Postoperative pain is common, with approximately one-third of surgical patients experiencing severe acute pain and 10–20% developing chronic post-surgical pain (CPSP). Evidence shows that female patients are at higher risk of pain after sex non-specific surgery, thus sex- or gender-specific differences in pain treatment efficacy with potential consequences for perioperative pain management are to be expected. Considering the clinical and societal burden of poorly managed postoperative pain, the GEPard project comprises two systematic reviews, GEPard 1: sex- and/or gender-specific differences in efficacy of perioperative pain management for certain (major) surgical procedures in adult patients; and GEPard 2: sex- and/or gender-specific differences in the dosing, efficacy and adverse effects of the most common systemic perioperative non-opioid- and co-analgesics across all sex non-specific surgical procedures in adult patients.

The reviews will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook. MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov and PsycINFO will be searched. We will include randomised controlled trials (RCTs) and systematic reviews/meta-analyses reporting outcomes disaggregated by sex and/or gender in adult surgical patients. For GEPard 1, this applies to selected major surgical procedures; for GEPard 2, to all non-sex-specific surgical procedures. Interventions include regional anaesthesia, systemic analgesics and psychological strategies for GEPard 1 and non-opioid- as well as co-analgesics for GEPard 2. Two reviewers will independently screen and extract the data. Cochrane Risk of Bias Tool 2.0 (RoB 2) and AMSTAR 2 tools will assess study quality. Random-effects or Bayesian meta-analyses will be performed where possible; otherwise, narrative synthesis will be applied. GRADE methodology will assess evidence certainty.

No ethical approval is required for these reviews. Findings will be disseminated via peer-reviewed publications, patient organisations and professional societies. Data will be shared via Zenodo or Open Science Framework (OSF), following FAIR principles.

The systematic review protocols for both reviews have been registered in PROSPERO on 29 August 2025 (Registration-ID: CRD420251121393 (GEPard1), CRD420251121536 (GEPard2).

The importance of conducting qualitative research alongside clinical trials of complex healthcare interventions is well established. There are various ways in which these two methodologies can be combined in mixed-methods research, including integrating data and/or results from the qualitative and quantitative strands during analysis, using techniques such as joint displays. The potential benefits of integration during data analysis include understanding intervention mechanisms, reasons for variation in outcomes, ways of tailoring interventions to individuals and barriers and facilitators to implementation. However, integration during data analysis may rarely be undertaken in practice, and the extent to which integration can provide valuable insights appears to be underappreciated in the field.

In this review, we aim to summarise current methods of integrating qualitative and quantitative raw data and/or results during analysis in clinical trials of complex healthcare interventions, and the yield of these different methods. Our specific research questions focus on (1) which integration techniques are used; (2) whether the results meet the study authors’ aims and/or answer their research questions; (3) the insights obtained and/or meta-inferences generated from these techniques (classified as either global or specific, and as relational, predictive, causal, comparative or elaborative); (4) any relationship between these insights and/or meta-inferences and the integration technique used and (5) the quality of these studies.

We will systematically search MEDLINE, Embase, PsycINFO, CENTRAL, CINAHL, Scopus and Web of Science, and manually search reference lists. We will include studies if they integrate, during data analysis, raw data and/or results from a clinical (randomised, non-randomised or single-arm) trial and an embedded or subsequent associated qualitative study of a complex, non-pharmaceutical healthcare intervention (where the effects on a health outcome were measured). Two independent reviewers will screen titles, abstracts and full texts and perform data extraction. We will develop a descriptive account of the data, including mapping the key characteristics of included studies and narratively reporting our findings in relation to each of our research questions. We will explore how integration was undertaken, what insights were obtained and/or meta-inferences generated, and whether and how these relate to the type of integration technique used.

This study does not require ethical approval. We intend to publish our findings in a peer-reviewed open-access journal and to present our findings at national and/or international conferences.

This protocol was registered with Open Science Framework on 22 October 2025 (ref osf.io/yxtb9).

Rheumatoid arthritis (RA) is a heterogeneous disease, which current treatment guidelines insufficiently accommodate, as they predominantly emphasise the suppression of disease activity. However, a step towards personalised medicine is preferred to further optimise treatment and requires homogeneous subgroups with similarities in pathophysiological mechanisms and treatment responses. Prior research has already demonstrated notable differences in the pathophysiology of patients with autoantibody-positive and autoantibody-negative RA, as well as differences in treatment responses, which may serve as a strong basis for personalised medicine. Additionally, there is evidence suggesting that an early treatment response is indicative of future courses. Based on these findings, we designed a personalised medicine trial in RA that compares the effectiveness and cost-effectiveness of a tailor-made approach with routine care.

The PeRsonalIsed Medicine in RA (PRIMERA) trial is a multicentre, open-label, randomised controlled trial that includes 300 adult patients with newly diagnosed, DMARD-naïve RA, according to 2010 American College of Rheumatology/EULAR criteria. Patients are randomised into either routine care or a tailor-made approach. Both management approaches use a treat-to-target strategy, aiming for low disease activity (LDA, Disease Activity Score using 44 joints (DAS) ≤2.4). In routine care, initial treatment consists of methotrexate along with a single intramuscular dose of glucocorticoids (GCs) and treatment can be intensified after 3, 7 and 10 months if LDA is not reached. Conversely, initial treatment in the tailor-made approach depends on the presence of autoantibodies, with patients with autoantibody-positive and autoantibody-negative RA starting with hydroxychloroquine or methotrexate together with a single intramuscular dose of GCs, respectively. Medication intensifications will be allowed at months 1, 3, 4, 7 and 10. Intensifications at months 1 and 4 depend on whether patients have an early sufficient response to GCs and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively. The tailor-made approach is superior to routine care if no more biological DMARDs (bDMARDs) or tsDMARDs are used after 10 months of treatment, while the mean DAS over time is lower. Our primary outcome is the proportional difference in bDMARD or tsDMARD usage after 10 months of treatment between routine care and the tailor-made approach. Secondary outcomes are DAS over time, time to achieve LDA, cost-effectiveness and patient-reported outcome measurements over time.

Ethical approval has been granted by Erasmus MC Medical Ethics Review Committee (MEC-2020-0825). The results will be disseminated through peer-review journals and medical congresses.

ISRCTN16170070.

The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

NCT06042621.

Health literacy (HL) is essential for making informed health-related decisions, for example enabling parents to reduce their child’s allergy risk. Health literacy does not, however, rely solely on an individual’s capacities, but is strongly influenced by external factors. Midwives provide important health advice to families, particularly since their relationship is close during a time of significant transition. This offers them a unique opportunity to positively influence the HL of parents, which in turn may support the health and well-being of the whole family. The aim of this study is to develop and evaluate an intervention that can support midwives in providing allergy prevention advice in a way that is in line with the concept of HL.

In accordance with the recommendations of the Medical Research Council framework in the first phase of this study, we will survey midwives (target sample size=379) in Germany regarding their practices, the potential barriers they face and enabling factors in providing advice on early childhood allergy prevention in an HL-responsive way. The data will be subjected to descriptive statistical analysis. Two co-design workshops will then be conducted with various stakeholders in two regions (Rhineland-Palatinate and Saxony) of Germany. Following the protocol proposed by the Stanford Design Thinking School, we will use design thinking to collect ideas for the intervention. Based on these ideas and our previous qualitative and quantitative study, we will develop an intervention in collaboration with didactic experts. The intervention will be piloted in three groups (midwives=10–15, midwives working as practice supervisors=5–10, students of midwifery=10–20). For the process evaluation, we will use observation protocols of the intervention conduct and qualitative interviews. For the outcome evaluation, we will use a questionnaire and observations in simulation laboratories with students of midwifery.

This study protocol was approved by the Ethics Committee of the University of Regensburg (ID 23-3441-101) and is in compliance with the Declaration of Helsinki. Participation in the study will only be possible after informed consent has been given. Our results will be presented at national and international conferences and published in scientific journals. Additionally, once it has been finalised, we will make the intervention available to educational institutions for (future) midwives.

Research for pandemic response needs to be timely to inform evidence-based decision making. The lack of epidemiological data at the start of the COVID-19 pandemic led experts to call for cohorts that could rapidly supply data about newly emerging infectious diseases. The ‘Bern, get ready’ (BEready) study aims to establish a prospective ‘pandemic preparedness cohort’ in the canton of Bern, Switzerland. This cohort can be pivoted to the needs of a new pandemic pathogen. The aim of this pilot study was to investigate the potential response and to test the feasibility of procedures for BEready.

Closed population-based cohort study.

Random sample of private households in the canton of Bern, Switzerland, that had previously responded to an online survey.

Adults, children and pets.

Enrolment as a percentage, associations between the agreement to participate and the demographic and socioeconomic variables of the invited household member, number of social contacts, proportion of samples collected, proportion of complete questionnaires and proportion of participants responding after 12 months.

After the initial in-person visit with venous blood sampling, participants were followed up for 1 year. We tested remote data collection methods, with online questionnaires and self-collected capillary blood and nasopharyngeal samples, and established a biobank.

The pilot study enrolled 106/1138 (9%) of invited households plus two additional households that had proactively contacted us. In total, we enrolled 193 people in 108 households (1.8 per household) and 44 pets between April and September 2023. We obtained and stored at least one venous and/or capillary baseline blood sample from 184/193 (95%) people and 40/44 (91%) pets. After 1 year, 172/193 (89%) people in 101/108 (94%) of households completed a follow-up survey, as did 22 owners of 34/44 (77%) pets. 151/172 (88%) respondents returned a follow-up capillary blood sample.

The response rate to the pilot study shows that obtaining high levels of participant enrolment in a pandemic preparedness cohort study is challenging. Data collection without face-to-face contact with a study team is feasible for household members and will be needed in BEready if control measures during a pandemic prevent in-person studies.

This study aimed to assess construct validity against commonly used patient-reported outcome measures (PROMs), test–retest reliability and responsiveness of seven Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CATs) in Dutch adults with type 2 diabetes (T2D), and assess their acceptability in healthcare providers and people with T2D.

A cross-sectional observational study in people with T2D and qualitative study involving both people with T2D and healthcare professionals.

Participants with T2D were recruited from the ongoing Hoorn Diabetes Care System cohort in the West-Friesland area of the Netherlands. Additionally, people with T2D and advanced chronic kidney disease were recruited at the outpatient clinics of Amsterdam University Medical Centre and ‘Niercentrum aan de Amstel’, both in the Amsterdam area of the Netherlands. The healthcare professionals involved in the qualitative part were recruited at the Amsterdam University Medical Centre.

314 people with T2D (age 64.0±10.8 years, 63.7% men).

Participants completed seven PROMIS CATs (assessing (1) Physical Function, (2) Pain Interference, (3) Fatigue, (4) Sleep Disturbance, (5) Anxiety, (6) Depression and (7) Ability to Participate in Social Roles and Activities), and PROMs measuring similar constructs. After 2 weeks and 6 months, participants completed the CATs measures again, together with seven Global Rating Scales (GRS) on perceived change in each domain. Construct validity was assessed using Pearson’s correlations. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC). Measurement error was assessed by the standard error of measurement (SEM) and minimal detectable change (MDC). Responsiveness was assessed by correlations between change scores on the PROMIS CAT and GRS. Acceptability was assessed through focus groups and interviews in healthcare providers and people with T2D.

Except for Fatigue, all PROMIS CAT domains demonstrated sufficient construct validity, since ≥75% of the results was in accordance with a priori hypotheses. All seven PROMIS CATs showed sufficient test–retest reliability (ICCs 0.73–0.91). SEM and MDC ranged from 2.1 to 2.7 and from 5.7 to 7.4, respectively. Responsiveness was rated as insufficient in this study design as there was almost no change in participants’ own rating of their health compared with 6 months ago according to a global rating of change.

During the focus groups and interviews, healthcare providers and people with T2D agreed that CATs could serve as a conversation starter in routine care, but should never replace personal consultations with a doctor. If implemented, participants would be willing to spend 15 min to complete the PROMIS CATs.

The PROMIS CATs showed sufficient construct validity and test–retest reliability in most domains in people with T2D. Responsiveness needs to be evaluated in a population with poorer diabetes control or in a study design with longer follow-up. The CATs are well accepted to be used in care to identify relevant topics, but should not replace personal contact with the doctor.

To determine whether hormonal contraceptives are associated with subsequent risks of suicidal behaviour and depression among women of reproductive age.

Nationwide register-based study.

Swedish national population using health and death registers. Nationwide registries provided individual-level information about the use of hormonal contraception, suicidal behaviour, depression and potential confounders.

All women in Sweden from 1 January 2006 to 31 December 2013.

Suicidal behaviour events or registered deaths due to suicide were identified through the National Patient Register and Cause of Death Register, respectively. Clinical diagnoses of depression were obtained from the patient register. Cox regression models were used to estimate HRs with 95% CIs of suicidal behaviour and depression in women using hormonal contraceptives.

We followed more than two million women for a median of 6.8 years (12.4 million person-years in total). No increased risk was observed among women using oral contraceptives or non-oral combined oestrogen/progestin formulations. Non-oral progestin-only contraceptives were associated with an increased risk of suicidal behaviour using both population-based (HR=1.17, 95% CI 1.13 to 1.21) and within-individual (HR=1.16, 95% CI 1.11 to 1.21) analyses. Age-stratified analyses revealed that during late adolescence (age 15–18), use of oral contraceptives or non-oral combined formulations was associated with an increased risk of suicidal behaviour (range of HRs: 1.09–1.35), an effect that was not observed in adulthood. In contrast, non-oral progestin-only contraceptives were associated with an increased risk of suicidal behaviour during both late adolescence and adulthood.

We found no overall increased risk of suicidal behaviour among women using oral contraceptives or non-oral combined formulations. However, the observed increased risk associated with hormonal contraceptive use during adolescence, as well as with non-oral progestin-only contraception—particularly gonane-containing formulations—across the entire reproductive window warrants attention and further investigation.

This study aims to assess the burden and predictors of age-related macular degeneration (AMD) among older age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia.

A multicentre cross-sectional study was conducted among older patients with diabetes using a systematic random sampling technique.

The study was conducted at five comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 8 June 2023.

The study included 832 diabetic individuals aged 40 years and above.

Data were collected using a pretested structured questionnaire and physical examinations.

In this study, a total of 832 participants were involved, with a response rate of 96.85%. The burden of AMD was 15.4% (95% CI 13.0% to 18.0%). Male sex (adjusted OR (AOR) 2.04, 95% CI 1.17 to 3.56), older age (AOR 6.91, 95% CI 3.17 to 15.08), diabetes duration of 10 and more years (AOR 3.00, 95% CI 1.91 to 4.69), higher body mass index (AOR 2.56, 95% CI 1.15 to 5.71), presence of hypertension (AOR 2.45, 95% CI 1.56 to 3.85) and family history of diabetes mellitus (DM) (AOR 2.29, 95% CI 1.40 to 3.76) were positively associated with AMD.

This study found that the prevalence of AMD among patients with diabetes was 15.4%. Older age, male sex, longer DM duration, higher body mass index, presence of hypertension and family history of DM were significantly associated with AMD. Targeted screening of at-risk individuals for AMD, public health awareness campaigns focusing on these factors and further research to understand the burden and underlying mechanisms of these associations with AMD are recommended.

Electronic health register's (eRegisters) use have recently gained popularity in Africa. eRegisters are used to capture real-time patient information on several encounters with a healthcare provider. Given poor maternal and child health outcomes in Lesotho, eRegisters provide a promising innovative means of enhancing health outcomes, especially those related to midwifery. eRegisters capture maternal and newborn care services provided at healthcare facilities. Such data are important for informing evidence-based midwifery practice. Lesotho, a landlocked, sub-Saharan African country, piloted use of an eRegister in 2018. However, factors promoting eRegister and data use have not been fully documented. Therefore, this study explored factors promoting eRegister and data use for midwifery practice in Lesotho.

The study used a descriptive qualitative approach with interviews and focus group discussions used to collect data. Descriptive content analysis as outlined by Erlingsson and Brysiewicz (2017) was followed during data analysis.

The study was conducted at three of the eRegister piloting facilities in Lesotho to examine eRegister implementation across different levels of care. Data collection occurred between December 2023 and March 2024.

Purposive sampling was used to recruit healthcare workers across the three facilities. Participants were selected to capture the range of relevant roles and experience with eRegister across each facility, and 7, 6 and 5 participants were recruited.

Five categories emerged as factors promoting eRegister and data use: system readiness, organisational environment, data value and utility in practice, human resource competency and digital literacy and governance and stakeholder engagement.

This study identified critical factors that promote the use of the eRegister and data in Lesotho. The findings suggest that while external funding and partner responsiveness have been pivotal in sustaining eRegister operations, long-term sustainability will require stronger national ownership, including domestic investment in infrastructure, technical support and digital health governance. Future studies should explore the effect of eRegister use on clinical outcomes and examine strategies for scaling up digital health interventions in resource-limited settings.

Hearing loss is highly prevalent and impacts many aspects of a person’s life, including communication, social engagement, employment, general health and well-being. Yet, many people do not access hearing healthcare and are unaware of the range of hearing healthcare options available. Barriers to hearing healthcare include poor understanding of hearing loss and its impact; poor knowledge of help-seeking for hearing healthcare options; minimal support to help decide which option is best; and stigma related to hearing loss. These barriers lead to many people not receiving the hearing healthcare they need. Guided by theories of behaviour change and implementation science, HearChoice, an online tailored decision support intervention, has been co-developed to empower adults with hearing difficulties by offering them choice and control over their own hearing healthcare. HearChoice aims to facilitate informed decisions, accessibility and uptake of hearing healthcare, including a wide range of interventions, for adults with hearing difficulties. The objectives of the trial are to evaluate the effectiveness, health economics and feasibility of HearChoice.

This online randomised controlled trial will recruit participants with hearing difficulties across Australia, with an anticipated sample size of 640. Participants will be randomised to either HearChoice (treatment) or an Australia-specific Hearing Option Grid (active control), both delivered online. Outcomes will be assessed at baseline when the interventions will be offered, at 7 days post-intervention (primary endpoint) and at 3 months post-intervention. An email reminder will be sent at 1-month post-intervention. The primary outcome is decisional conflict. Secondary outcomes include measures of readiness and self-efficacy to take action, hearing-related quality of life and empowerment, assessment of the value and impact of HearChoice, work performance and health, and feasibility measures. Primary analysis will compare outcomes between HearChoice and the active control at the primary endpoint.

The study was approved by the Curtin University Human Ethics Committee (HRE2023-0024). All participants will provide written informed consent prior to participation. A broad dissemination plan of the study findings includes peer-reviewed publications, scientific conference presentations, articles and presentations for the wider community and public written in lay and accessible language, and social media.

Australian New Zealand Clinical Trials Registry (ACTRN12624001139561).

Research on modelling geographical accessibility to healthcare services has witnessed rapid methodological advancement and refinement. One of the contributing factors is the increasing availability of big data detailing the link between the population in need of care and the health facility such as infrastructure, travel modes and speeds, traffic congestion and the quality of road network. This has allowed more granular computation of geographic access metrics, particularly in low-and-middle income countries where data are scarce. However, there are no reviews providing a comprehensive overview of the availability and use of big data for assessing geographical accessibility to healthcare. This protocol aims to describe a methodological approach that will be used to review the existing literature on the application of big data (past or potential) in evaluating geographical accessibility to healthcare.

To characterise the big data that can be used to model geographical accessibility to healthcare, a scoping review will be undertaken and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for Scoping Reviews guidelines. We will search seven scientific databases (PubMed, Scopus, Web of Science, EBSCOhost-CINAHL, Cochrane, Embase and MEDLINE via Ovid), grey literature, reference lists of identified publications and conference proceedings. Search engines will be used to identify relevant big data services not yet used in published academic literature. All literature published in English or French will be included, regardless of publication type, geographical location or year of publication provided it describes or mentions big data that may be useful for evaluating geographical accessibility to healthcare. Study selection and data extraction will be performed independently by two researchers with a third resolving any discrepancies. Analysis will be conducted to summarise big data providers, their characteristics and their usefulness in terms of types of spatial accessibility metrics that can be derived.

Formal ethical approval is not required, as primary data will not be collected in this review. Findings will be disseminated through peer-reviewed publication in a journal, conference presentation and condensed summaries for stakeholders through professional networks and social media summaries.

Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/S496F.

Gestational trophoblastic disease, characterised by abnormal proliferation of trophoblastic tissue in the placenta during pregnancy, contributes to maternal morbidity and mortality. This study aimed to estimate the pooled prevalence and histopathological patterns of gestational trophoblastic disease in Africa, where previous studies have reported inconsistent findings.

Systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

We searched PubMed, ScienceDirect, Hinari and Google Scholar for studies published between January 2000 and January 2024.

Institution-based observational studies from African countries reporting the prevalence and/or histopathological patterns of gestational trophoblastic disease, using total deliveries as the denominator.

Data were extracted into Excel and analysed using Stata V.17. Pooled estimates were calculated using a random-effects model with Knapp-Hartung adjustment. Heterogeneity was assessed with Cochran’s Q test and the I² statistic, and study quality was evaluated using the Joanna Briggs Institute tool.

Of the 2252 studies identified, 33 were included, comprising 2885 gestational trophoblastic disease cases from eight countries. The pooled prevalence of gestational trophoblastic disease in Africa was 4.35 per 1000 deliveries (95% CI 3.26 to 5.45, I²=99.8%). The pooled prevalence of hydatidiform mole, invasive mole and choriocarcinoma in Africa was 3.49 per 1000 deliveries (95% CI 2.45 to 4.52, I²=99.7%), 0.47 per 1000 deliveries (95% CI 0.14 to 0.79, I²=72.2%) and 0.97 per 1000 deliveries (95% CI 0.54 to 1.40, I²=99.1%), respectively.

This review indicated the prevalence of gestational trophoblastic disease was high. Hydatidiform mole was the predominant histopathological pattern observed. Routine antenatal screening is needed for early detection. Further research should be conducted to identify risk factors and evaluate strategies for the prevention and management of the disease.

CRD42024504268.

Mental disorders are among the leading causes of the global burden of disease and are often associated with severe functional impairment and high societal costs. Psychotherapeutic, psychopharmacological and internet-based mental health interventions have proven to be helpful, but challenges remain, including only moderate response rates, high relapse rates and barriers to accessing mental healthcare. Much of the existing evidence stems from studies conducted in controlled, often standardised settings that only partially reflect real-world conditions, contributing to a ‘scientist-practitioner gap’. Moreover, the mechanisms of change, such as the interaction between treatment intensity, common factors (eg, the therapeutic relationship) and specific intervention techniques, have not been sufficiently investigated. In particular, the relationship of changes in personality functioning (PF) with mental and physical health has not yet been extensively researched.

The PSYMPACT (Psychological Impact Factors of Mental Health Treatments) study will use a longitudinal study design with a naturalistic sample (N 3000) to examine changes in psychopathology, PF and allostatic load in psychotherapeutic, psychopharmacological and internet-based treatments. The aim is to identify factors contributing to improvements and deteriorations in mental and physical health across different settings, including common and specific factors. Additionally, to provide patient perspectives, qualitative interviews will be conducted with individuals with varying levels of severity of mental health problems. Allostatic load will be assessed using repeated hair cortisol measurements. Furthermore, ecological momentary assessment will be used to examine the diurnal variability of PF as well as its more momentary correlates and longer-term outcomes. The central research questions and aims include (1) the assessment of common factors across different treatment settings, (2) associations of specific and common factors with improvements in mental health, including PF, (3 and 4) the importance of treatment intensity and interaction effects with common and specific factors, (5) the association of changes in psychopathology with changes in allostatic load, (6) the trait and state variability of PF, (7) the identification of patients who deteriorate under specific treatments and (8) patients’ perspectives on the effectiveness of different treatment modalities.

Approval was obtained from the Ethics Committee of the Department of Education and Psychology at the Freie Universität Berlin, Germany. Results will be submitted to peer-reviewed specialised journals and presented at national and international conferences.

Before data collection started in November 2024, the study was registered in the German Clinical Trials Register (https://www.drks.de/search/de/trial/DRKS00035560).

Ovarian cancer remains a significant clinical challenge due to its aggressive nature and high mortality rate. Tumour-infiltrating lymphocytes (TILs) play a critical role in the tumour microenvironment, influencing treatment response and patient survival across various cancer types, including ovarian cancer. A systematic review is warranted to consolidate evidence on TILs as prognostic biomarkers in ovarian cancer, with the goals of integrating them into clinical practice to enhance patient outcomes. This study aims to assess the prognostic significance of TILs in ovarian cancer.

A comprehensive literature search will be conducted across multiple databases, including PubMed, Embase, Web of Science, Scopus, Cochrane Library, CINAHL, ScienceDirect and LILACS. No restrictions regarding publication date or language will be applied. Original studies evaluating the role of TILs in women with ovarian cancer will be considered for inclusion. Two independent authors will screen titles and abstracts, and any discrepancies will be resolved through discussion with a third author. The risk of bias in included studies will be assessed using the Quality in Prognosis Studies (QUIPS) tool. Data synthesis will be performed using R software (V.4.3.1).

This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal.

CRD42024543955.

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

A retrospective cohort study.

University of Gondar Comprehensive Specialized Hospital, northwest, Ethiopia.

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

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

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

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

Severe mental disorders are associated with increased risk of metabolic dysfunction. Identifying those subgroups at higher risk may help to inform more effective early intervention. The objective of this study was to compare metabolic profiles across three proposed pathophysiological subtypes of common mood disorders (‘hyperarousal-anxious depression’, ‘circadian-bipolar spectrum’ and ‘neurodevelopmental-psychosis’).

751 young people (aged 16–25 years; mean age 19.67±2.69) were recruited from early intervention mental health services between 2004 and 2024 and assigned to two mood disorder subgroups (hyperarousal-anxious depression (n=656) and circadian-bipolar spectrum (n=95)). We conducted cross-sectional assessments and between-group comparisons of metabolic and immune risk factors. Immune-metabolic markers included body mass index (BMI), fasting glucose (FG), fasting insulin, Homeostasis Model Assessment-Insulin Resistance (HOMA2-IR), C reactive protein and blood lipids.

Individuals in the circadian-bipolar spectrum subgroup had significantly elevated FG (F=5.75, p=0.04), HOMA2-IR (F=4.86, p=0.03) and triglycerides (F=4.98, p=0.03) as compared with those in the hyperarousal-anxious depression subgroup. As the larger hyperarousal-anxious depression subgroup is the most generic type, and weight gain is also a characteristic of the circadian-bipolar subgroup, we then differentiated those with the hyperarousal-anxious subtype on the basis of low versus high BMI (2 vs ≥25 kg/m², respectively). The ‘circadian-bipolar’ group had higher FG, FI and HOMA2-IR than those in the hyperarousal-anxious-depression group with low BMI.

Circadian disturbance may be driving increased rates of metabolic dysfunction among youth with emerging mood disorders, while increased BMI also remains a key determinant. Implications for assessment and early interventions are discussed.

Bangladesh is highly prone to recurrent flooding that disrupts all four pillars of food security. This study aimed to explore the effect of household food insecurity on the underweight status of women in flood-affected areas of Bangladesh, which remains underexplored.

This is a cross-sectional analysis.

This study was conducted in eight sub-districts (upazilas) across eight districts in Bangladesh that experience severe to moderate river flooding, flash floods and substantial tidal surges.

A total of 532 women participated in the study. The inclusion criteria for participation were as follows: (1) being at least 18 years of age, (2) residing in the household for at least 1 year and (3) having experienced limited food access in the 4 weeks before data collection due to flood-related constraints.

Household food insecurity was measured using the U.S. Agency for International Development Household Food Insecurity Access Scale questionnaire. An underweight status was evaluated through anthropometric measurements of women. Adjusted prevalence ratios (aPRs) were estimated using robust log-linear models.

Moderate food insecurity was the most common (58.3%) among the participants. The prevalence of underweight was the highest (52.1%) in the severely food-insecure group and decreased significantly with improved food security. Severe household food insecurity was strongly associated with a higher prevalence of underweight individuals (aPR = 4.12; 95% CI, 1.60 to 10.60). An underweight status was also prevalent in women from moderately food-insecure households (aPR = 1.75; 95% CI, 0.68 to 4.55).

This study reveals a significant association between household food insecurity and underweight status, highlighting the major challenges faced by women living in flood-prone areas of Bangladesh. These findings emphasise the urgent need to address household food insecurity to improve nutritional outcomes for women in vulnerable communities.

Although poor mental health among young people has been increasing in the past decades, many young people are reluctant to use traditional mental healthcare. To cater to the needs of young people, various youth-friendly treatment options have been developed. These include the youth-friendly health service (YFHS) standards put forth by the WHO in 2012 and the integrated youth services (IYS) for mental health developed in certain countries globally. However, no synthesis of the effect of these services on youth mental health has been conducted. The aim of the proposed study is to conduct a systematic review of the effect of mental health treatments conducted within YFHS and IYS clinics. The primary research question is what effect mental health interventions given at ‘youth-friendly’ clinics for treating mental health, such as IYS and YFHS, have on the mental health and quality of life (QoL) of young people?

A preliminary search for other reviews on the topic was conducted during the first half of 2024, after which a protocol of the present study was registered in PROSPERO. In May 2024, a search was carried out in the PubMed, PsycINFO, CINAHL and Web of Science databases, which gave references for 12 738 papers to be screened for inclusion in the review, and a follow-up search was carried out in April 2025, yielding a further 2182 references. For inclusion, studies must have participants between 12 and 25 years of age; interventions be given at clinics designed to be ‘youth-friendly’ or given at an IYS; control condition, if any, consisting of standard care or waiting list; outcomes must be mental health symptomology or QoL. To be included, studies must be published from 2012 and onwards. Screening of titles and abstracts in the initial search was carried out independently by two reviewers. Screening of studies found in the follow-up search and in the reference lists of included articles will be carried out in the same way. Data analysis of the initial search was conducted in the latter half of 2024, while final data analysis including the results from the follow-up search is ongoing. The Cochrane risk of bias assessment tools will be used to assess bias of included articles, and certainty of the evidence will be evaluated according to the GRADE methodology. A meta-analysis of the results will be performed if a sufficient amount of homogenous data is found; otherwise, a synthesis without meta-analysis will be conducted.

The proposed review may form a valuable synthesis of the state of the art of treatment options catering to young people. Investigating the effectiveness of YFHS or IYS in treating young people’s mental health may inform future directions for development and research. The present study does not need ethical approval, since only previously published, ethically approved data are used in the current study. The findings of the study will be disseminated through submissions to peer-reviewed journals and international conferences, as well as disseminated within the Swedish YFHS community.

ID nr CRD42024528687.