This study applied an interpretable ML model to effectively predict early CKD. Even when using the relatively low-cost “blood routine + urinalysis + basic information” combination, the model still demonstrated high prediction accuracy. This method has potential clinical application prospects and may help identify early CKD, reducing the risk of disease progression.
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Rare Variant Association Analysis Uncovers Involvement of VNN2 in Stroke Outcome
Stroke, Ahead of Print. BACKGROUND:A stroke’s functional outcome presents vast variability among patients, which is influenced by age, sex, characteristics of the lesion, and genetic factors. However, there is little knowledge about stroke recovery genetics. Recently, some GWAS (Genome-Wide Association Studies) have highlighted the involvement of common or low-frequency variants near or withinPATJ,PPP1R21,PTCH1,NTN4, andTEK genes, whereas the role of rare variants is still unclear. This study aims to identify the genetic contributions to differences in stroke outcomes by analyzing the effect of rare variants.METHODS:We performed a pilot study analyzing 90 exomes of extreme good and bad recovery (modified Rankin Scale score at 3 months, 0–1 versus 4–5) to select target genes involved in stroke recovery. To expand this study, 702 additional samples were sequenced by targeted next-generation sequencing capturing loci selected from the pilot study, GWASs, and literature input. Here, we performed continuous (modified Rankin Scale score, 0–6) and dichotomous (modified Rankin Scale score, 0–1 versus 3–6) analyses, yielding 1 candidate gene. All samples were selected by a retrospective cohort study from incidental stroke cases collected at Spanish Hospitals between 2000 and 2018. The identifiedVNN2variants were assessed for protein structure and stability analysis, and an analysis of their effect on basal inflammation levels was performed using UK Biobank data.RESULTS:Our work identified rare coding variants inVNN2associated with patients with better stroke recovery (∆ deviance information criterion >10, equivalent toP1.6 kcal/mol); meanwhile, another variant, located in the active site, could affect the electrostatic surface.CONCLUSIONS:We propose thatVNN2might play a role in stroke outcomes by modulating poststroke inflammation. A potentially affected function would be neutrophil cell adhesion and migration.
Non-randomised prospective clinical trial to improve follow-up adherence, survivorship knowledge and late effects documentation at a childhood cancer clinic in Western Kenya: a study protocol
Introduction
International survivorship guideline consortia have developed strategies to prevent, detect and manage late effects of childhood cancer survivors. However, recommendations do not adequately reflect the everyday reality of paediatric oncology care in low- and middle-income countries. In this study protocol, a survivorship intervention programme, comprising an educational component and a follow-up component, is described. The Educational Programme aims to improve follow-up adherence of childhood cancer survivors through increasing survivorship knowledge of caregivers. The Follow-up Programme aims to map late effects by implementing a follow-up form at the outpatient clinic to be used by trained healthcare providers.
Methods and analysis
This non-randomised prospective clinical trial will be performed at a referral hospital in Western Kenya. 100 caregivers of children diagnosed with cancer, who will complete treatment within 2 months, will be enrolled and followed for 24 months after completion of treatment. A caregiver control group receiving usual care will be recruited, and sequentially, caregivers will be included in an intervention group to attend an educational group session where they receive educational materials (video, booklet and Survivorship Card). Primary study outcome will be survivors’ follow-up adherence. Survivors will be considered lost to follow-up after they miss a scheduled appointment and do not revisit the clinic for more than 6 months. Mixed models regression analyses will be performed to determine intervention effects on follow-up adherence and on caregiver survivorship knowledge uptake. Additionally, healthcare providers will be trained on follow-up care, whereafter a form will be introduced at the outpatient clinic to document late effects in paediatric survivors attending the clinic for the period of a year. Secondary outcomes will be late effects prevalence as documented in the follow-up form and caregiver and healthcare provider survivorship knowledge uptake. Implementation measures (reach, potential effectiveness, adoption, satisfaction and maintenance) will be evaluated for both programmes.
Ethics and dissemination
The Institutional Research and Ethics Committee has approved the study protocol. Findings will also be shared with governmental and non-governmental organisations that support children with cancer in Kenya to inform their target audiences and guide their policy development.
Lessons learnt from this study could inform healthcare providers and policy makers on how to shape survivorship programmes in the Kenyan context and possibly implement similar programmes in other centres in Sub-Saharan Africa.
Trial registration number
NCT06680687.
Development of a Physical Activity Maintenance intervention for people with PERsistent musculoskeletal pain (PAMPER): a mixed-methods study protocol
Introduction
Persistent musculoskeletal pain is a leading cause of disability and need for rehabilitation globally. Many people with the condition attend pain management programmes (PMPs) for rehabilitation and support with self-management. Physical activity (PA) is an essential self-management strategy facilitated on PMPs as it benefits symptoms, general health and well-being. PA needs to be maintained in the long term to continue to be beneficial. However, while many patients increase their PA during or immediately after a PMP, they commonly find it difficult to maintain it in the long term. This study aims to address this problem by developing an intervention to support PA maintenance after a PMP.
Methods and analysis
This mixed-methods study will be guided by the Medical Research Council guidelines for developing complex interventions and the Behaviour Change Wheel intervention development framework. Participants will be recruited from multiple UK National Health Service PMPs. Participants will include patients with persistent musculoskeletal pain who have completed PMPs, their PA partners (people who support them with PA) and healthcare professionals who facilitate PA on PMPs. The study will be conducted in three phases. In phase 1, qualitative interviews will explore the experiences, barriers and facilitators of PA maintenance after a PMP and potential characteristics for a PA maintenance intervention from patient, PA partner and healthcare professional perspectives. Phase 2 will consist of a prospective longitudinal pilot study to identify factors associated with PA maintenance after a PMP. Phase 3 will involve developing a logic model and co-designing the intervention with patient, PA partner and healthcare professional stakeholder groups.
Ethics and dissemination
The project received research ethics committee (REC) and Health Research Authority approval on 4 June 2024 (REC: North West—Liverpool Central, REC reference: 24/NW/0174, IRAS Project ID: 340674). Findings will be disseminated by peer-reviewed publications, conference presentations, social media and lay summaries for patients and the public.
Progress and determinants of household access to improved drinking water in India using a Water Access Index: insights from the National Family Health Survey towards achieving SDG 6.1
Background and objective
Access to clean drinking water is essential for health and development. Despite global and national initiatives, many regions in India continue to face inadequate water access. This study assesses progress, sociodemographic determinants and geographic disparities in access to drinking water in India, aligning with Sustainable Development Goal (SDG) 6.1.
Design
This study used secondary data from five rounds of the National Family Health Survey (NFHS-1 to NFHS-5; 1992–2021), nationally representative surveys conducted across India. Logistic regression was employed to examine the association between household sociodemographic characteristics and access to improved drinking water. A Water Access Index (WAI) was constructed using Principal Component Analysis (PCA) based on four indicators: access to improved sources, on-premises availability, 5-minute round-trip access and household water treatment. The scores were normalised to a 0–100 scale.
Setting and participants
The study used household data from NFHS-1 (88 562 households), NFHS-2 (92 477), NFHS-3 (109 041), NFHS-4 (601 506) and NFHS-5 (636 699), covering all 36 states/union territories in India.
Results
There has been a notable improvement in access to improved sources, on-premises water and timely availability. Factors such as higher educational attainment, pucca housing and the absence of a below poverty line card were positively associated with better access. Based on WAI scores, 343 districts (49%) were categorised as front runners (65–99%), 142 districts (20%) as performers (50–64%) and 221 districts (31%) as aspirants (0–49%). Only one district (0.1%) achieved universal access. Many districts in West Bengal, Bihar, Odisha, Jharkhand and other states still exhibit low-to-moderate water access.
Conclusion
While access to improved drinking water has advanced, regional and socioeconomic disparities remain stark. Targeted, multisectoral policies are essential to ensure equitable progress towards SDG 6.1 across all districts and population groups in India.
ARBOR-Telehealth study: an examination of telerehabilitation to improve function and reduce opioid use in persons with chronic low back pain in rural communities – protocol of a pragmatic, individually randomised group treatment trial
Introduction
Chronic low back pain (LBP) imposes significant burden on patients, healthcare systems and society. Physical therapy is a cost-effective method for improving pain and disability; however, only a small number of patients (7–13%) with LBP ever receive physical therapy services. Patients report obstacles to accessing physical therapy, such as transportation, provider availability and missed work. Access is especially limited in rural communities, where approximately 40% fewer physical therapists are available per capita than in metropolitan regions. This lack of access likely contributes to the greater rates of LBP-related disability and opioid consumption in rural communities. Innovative methods for improving access to physical therapy for patients with chronic LBP are urgently needed; these can help address differences in health outcomes and mitigate opioid dependence for patients with chronic LBP living in rural communities. Telerehabilitation increases access to physical therapy, which can potentially improve health outcomes for these patients.
Methods and analysis
This prospective, individually randomised group treatment trial will involve primary care clinics serving rural communities on Maryland’s Eastern Shore. We will enroll 434 individuals with chronic LBP. Eligible patients will be randomised to either standardised education for back pain delivered via website or to a risk-informed telerehabilitation. Standardised education will be delivered via a study website containing information consistent with materials provided by primary care providers. Risk-informed telerehabilitation will be delivered by trained physical therapists using a web-based, video-enabled telehealth platform. The primary outcome is LBP-related disability. Secondary outcomes are opioid use, pain intensity, health-related quality of life and LBP-related healthcare use assessed using standard patient-reported outcome measures, participant self-report and medical chart abstraction. Implementation outcomes are acceptability, adoption, feasibility and fidelity of our treatment approach guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework and assessed using surveys, semi-structured interviews and key performance metrics.
Ethics and dissemination
Ethics approval was obtained from the Johns Hopkins Medicine Institutional Review Boards (IRB), which serves as the single IRB for this trial. Upon completion, study data will be shared in compliance with National Institutes of Health guidelines.
Trial registration number
NCT06471920.
Effectiveness of the BioFire FilmArray for the rapid detection of bloodstream infection in haematological patients with febrile neutropenia (the ONFIRE study): study protocol of a prospective, multicentre observational study at three reference university hospitals in Spain
Introduction
Bloodstream infection (BSI) due to multidrug-resistant Gram-negative bacilli is a serious global health problem that has a profound impact on severely immunosuppressed neutropenic haematological patients. Prompt institution of appropriate antimicrobial therapy is crucial for improving outcomes in these patients, and in an era of multidrug resistance, antimicrobial stewardship programmes are mandatory. Blood cultures, the current gold standard for the diagnosis of BSI, present two main drawbacks: the prolonged time to results and their low sensitivity, especially if the patient has received antimicrobial treatment before blood extraction. The aim of this study is to determine whether a molecular technique, the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel, achieves higher sensitivity and specificity than conventional blood cultures for the microbiological diagnosis of BSI in haematological patients with febrile neutropenia.
Methods and analysis
This multicentre, prospective, observational study will be conducted at three reference university hospitals in Spain. The population will comprise haematological patients scheduled to undergo diagnostic blood cultures as standard care for the microbiological diagnosis of the febrile neutropenia episode. The BioFire FilmArray panel will be performed in patients with positive blood cultures at the time of blood culture positivity and in patients with negative blood cultures at 48 hours of incubation. The primary endpoint will be the sensitivity and specificity of the BioFire FilmArray BCID2 panel compared with conventional blood cultures. The secondary endpoints will be this same comparison in the subgroup of patients with recent (
Respiratory Syncytial Virus Vaccination
To the Editor The Research Letter by Dr Karaba and colleagues, “Antibody Response to Respiratory Syncytial Virus Vaccination in Immunocompromised Persons,” provides interesting real-world data on the effectiveness of the respiratory syncytial virus (RSV) vaccine in patients with self-reported immunocompromising conditions from a prospective national cohort. The heterogeneity and low immunogenicity response to the vaccine are noteworthy, as 40% of patients did not achieve seroconversion or reach the predefined threshold of neutralizing antibodies. This finding differs from the high overall efficacy that has been described among older adults in the general population (72%-94% and 62%-85.7%, respectively, in 2 studies evaluating prefusion F vaccines).
Active Monitoring for Low-Risk Ductal Carcinoma In Situ
To the Editor The COMET trial compared active monitoring with guideline-concordant care in patients with low-risk ductal carcinoma in situ (DCIS).
Active Monitoring for Low-Risk Ductal Carcinoma In Situ—Reply
In Reply The Letter from Dr Lin and colleagues raises important points regarding the recent publication of the COMET trial for low-risk DCIS that merit further consideration.
Perinatal outcomes for infants exposed to systemic cancer treatment during gestation: a systematic review and meta-analysis
Objectives
The incidence of cancer diagnosed during pregnancy is increasing, but data relating to perinatal outcomes for infants exposed to systemic cancer treatment in utero remain limited. This systematic review and meta-analysis aimed to synthesise evidence from the available literature to investigate whether perinatal outcomes for babies born to women with gestational cancer differ based on whether they are exposed to systemic cancer treatment in utero.
Design
A systematic review was conducted according to PRISMA-P guidelines. We extracted raw data from the eligible studies to calculate ORs and 95% CIs for perinatal outcomes reported in the included studies.
Data sources
A comprehensive search of Medline, Embase, Cochrane Library and CINAHL databases identified studies published between January 2001 and May 2025.
Eligibility criteria
Studies were eligible for inclusion in the review that reported on both a study group (women with gestational cancer who received systemic therapy during pregnancy) and a comparison group (women with gestational cancer who did not receive systemic therapy during pregnancy).
Data extraction and synthesis
Two independent reviewers extracted data. Perinatal outcomes included spontaneous abortion, pregnancy termination, intrauterine growth restrictions (IUGR), stillbirth, intrauterine foetal death, neonatal mortality, preterm birth (
Alcohol Use and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Circulation, Ahead of Print. Alcohol is one of the most commonly consumed substances in the world, exhibiting complex relationships with multiple aspects of cardiovascular health and disease. The majority of the research on the topic is observational and therefore prone to bias and confounding. The available evidence suggests no risk to possible risk reduction when alcohol is consumed in low amounts (such as no more than 1 to 2 drinks a day) in regard to coronary artery disease, stroke, sudden death, and possibly heart failure. The risk associated with consuming 1 to 2 drinks a day on atrial fibrillation remains unknown. More randomized trials of low to moderate alcohol consumption are needed for more definitive conclusions. In stark contrast, heavier alcohol consumption such as binge drinking or consuming on average ≥3 drinks/d is consistently associated with worse outcomes in every cardiovascular disease entity studied. Considering the level of evidence, it remains unknown whether drinking is part of a healthy lifestyle and therefore clinicians should reinforce healthy lifestyle behaviors such as regularly engaging in physical activity, avoiding tobacco use, and maintaining healthy body weight.
Primary care practitioners and patients views on the benefits and challenges of remote consulting for anxiety and depression in UK general practice: a qualitative interview study
Objective
To explore primary care patients’ and practitioners’ views and experiences of remote consulting for common mental disorders (CMDs), to optimise their management in primary care.
Design
Qualitative study using in-depth interviews and thematic analysis. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded, transcribed verbatim and analysed thematically. There was patient and public input throughout.
Setting
Participants were recruited from general practices. Interviews were held by telephone or videocall between March 2023 and October 2023.
Participants
We interviewed 20 practitioners and 21 patients.
Results
Interviewees suggested benefits included convenience, increased anonymity and were easier for those feeling very low or anxious. Challenges included practitioners finding it hard to assess risk, which lengthened consultation duration or led to further contact, increasing practice workload and patients feeling anxious waiting for the practitioner to call. In-person appointments were viewed as important for initial consultations and providing a safe space. Continuity of care and practitioner training were identified as facilitators for telephone consultations, and both patients and practitioners identified training needs around how to deliver mental healthcare remotely.
Conclusions
Practitioners should aim to offer continuity of care and in-person appointments when patients initially seek help. Remote consultations may not be more time or cost-efficient for individuals with CMDs as risk is harder to assess. There is a need to evaluate existing training on delivering remote consultations to identify whether remote mental healthcare is included or should be incorporated in the future.
Exploring perspectives regarding death cafes for people experiencing homelessness: a qualitative study
Background
People experiencing homelessness (PEH) often die at a younger age than the general population. Advanced ill-health often occurs late in its trajectory (if at all), leaving many PEH to die without adequate support from hospital-based, hospice-based or community-based palliative care services. Despite the high rate of bereavement and exposure to death among PEH, there are rarely opportunities for them to reflect on their experiences, thoughts and preferences around death or receive bereavement support. Death cafés are a global social franchise, providing a space for people to participate in an open group discussion about death, dying and bereavement. They are free to attend and unstructured but facilitated.
Objectives
To explore the perspectives of PEH and the professionals that support them with regards to the potential acceptability, benefits and challenges of death cafes.
Methods
A qualitative study comprising of interviews with nine homelessness and/or palliative care professionals with experience of running death cafés for, or supporting PEH in other ways, and two focus groups with nine people with lived experience of homelessness. The research was co-produced with a lived experience co-researcher forming a core part of the research team. Reflexive thematic analysis was utilised to develop themes.
Results
Five themes were developed to highlight the perspectives and experiences of death cafés for PEH: choice; expertise in facilitation: recognising risk and the unstructured nature; promoting safety against potential risk; potential benefits and potential practical considerations. Themes highlight the need for a trauma-informed approach. Death cafés could be impactful, where done well, but they are not without risk.
Conclusions
Death cafés for PEH pose risks that require comprehensive consideration and trauma-informed, expert facilitation. However, this research highlighted that a low-pressure space to explore thoughts around death, dying and bereavement is currently an unmet need within this population.
Healthcare professionals and patients views and experiences of surgical and medical treatment for nasal obstruction: a qualitative interview study for a Nasal Airway Obstruction Study (NAIROS)
Objectives
To understand healthcare professionals’ and patients’ views and experiences of septoplasty and medical management (ie, nasal steroid and saline sprays) for nasal obstruction.
Design
Nested qualitative study as part of the Nasal Airway Obstruction Study (NAIROS) trial. We used in-depth interviews to develop a coding framework based on thematic analysis.
Setting
NAIROS was a trial based in the UK from January 2018 to December 2020 that aimed to compare the effectiveness of septoplasty versus medical management.
Participants
We purposively sampled and interviewed 14 healthcare professionals (surgeons, research nurses) and 31 patients involved in the NAIROS trial across 14 UK hospital sites.
Results
In usual practice, surgeons’ decisions regarding treatment for nasal obstruction are based on a complex assessment of patients’ symptoms, history and anatomy. Surgeons viewed septoplasty as a complex although routine operation, which is not guaranteed to improve symptoms of nasal obstruction. Some patients saw septoplasty, intuitively, as a ‘fix’ for a bent septum, whereas others were keen to avoid surgery if possible. Healthcare professionals welcomed the increased use of standard measurements if these were shown to provide a reliable guide to patient outcomes. However, they felt that it was important to retain an element of clinical judgement. Despite generally good outcomes from septoplasty, some patients still felt they had received little to no benefit from the operation. Patients also reported being underprepared for postsurgery recovery. Experiences were more varied with medical management, with some experiencing symptom improvement, but others discontinuing treatment due to difficulty or pain using the sprays, or perceived ineffectiveness. Remembering to use the sprays could be perceived as burdensome, although most patients were able to incorporate this into their daily routines.
Conclusions
Our qualitative study demonstrated varied individual experiences among patients undergoing septoplasty and medical management. Surgeons welcomed more standard measurements to guide decision-making for septoplasty. For patients, better information about treatment mechanisms, treatment delivery and aftercare, and the development of decision support tools would enable shared decision-making and help to provide optimal patient experience of the treatments.
Trial registration number
ISRCTN16168569.
Characterisation of MRGPRX2+ mast cells in irritable bowel syndrome
Background
Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown.
Objective
We investigated whether MRGPRX2-mediated mast cell activation plays a role in abdominal pain development in patients with IBS.
Design
MRGPRX2 expression in mast cells and other immune cells was characterised across colon layers using flow cytometry. We evaluated whether MRGPRX2 agonists trigger mast cell degranulation and transient receptor potential vanilloid 1 (TRPV1) sensitisation in healthy human colonic submucosal plexus samples using live imaging. Rectal biopsies were then collected from patients with IBS and healthy volunteers (HV) and MRGPRX2+ mast cell frequency, MRGPRX2 expression per cell, mast cell degranulation kinetics in response to MRGPRX2 agonists, MRGPRX2 agonistic activity and presence of MRGPRX2 agonists in biopsy supernatants were assessed.
Results
MRGPRX2+ mast cells are enriched in the submucosa and muscularis of the healthy human colon. MRGPRX2 agonists induce mast cell degranulation and TRPV1 sensitisation in the healthy colon submucosa. While the frequency of rectal MRGPRX2+ mast cells was unaltered in IBS, submucosal mast cells showed increased degranulation in response to MRGPRX2 agonists in IBS compared with HV. MRGPRX2 agonistic activity was increased in IBS rectal biopsy supernatant compared with HV, which was associated with increased levels of substance P.
Conclusion
The MRGPRX2 pathway is functionally upregulated in the colon of patients with IBS, supporting its role in abdominal pain in IBS.