Nevin Manimala

Stem Cells Transl Med. 2026 Aug 18;15(9):szag069. doi: 10.1093/stcltm/szag069.

ABSTRACT

OBJECTIVE: To compare the therapeutic effects of exosomes from different cell sources and doses in rat knee osteoarthritis models using network meta-analysis, and to identify potential optimal strategies for preclinical optimization and clinical hypothesis generation.

METHODS: A systematic search of PubMed, Web of Science, Embase, and Scopus identified 27 eligible randomized controlled trials (456 rats). Traditional random-effects meta-analysis and frequentist network meta-analysis were conducted. Treatments were ranked using SUCRA values.

RESULTS: A total of 27 studies were included, comprising 456 rats. Traditional meta-analysis revealed that exosome therapy significantly reduced joint cartilage histopathological damage (reduced OARSI score: SMD = -3.78, 95% CI: -4.76, -2.80), promoted type II collagen synthesis (SMD = 3.41, 95% CI: 1.87, 4.95), and suppressed the expression of the inflammatory cytokine IL-1β (SMD = -3.26, 95% CI: -4.08, -2.44). Network meta-analysis further indicated that under high-dose conditions (≥100 μg), exosomes derived from human amniotic fluid stem cells (hAFSCs-Exo) and human umbilical cord mesenchymal stem cells (hUCMSCs-Exo) ranked highest in relative efficacy for improving the OARSI score. hUCMSCs-Exo also demonstrated the most potent anti-inflammatory effect by reducing IL-1β. Overall, exosome therapy exhibited a dose-related trend in efficacy, with high-dose transplantation showing higher probabilistic SUCRA rankings across most outcome measures. However, assessment of publication bias revealed marked asymmetry; after trim-and-fill correction, the effect size for type II collagen expression decreased from SMD = 3.41 to 1.26, suggesting that the magnitude of the treatment effect may have been overestimated. This overestimation reduces the certainty of the observed treatment effects. Despite the presence of publication bias and methodological limitations, the main conclusions remained statistically robust after trim-and-fill correction.

CONCLUSION: Current evidence from rat models suggests that exosome therapy may substantially ameliorate the pathological progression of KOA, with exosomes derived from early developmental tissues, particularly hAFSCs-Exo and hUCMSCs-Exo, showing favorable chondroprotective and anti-inflammatory effects in the probabilistic ranking when administered at high doses. Nevertheless, the findings from publication bias and trim-and-fill analyses indicate that the existing effect sizes are likely overestimated. These results require confirmation in larger-scale, methodologically more rigorous preclinical studies.

PMID:42613148 | DOI:10.1093/stcltm/szag069

Ann Oncol. 2026 Sep;37(9):1220-1229. doi: 10.1016/j.annonc.2026.05.697. Epub 2026 Jul 24.

ABSTRACT

BACKGROUND: The phase 3 RxPONDER trial compared endocrine therapy (ET) alone or with chemotherapy (CET) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with recurrence score (RS) ≤25. CET benefit for the primary outcome, invasive disease-free survival (IDFS), was limited to premenopausal women who largely did not receive ovarian function suppression. In this study, we assessed hormones associated with ovarian reserve to further refine the prediction of CET benefit.

PATIENTS AND METHODS: Pretreatment serum estradiol, progesterone, follicule-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and inhibin B (INHB) were assessed in a blinded fashion from 1556 participants aged <55 years. All markers used a predefined cut point. Associations with markers and IDFS and distant relapse-free survival (DRFS) were evaluated for prediction of CET benefit, adjusting for RS. Cox regression analyses of assigned treatment and its interaction with potential markers were adjusted for multiplicity.

RESULTS: Baseline estradiol, progesterone, LH, and FSH were not predictive for CET benefit. AMH ≥10 pg/ml showed significant interaction with chemotherapy benefit for IDFS (P_adj = 0.0034). In 64% of women with AMH ≥10 pg/ml (cut-off for normal ovarian reserve), IDFS was superior with CET compared with ET alone [hazard ratio (HR) 0.46, 95% CI 0.33-0.65, P_adj = 0.00012], whereas CET was not beneficial in the 36% with low ovarian reserve (AMH <10 pg/ml; HR 1.27, 95% CI 0.81-1.99, P_adj = 0.47). DRFS showed a similar pattern of results for AMH. Ultrasensitive INHB measured in the pg/ml range was also predictive of CET benefit.

CONCLUSION: Among premenopausal patients aged <55 years, participants with baseline AMH <10 pg/ml did not benefit from CET. AMH was a significantly better indicator of CET benefit than menopause status, age, or other hormones. Measures of ovarian reserve may refine the selection of patients for CET.

PMID:42613139 | DOI:10.1016/j.annonc.2026.05.697

Biostatistics. 2026 Jan 20;27(1):kxag028. doi: 10.1093/biostatistics/kxag028.

ABSTRACT

Advances in cellular imaging technologies, especially those based on fluorescence in situ hybridization (FISH), now allow detailed visualization of the spatial organization of human or bacterial cells. Quantifying this spatial organization is crucial for understanding the function of multicellular tissues or biofilms, with implications for human health and disease. To address the need for better methods to achieve such quantification, we propose a flexible multivariate point process model that characterizes and estimates complex spatial interactions among multiple cell types. The proposed Bayesian framework is appealing due to its unified estimation process and the ability to directly quantify uncertainty in key estimates of interest, such as those of inter-type correlation and the proportion of variance due to inter-type relationships. To ensure stable and interpretable estimation, we consider shrinkage priors for coefficients associated with latent processes that induce dependencies among point patterns. Model selection and comparison are conducted using a deviance information criterion designed for models with latent variables, providing a practical criterion for balancing model fit and complexity. Furthermore, we use a Bayesian hierarchical pooling model to synthesize image-specific posterior summaries, allowing inference at both the global- (across subjects) and subject-specific levels. An R package, mspatPPM, implements an efficient computational scheme based on Hamiltonian Monte Carlo and adaptive Metropolis-Hastings algorithms. Numerical studies evaluate the practical performance of the proposed framework for model selection and for estimating quantities that characterize the multivariate spatial distribution of cell types. We apply the proposed method to microbial biofilm image data from the human tongue dorsum and find that specific taxon pairs, such as Streptococcus mitis-Streptococcus salivarius and S. mitis-Veillonella, exhibit strong positive spatial correlations, while others, such as Actinomyces-Rothia, show slight negative correlations. For most of the taxa, a substantial portion of spatial variance can be attributed to inter-taxon relationships.

PMID:42613133 | DOI:10.1093/biostatistics/kxag028

BMJ Open. 2026 Aug 18;16(8):e116968. doi: 10.1136/bmjopen-2026-116968.

ABSTRACT

OBJECTIVE: To elicit and quantify registered nurses’ (RNs’) preferences for key shift attributes and to estimate the trade-offs between shift pattern characteristics and pay.

DESIGN: Cross-sectional online discrete choice experiment with d-efficient design; 12 choice tasks per respondent. Preferences were estimated using multinomial logit models with clustered standard errors; willingness to accept (WTA) values were derived as ratios of attribute coefficients to the pay coefficient.

SETTING: United Kingdom.

PARTICIPANTS: 1449 registered nurses (RNs) recruited via the Nursing and Midwifery Council distribution list.

PRIMARY AND SECONDARY OUTCOME MEASURES: Utility coefficients (β) for shift length, schedule predictability, shift request flexibility, weekend working frequency, pay level and night-shift frequency; WTA derived from the pay attribute; subgroup and interaction analyses by age, pay band, current shift status, caring responsibilities, sector and satisfaction.

RESULTS: All six attributes were statistically significant predictors of shift pattern choices. The strongest aversions were to night-only working (β=-1.113) and having no whole weekends off (β=-0.790), which required an estimated 29% additional compensation in the primary model and 21% additional compensation, respectively. Unpredictable rotas (β=-0.220), restricted shift-choice flexibility (β=-0.189 for only swaps) and absence of pay increase (β=-0.525) also reduced utility. Nine-to-ten-hour shifts were preferred over 8-hour shifts (β=0.144), whereas 12.5-hour shifts were disliked (β=-0.179). Subgroup analyses showed significant heterogeneity by age and current shift status, with more limited evidence of pay-band differences. Interaction analyses suggested broadly consistent aversion to night work and weekend loss across the nursing workforce.

CONCLUSIONS: Nurses strongly prefer rota designs that avoid exclusive night work and protect whole weekends off. Predictability and meaningful scope to request shifts also matter. These preference estimates provide policy-relevant benchmarks for rota design and unsocial-hours compensation.

PMID:42613123 | DOI:10.1136/bmjopen-2026-116968

BMJ Open. 2026 Aug 18;16(8):e111016. doi: 10.1136/bmjopen-2025-111016.

ABSTRACT

BACKGROUND: The use of core outcome sets (COSs) in health research is widely recommended. COSs are developed with input from key decision makers, patients being a vital group to ensure COS relevance. However, recruitment to COS studies can be challenging.

OBJECTIVES: The study aimed to explore what patients and the public think of COS study invitations, which are usually the first document a patient reads about a COS study.

DESIGN: Qualitative study involving focus groups and interviews. Analysis of transcribed data drew on reflexive thematic analysis.

PARTICIPANTS AND SETTING: Focus groups and interviews were conducted with a diverse range of patients and the public (n=31) from community and patient groups in North West England, exploring their perceptions of a sample of COS study invitations. Participants were eligible if aged over 18 years, they could speak English and had never previously participated in a COS study.

RESULTS: Themes identified included understanding, engagement, safety and accessibility. Participants were concerned about excessive information in the invitations which made them confused. Fear of cybercrime caused numerous concerns and participants were reluctant to click on links or attachments. Trust in the people sending the invitations was key. Participants wanted to see messages that COS studies had a meaningful purpose to feel their contributions were valuable. They were keen to contribute to improving future ‘treatment’ but less motivated to improve ‘research’. Messages that evoked a feeling of connection with others who they could relate to were positively regarded. Participants also highlighted ways that invitations could be made more accessible.

CONCLUSION: COS invitations can present numerous challenges for potential participants, but our study indicates ways that COS developers can address these challenges and make their invitations more appealing to potential participants. As part of the wider Good Research Invitation Study the findings have been used to inform guidance on designing a good COS invitation.

PMID:42613120 | DOI:10.1136/bmjopen-2025-111016

BMJ Open. 2026 Aug 18;16(8):e122147. doi: 10.1136/bmjopen-2026-122147.

ABSTRACT

INTRODUCTION: Music-based interventions are increasingly used as supportive, non-pharmacological approaches in clinical care, yet nursing roles are often described inconsistently and intervention terminology and reporting remain heterogeneous. This scoping review will map the available evidence on music-based interventions with an explicit nursing role, referred to collectively in this review as nurse-led music-based interventions, for patients or care recipients across clinical care settings, with attention to populations, nursing roles, intervention characteristics, reported outcomes and implementation issues.

METHODS AND ANALYSIS: The review will follow Joanna Briggs Institute (JBI) scoping review methodology and will be reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Preliminary searches of MEDLINE, CINAHL, Embase, Scopus, Web of Science Core Collection, PsycINFO, CNKI, Wanfang Data and VIP Information were conducted on 4 May 2026 solely to validate the database-specific search strategies; the formal search has not commenced. Formal searches of these databases and planned grey literature sources will be conducted from 1 to 7 September 2026, with an update search in February 2027 and completion anticipated in March 2027. Eligible sources will report an explicit and identifiable nursing role in a music-based intervention. Primary roles will be classified using prespecified responsibility-based definitions as nurse-led, nurse-managed, nurse-coordinated, nurse-delivered, nurse-facilitated or multidisciplinary with an explicit nursing role; all reported nursing activities and multidisciplinary involvement will also be retained. Two reviewers will independently undertake each stage of study selection and data charting, with adjudication when consensus cannot be reached. Findings will be presented through descriptive summaries, evidence mapping, tabular displays and narrative synthesis.

ETHICS AND DISSEMINATION: Ethical approval is not required because this review will use published and publicly accessible sources. Findings will be disseminated through peer-reviewed publication and conference presentations.

REGISTRATION DETAILS: The protocol was registered on the Open Science Framework on 11 April 2026 (https://osf.io/c6ytn).

PMID:42613119 | DOI:10.1136/bmjopen-2026-122147

BMJ Open. 2026 Aug 18;16(8):e115951. doi: 10.1136/bmjopen-2025-115951.

ABSTRACT

OBJECTIVES: To clarify the epidemiology and risk factors for sepsis among trauma patients admitted to the intensive care unit (ICU) using the Japan Trauma Data Bank (JTDB).

DESIGN: Retrospective cohort study.

SETTING: Analysis of nationwide JTDB data collected between 2004 and 2019 in Japan.

PARTICIPANTS: A total of 126 433 adult trauma patients with an Abbreviated Injury Scale score ≥3 who survived for at least 72 hours after ICU admission were included.

PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was in-hospital mortality among patients who developed sepsis after trauma. The secondary outcome was identification of risk factors associated with post-traumatic sepsis using multivariable logistic regression analysis.

RESULTS: Sepsis developed in 972 patients (0.77%) and was associated with significantly higher in-hospital mortality compared with patients without sepsis (42.4% vs 4.6%, p<0.001), as well as longer hospital stay (47 vs 20 days, p<0.001). Independent risk factors for sepsis included older age (adjusted OR (aOR) 1.02, 95% CI 1.02 to 1.03), male sex (aOR 1.48, 95% CI 1.27 to 1.73), higher Injury Severity Score (ISS) (aOR 1.58, 95% CI 1.39 to 1.80), blood transfusion within 24 hours of arrival (aOR 2.78, 95% CI 2.36 to 3.26), abdominal or pelvic trauma (aOR 2.28, 95% CI 1.91 to 2.73) and lower extremity trauma (aOR 1.66, 95% CI 1.42 to 1.94). Conversely, head trauma was associated with a lower risk of sepsis (aOR 0.67, 95% CI 0.55 to 0.80). Similar trends were observed in subgroup analyses stratified by ISS.

CONCLUSIONS: Although post-traumatic sepsis was uncommon, it was associated with markedly increased mortality. Older age, male sex, severe injury, early blood transfusion and abdominal/pelvic or lower extremity trauma were identified as major risk factors for sepsis after trauma.

PMID:42613118 | DOI:10.1136/bmjopen-2025-115951

BMJ Open. 2026 Aug 18;16(8):e118825. doi: 10.1136/bmjopen-2026-118825.

ABSTRACT

INTRODUCTION: The mental health of primary healthcare (PHC) workers is a determinant of service quality and sustainability in the Brazilian Unified Health System (SUS). Brazilian observational studies report symptoms of common mental disorders, anxiety, depression, burnout, insomnia and stress among PHC workers, but the evidence is fragmented across settings, occupational categories, instruments and time periods. This protocol describes a systematic review and prevalence meta-analysis to consolidate prevalence estimates and synthesise associated sociodemographic, occupational and organisational factors among PHC workers in Brazil.

METHODS AND ANALYSIS: We will conduct a systematic review and prevalence meta-analysis in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and report the completed review following PRISMA 2020. We searched MEDLINE (via PubMed), Embase, PsycINFO, CINAHL and BVS/LILACS from inception to 16 September 2025, complemented by grey literature searches (Google Scholar and CAPES Theses and Dissertations) and reference-list screening. Eligible studies will be quantitative observational studies conducted in Brazil with workers linked to PHC within the SUS, including health professionals and other occupational groups (eg, community health workers and administrative/operational staff). Studies must report prevalence based on validated instruments for use in Brazilian populations and an explicit case definition/cut-off for common mental disorders, anxiety symptoms, depression, burnout, insomnia and stress. Two independent reviewers will screen records and full texts in Rayyan; disagreements will be resolved by consensus or a third reviewer. Risk of bias will be assessed using the Joanna Briggs Institute checklist for prevalence studies. We will pool prevalence estimates by outcome using random-effects models (primary approach: binomial models), quantify heterogeneity (I², τ², Q) and estimate prediction intervals. Prespecified subgroup/sensitivity analyses will explore geographic region, occupational category, instrument/cut-off, sampling approach, risk of bias and data collection period, classified as prepandemic, pandemic/postpandemic or mixed. Associated factors will be synthesised as a structured narrative by domain; meta-analysis of associations will be considered only when exposure definitions and effect measures are sufficiently comparable.

ETHICS AND DISSEMINATION: Ethics approval is not required because this study uses secondary data from published reports. For queries related to research integrity, please contact the Research Ethics Committee of the Federal University of Espírito Santo ([email protected]). Findings will be disseminated through publication in a peer-reviewed journal and presentations at scientific meetings.

PMID:42613114 | DOI:10.1136/bmjopen-2026-118825

BMJ Open. 2026 Aug 18;16(8):e105911. doi: 10.1136/bmjopen-2025-105911.

ABSTRACT

OBJECTIVES: To assess access, barriers and health outcomes of abortion and postabortion care in humanitarian and fragile settings across Africa.

DESIGN: Systematic review following Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines.

DATA SOURCE: Scopus, PubMed, Epistemonikos, along with websites like Google and Google Scholar were searched through 15 February 2025.

ELIGIBILITY CRITERIA: Studies conducted in African humanitarian settings that focus on abortion, postabortion care and abortion-related complications were included, regardless of study design or language.

DATA EXTRACTION AND SYNTHESIS: Before commencing actual data extraction, a prior data extraction template was developed by reviewers through using a sample of two included articles. The thematic content analysis was conducted using MAXQDA software, guided by the socioecological model.

RESULTS: Humanitarian conditions increased unintended pregnancies and demand for abortion services while health system disruptions limited access to safe care. Women were frequently resorting to unsafe abortion methods using traditional substances, detergents or harmful objects because of legal restrictions, stigma and limited access to family planning. Delays in abortion care are often driven by distance, cost, lack of confidentiality and fear of legal consequences. Cultural influences and cost concerns also led women to delay seeking healthcare, resulting in complications. Common challenges across many humanitarian settings included limited access to family planning, inadequate health system infrastructure and shortages of trained healthcare providers. Barriers are operated across individual, community, health system and policy levels, reinforcing inequities in access and outcomes.

CONCLUSIONS: In African humanitarian settings, barriers to safe abortion and postabortion care are amplified in humanitarian settings through interconnected social, structural and policy factors including legal ambiguity. Implementing comprehensive strategies such as empowering women, engaging communities, reforming policies and strengthening health systems can help improve access, safety and maternal health outcomes in humanitarian settings, thereby reducing unsafe abortions and enhancing postabortion care.

TRIAL REGISTRATION NUMBER: CRD420251026961.

PMID:42613113 | DOI:10.1136/bmjopen-2025-105911

BMJ Open. 2026 Aug 18;16(8):e122680. doi: 10.1136/bmjopen-2026-122680.

ABSTRACT

INTRODUCTION: Long-term sickness absence represents a major public health challenge with far-reaching consequences for both individuals and society. Musculoskeletal disorders (MSDs) are among the leading causes of sickness absence. Although mobile apps show promise for supporting self-management of MSDs, high-quality evidence remains limited, and outcomes related to work participation are rarely examined. This trial aims to evaluate whether an individually tailored, app-based self-management intervention (SmaRTWork), provided in addition to usual care, improves return-to-work compared with usual care alone among individuals on sick leave due to MSDs.

METHODS AND ANALYSIS: We will conduct a randomised controlled trial with two parallel arms: 1) SmaRTWork in addition to usual care and 2) usual care alone. Individuals 20-59 years old who have been sick-listed for <12 weeks due to back, neck or widespread pain will be recruited through clinicians in primary health care. Eligible participants are randomised 1:1 to one of the two arms. We aim to include 298 participants, 149 in each arm. The primary outcome is time to sustainable return-to-work, defined as one consecutive month without receiving medical benefits, assessed over a 12-month period using registry data. Secondary outcomes include health-related measures assessed at baseline, 3, 6 and 12 months. The trial will also incorporate qualitative studies, a process evaluation and a health economic evaluation.

ETHICS AND DISSEMINATION: The trial is approved by the Committees for Clinical Trials of Pharmaceuticals and Medical Devices (Ref. 563919). Results will be published in peer-reviewed journals and presented at national and international conferences.

TRIAL REGISTRATION: NCT07034040.

PMID:42613108 | DOI:10.1136/bmjopen-2026-122680