BMC Medicine[JOURNAL]
Sun
200 papers
Therapeutic activation of PPARα contributes to NOTCH1 inhibition in T-cell acute lymphoblastic leukemia.
Li W, Zhou H, Qin D … +5 more , Lin J, Jia S, Weng J, Xu B, Zha J
BMC Med · 2026 Jul · PMID 42401925 · Full text
BACKGROUND: The aberrant activation of the NOTCH1 signaling pathway underlies the aggressive malignancy and poor prognosis of T-cell acute lymphoblastic leukemia (T-ALL). METHODS: T-ALL cell lines (Jurkat and Molt4) were...
BACKGROUND: The aberrant activation of the NOTCH1 signaling pathway underlies the aggressive malignancy and poor prognosis of T-cell acute lymphoblastic leukemia (T-ALL). METHODS: T-ALL cell lines (Jurkat and Molt4) were treated with chiglitazar to evaluate viability, proliferation, apoptosis, and cell cycle. RNA-seq, qRT-PCR, and Western blotting were used to examine NOTCH1 signaling. Mechanistic assays included luciferase reporter, DNA affinity precipitation, co-immunoprecipitation, and ChIP. In vivo, cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models were generated by intravenous engraftment of leukemic cells into sublethally irradiated mice, followed by treatment with chiglitazar alone or combined with venetoclax. Therapeutic efficacy was assessed by survival, flow cytometric tumor burden, and histopathology (HE and IHC). RESULTS: We report that therapeutic activation of peroxisome proliferator-activated receptor α (PPARα) significantly represses the leukemogenesis of T-ALL in vitro and in vivo by blocking the NOTCH1 signaling pathway. Mechanistically, PPARα directly binds to the promoter region of the NOTCH1 gene and inhibits its transcriptional activity. Furthermore, PPARα interacts with signal transducer and activator of transcription 3 (STAT3) and attenuates the transcriptional activation effect of STAT3 on the NOTCH1 gene promoter. Importantly, we also found that therapeutic activation of PPARα using chiglitazar synergizes with venetoclax to suppress T-ALL progression in PDX models. CONCLUSIONS: We conclude that targeting PPARα to suppress T-ALL progression by blocking the NOTCH1 pathway represents a potential novel therapeutic strategy for the treatment of T-ALL.
Social vulnerability index and inflammation: a proteomic analysis linking social context to biological risk in older black adults.
Yaskolka Meir A, Adeola HA, Tasaki S … +6 more , Liang L, Robinson RAS, Lange-Maia BS, Lamar M, Capuano AW, Barnes LL
BMC Med · 2026 Jul · PMID 42401874 · Full text
BACKGROUND: Inflammation is a key driver of age-related disease and has been associated with social conditions. We examined how cumulative community-level social and structural disadvantage is associated with inflammator...
BACKGROUND: Inflammation is a key driver of age-related disease and has been associated with social conditions. We examined how cumulative community-level social and structural disadvantage is associated with inflammatory proteomic profiles in older Black adults. METHODS: We employed data from the Minority Aging Research Study and the Rush Clinical Core, including the Social Vulnerability Index (SVI; global score and four domains) and 92 plasma inflammatory proteins (Olink® Target-96 Inflammation). Cross-sectional associations between each SVI metric and inflammatory proteins (principal component (PC)-derived global proteomic profile and protein-specific) were assessed using multivariable linear models (demographic, behavioral, and individual-level socioeconomic factors adjusted), with additional sex-by-SVI interaction terms. In a secondary analysis, we replaced SVI with the Index of Concentration at the Extremes (ICE) for household income (ICE). RESULTS: A total of 580 participants (mean (SD) age of 74.9 (6.50) years; 79.7% women) had global SVI and proteomics assessed. Lower household composition (SVI) was associated with the primary global proteomic profile, represented by the 1 proteomic PC (beta = -0.429, p-value = 0.019). A secondary exploratory analysis using the first five proteomic PCs showed that higher minority status/language (SVI) and socioeconomic status (SVI) were associated with an inflammatory proteomic profile (SVI-PC3: beta=0.160, p-value = 0.048; SVI-PC2: beta = 0.286, p-value = 0.012). In protein-specific analyses, no SVI-protein associations were found. We found an SVI-by-sex interaction for interleukin-10 receptor alpha (IL-10RA; beta = -0.258, p-value = 5.01×10), and among men, SVI was associated with Sirtuin 2 (beta = -0.397, p-value = 8.51×10) and STAM binding protein (beta = -0.304, p-value = 9.87×10). ICE was inversely associated with the global proteomic profile (beta = -0.233, p-value = 0.051), and an ICE-by-sex interaction was found for IL-10RA (beta=0.279, p-value = 4.66×10). CONCLUSIONS: By analyzing associations between community-level factors and inflammation-related proteins, our study provides new molecular insights into how social context may relate to biological risk, identifies proteomic patterns that could inform the development of community-level interventions, and underscores the utility of integrating multi-omics approaches to investigate biological pathways relevant to health disparities research.
Efficacy of remote ischemic conditioning on cerebral blood flow regulation in patients with endovascular stenting: a randomized controlled trial.
Hou YT, Xu BF, Zhang HM … +9 more , Zhang P, He QY, Qu Y, Qi S, Liu J, Zhang PD, Zan W, Yang Y, Guo ZN
BMC Med · 2026 Jul · PMID 42401872 · Full text
BACKGROUND: Postoperative stroke can undermine the benefits of endovascular stenting for cerebrovascular stenosis. This trial investigated whether adjunctive remote ischemic conditioning (RIC) improves cerebral blood flo...
BACKGROUND: Postoperative stroke can undermine the benefits of endovascular stenting for cerebrovascular stenosis. This trial investigated whether adjunctive remote ischemic conditioning (RIC) improves cerebral blood flow (CBF) regulation and reduces the risk of postoperative stroke. METHODS: A total of 104 patients with intracranial or extracranial cerebrovascular stenosis who underwent endovascular stenting were enrolled and randomized to receive either RIC or sham-RIC (1:1). The intervention was administered twice daily for 7 consecutive days postoperatively. CBF regulation was assessed bilaterally using transfer function analysis of spontaneous blood pressure and CBF oscillations at baseline and on day 7 or at discharge. The primary outcomes were phase difference (PD) and gain, whereas the secondary outcomes were 90-day stroke incidence and safety. RESULTS: Significantly higher PD values were observed in the RIC group than in the sham-RIC group on the affected side (40.67° [26.76°-58.28°] vs. 20.51° [10.90°-41.73°], P < 0.001) and the unaffected side (36.04° [21.66°-54.53°] vs. 26.80° [11.94°-44.83°], P = 0.022), indicating improved CBF regulation. Intragroup comparisons revealed significant PD improvement from baseline to day 7 or discharge in the RIC group (affected side: 20.57° [8.70°-34.24°] vs. 40.67° [26.76°-58.28°], P < 0.001; unaffected side: 26.06° [8.70°-44.37°] vs. 36.04° [27.66°-54.53°], P = 0.001). The 90-day stroke incidence was significantly lower in the RIC group (0.00% vs. 9.62%, P = 0.022). CONCLUSIONS: Adjunctive RIC safely enhanced CBF regulation and substantially reduced postoperative stroke in patients after cerebrovascular stenting, suggesting a promising non-pharmacological strategy to improve outcomes. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05970653).
Brief digital narrative intervention for adolescent depression, anxiety, and insomnia during academic stress: a cluster randomized controlled trial.
Luo Y, Fan J, Zang Y
BMC Med · 2026 Jul · PMID 42400035 · Full text
BACKGROUND: High-stakes examinations represent a significant but underrecognized threat to adolescent mental health, contributing to elevated symptoms of depression, anxiety, and insomnia. Despite the global scale of thi...
BACKGROUND: High-stakes examinations represent a significant but underrecognized threat to adolescent mental health, contributing to elevated symptoms of depression, anxiety, and insomnia. Despite the global scale of this problem, effective interventions during these critical periods remain scarce, largely due to implementation barriers in both clinical and educational settings. Scalable, low-resource solutions are urgently needed to address this mental health gap in adolescent care. METHODS: In a cluster randomized controlled trial (ChiCTR2200058881, N = 587), we examined the efficacy of the Guided Narrative Technique (GNT), a brief digital writing intervention, compared to a neutral writing group (NWG). Adolescents preparing for China's College Entrance Examination within 100 days (M = 18.23, SD = 0.60) were assigned to GNT (n = 290) or NWG (n = 297) through class-level cluster randomization and completed three consecutive 20-minute daily sessions. The primary outcome was test anxiety, assessed across the intervention and follow-up period. Secondary outcomes were depression, general anxiety, and insomnia, assessed at baseline, post-intervention, and 15-day follow-up. RESULTS: For the primary outcome, GNT did not produce significantly greater reductions in overall test anxiety than NWG in the full sample. However, GNT was associated with greater reductions on the TAI worry subscale, representing the cognitive component of test anxiety (d = 0.18, 95% CI [0.01, 0.36]) in exploratory subgroup analyses among adolescents with elevated baseline test anxiety. For secondary outcomes, compared with NWG, GNT resulted in significantly greater reductions in depression (d = 0.35, 95% CI [0.16, 0.54]), general anxiety (d = 0.37, 95% CI [0.18, 0.56]), and insomnia (d = 0.23, 95% CI [0.04, 0.42]) during the intervention, with between-group differences also observed for depression and general anxiety at follow-up. CONCLUSIONS: GNT did not significantly reduce overall test anxiety, but showed preliminary benefits for depression, general anxiety, insomnia, and the worry component among adolescents with high baseline anxiety, warranting further evaluation in adequately powered trials. TRIAL REGISTRATION: The study was registered as ChiCTR2200058881.
Effect of Vitamin C on bleeding and pain after kidney biopsy: a randomized controlled trial.
Li J, Zhao F, Lu R … +15 more , Zha Y, Chang F, Li X, Gao J, Shen X, Jia Q, Zhao J, Che X, Xu X, Wu M, Zhang H, Zhang Y, Chen Y, Tan X, He L
BMC Med · 2026 Jul · PMID 42399956 · Full text
BACKGROUND: Percutaneous renal biopsy (PRB) is an essential diagnostic procedure for kidney diseases, yet postbiopsy perirenal hematoma and pain remain frequent complications. Vitamin C has emerging evidence supporting i...
BACKGROUND: Percutaneous renal biopsy (PRB) is an essential diagnostic procedure for kidney diseases, yet postbiopsy perirenal hematoma and pain remain frequent complications. Vitamin C has emerging evidence supporting its role in reducing perioperative bleeding and pain, but its efficacy in the context of PRB is unknown. METHODS: This single-center, prospective, open-label, randomized controlled trial enrolled 710 adults with chronic kidney disease (CKD) scheduled for an ultrasound-guided native kidney biopsy. Participants were randomly assigned (1:1) to receive perioperative intravenous vitamin C (20 mg/kg at 6 h before and 18 h after biopsy) or standard care alone. The primary outcomes were the area of perirenal hematoma on renal ultrasound at 24 h and self-reported pain intensity (Visual Analogue Scale, VAS) at 2, 12, and 24 h post-biopsy. RESULTS: All 710 randomized participants were included in the analysis. The adjusted mean difference in hematoma area at 24 h was 4.44 mm² (95% CI, -52.31 to 61.18; P = 0.878). After multiple testing correction, there were no significant differences in the primary pain outcome (VAS scores) between groups at any time point; however, an exploratory analysis of pain severity categories indicated a less favorable distribution in the Vitamin C group at 12 h (P for trend =0.033). The incidence of any perirenal hematoma was 56.3% in the vitamin C group versus 50.1% in the control group (risk ratio, 1.12; 95% CI, 0.98-1.29; P = 0.098). Rates of other bleeding complications and adverse events were low and comparable between groups. CONCLUSIONS: In CKD patients undergoing PRB, perioperative intravenous vitamin C did not reduce the size of perirenal hematoma, alleviate postbiopsy pain, or decrease the incidence of bleeding complications within 24 h. These findings do not support the routine use of vitamin C for preventing complications after kidney biopsy.
Impact of gestational diabetes on future diabetic retinopathy and microvascular complications: a nationwide cohort study.
Lee SH, Lee KS, Lee JY … +6 more , Choi SW, Lee EK, Yoon CK, Park UC, Park KH, Bae K
BMC Med · 2026 Jul · PMID 42399945 · Full text
BACKGROUND: Gestational diabetes mellitus (GDM) is a well-established risk factor for subsequent type 2 diabetes mellitus (T2DM). However, its long-term association with diabetic microvascular complications, particularly...
BACKGROUND: Gestational diabetes mellitus (GDM) is a well-established risk factor for subsequent type 2 diabetes mellitus (T2DM). However, its long-term association with diabetic microvascular complications, particularly diabetic retinopathy (DR), and the joint role of polycystic ovary syndrome (PCOS) remain incompletely understood. METHODS: Using the Korean National Health Insurance Service database, we conducted a nationwide retrospective cohort study including 406,309 women who had their index delivery between 2005 and 2012. Standard Cox proportional hazards models were used to evaluate the incidence of T2DM and systemic complications. For DR and vision-threatening DR (VTDR), time-varying covariate Cox models were applied in the full cohort, with incident T2DM treated as a time-dependent variable. Sensitivity analyses restricted to women who developed T2DM were also performed. Stratified analyses evaluated the joint and independent effects of coexisting PCOS. RESULTS: During follow-up, women with prior GDM had a higher risk of developing T2DM (adjusted hazard ratio [aHR] 3.52; 95% CI 3.26-3.80). In time-varying analyses, prior GDM was associated with an increased risk of vision-threatening DR (VTDR) (aHR 2.28; 95% CI 1.06-4.92), whereas overall DR did not show a consistent positive association across analysis. Women with both GDM and PCOS had the highest risk of T2DM and VTDR compared with those with neither condition (aHR 4.96 and 31.90, respectively). In contrast, although some macrovascular outcomes showed statistically significant associations, the overall magnitude of risk increase was modest. CONCLUSIONS: A history of GDM was associated with an increased long-term risk of severe diabetic retinal outcomes, particularly VTDR, after the onset of T2DM. The coexistence of PCOS is associated with a higher overall risk burden, with women having both conditions showing the highest risks. These findings support the need for individualized metabolic and ophthalmic surveillance in women with prior GDM, particularly those with coexisting PCOS.
Convergence of schizophrenia risk genes on CALN1 disrupts human forebrain development and drives core psychotic behaviors including hallucination-like perception.
Li HJ, Yu X, Liu X … +7 more , Chen X, Xu J, Chen J, Cheng T, Chung S, Shu Y, Shao Z
BMC Med · 2026 Jul · PMID 42399934 · Full text
BACKGROUND: Schizophrenia, a highly heritable neurodevelopmental disorder characterized by core clinical symptoms such as hallucination, remains poorly understood its polygenic pathogenesis. METHODS: We selected 11 key s...
BACKGROUND: Schizophrenia, a highly heritable neurodevelopmental disorder characterized by core clinical symptoms such as hallucination, remains poorly understood its polygenic pathogenesis. METHODS: We selected 11 key schizophrenia risk genes and generated single-gene-knockout-precise-dorsal/ventral-forebrain-organoids via CRISPR-Cas9 system to investigate the polygenic effects of these schizophrenia risk genes on forebrain development via bulk and scRNA-sequencing, multi-electrode array recording and knockout mouse model. RESULTS: We found that knockout of 11 risk genes leads to different levels of deficits in human dorsal/ventral forebrain organoids. Notably, CALN1 knockout significantly impacted pathways involved in forebrain development and the set of prioritized schizophrenia risk genes. Importantly, Caln1-KO mice exhibited a broad spectrum of schizophrenia-like behaviors, encompassing deficits in spatial memory, social ability and pre-pulse inhibition, alongside spontaneous startle behavior, head-twitch response and hallucination-like perception. At the cellular level, Caln1-deficient mice exhibit abnormal spontaneous abrupt burst spiking in mature layer-5 pyramidal neurons of the prefrontal cortex, and snRNA-seq analysis of Caln1 mice revealed severe transcriptional and gene network dysregulation in layer-5 excitatory neurons. CONCLUSIONS: This study reveals that CALN1 as a pivotal role in schizophrenia risk genes robustly perturb human forebrain development and cause a broad spectrum of schizophrenia behaviors in mice.
Efficacy of leflunomide in active Takayasu arteritis: a randomized double-blind placebo-controlled trial subtitle: Takayasu arteritis clinical trial in China (TACTIC).
Sun Y, Kong X, Dai X … +10 more , Wu R, Pan L, Wu L, Chen X, Yang P, Chen H, Ma L, Jin X, Zhang W, Jiang L
BMC Med · 2026 Jul · PMID 42399917 · Full text
BACKGROUND: Leflunomide (LEF) shows promising effect in Takayasu arteritis (TAK), but evidence from randomized controlled trials is lacking. This study aims to investigate the efficacy and safety of LEF versus placebo co...
BACKGROUND: Leflunomide (LEF) shows promising effect in Takayasu arteritis (TAK), but evidence from randomized controlled trials is lacking. This study aims to investigate the efficacy and safety of LEF versus placebo combined with prednisone for the treatment of TAK. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial at six sites across China, conducting from December 22, 2016, to November 4, 2022. A total of 116 eligible patients were recruited and randomized 1:1 to receive LEF (20 mg/d, p.o.) or matched placebo for 24 weeks, with all patients having initial prednisone of 0.6 mg/kg/d and following a taper starting at week 4. By week 24, patients in the LEF group who did not achieve clinical remission discontinued the study; all other patients (both LEF and placebo groups) received LEF (20 mg/d) from week 25 to week 52. The primary outcome was clinical remission at week 24. Secondary outcomes were time-to-clinical remission, mean prednisone dose at week 24, clinical remission in those who switched to LEF from week 25, disease recurrence and time-to-recurrence, imaging changes, and safety. RESULTS: Fifty-four and 57, 45 and 48 patients were included in LEF and placebo group of modified intention-to-treat (mITT) and per-protocol set (PPS). In mITT set, clinical remission was achieved in 44/54 (81.5%) LEF- and 45/57 (78.9%) placebo-treated patients (risk difference: 2.6, 95%CI: -12.5, 17.2) at week 24. The same trend was observed in the sensitivity analyses. Post hoc analyses indicated greater risk differences (LEF minus placebo) in the female subgroup, ≤ 40 years subgroup, refractory subgroup, systemic symptoms subgroup, imaging type II subgroup and in those achieving the composite endpoint of both clinical remission and stable/improved imaging. At week 24, LEF group had a lower mean prednisone dose (mean difference: -2.1, [-4.3, 0.1] mg/d). Adverse events were observed in 13 (24.5%) LEF- and 22 (39.3%) placebo-treated patients. Serious adverse events were reported in six LEF- and four placebo-treated patients. One death was reported in placebo group. CONCLUSIONS: Although the primary endpoint was not met, our results still provide evidence supporting LEF as a potential alternative treatment option for TAK. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02981979.
Refined AI-ASPECTS with modified atlas and lesion-load thresholds: advancing acute ischemic stroke imaging and prognostic prediction.
Jiang L, Deng X, Li C … +23 more , Zhou Y, Huang H, Xu Q, Cao Z, Nie Z, Cheng X, Shi Y, Peng M, Deng Q, Fang X, Pan C, Ye J, Jiang Z, Guo C, Mantini D, Ding Z, Lu G, Shi F, Yin X, Wang S, Zhu W, Zhang Z, Multi-Center Cooperative Clinical Study Group for “Lesion-Phenotype Brain Mapping in Acute Stroke”
BMC Med · 2026 Jul · PMID 42399913 · Full text
BACKGROUND: The artificial intelligence-assisted ASPECTS (AI-ASPECTS) system has become an increasingly common tool in clinical practice for assessing acute ischemic stroke (AIS). However, current AI-ASPECTS implementati...
BACKGROUND: The artificial intelligence-assisted ASPECTS (AI-ASPECTS) system has become an increasingly common tool in clinical practice for assessing acute ischemic stroke (AIS). However, current AI-ASPECTS implementations still rely on the conventional expert-evaluation framework, which uses a simplified two-slice atlas and arbitrarily selected lesion-load thresholds. Our study aimed to develop a refined AI-assisted ASPECTS (Ref-AI-ASPECTS) framework featuring a seamless & whole middle cerebral artery (MCA) territory atlas and region-specific, optimally determined lesion-load thresholds, and comprehensively evaluate the performance of this framework across various clinical scenarios for AIS. METHODS: We enrolled a cohort of 7,655 AIS patients from eleven centers. Modified atlas was created by expanding conventional atlas based on full MCA territory. Ref-AI-ASPECTS with modified atlas and specific lesion-load thresholds was established using a genetic algorithm. The clinical utility of Ref-AI-ASPECTS was assessed by comparing it to the conventional framework (Con-AI-ASPECTS) in terms of correlation with NIHSS scores on admission, dichotomized prediction of mRS at 3 months, and consistency with expert scoring across the training DWI data, external DWI data, expanded CT data, and real-world prospective DWI data. RESULTS: The Ref-AI-ASPECTS frameworks with modified atlas and specific lesion-load thresholds (2% to 29%) achieved correlation coefficients (r) of -0.414/-0.438/-0.375 and AUC values of 0.665/0.723/0.707 in the training/internal validation/external validation sets, surpassing both Con-AI- (r: -0.336/-0.402/-0.331; AUC: 0.615/0.654/0.654) and expert-ASPECTS (r: -0.196/-0.206/-0.173; AUC: 0.600/0.641/0.644) (all P < 0.01). The intraclass correlation coefficients for expert- and Ref-AI-ASPECTS were 0.82 and 0.81 in the training and external validation DWI sets, respectively, exceeding those of expert- and Con-AI-ASPECTS (0.69/0.67; both P < 0.01). These improvements were consistently validated across expanded CT datasets (AUC: 0.696 and 0.679) and in a real-world prospective cohort (AUC: 0.710). CONCLUSIONS: The Ref-AI-ASPECTS framework outperformed conventional approaches in evaluating baseline neurological deficits and predicting functional outcomes in AIS. Our findings support the potential for its wider implementation in AI-ASPECTS systems. Prospective external real‑world validation remains necessary. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04775147; chictr.org.cn Identifier: ChiCTR2400092230.
Diet quality and progression from health to chronic disease, multimorbidity and mortality in the UK Biobank.
Vázquez-Fernández A, Yévenes-Briones H, Lana A … +3 more , Baylin A, Caballero FF, Lopez-Garcia E
BMC Med · 2026 Jul · PMID 42399732 · Full text
BACKGROUND: Diet quality may influence the progression from health to chronic disease, multimorbidity, and death, but current evidence is limited. METHODS: We aimed to assess the association between diet quality and the...
BACKGROUND: Diet quality may influence the progression from health to chronic disease, multimorbidity, and death, but current evidence is limited. METHODS: We aimed to assess the association between diet quality and the risk of transitioning among four health states using multi-state models: from a healthy (disease-free) state to developing one predefined chronic disease, to multimorbidity and lastly, to death. A total of 84,293 healthy individuals (40-70 years) from the UK Biobank were included and diet quality was assessed through four separate exposures using well-established scores: the Alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), the Alternative Healthy Eating Index 2010 (AHEI-2010), and the healthful Plant-based Diet Index (hPDI). RESULTS: Over 11.2 years follow-up, 22,723 participants developed one predefined chronic disease and 4368 progressed to multimorbidity. A total of 2886 deaths occurred: 770 after multimorbidity, 1512 after one chronic condition, and 604 among participants who did not develop any of the diseases under study. Higher adherence to aMED, DASH, and AHEI-2010 was associated with a reduced risk of developing one chronic disease [HR (95% CI) for highest vs. lowest tertile: 0.92 (0.89, 0.95), 0.94 (0.91, 0.98), and 0.92 (0.89, 0.95)]. aMED was also associated with lower risk of death without any disease [HR: 0.72 (0.56, 0.92)]. aMED and DASH were associated with lower risk of progression to multimorbidity [HRs: 0.92 (0.86, 0.98) and 0.90 (0.83, 0.98)]. aMED and hPDI were associated with lower risk of death after a first disease [HRs: 0.89 (0.79, 1.00) and 0.87 (0.77, 0.98)]. All scores except hPDI were associated with a reduced risk of death after multimorbidity [0.76 (0.61, 0.95) for aMED, 0.71 (0.59, 0.86) for DASH, and 0.80 (0.65, 0.97) for AHEI-2010]. CONCLUSIONS: Our findings indicate that greater adherence to healthy dietary patterns was associated with a reduced risk of progression towards one predefined chronic condition, multimorbidity and death, highlighting their potential protective role in long-term health.
Factors influencing the trustworthiness of non-randomized studies of interventions: a survey of international experts.
Yaacoub S, Ioannidis JPA, Hróbjartsson A … +3 more , Porcher R, Ravaud P, Boutron I
BMC Med · 2026 Jul · PMID 42393714 · Full text
BACKGROUND: Perceived trustworthiness of research may be influenced by factors beyond the risk of bias, including study-related characteristics, research context, and external circumstances. Identifying these factors is...
BACKGROUND: Perceived trustworthiness of research may be influenced by factors beyond the risk of bias, including study-related characteristics, research context, and external circumstances. Identifying these factors is essential for gauging the credibility of non-randomized studies of interventions (NRSIs) as they are interpreted and used in systematic reviews, and for improving their design to ensure that they provide reliable evidence for decision-making. Our objective was to identify factors, not covered in risk of bias assessment tools, that could influence the trustworthiness of NRSIs. METHODS: We conducted a cross-sectional survey of international experts. We defined trustworthiness as the proper, justified or rational trust in the study findings. Using convenience sampling, we recruited participants who were top-cited scientists in the field of epidemiology, members of the Cochrane Bias Group and Cochrane Non-Randomized Studies Methods Group, authors of initiatives related to observational studies and corresponding authors of NRSIs. Through an online survey, we asked them to identify factors that they believe could influence the trustworthiness of NRSIs. We analyzed qualitative data using an inductive thematic approach. We first coded the responses, which were redefined into factors and grouped under themes. We summarized findings in frequencies and percentages. RESULTS: 130 participants out of 1488 contacted completed the survey. Of the 130 participants, 40 (31%) were methodologists and 61 (47%) had 21-40 years of experience in research. The level of expertise in NRSIs ranged from intermediate (35%) to advanced (30%) and expert (30%).We identified a total of 56 factors, with a median of 6 factors per participant (IQR 3; 9, range 0-20). We grouped the factors under 20 domains, when relevant, and eventually under eight overarching themes: Open Science (e.g., transparency, registration), Research Question (e.g., appropriate rationale and hypothesis), Study Methodology (e.g., study design, participants, statistical considerations), Data Source (e.g., quality), Findings and Interpretation (e.g., plausibility of effect estimate), Writing (e.g., appropriate writing), Oversight (e.g., investigators, journal), and Artificial Intelligence (e.g., no suspicion of use in writing or synthesis). CONCLUSIONS: Our findings provide insight to gauge and improve the quality and uptake of NRSIs, with important implications for strengthening evidence-based decision-making in both research and practice.
Structural-functional network decoupling in early stage amyotrophic lateral sclerosis reveals cell-type specific transcriptional signatures.
Luan J, Yun Y, Jiao Y … +15 more , Wang Y, Ma M, Shan D, Wang H, Ji X, Tang Y, Li J, Zhan Z, Sun X, Gao N, Lin P, Yan C, Yu D, Liu S, Liu F
BMC Med · 2026 Jul · PMID 42393685 · Full text
BACKGROUND: Amyotrophic lateral sclerosis (ALS) involves widespread brain network dysfunction, yet the molecular mechanisms linked to these alterations remain poorly understood. We investigated macroscopic structural-fun...
BACKGROUND: Amyotrophic lateral sclerosis (ALS) involves widespread brain network dysfunction, yet the molecular mechanisms linked to these alterations remain poorly understood. We investigated macroscopic structural-functional coupling abnormalities in early-stage ALS (ALS-ES) and their underlying transcriptomic signatures. METHODS: We analyzed multimodal MRI data from 73 patients with sporadic ALS-ES and 74 age- and sex-matched healthy controls. Structural-functional (SC-FC) coupling was quantified using diffusion tensor imaging and resting-state functional MRI. Machine learning models were constructed to distinguish patients from controls based on network features. Coupling alterations were spatially correlated with neurotransmitter receptor maps and gene expression profiles from the Allen Human Brain Atlas. Key transcriptomic findings were validated using independent single-cell RNA sequencing datasets. RESULTS: While structural connectivity remained largely preserved, functional connectivity was significantly reduced in the somatomotor network (SMN). This mismatch manifested as significant SC-FC network decoupling, particularly within the SMN (p = 0.001). A gradient boosting machine model accurately classified patients, identifying SC-FC coupling in the left precentral gyrus as a primary statistical contributor to the classification model. Decoupling spatially correlated with 5-HT2A and mGluR5 receptor distributions. Imaging-transcriptomics linked network failure to a gene signature enriched for synaptic pathways and microglial markers. Single-cell analysis identified FMN1 as a candidate gene whose glial expression spatially associates with network decoupling. CONCLUSIONS: Early-stage ALS is characterized by significant structural-functional network decoupling, primarily in motor systems. This macroscopic failure is linked to specific microglial dysregulation, particularly FMN1 downregulation, providing a multiscale framework bridges statistical neuroimaging signatures with potential cellular pathology.
A lesion-derived brain network of somatic symptoms for transdiagnostic individual application.
Yu Y, Xu W, Ji Y … +13 more , Qi L, Wu Y, Guo Y, Hua Q, Wang L, Qian R, Bai T, Li Q, Geng F, Wan Y, Wang K, Ji GJ, Tian Y
BMC Med · 2026 Jul · PMID 42393674 · Full text
BACKGROUND: Somatic symptoms is an umbrella term that describes distressing somatic complaints occurring across a wide spectrum of diseases. However, their underlying neural mechanisms remain poorly understood. Elucidati...
BACKGROUND: Somatic symptoms is an umbrella term that describes distressing somatic complaints occurring across a wide spectrum of diseases. However, their underlying neural mechanisms remain poorly understood. Elucidating their mechanisms could therefore benefit patients with diverse conditions. METHODS: Using a recently validated lesion network mapping method and a large-scale healthy connectome database (n = 652, recruited in Anhui Province, China), we identified a somatic network from brain lesions causing somatic symptoms. The lesion-derived network was validated using independent multimodal neuroimaging signatures of somatic symptoms and interoceptive processing. It was further characterized by transcriptomic, neurochemical, and cognitive meta-analytic mapping. We further assessed the therapeutic potential of the somatic network by quantifying its spatial convergence with empirically validated neuromodulation targets. Finally, to determine whether the group-level network can predict personalized symptom severity across diagnoses, we built a normative model of gray matter volume using Gaussian process regression based on 1,342 healthy controls from Anhui. This model was then used to generate personalized atrophy maps in 399 local somatic patients with anxiety, depression, schizophrenia and bipolar disorder. We then assessed whether individual atrophy volume within the somatic network was associated with somatic symptom severity. RESULTS: We found that 21 heterogeneous lesions associated somatic symptoms occurred in many different brain locations but were characterized by a common brain network, with the hub region of the right insula and putamen. The somatic network demonstrated strong spatial alignment with multimodal somatic imaging abnormalities from 66 independent studies and interoceptive processing circuits from 69 task-fMRI studies. 11 effective brain stimulation targets were colocalization with the somatic network. In individual transdiagnostic patients, greater atrophy volume within the somatic network was significantly correlated with somatic symptom severity (r = 0.182, p = 0.004), but not with anxiety or depression symptoms. CONCLUSIONS: These convergent findings establish a unified somatic network framework, advancing both mechanistic understanding and precision medicine applications.
Evaluation and analysis of renal injury in patients with advanced renal cell carcinoma receiving first-line benmelstobart plus anlotinib: results from the ETER100 study.
Li J, Tian H, Xu H … +10 more , Yan X, Tang B, Li S, Zhou L, Wu X, Chi Z, Cui C, Si L, Guo J, Sheng X
BMC Med · 2026 Jul · PMID 42387482 · Full text
BACKGROUND: Combination treatment with anti-angiogenic agents and immune checkpoint inhibitors has demonstrated significant efficacy in advanced renal cell carcinoma (RCC). However, data on treatment-emergent renal injur...
BACKGROUND: Combination treatment with anti-angiogenic agents and immune checkpoint inhibitors has demonstrated significant efficacy in advanced renal cell carcinoma (RCC). However, data on treatment-emergent renal injury during combination therapy and its prognostic implications remain limited. This study analyzed renal injury and its association with survival outcomes in patients with advanced RCC receiving first-line benmelstobart combined with anlotinib in the ETER100 trial. METHODS: All randomized patients in the ETER100 (NCT04523272) trial treated with at least one dose of study treatment were included in this analysis. Baseline characteristics, laboratory test results, and information on objective responses, disease progression, and death events were collected. The primary outcomes of this study included renal function changes during therapy, risk factors for renal function abnormalities, clinical outcomes of patients with renal function abnormalities, and the association between renal function abnormalities and survival outcomes. RESULTS: Compared with sunitinib monotherapy, patients receiving benmelstobart combined with anlotinib showed no significant differences in the incidence of serum creatinine elevation (p = 0.0538), percentage decrease in creatinine clearance (p = 0.2546), absolute decrease in creatinine clearance (p = 0.7343), or proteinuria (p = 0.0728). Multivariate analysis identified a history of nephrectomy and estimated glomerular filtration rate <90 mL/min/1.73 m² as independent predictors of serum creatinine elevation in patients receiving combination therapy. As of January 2024, 64.00% of patients (64/100) who developed serum creatinine elevation during combination therapy had recovered to normal levels, and 6.00% (6/100) showed improvement. Besides, 45.56% of patients (77/169) who had proteinuria recovered to normal, and 22.49% (38/169) experienced improvement. Multivariate Cox regression analysis showed that both serum creatinine elevation (progression-free survival [PFS]: p = 0.3526; overall survival [OS]: p = 0.0521) and proteinuria (PFS: p = 0.5831; OS: p = 0.1224) were not independent risk factors for progression-free survival or overall survival in patients receiving combination therapy. CONCLUSIONS: For patients with advanced RCC in the ETER100 trial, combination therapy with anti-angiogenic agents and immune checkpoint inhibitors did not increase the risk of renal injury, and in this treatment context, renal function abnormalities occurring during treatment were not significantly associated with survival outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04523272.
Adverse and positive childhood experiences and suicidal ideation onset in a US pre-early adolescent cohort.
Powers M, Lu M, Koning SM … +3 more , McClendon J, Yang W, Clements-Nolle K
BMC Med · 2026 Jul · PMID 42387476 · Full text
BACKGROUND: Suicide rates among U.S. pre-early adolescents have increased in the past two decades. Exposure to adverse childhood experiences (ACEs) is a strong risk factor for suicidality; however, little is known about...
BACKGROUND: Suicide rates among U.S. pre-early adolescents have increased in the past two decades. Exposure to adverse childhood experiences (ACEs) is a strong risk factor for suicidality; however, little is known about the protective influence of positive childhood experiences (PCEs) in this age group. We investigated whether PCEs at the family, peer, school, and neighborhood levels have a protective association with onset of suicidal ideation in the presence of ACEs (compensatory protection) and buffer the association between ACEs and suicidal ideation (moderating protection) in a cohort of pre-early adolescents. METHODS: This study utilized a community-based cohort of the Adolescent Brain Cognitive Development (ABCD) study, which recruited 9-10 year olds at baseline. We longitudinally analyzed baseline (2016-2018) to year-5 (2021-2023) data (N = 7361). A DSM-V module measured suicidal ideation, and standardized scales were used to assess PCEs. We used mixed logistic regression to assess whether PCEs are associated with first onset of suicidal ideation in the presence of ACEs and moderate the association between ACE exposure and suicidal ideation. All the models accounted for study site clustering and controlled for demographics and medical factors. RESULTS: There was a graded relationship between ACEs and first onset of suicidal ideation. However, prosocial peer involvement (aOR:0.84, 95%CI: 0.78,0.90) and school engagement (aOR:0.71, 95%CI: 0.66,0.77) remained protective in the presence of ACEs. None of the PCEs buffered the association between ACE exposure and suicidal ideation. CONCLUSIONS: We found evidence of compensatory protection through prosocial peer involvement and school engagement. Trauma-informed interventions in school environments are warranted.
Dual-drug-loaded nanohydrogel for intraoperative local application: sequential release-mediated spatiotemporal targeting of diverse secondary injury mechanisms to improve long-term prognosis in traumatic brain injury.
Zhang B, Yang M, Ma S … +8 more , Wang Y, Zhang X, Zhu C, Zheng S, Chen X, Zhang Y, Bai M, Shi G
BMC Med · 2026 Jun · PMID 42381038 · Full text
BACKGROUND: Traumatic brain injury (TBI) can induce both primary and secondary brain injuries. Hampered by a multitude of constraints, including the complexity of secondary injury pathophysiological mechanisms, the selec...
BACKGROUND: Traumatic brain injury (TBI) can induce both primary and secondary brain injuries. Hampered by a multitude of constraints, including the complexity of secondary injury pathophysiological mechanisms, the selective permeability of the blood-brain barrier (BBB), and the side effects of therapeutic agents, systemic monotherapy has demonstrated limited efficacy in improving the long-term prognosis of TBI patients. Therefore, there is an urgent need to develop novel therapeutic strategies that can bypass the BBB, avoid systemic complications, and target multiple secondary injury mechanisms simultaneously. METHODS: An injectable dual-drug-loaded nanohydrogel system was synthesized and its characteristics were evaluated. A mouse controlled cortical impact (CCI) model was established, and the nanohydrogel was locally administered intraoperatively. The neurological prognosis of mice was observed in both acute and chronic phases. Multiple methods, including evans blue assay, magnetic resonance imaging, transmission electron microscopy, western blot, enzyme-linked immunosorbent assay, and immunofluorescence staining, were used to evaluate the cerebral edema, BBB integrity, neuroinflammation, neuronal death/survival, angiogenesis, and neurogenesis after TBI. RESULTS: The nanohydrogel hybridizes hemoglobin (Hb) nanoparticles (NPs) with brain-derived neurotrophic factor (BDNF), uses these as the core to synthesize polydopamine (PDA) NPs, and loads dexamethasone (DEX) on their surface. In vitro drug release experiments confirmed that BDNF@Hb-PDA@DEX@gel had a high drug-loading rate and sequential sustained-release characteristics. The hydrogel matrix exhibited hemostatic and antibacterial effects. Both in vitro and in vivo experiments showed that the nanohydrogel could effectively reduce the acute-phase inflammatory response, protect BBB integrity, and alleviate cerebral edema by releasing DEX. In the late stage, it could promote brain tissue repair by releasing BDNF, including angiogenesis, neurogenesis, and neuron survival. The therapeutic efficacy of this dual-drug sequential delivery system was significantly superior to that of DEX monotherapy, and it could improve both acute and chronic neurological functions. CONCLUSIONS: By virtue of local sequential and sustained release of multiple drugs, the injectable nanohydrogel-based dual-drug delivery system can target multiple secondary injury mechanisms of TBI and exert spatiotemporal therapeutic effects, which provides a new strategy for the effective management of complex secondary brain injury and the improvement of long-term prognosis in TBI.
Single-nucleus analysis of menstrual fluid highlights gene expression differences in epithelial cells of endometriosis donors.
Leap K, Lepelletier A, Liorzou E … +3 more , Doridot L, Brulport A, Berthelot C
BMC Med · 2026 Jun · PMID 42381032 · Full text
BACKGROUND: Endometriosis is a common complex gynecological condition that is difficult to efficiently diagnose and remains poorly understood. Menstrual fluid provides a non-invasive source of disease-relevant tissue and...
BACKGROUND: Endometriosis is a common complex gynecological condition that is difficult to efficiently diagnose and remains poorly understood. Menstrual fluid provides a non-invasive source of disease-relevant tissue and has been identified as promising for endometriosis diagnostics. Peripheral blood-based assays have yielded few clinically relevant targets, thus we hypothesize that cells specific to the uterus will exhibit more disease-related differences and may lead to insights into disease development and potential diagnostic markers. METHODS: We profiled 10 menstrual fluid samples, from 5 donors with endometriosis and 5 donors without, using both single-nucleus RNA sequencing and bulk RNA sequencing. We tested for differential abundance of cell types, differential gene expression within cell types, and differential cell communication between cell types by disease status. Finally, we compared the results of both single-nucleus and bulk RNA sequencing analyses to identify potential diagnostic targets. RESULTS: We identified endometrial and immune cell types present in menstrual fluid, with large inter-individual heterogeneity in cell type representation. While most cells were immune, the cell types with the greatest number of differentially expressed genes were endometrial epithelial cells followed by stromal cells. Epithelial cells in particular recapitulated some gene expression differences previously described in the context of endometriosis, although most identified differences were novel. Cell-cell communication in endometriosis was characterized by a loss of interactions between epithelial and stromal cells related to developmental and growth genes WNT2B, IGF2 and TGFB2, but a gain of cell-cell communications between dendritic cells and other cell types, especially within the BMP signaling pathway. Bulk RNA sequencing revealed that some of the differentially expressed genes found in epithelial cells could be replicated in the whole tissue, highlighting the following genes as biomarker candidates: TIMP2, AKR1C2, DMBT1, FERMT1, and KCNK5. CONCLUSIONS: We identified a set of promising genes that may contribute to endometriosis pathophysiology understanding and have potential as diagnosis biomarkers in whole menstrual blood. Further assessment of their stability over time within each patient and in a larger cohort will confirm whether this represents a viable non-invasive strategy to reduce diagnostic delays.
Impact of hepatotoxicity and lipid metabolism-related toxicity on survival and quality of life in patients with high-volume metastatic hormone-sensitive prostate cancer treated with rezvilutamide in the CHART trial: a post hoc analysis.
Wu JL, Jiang SS, Luo H … +24 more , Dong P, Wang ZJ, Xing NZ, Ma T, Wang ZP, Gu XQ, Zhou GC, Xue XY, Sun ZQ, Yang Y, Wang CX, Shan GY, Zhang AL, Ding DG, Wang LP, Duan XH, Wang TT, He T, Lin CY, Zhong XW, Lian JP, Wang WL, Ye DW, Dai B
BMC Med · 2026 Jun · PMID 42380973 · Full text
BACKGROUND: The CHART study demonstrated that rezvilutamide plus androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus bicalutamide plus...
BACKGROUND: The CHART study demonstrated that rezvilutamide plus androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus bicalutamide plus ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), with an acceptable safety profile. This post hoc analysis evaluates the impact of hepatotoxicity and lipid metabolism-related toxicity (LMRT) on long-term survival and quality of life (QoL) in this population. METHODS: Data from 323 patients with high-volume mHSPC who received rezvilutamide plus ADT were analyzed. Hepatotoxicity was defined as elevations in γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, or bilirubin, whereas LMRT included hypertriglyceridemia, hypercholesterolemia, and weight gain. All P values were nominal. RESULTS: Any-grade hepatotoxicity and LMRT occurred in 24.6% (79/323) and 56.7% (183/323) of patients, respectively. No significant differences in rPFS (hazard ratio [HR], 0.716; 95% confidence interval [CI], 0.434-1.181; P = 0.1908), OS (HR, 0.890; 95% CI, 0.532-1.489; P = 0.6569), or QoL were observed between patients with and without hepatotoxicity. In contrast, patients who developed LMRT showed longer rPFS (HR, 0.594; 95% CI, 0.400-0.883; P = 0.0100) and OS (HR, 0.594; 95% CI, 0.383-0.922; P = 0.0201) than those without LMRT. Patients experiencing grade ≥3 LMRT demonstrated greater improvements in QoL scores from baseline. CONCLUSIONS: This is the first study to evaluate the association of hepatotoxicity and LMRT with clinical outcomes in patients with high-volume mHSPC treated with rezvilutamide plus ADT. Hepatotoxicity was not significantly associated with survival or QoL, whereas LMRT was associated with prolonged rPFS and OS, and grade ≥3 LMRT was associated with more pronounced improvements in QoL. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03520478.
The impact of public health and social measures on social contact patterns and transmission of COVID-19 in Hong Kong.
Choi H, Prem K, Kwok S … +5 more , Lau E, Leung GM, Jit M, Leung K, Wu JT
BMC Med · 2026 Jun · PMID 42380961 · Full text
BACKGROUND: Public health and social measures (PHSMs) are key interventions during pandemics. This study quantifies temporal changes in daily interpersonal contacts associated with PHSM implementation and their potential...
BACKGROUND: Public health and social measures (PHSMs) are key interventions during pandemics. This study quantifies temporal changes in daily interpersonal contacts associated with PHSM implementation and their potential impact on disease transmission across different phases of the COVID-19 pandemic in Hong Kong from 2021 to 2023. METHODS: We recruited 7,053 individuals from the general population and 3,462 participants from selected high-contact groups between September 2021 and December 2023. The study period spanned the infection-naïve phase before 2022 through the city's fifth wave of COVID-19 (January-April 2022) driven by the Omicron BA.2 variant. Reported cumulative incidence was < 0.2% of the population before the fifth wave and rose to 16% afterward. The onset of the fifth wave prompted the government to impose unprecedentedly stringent PHSMs. Participants reported their daily number of contacts via contact surveys, from which we constructed social contact matrices. We then compared the dominant eigenvalues of these contact matrices to estimate the potential association of PHSMs with changes in the basic reproduction number ([Formula: see text]). RESULTS: Among the general population, the average number of daily contacts dropped significantly from 6.2 (mean; 95% confidence interval [CI]: 5.9-6.5) during pre-fifth wave to 5.1 (5.0-5.3) during the fifth wave. After the fifth wave, the average number of contacts remained low at 5.1 (5.0-5.3) when some PHSMs such as mask-wearing policies were still in place. Once all PHSMs were lifted after March 2023, the average number of contacts increased to 8.4 (8.3-8.5). Compared to the general population, participants from the selected high-contact groups reported more contacts by 23% (95% CI: 21%-26%) on average. Compared to pre-fifth wave levels, PHSMs imposed during the fifth wave were associated with a 20% reduction (median; 95% percentile interval: 1%-40%) in [Formula: see text]. Relaxation of PHSMs in the post-pandemic period suggested an increase in [Formula: see text] by 109% (61%-151%) relative to pre-fifth wave levels. CONCLUSIONS: During the COVID-19 pandemic in Hong Kong, PHSMs were temporally associated with reduced social contacts and, potentially, disease transmission. These quantitative estimates may indicate the potential value of PHSMs for informing future pandemic preparedness and response.
Leveraging primary care data to understand military veteran health in England: feasibility study and matched-control comparison of recorded conditions.
Almeida-Meza P, Dregan A, Croak B … +3 more , Hettiaratchy S, Fear NT, Stevelink SAM
BMC Med · 2026 Jun · PMID 42380894 · Full text
BACKGROUND: Evidence on the health needs of UK veterans accessing primary care is limited. Electronic health records (EHRs) offer an opportunity to address this evidence gap if veterans are correctly identified. This stu...
BACKGROUND: Evidence on the health needs of UK veterans accessing primary care is limited. Electronic health records (EHRs) offer an opportunity to address this evidence gap if veterans are correctly identified. This study validated the identification of veterans in the Clinical Practice Research Datalink (CPRD) and assessed its feasibility for examining their health compared with non-veterans. METHODS: We conducted a matched cohort study in CPRD, the largest primary care database in the UK, identifying veterans using military-related codes in patients' EHRs. Each veteran was matched to one or two non-veterans on age, gender, practice, and index date. Validation was undertaken through general practitioner confirmation of veteran status. We compared demographics, risk factors and recorded health conditions using descriptive statistics. Poisson regressions assessed the association between veteran status and various physical and mental health conditions. RESULTS: 122,484 veterans and 244,573 matched non-veterans were identified. 95% were captured using definite military terms, and validation showed substantial agreement with GP records. Veterans had higher recorded prevalence across all conditions. The largest differences were observed for PTSD (adjusted prevalence ratio [aPR] 16.43, 95% CI 14.89-18.13), followed by Alzheimer's disease (aPR 2.74, 95% CI 2.56-2.92), alcohol use disorder (aPR 2.23, 95% CI 2.09-2.39), hearing loss (aPR 2.09, 95% CI 2.02-2.15), and osteoarthritis (aPR 1.98, 95% CI 1.93-2.03). Recorded prevalence was also higher among veterans for COPD (aPR 1.83, 95% CI 1.77-1.89), depression (aPR 1.83, 95% CI 1.79-1.87), prostate cancer (aPR 1.83, 95% CI 1.73-1.94), coronary heart disease (aPR 1.78, 95% CI 1.72-1.84), lower back pain (aPR 1.73, 95% CI 1.70-1.77), and myocardial infarction (aPR 1.65, 95% CI 1.56-1.75). Differences for anxiety and breast cancer were modest. CONCLUSIONS: This study establishes a foundation for UK veterans' health research using primary care data. Provided that identification and recording of veteran status improve in NHS records, CPRD offers considerable potential to monitor veteran health trends, identify needs, and evaluate interventions at scale.
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