Endometriosis is a chronic condition affecting up to 11% of people presumed female at birth by the age of 44 years, characterised by the growth of tissue similar to the lining of the uterus on other organs. Endometriosis significantly impacts health-related quality of life (HRQoL) and imposes a substantial burden on both individuals and the healthcare system. International guidelines recommend the interdisciplinary management of endometriosis due to its significant biopsychosocial burden; however, research aimed at exploring psychological approaches for endometriosis is limited. This trial aims to evaluate the effectiveness of CodeEndo, an online co-designed interdisciplinary supportive care program, compared with a waitlist control (WLC), on HRQoL and biopsychosocial outcomes in people with a diagnosis of endometriosis.

A hybrid type 1 effectiveness and implementation randomised controlled trial (RCT) will be conducted. Eligible participants will be randomly allocated to either the CodeEndo program (n=176) or WLC group (n=176) for 8 weeks. The primary outcome will be HRQoL, and secondary outcomes will include psychological symptoms (anxiety, depression, stress), self-efficacy, menstrual, bladder and gastrointestinal symptoms, pain, fatigue, sleep, exercise, diet, symptom bothersomeness and physical and psychological well-being, measured at 8 weeks post-randomisation (T2) and 6-month follow-up (T3). Cost-effectiveness will also be examined. Longitudinal qualitative individual interviews (up to n=40) will be conducted with participants who complete the CodeEndo program to explore benefits, barriers and facilitators of ongoing use. Additionally, the CodeEndo program will undergo evaluation by a group of endometriosis healthcare providers, who will assess potential barriers and facilitators to its real-world implementation. Various process evaluation strategies will also be measured to inform future implementation. Data analyses will incorporate mixed-effects regression models on an intention-to-treat basis, cost-consequences and cost-utility, dietary and qualitative thematic analysis.

This protocol received ethics approval from Deakin University Research Ethics Committee (DUREC Ref: 2024-157). Dissemination is expected to include peer-reviewed journal articles, reports, conference presentations as well as websites or social media platforms of relevant chronic pain organisations. Participants will be sent a summary of trial results.

ACTRN12623000598684p.

Patients living with chronic obstructive pulmonary disease (COPD) experience periods of disease stability and exacerbations (ECOPD). COPD imposes a negative and impactful extrapulmonary impairment and commonly overlaps with multimorbidity, particularly cardiovascular disease. Pulmonary rehabilitation (PR) aims to improve physical activity (PA) and quality of life, while behavioural change interventions (BCIs) aim to promote lifestyle changes and autonomy. However, after ECOPD, a variety of barriers often delay patient referral to PR. This study aims to assess the effects of a BCI for patients after ECOPD, focusing on cardiovascular health, PA and functionality. Additionally, the study will assess 6-month sustainability of PA and conduct a cost-utility analysis comparing a non-intervention group in the Unified Health System.

This randomised clinical trial will assess patients with ECOPD over 12 weeks using a BCI based on self-determination theory to increase daily steps. First, the cardiovascular and functional profile will be evaluated. Afterwards, the patients will receive an accelerometer to monitor the PA level. After 7 days, questionnaires will be applied on quality of life, symptoms and motivational levels for PA. Patients will be randomised into control group or intervention groups, both will receive educational booklets and IG will also receive an educational interview. PA will be tracked using activPAL accelerometer at weeks 1, 4 and 12, and follow-up at 6 months. Data analysis will include unpaired Student’s t-test or Mann-Whitney test for group comparison, and a linear mixed model to assess intervention effects over time. Economic evaluation, using STATA (V.14), will involve correlation analysis, and p

This study has been approved by the Federal University of São Carlos’ Ethics Committee, Irmandade Santa Casa de Misericórdia de São Carlos and Base Hospital of São José do Rio Preto. All procedures will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and applicable regulatory requirements. All results will be presented in peer-reviewed medical journals and international conferences.

Brazilian Registry of Clinical Trials under the registration number RBR-6m9pwb7.

The only supportive therapy for patients with severe acute kidney injury (AKI), a common complication among the critically ill, is dialysis. Based on the literature and current guidelines, continuous renal replacement therapy (CRRT) with a total effluent dose of 20–25 mL/kg/hour and adjustments to ensure such dose is delivered despite down time (eg, due to surgical procedures) is recommended. However, experimental and clinical studies suggest that azotaemia, which can be induced by lowering the effluent dose, may accelerate renal recovery. This clinical study investigates whether a lower effluent dose (10–15 mL/kg/hour) for a maximum of 7 days or until successful (>24 hours) liberation of CRRT in critically ill patients with a dialysis-dependent AKI accelerates renal recovery and reduces time on CRRT compared with guideline-directed standard dose (25–30 mL/kg/hour).

The Ketzerei trial is an international, multicentre randomised, controlled trial, designed to investigate if a lower effluent dose (10–15 mL/kg/hour) accelerates renal recovery and reduces the time on CRRT compared with the guideline directed standard effluent dose (25–30 mL/kg/hour). The study aims to enrol 150 critically ill patients with a dialysis-dependent AKI. Eligible patients will be randomised to receive either a standard effluent dose (control group, 25–30 mL/kg/hour) or lower effluent dose (interventional group, 10–15 mL/kg/hour). The primary endpoint is the number of days free from CRRT and alive (from randomisation through day 28). Key secondary endpoints include the number of (serious) adverse events due to potential uremia, the duration of RRT and intensive care unit survival.

The Ketzerei trial has been approved by the Ethics Committee of the Chamber of Physicians Westfalen-Lippe (2023–343 f-s), the University of Muenster and subsequently by the corresponding Ethics Committee of the participating sites. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.

clinicaltrials.gov (NCT06021288).

To estimate the frequency of antidiabetic prescriptions in type 2 diabetes mellitus (T2DM) in Spain and describe changes in prescription patterns between 2018–2022 and 2023-2024.

Observational study.

Patients from primary care centres newly diagnosed with T2DM in 2018–2022 and 2023–2024.

In each period, the prescription frequency of an antidiabetic medication at the diagnosis of T2DM was calculated and subsequently subdivided into monotherapy and combination therapy. The prescription frequency of the most common antidiabetic drugs was also calculated. Calculations were made for the entire group of subjects and stratified by sex and age (under 60 years and 60 years or older). Comparison of the frequencies between the two periods was performed using the chi-square test.

In 2018–2022 and 2023–2024, 78.4% and 88.9% of patients, respectively, were prescribed an antidiabetic medication. The prescription frequencies for monotherapy and combination therapy were 66.1% and 33.9% in the first period and 57.4% and 42.6% in the second. The prescription frequencies for metformin as monotherapy and combination therapy were 57.4% and 27.8% in the first period and 46.6% and 39.8% in the second. Prescribing metformin with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and/or glucagon-like peptide receptor 1 agonists (GLP1a) was the most frequent combination therapy: 12.8% in 2018–2022 and 29.5% in 2023–2024. With a few exceptions, the prescribing pattern was similar by sex and age. The difference between the prescribing distributions in the two periods is significant.

Antidiabetic medication prescribing at the diagnosis of T2DM was high. Most prescriptions contained metformin. Monotherapy decreased in 2023–2024 compared with 2018–2022, while combination therapy increased due to increased prescriptions of metformin with SGLT2i and/or GLP1a.

Patients receiving long-term ventilation (LTV) in out-of-hospital intensive care facilities often suffer from persistent impairments of their cognition, mental health and physical health, limiting their social participation. Chronically ill patients are often unable to express their care preferences. Thus, their medical care often lacks integration of patients’ wishes and values. Telemedicine may be used to collect patient-reported outcome measures (PROMs) from these patients to align medical care with their preferences. Early integration of teleconsultation to provide rapid support for specific patient symptoms can reduce economic costs.

This is a multicentre, prospective, non-blinded, single-arm interventional trial with a pre-post design and follows the Standard Protocol Items: Recommendations for Interventional Trials statement. 10 out-of-hospital intensive care facilities in Berlin and Brandenburg, Germany, are grouped into three clusters. The study population includes adult patients (≥18 years) receiving LTV and residing in participating care facilities. During the preintervention phase, standard patient care remains unchanged. From the start of the intervention phase, enrolled patients receive telemedicine rounds in addition to standard care. These telemedicine rounds, conducted at least weekly, involve on-site healthcare professionals, patients and their relatives. Data are collected at predefined time points—study months 1,3, 9, 15 and 21—with a target of 57 participants at each time point. The study aims to evaluate whether a structured telemedicine intervention (1) increases the proportion of patients receiving record-documented PROMs in routine care and (2) reduces hospital readmissions. Secondary outcomes include the evaluation of post-intensive care syndrome, healthcare costs and the usability, applicability and perceived benefits of telemedicine. Additionally, qualitative interviews with patients, their relatives and healthcare professionals will explore individual experiences with chronic critical illness, the perceived quality of life of the patients and how team members manage moral distress in caregiving contexts. A mixed-effects logistic regression model will be used to analyse patients’ access to PROMs, while a mixed-effects Poisson regression model will be employed to evaluate hospital readmission rates. The findings may provide valuable insights into how telemedicine can improve patient-centred care for this particular patient group.

This study protocol received approval from the Ethics Committee of Charité—Universitätsmedizin Berlin, Germany (EA2/136/22). The findings will be disseminated through publication in a peer-reviewed scientific journal and presented at international conferences.

This study was registered in the ‘German Register of Clinical Studies’ (DRKS; DRKS00029326).

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

Video games have been linked to a range of positive and negative effects on the mental health of adolescents and young adults. However, to better understand how games affect the mental health of young people, their use and experiences must be situated in the sociocultural and personal life contexts of individuals. Drawing from a cultural-ecosocial approach, this study combines cross-sectional and digital phenotyping measures to examine the effects of video games on the mental health of youth.

Participants will be young people aged 16–25 years from the community and living in the province of Quebec, Canada. An initial sample of 1000 youth will complete a cross-sectional survey online, including measures of socio-demographic context, gaming practices and experiences, streaming practices and experiences, as well as personality and well-being. Qualitative questions will explore personal views on games and mental health. A subsample of 100 participants will be selected for digital phenotyping, including daily surveys of well-being, gaming, streaming and social experiences, combined with passive mobile sensing (eg, geolocation). Analyses will include regression and mixed models for quantitative data, reflexive thematic analysis for qualitative data, and an integration of quantitative and qualitative results using participatory methods.

The study received ethical approval from the Institutional Review Board of McGill University (24-02-015). The dissemination of results will be conducted in partnership with a multi-stakeholder advisory committee, including youth who play video games, and will involve peer-reviewed publications, presentations to policymakers in Quebec, and workshops for clinicians and researchers.

Multimorbidity is prevalent and associated with complex treatment requirements. In order to assist general practitioners (GPs) addressing these requirements, the web application gp-multitool.de has been designed, which facilitates implementation of the German clinical practice guideline for multimorbidity. We will conduct a cluster-randomised clinical trial evaluating an intervention based on this tool. This protocol summarises methods and discusses ethics and dissemination of this study.

Participating patients are recruited by cooperating GP practices. Inclusion criteria are an age of 65 years or older, enrolment in any disease management programme and multimorbidity operationalised by two additional chronic conditions. To avoid postrandomisation selection bias, practices are randomised as clusters after baseline assessment of all participating patients from the respective practice. In our intervention, patients receive access to different assessments including patient preferences by email, fill out the electronic assessment forms on any device with access to the internet, receive a medication review and discuss the assessment results with their GPs. GPs in the control group do not have access to the digital tool and provide care as usual. The primary outcome is staying at least once for at least one night in hospital during the 12-month observation period. Secondary outcomes are contacts with GPs and outpatient specialists, self-reported health, health-related quality of life, patient satisfaction and GP-reported and patient-reported quality of care. A sample size of 660 patients from 66 GP practices is needed. Data are analysed by mixed effects regression models.

Ethics approval was obtained by the ethics committee of the Medical Association of Hamburg (2022–1 00 786-BO-ff). Study results will be presented on scientific conferences and published in journal articles. In addition, healthcare professionals, patient representatives and the interested public will be informed about study results at a symposium.

The study was registered in clinicaltrials.gov (NCT06831994).

Non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases and cancer, are major global public health concerns. Diet quality—particularly the consumption of ultra-processed foods—has been associated with increased risk of NCDs. Traditional cohort studies are often expensive and logistically complex. The NutriNet-Brasil cohort leverages a web-based approach, offering a cost-effective and practical solution for comprehensive data collection and long-term follow-up.

Recruitments began in January 2020 through mass media, social media campaigns and collaborations with health organisations. Eligible participants are adults (aged ≥18 years) living in Brazil with internet access. Participants complete self-administered online questionnaires covering dietary intake, health status and other health determinants. Dietary assessment is based on the Nova classification system, which categorises foods by their level of processing.

Over 88 000 participants have completed the initial questionnaire. The cohort is predominantly women (79.9%) and highly educated (67.9% had completed higher education). The web-based design enabled the development and application of innovative dietary assessment tools, including the Nova24h and the Nova24hScreener, specifically designed to evaluate food processing levels. These tools have shown good performance in capturing dietary patterns and are central to the cohort’s aim. The online platform facilitates efficient recruitment, data collection and participant retention.

NutriNet-Brasil is pioneering the development of web-based cohort methodologies and instruments tailored to food processing research. Future work includes leveraging collaborations with national and international research centres to conduct multidisciplinary analyses and inform public health policies.

SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland.

We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil.

We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022.

Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection.

From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: 12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: 12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)).

Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.

Exposure is a central component in the treatment of a range of mental disorders. However, despite high efficacy and efficiency, dissemination of exposure-based treatments is limited. Important factors that contribute to this limited dissemination are negative beliefs about exposure on the part of the public, the therapists, and the patients. While patients perceive exposure therapy as burdensome, therapists are concerned about putting too much strain on their patients during exposure, leading to suboptimal delivery of exposure. In a previous study, in which healthy participants underwent a differential fear conditioning paradigm, we found initial evidence that the integration of a therapy dog into exposure reduces participants’ anxiety and increases participants’ positive affect without causing poor treatment outcome. Thus, the integration of a therapy dog into exposure might be a promising approach to address patients’ and therapists’ concerns and, thus, to (1) foster dissemination of exposure that is (2) delivered in an optimal manner. To scrutinise our findings in a clinical sample, we designed the present study. We test the following hypotheses: (H1) participants in the dog group report significantly less anxiety during the course of the treatment than participants in the control group. (H2) Participants in the dog group report significantly more positive affect during the course of the treatment than participants in the control group. (H3) Participants in the dog group report significantly higher therapy motivation than participants in the control group. (H4) Participants in the dog group report significantly lower anticipatory anxiety than participants in the control group. (H5) The treatment in the dog group is not inferior to the treatment in the control group.

In this parallel randomised controlled trial of two groups, n=88 participants (spider phobics without: a current diagnosis of a mental disorder other than a specific phobia, insect bite allergy, dog hair allergy, fear of dogs, current psychopharmacological treatment, and current psychotherapeutic treatment; the sample size calculation is based on the results from our previous study) are randomly allocated (with a 1:1 allocation as per a computer-generated randomisation schedule) to either an ambulant one-session in vivo exposure treatment of spider phobia with a therapy dog (dog group) or without a dog (control group). Due to the nature of the intervention, neither participants nor therapists can be blinded once participants are allocated to one of the two groups. However, the person conducting screening and diagnostics is blind to the allocation, participants are blind to the hypotheses and the respective other group, and the researchers are blind to the allocation while analysing the data. We will test (H1) and (H2), concerned with our primary outcomes, by means of 2x4 mixed analyses of variance with the between-subjects factor group (dog group vs. control group), the within-subjects factor time (with four levels, one for each time point anxiety and affect are measured during treatment), and anxiety or positive affect as the dependent variable, respectively. We will test (H3) and (H4) by means of an analyses of covariance with therapy motivation/anticipatory anxiety at baseline as the covariate, the between-subjects factor group (dog group vs. control group) and therapy motivation/anticipatory anxiety at pre-treatment as the dependent variable, respectively. We will test (H5) by means of 95% CIs and non-inferiority zones.

This trial was approved by our university’s ethics committee (reference number 24–11). Any deviations from this study protocol or the preregistrations as well as any adverse events potentially arising in the course of the trial, will be made explicit in the publication of the trial results. All participants provided written informed consent prior to the inclusion into the trial. The findings from this trial will be disseminated by means of common academic pathways, including peer-reviewed publications and conference presentations. Following common open science practices, data and analysis code will also be made publicly available in anonymised form on the Open Science Framework (osf.io).

On 18 June 2024, this study was registered at the German Clinical Trials Register (ID: DRKS00034494; https://drks.de/search/de/trial/DRKS00034494) and preregistered at AsPredicted (https://aspredicted.org/JRP_SCF).

Post-COVID-19 conditions (PCC) may include pulmonary sequelae, fatigue and other symptoms, but its mechanisms are not fully elucidated.

This study investigated the correlation between fatigue and the presence of pulmonary abnormalities in PCC patients with respiratory involvement 6–12 months after hospitalisation.

Cross-sectional study.

A tertiary hospital in Brazil.

315 patients, aged ≥18 years, were considered eligible based on SARS-CoV-2 infection confirmed by reverse transcription-PCR.

Pulmonary function tests (PFT), cardiopulmonary exercise tests (CPET), chest CT and hand grip were performed. The following scales were applied: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, Euroqol 5 Dimensions quality of life (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Participants were divided between the fatigue group (FACIT-F≤30) and the non-fatigue group (FACIT-F>30). For the statistical analysis, the primary outcome was the difference in the diffusing capacity of the lungs for carbon monoxide (DLCO) between groups. Considered secondary outcomes were differences in PFT, CPET, chest CT, hand grip, EQ-5D and HADS.

The fatigue group had 81 patients (25.7%) against 234 (74.3%). PFT and CPET showed no significant difference in DLCO and oxygen consumption peak values between groups. The fatigue group had a lower workload (mean 55.3±21.3 watts vs 66.5±23.2 watts, p=0.003), higher breathing reserve (median 41.9% (33.8–52.5) vs 37.7% (28.9–47.1), p=0.028) and lower prevalence of ground glass opacity (60.8% vs 77.7%, p=0.003) and reticulation (36.7% vs 54.9%, p=0.005) in chest CT. The fatigue group had higher anxiety (57% vs 24%, p

Fatigue in patients with PCC 6–12 months after hospitalisation is relatively common and had weak correlation with pulmonary disorders. Our results suggested fatigue could be strongly related with peripheral disorders such as reduced musculoskeletal strength or psychosocial limitations.

The prevalence of women with primary dysmenorrhoea is high and negatively impacts physical and mental health. The intense cyclic episodes of pain generate central nervous system dysfunctional processing. In this sense, strategies focused on the central nervous system are important to re-establish normal functioning. Home-based self-administered transcranial direct current stimulation (tDCS) emerges as a strategy to modulate dysfunctional brain areas and improve the symptoms. This protocol aims to evaluate the effects of home-based self-administered tDCS for pain, premenstrual symptoms, physical performance, quality of life, electroencephalography and patient global impression in women affected by primary dysmenorrhoea.

This is a single-centre, parallel, randomised, double-blinded clinical trial protocol. 40 women affected by primary dysmenorrhoea will be randomised into two groups (active-tDCS or sham-tDCS). Then, 20 consecutive sessions of home-based self-administered tDCS will be performed. The assessments will occur at five time points: baseline, after the 20th sessions, at the first, second and third cycles after tDCS interventions (follow-ups). Primary outcome will be pain according to visual analogue scale. Quality of life, premenstrual symptoms screening, depression, anxiety, physical performance, electroencephalography and participants’ satisfaction will be the secondary outcomes. A mixed analysis of variance will calculate the effect of stimulation.

The study was approved by the ethics committee of the Federal University of Rio Grande do Norte (No. 6.037.756) and registered in the Brazilian Clinical Trials Registry (n° RBR-747k8vb). Participants may withdraw at any time without penalty. Free support will be available from the lead researcher if needed. All procedures will follow Good Clinical Practice and international ethical standards.

https://ensaiosclinicos.gov.br/rg/RBR-747k8vb

Histopathological evaluation of prostate biopsies using the Gleason scoring system is critical for prostate cancer diagnosis and treatment selection. However, grading variability among pathologists can lead to inconsistent assessments, risking inappropriate treatment. Similar challenges complicate the assessment of other prognostic features like cribriform cancer morphology and perineural invasion. Many pathology departments are also facing an increasingly unsustainable workload due to rising prostate cancer incidence and a decreasing pathologist workforce coinciding with increasing requirements for more complex assessments and reporting. Digital pathology and artificial intelligence (AI) algorithms for analysing whole slide images show promise in improving the accuracy and efficiency of histopathological assessments. Studies have demonstrated AI’s capability to diagnose and grade prostate cancer comparably to expert pathologists. However, external validations on diverse data sets have been limited and often show reduced performance. Historically, there have been no well-established guidelines for AI study designs and validation methods. Diagnostic assessments of AI systems often lack preregistered protocols and rigorous external cohort sampling, essential for reliable evidence of their safety and accuracy.

This study protocol covers the retrospective validation of an AI system for prostate biopsy assessment. The primary objective of the study is to develop a high-performing and robust AI model for diagnosis and Gleason scoring of prostate cancer in core needle biopsies, and at scale evaluate whether it can generalise to fully external data from independent patients, pathology laboratories and digitalisation platforms. The secondary objectives cover AI performance in estimating cancer extent and detecting cribriform prostate cancer and perineural invasion. This protocol outlines the steps for data collection, predefined partitioning of data cohorts for AI model training and validation, model development and predetermined statistical analyses, ensuring systematic development and comprehensive validation of the system. The protocol adheres to Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis+AI (TRIPOD+AI), Protocol Items for External Cohort Evaluation of a Deep Learning System in Cancer Diagnostics (PIECES), Checklist for AI in Medical Imaging (CLAIM) and other relevant best practices.

Data collection and usage were approved by the respective ethical review boards of each participating clinical laboratory, and centralised anonymised data handling was approved by the Swedish Ethical Review Authority. The study will be conducted in agreement with the Helsinki Declaration. The findings will be disseminated in peer-reviewed publications (open access).

Major depressive disorder (MDD) is a major global healthcare challenge. This is, in part, due to the lack of treatment response and chronic course of MDD. Such a course of illness is often termed treatment-resistant depression (TRD) and is seen in over one-third of people with MDD. Reasons for treatment resistance are not well established, nor is the definition of TRD. Duration and severity of depression, however, are associated with TRD and are also associated with cognitive deficits. Thus, TRD could be particularly prone to cognitive deficits and at heightened risk for neuroprogression. While the cognitive profile of MDD has been investigated in several systematic reviews, no systematic review of cognition in TRD exists to date. The present study will fill this gap in the literature. It is expected that TRD will show more severe cognitive deficits than generally reported in MDD and deficits in all cognitive functions are expected.

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be performed of the databases Embase, Pubmed/MEDLINE, PsychINFO and Cochrane including peer-reviewed studies on humans using standardised cognitive tests. Pilot searching was performed in January 2025 and the full search will be commenced in June 2025, with additional searches following completion. Where sufficient data are reported, a meta-analysis comparing deficits in TRD with MDD and healthy control participants will be performed; alternatively, effects based on norms will be calculated. Meta-regression, subgroup and sensitivity analyses will be conducted to explore moderators that are sufficiently reported in the literature. The quality of studies will be assessed by the Newcastle-Ottawa Scale.

Ethical approval is not necessary to perform the study, and results will be presented at a suitable conference and published in a peer-reviewed journal.

CRD42024538898.

The aim of the study was to analyse patients’ experiences, usability and acceptability of a 12-week self-directed m-health exercise intervention for patients with knee osteoarthritis (OA).

This qualitative study was included in a randomised controlled trial. After completion of a 12-week m-health exercise intervention, 14 structured telephone interviews were conducted in patients with knee OA. The interviews were audio recorded, transcribed and analysed using a combined deductive and inductive content analysis approach.

The study was conducted at a university hospital in southern Germany.

Four themes were identified: (1) facilitators and (2) barriers for (correct) digital exercise participation, (3) ease of use and (4) outcomes. Participants valued ease of use, comprehensibility, flexibility and certain app features (eg, push notifications as reminders, instruction videos, real-time biofeedback) that facilitated guidance, control and motivation to complete exercises. However, some participants requested some kind of human support.

The participants demonstrated predominantly positive experiences and acceptability with the self-directed m-health exercise intervention. As some participants lacked human support, we suggest that the optimal treatment option should be selected according to the preferences and needs of the individual patient.

DRKS00023269.