Microcirculatory dysfunction drives the end-organ pathophysiology of circulatory shock but is not reflected within existing clinical indices of perfusion, such as blood pressure. The choroidal vasculature of the retina can be measured non-invasively and we hypothesised that this may reflect dysfunction in other organs. We tested the feasibility of measuring the choroid in intensive care and explored associations between choroidal measurements and clinical parameters.

A pilot study of optical coherence tomography conducted in a sample of general intensive care unit (ICU) patients.

A tertiary mixed ICU within the UK.

15 patients were recruited. One patient was excluded following withdrawal of active treatment. 12/14 (86%) of the remaining patients had successful baseline imaging and 6 (40%) of these had follow-up imaging within intensive care. These patients had a mean age of 56.3 years, were 71% (10/14) male and mean Acute Physiology and Chronic Health Evaluation 2 (APACHE2) score on ICU admission was 20.4.

Choroidal anatomy, including choroidal and suprachoroidal thickness, as well as volumetric analysis of intrachoroidal blood vessels, was assessed using automated image segmentation along with clinical, physiological and biochemical data at ICU admission and after an interval of 12–72 hours. Feasibility and safety data were assessed throughout ICU admission.

Baseline choroidal vascular index and choroidal thickness were positively associated with fluid balance, and negatively with APACHE2 score, haematocrit and albumin content. A measurable suprachoroidal space was seen in nine (75%) patients (range 25.0–110.0 microns) and was inversely associated with heart rate. There was substantial intraindividual variation in choroidal measurements over time. There were no safety concerns.

Measuring the choroid is feasible in patients with Intensive Care Society Level 2 or Level 3 requirements. The suprachoroidal space may be markedly enlarged in these patients. Exploratory associations with systemic variables suggest that the choroid may provide information about the microvascular function of other major organs. Size and change of choroidal measurements may reflect perfusion pressure and vascular leakage.

Post-COVID-19 syndrome (PCS) is characterised by persistent symptoms, such as fatigue, dyspnoea, depression and sleep problems, following SARS-CoV-2 infection. The long-term course and impact on quality of life remain unclear. This review aims to synthesise evidence on longitudinal changes in symptom prevalence, severity and health-related quality of life (HRQoL) in adults with PCS.

This systematic review will include longitudinal studies (randomised controlled trials, non-randomised trials, prospective and retrospective cohort studies) of adults (≥18 years) with PCS, defined by symptoms persisting beyond 4 weeks after acute infection. Eligible studies must report changes in prevalence or severity of fatigue, dyspnoea, depression, sleep problems or HRQoL from baseline to at least one follow-up visit.

We will systematically search MEDLINE, Embase, PsycINFO, Web of Science, Scopus, CINAHL and Epistemonikos, with no restrictions on language, date or publication status. Two reviewers will independently screen studies, extract data and assess risk of bias using validated tools appropriate to study design. Disagreements will be resolved by consensus or a third reviewer.

A narrative synthesis will summarise study characteristics and symptom trajectories. Where sufficient data are available, random-effects meta-analyses will be conducted to estimate pooled changes in symptom prevalence (ORs), severity ((standardised) mean differences) and HRQoL ((standardised) mean differences). Meta-regression and subgroup analyses will explore potential effect modifiers. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

No ethical approval is required. Findings will be disseminated via peer-reviewed publication, conference presentations and plain language summaries.

CRD420251011612.

High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings.

Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease.

We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds.

WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium.

NCT05845112.

Increased risks and concerns regarding patient safety in early-phase studies exist because knowledge about the new intervention is still accumulating. This means that narrow eligibility criteria are needed. However, if early-phase studies are narrow in their inclusion, for example, by not including diverse populations, there is a potential risk that new therapies have insufficient relevant efficacy and safety data. Existing research has explored equity, diversity and inclusion (EDI) factors in early-phase pharmaceutical studies, but it has not been possible to find studies that have systematically examined whether EDI factors have been considered in surgical studies reporting innovative procedures. We aim to examine how EDI factors are considered in early-phase surgical studies and surgical innovation reports to explore how this may impact on later-phase evaluation and inclusive intervention implementation.

A scoping review following the JBI (Joanna Briggs Institute) and Arksey and O’Malley’s five-step process is being conducted. We will search Scopus, PubMed and Web of Science for surgical early-phase studies. A two-step screening process for eligibility is being used. Independent double screening will take place for 20% of the papers. Eligible articles will report early evaluation of an innovative surgical/invasive procedure. Excluded will be comparative and later-phase studies and early evaluations of pharmaceutical products even in a surgical setting. Data on article details, patient eligibility and whether protected characteristics are reported and considered will be extracted. Information about EDI considerations reported in the introduction or discussion of the papers will also be extracted. Findings will be discussed with a patient advisory group. A content synthesis approach will be undertaken and descriptive summaries presented.

This study does not require ethical approval being a secondary analysis. The findings will be disseminated through academic journal publications and oral presentations.

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas that primarily affects the skin and can mimic inflammatory dermatoses. Unlike many skin diseases, CTCL can lead to disabling symptoms, and advanced CTCL can even be fatal. Early studies investigating health-related quality of life (HRQOL) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), common subtypes of CTCL, demonstrated significant impairment across numerous domains. The aim of this current study is to develop a core domain set (CDS) to identify the essential aspects of MF/SS that influence HRQOL that should be measured in therapeutic clinical trials. In the future, this set of core concepts will be used to identify the best patient- reported outcome measure(s) (PROM) for HRQOL for MF/SS clinical research.

Multiple strategies will be used to generate candidate concepts: systematic review of the literature, qualitative study and a survey study of healthcare providers. A Delphi consensus process including a comprehensive group of stakeholders (patients, caregivers/care partners, a multidisciplinary group of healthcare professionals, patient advocacy groups, pharmaceutical industry representatives, methodologists and government agencies) will be used to achieve consensus. Statistical corrections for multiple significance testing and false positive findings will be undertaken.

The study was submitted for and received institutional review board approval at the University of Washington (IRB# STUDY00018890 and STUDY00019407). Informed consent will be obtained from all participants where necessary. We will disseminate our findings through peer-reviewed, open access publications and presentations at national/international conferences. We will provide a plain language summary in lay terms for patients and families to patient advocacy groups for distribution to their network.

The protocol is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database.

Persistent postsurgical pain (PPSP) affects up to 15% of patients after major surgery, impairing physical function, quality of life and increasing risk for long-term opioid use. Current PPSP prediction models rely on static or retrospective data and fail to incorporate dynamic perioperative factors. The Personalised Prediction of Persistent Postsurgical Pain (P5) study aims to develop individualised, multimodal prediction models by integrating preoperative behavioural, psychophysical and neurocognitive assessments and high-frequency symptom monitoring.

P5 is a prospective, single-centre cohort study enrolling 2500 adults aged 18–75 undergoing major surgery at a tertiary academic hospital. Participants complete baseline surveys, cognitive testing and quantitative sensory testing preoperatively. Ecological momentary assessments (EMAs) are collected via smartphone three times per day through 30 days postoperatively, capturing pain, mood, catastrophising and medication use. Participants are assessed on postoperative day 1 and complete online surveys at 3 and 6 months, evaluating pain persistence, interference, neuropathic symptoms and related outcomes. Clinical and perioperative data are extracted from the electronic health record. The primary outcome is PPSP at 3 months. Predictive models will be developed using supervised machine learning and dynamic structural equation modelling to extract latent features from EMA data. Model performance will be assessed using area under the receiver operating characteristic curve, area under the precision-recall curve and SHapley Additive exPlanations for interpretability.

This study has received ethics approval from the Washington University School of Medicine Institutional Review Board #202101123. Informed consent is required. Results will be submitted for publication in peer-reviewed journals and presented at research conferences.

NCT04864275.

Patient-reported experience measures (PREMs) are measures of patients’ perceptions of care they receive. PREMs are critical in developing and evaluating programmes that aim to improve patient healthcare experiences and quality of care (QoC) according to patient-defined needs. This review aims to map key domains of PREMs across distinct healthcare technical areas and life stages from globally available literature.

A scoping review adapting Arksey and O’Malley’s framework and Joanna Briggs Institute’s guidelines for the conduct of scoping reviews.

Google Scholar, PubMed, WHO, US Academy of Medicine and USAID Momentum.

PREMs literature from electronic repositories of grey and peer-reviewed publications, published in English historically up to September 2023.

Two lead reviewers with support from the technical working group co-created a review framework of healthcare technical areas, life stages and PREMs domains. We screened eligible articles, prioritising reviews except for technical areas with no reviews, where we then selected individual studies. We charted, analysed and synthesised data from 52 eligible articles.

PREMs literature has recently increased, especially in low-income and middle-income countries (LMICs), although studies in high-income countries (HICs) dominate in proportion (n=38; 73.1%). Out of 52 eligible articles, technical areas with most publications were sexual and reproductive health (n=21; 40.4%) and general outpatient care (n=11; 21.2%). Studies in adulthood (n=24; 46.2%) and from pregnancy and birth to postnatal (n=16; 30.8%) were most represented. PREMs studies reported mostly on communication and rapport (n=33; 63.5%) and respect and dignity (n=42; 80.8%) domains. Nearly a quarter (n=12; 23.1%) of the articles included only validated tools; the rest included a combination of validated and unvalidated measures. Of the tools relating to life stages of babies, younger children and older adults, the majority (n=17; 94.4%) included patient proxies.

PREMs, as an important component of QoC measurement, are increasing across several healthcare technical areas and life stages with commonalities and notable distinctions in measurement domains and tools. Evidence on PREMs largely comes from HICs. Evidence on critical, yet sometimes overlooked domains, highlights key QoC implementation gaps. The adaptation and utilisation of PREMs in programmes, especially in LMICs and under-represented technical areas, present opportunities to close the QoC disparities in those settings. Strategic, concerted efforts towards the harmonisation of PREMs tools across multiple life course stages and technical areas are critically needed in high-level quality improvement efforts.

Studies have demonstrated the positive impact of falls prevention interventions for high-risk older adults who have experienced a severe fall. However, uptake and adherence rates remain low. The purpose of this study is to assess the capabilities, opportunities and motivations of older adults following a fall with subsequent presentation to the emergency department and direct discharge home in relation to falls prevention measures.

This study, conducted as part of the ‘Sentinel fall presenting to the emergency department’ project at the Carl von Ossietzky University Oldenburg in Germany, involved a participatory research team (PRT). It was a qualitative study based on focus group interviews undertaken between June and October 2022, analysed in accordance with qualitative content analysis following Kuckartz. The Theoretical Domains Framework forms the basis of the deductive category system. PRT members collaborated as co-researchers in conducting and analysing the focus groups.

12 focus groups were conducted (N=52). The participants were older adults (≥60 years) who had received outpatient care in an emergency department following a fall (N=41) and their relatives (N=11).

Interviewees indicated that both knowledge of available support options and the ability to self-evaluate are important following a fall. Additionally, health circumstances, such as limitations resulting from fall-related consequences, influence the adoption of falls prevention measures. Social influences, as well as environmental context and resources, were also discussed, reflecting participants’ preferences for intervention design, such as having a central point of contact and specific courses on fall training. Moreover, the fall event itself may strengthen the perceived need for preventive measures, whereas a fear of falling can lead to reduced or modified activity levels.

To improve the engagement of older adults in falls prevention interventions following a fall, the establishment of a central point of contact could be considered. Individual tailored interventions, including psychological support as well as specific fall training, are needed.

DRKS00025949.

This study describes the prototype testing and clinical validation of the Fit-Frailty App, a fully guided, interactive mobile health (mHealth) app to assess frailty and sarcopenia. This multi-dimensional tool is freely available on the App Store and considers medical history, physical performance, cognition, nutrition, daily function and psychosocial domains. To guide management, a total frailty score and clinical summary of underlying "risk flags" are provided. Our objectives were to examine usability, feasibility, criterion and construct validity.

Cross-sectional

Outpatient geriatric medicine clinic

Community-dwelling older adults, age 65 years or older

The primary outcome of the clinical validation study was criterion validity. A research nurse administered the Fit-Frailty App during a routine clinic appointment. Clinicians simultaneously completed a paper-based frailty index (FI) tool with similar items from a comprehensive geriatric assessment (FI-CGA). Total scores for both assessments were computed using the cumulative deficits frailty index scoring method. Intraclass and Pearson correlation coefficients and 95% CIs were calculated to examine criterion validity. Secondary outcomes were construct validity, feasibility (eg, completion rates, safety occurrences, resources) and usability (eg, ratings on ease of use, time to complete the app).

In the clinical validation study (n=75, mean age 79.2, SD=7.0, 53% female), the mean total Fit-Frailty App score was 0.33 (SD=0.13) with 73% of our sample considered frail or severely frail. The app presented comparable results to FI-CGA (moderate to good validity; ICC=0.65, 95%CI=0.50–0.76) with a strong association between the measures (r=0.74, 95%CI=0.62–0.83). In our prototype and clinical cohorts, the app had a 100% completion rate with no safety occurrences and had high usability ratings.

The Fit-Frailty App is a feasible and valid tool that can be used in research and clinical settings to comprehensively assess frailty and sarcopenia by non-geriatricians and could assist with developing targeted interventions.

Endometriosis is a common, benign, chronic inflammatory disease with multiple consequences, from chronic pain to systemic comorbidities and poor quality of life. As it usually affects people of reproductive age, one of the most distressing consequences is infertility, which can be only partly overcome by medically assisted reproduction. Poor outcomes are, in fact, frequent adverse events. As no definitive therapy exists for endometriosis-related infertility, affected women often tend to try either complementary and alternative medicine or self-management strategies to improve their quality of life, with the hope of also enhancing their fertility. Among available options, dietary interventions are commonly explored, even if no robust evidence is available on the optimal type of diet and its effects on reproductive outcomes. This trial will investigate whether an anti-inflammatory dietary intervention can improve fertility outcomes in women affected by endometriosis undergoing in vitro fertilisation (IVF).

The DietAry interveNtion in ameliorating fertiliTy parameters in women with Endometriosis undergoing IVF (DANTE) study is a single-centre, randomised, controlled, non-pharmacological interventional trial in patients living with endometriosis who are infertile and require IVF. Participants will be allocated to either a 12-week intervention based on an anti-inflammatory diet or no diet before the beginning of controlled ovarian stimulation. Following baseline assessment, 438 participants aged

The study has received ethics approval from Comitato Etico Territoriale Lombardia 3 (#5587_18.12.2024). Results will be presented in peer-reviewed journals and at international conferences.

NCT06885125.

We explored how key sociodemographic characteristics were associated with correct knowledge about antibiotics and antibiotic resistance (ABR) and appropriate usage of antibiotics from a One Health perspective among rural community members in Bangladesh.

Cross-sectional single-period survey.

Rural villages in Cumilla district, Bangladesh.

Eligibility criteria: aged ≥18. Across 50 clusters of villages, we approached 2160 community members and 2187 (98.8%) agreed to participate.

Primary outcomes: we collected two knowledge outcomes measuring the number of correctly answered binary/multiple-choice questions about (1) antibiotics and ABR and appropriate usage of antibiotics in relation to human illness and (2) antibiotics and ABR and appropriate usage of antibiotics in relation to animal health and the environment. Secondary outcomes: self-reported awareness of (1) antibiotics and (2) ABR.

Several sociodemographic characteristics were associated with variation in both knowledge outcomes. Education showed the strongest associations, with higher education levels associated with higher knowledge scores. For example, compared with having no formal/incomplete primary education, having higher education was associated with 10 percentage points (95% CI 8 to 12) and 6 percentage points (95% CI 3 to 8) higher mean knowledge scores for the knowledge outcomes 1 and 2, respectively. Having worked in the last month compared with not having worked was also weakly positively associated with both knowledge outcomes, and being female compared with being male was also weakly negatively associated with both knowledge outcomes.

Better public education is required to tackle ABR in Bangladesh but correct knowledge about antibiotics and ABR and appropriate usage of antibiotics in relation to humans, animals and the environment varies in relation to individuals’ education level, sex and working status. To maximise their effectiveness, interventions to tackle ABR must be flexible given recipients’ sociodemographic characteristics and pre-existing knowledge levels.

Many people with long-term conditions such as pain and arthritis struggle with their health and well-being. To support better self-management, a new peer-delivered coaching intervention (Health Connect Coaching) was set up at a National Health Service integrated care organisation in Southwest England. Based on principles of personalised care and supported goal setting, the one-to-one coaching programme, targeting patients with low activation, delivered coaching sessions in a step-down approach over 6 months. A randomised controlled feasibility trial (fRCT) of Health Connect Coaching was conducted to inform the design of a definitive randomised controlled trial. This article reports the embedded qualitative component of the fRCT, describing the experiences of coaches, peers and staff of implementing and participating in the intervention and trial that ultimately struggled to recruit sufficient peers.

Semi-structured online interviews were conducted with coaches (n=16) and peers (n=6), and informal discussions held with staff (n=7). Interviews were recorded and transcribed verbatim, and summaries of informal discussions were made. Data were analysed using thematic framework analysis.

Four themes were identified from the interview and discussion data: (1) motivation for participation, (2) balance, (3) flexibility and (4) connection and building relationships.

One-to-one peer coaching demonstrates potential as an intervention to enable people to better manage their chronic health condition. However, in people with low activation, programmes and effectiveness studies need to pay close attention in their design to the motivation of peers, flexible delivery models that enable connection but can accommodate fluctuating needs and facilitating links between coaching services and clinical teams.

ISRCTN12623577.

Deaths related to drug overdose and suicide in the USA have increased 500% and 35%, respectively, over the last two decades. The human and economic costs to society associated with these ‘deaths of despair’ are immense. Great efforts and substantial investments have been made in treatment and prevention, yet these efforts have not abated these increasing trajectories of deaths over time. The COVID-19 pandemic has exacerbated and highlighted these problems. Notably, some geographical areas (eg, Appalachia, farmland) and some communities (eg, low-income persons, ‘essential workers’, minoritised populations) have been disproportionately affected. Risk factors have been identified for substance use and suicide deaths: forms of adversity, neglect, opportunity indexes and trauma. Yet, the biological, psychological and social mechanisms driving risk are not uniform. Notably, most people exposed to risk factors do not become symptomatic and could broadly be considered resilient. Achieving a better understanding of biological, psychological and social mechanisms underlying both pathology and resilience will be crucial for improving approaches for prevention and treatment and creating precision medicine approaches for more efficient and effective treatment.

The State of Ohio Adversity and Resilience (SOAR) study is a prospective, longitudinal, multimodal, integrated familial study designed to identify biological, psychological and social risk and resilience factors and processes leading to mental health disorders, substance use disorders, substance overdose, suicide and associated psychological/medical comorbidities which reduce life expectancy and quality of life. It includes two nested longitudinal samples: (1) WD Survey: an address-based random population epidemiological sample of 15 000 individuals (unique households) representative of the state of Ohio assessed for psychosocial, psychiatric, behavioural health and substance use factors and (2) Brain Health Study: a family-based, multimodal, deep-phenotyping study conducted in 1200 families (up to 3600 persons aged 12–72 years) including MRI, electroencephalography, blood biomarkers and psychiatric diagnostic interviews, as well as neuropsychological, psychosocial functioning and family/community history, dynamics and support assessments. SOAR is designed to discover, develop and deploy advanced predictive analytics and interventions to transform mental health prevention, diagnosis, treatment and recovery.

All participants will provide written informed consent (or parental permission and assent for minors). The study was approved by The Ohio State University Institutional Review Board (study numbers 2023H0316 (Brain Health) and 2023H0350 (Wellness Survey). The Brain Health study was also approved by institutional review boards at each partnering institution involved in conducting participant assessments. Findings will be disseminated to academic peers, clinicians and healthcare consumers, policymakers and the general public, using local and international academic channels (academic journals, evidence briefs and conferences) and outreach (workshops and seminars).

In the last 60 years, newborn bloodspot screening (NBS) has expanded as a public health intervention from a single severe childhood genetic disease (SCGD) to up to as many as 80 SCGD and testing of ~40 million newborns/year worldwide. However, the gap between current NBS and its potential to increase the efficiency, effectiveness and global equity of healthcare delivery for SCGD is large and rapidly growing. There are now effective therapeutic interventions—drugs, diets, devices and surgeries—for up to 2000 SCGD. Since almost all SCGD can be identified by bloodspot genome sequencing, it has been a longstanding goal to supplement current NBS with genome sequencing-based NBS (gNBS) for all eligible SCGD. We recently described a novel gNBS platform (named Begin Newborn Genome Sequencing (BeginNGS)) with the potential to overcome several major challenges to gNBS (cost, scalability, false positives and an unprepared healthcare workforce). A pilot clinical trial of BeginNGS for 412 SCGD in a level IV neonatal intensive care unit (NICU) had a true positive rate of 4.2%, sensitivity of 83%, positive predictive value of 100% and clinical utility rate of 4.2%, indicating readiness of the platform for use in a powered, multicentre study.

The BeginNGS study is a single group, international, multicentre, adaptive clinical trial to compare utility, acceptability, feasibility and cost-effectiveness of BeginNGS gNBS (experimental intervention) with standard NBS (control). A minimum of 10 000 neonates (aged 50 000 US children per year.

This study was approved by the WCG Clinical institutional review board on 14 February 2024, and the most recent amendment approved on 7 October 2025 (approval number 20235517). Study findings will be shared through research consortium workshops, national and international conferences, community presentations and peer-reviewed journals.

NCT06306521.