors among adolescent girls and young women (AGYW) enrolled in prevention of mother-to-child transmission of HIV (PMTCT) services in Tanzania.

Prospective cohort study.

The study was conducted in three regions of Tanzania: Kagera, Tabora and Dar es Salaam across 543 public and private health facilities.

A total of 10 147 pregnant and postpartum AGYW living with HIV attending PMTCT services between 1 January 2018 and 31 December 2020 were included in this study and followed prospectively until they were censored at the last appointment date or 31 December 2023, whichever was earlier.

The primary outcome was time to HIV care attrition, defined as death, discontinuation of antiretroviral treatment (ART) or loss to follow-up (LTFU). LTFU was defined as failure to attend a scheduled clinic appointment and being absent from care for ≥90 consecutive days following a missed appointment among non-transfers. Kaplan-Meier analyses were used to estimate time to first attrition. The Anderson-Gill proportional hazard model estimated the risk factors for repeated care interruptions, adjusted for baseline characteristics and stratified by ART status at PMTCT enrolment.

A total of 3259 attrition events were observed, of which 79% occurred within the first year, with the median time to first attrition of 4 months (IQR: 1–8), 96.3% were due to LTFU. Over two-thirds of first-year attrition occurred among AGYW newly started on ART at PMTCT enrolment, who had more than twice the attrition rate of those already on ART (28.6 vs 11.2 per 100-person-years). Of AGYW lost to follow-up, 44.8% returned to care and 20.9% experienced subsequent attrition. Among AGYW new on ART, attrition was higher in those enrolled late in their third trimester (adjusted HR (aHR) 1.20; 95% CI 1.01 to 1.42) versus those in the first trimester and lower during the postpartum period (aHR 0.58; 95% CI 0.43 to 0.79). In AGYW already on ART, attrition rate was higher among adolescents 18–19 years (aHR 1.37; 95% CI 1.13 to 1.66) and those enrolled late; during the second (aHR 1.41; 95% CI 1.16 to 1.72) and third trimesters (aHR 1.57; 95% CI 1.23 to 2.00) or post partum (aHR 1.36; 95% CI 1.09 to 1.70) compared with the first trimester. AGYW with early-stage HIV, on second-line regimens and attending facilities with fewer AGYW, had a lower attrition rate in contrast to comparison groups.

AGYW newly started on ART at PMTCT enrolment are more likely to have early and recurring dropout. Given the cyclical nature of HIV care engagement, tailored and repeated interventions are needed to support continuous retention and re-engagement for pregnant and postpartum AGYW with HIV.