Tag: pubmed

Implement Sci Commun. 2025 Jun 16;6(1):72. doi: 10.1186/s43058-025-00756-3.

ABSTRACT

BACKGROUND: The Normalization MeAsure Development (NoMAD) questionnaire is used to assess implementation processes based on Normalization Process Theory (NPT). However, its psychometric properties have not been extensively evaluated. This study aimed to examine the factorial validity, internal consistency, and measurement invariance at both scale and item levels of the NoMAD across three hybrid effectiveness-implementation studies determining the impact of routine symptom surveillance and guideline-based symptom management interventions in ambulatory oncology care settings.

METHODS: A cross-sectional survey was conducted with 328 healthcare personnel (74.% clinicians) participating in the Improving the Management of SymPtoms during And following Cancer Treatment (IMPACT) Research Consortium between 2019 and 2024. Confirmatory factor analysis (CFA) tested the hypothesized four-factor structure (coherence, cognitive participation, collective action, reflexive monitoring). Internal consistency was assessed with McDonald’s omega and Cronbach’s alpha coefficients (> 0.70 acceptable). Measurement invariance was tested across research centers, professional roles, and years in current roles using multi-group CFA. Model fit was defined by standard fit indices (Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI) values ≥ 0.95, Root Mean Square Error of Approximation (RMSEA) values ≤ 0.06, and Standardized Root Mean Square Residual (SRMR) values ≤ 0.08. Differential item functioning (DIF) was evaluated using ordinal logistic regression and item response theory methods (ΔR2 ≥ 0.02 indicative of meaningful DIF).

RESULTS: The four-factor model demonstrated good fit to the data (CFI = 0.97, TLI = 0.96, RMSEA = 0.06, SRMR = 0.05). All factor loadings were statistically significant (p < 0.001), ranging from 0.606 to 0.871. Internal consistency was satisfactory for all four constructs (Omega range: 0.789-0.864, Cronbach’s alpha range: 0.782-0.863). The NoMAD exhibited configural, metric, and scalar invariance across research centers, roles, and years in the current role. One item (“The staff agree that the intervention is worthwhile”) showed uniform DIF across healthcare systems (ΔR2 = 0.047), but no DIF was found by role or years in the current role.

CONCLUSIONS: This study supports the factorial validity, internal consistency, and measurement invariance of the NoMAD across three oncology implementation efforts. The presence of DIF in one item provides an opportunity for refinement in this healthcare context. Researchers and practitioners can use the NoMAD to assess and compare implementation processes, informing the development and evaluation of implementation strategies.

TRIAL REGISTRATION: (ClinicalTrials.gov ID NCT03850912, NCT03892967, NCT03988543).

PMID:40524282 | DOI:10.1186/s43058-025-00756-3

Disaster Med Public Health Prep. 2025 Jun 17;19:e153. doi: 10.1017/dmp.2025.10069.

ABSTRACT

OBJECTIVES: As the global incidence of heat-related illnesses escalates in the wake of climate change-induced heat waves, the critical necessity for reliable diagnostic tools becomes apparent. This scoping review aimed to summarize the existing body of published evidence on biomarkers that could potentially be utilized for the diagnosis of heat-related illness in the clinical setting.

METHODS: We conducted a thorough search of 3 databases, including Embase, MEDLINE, on Ovid, and The Cochrane Library (Wiley) databases from October 11, 2022 up until January 15, 2024. We also manually included studies by searching the reference lists of the included articles. Studies that performed statistical validation were summarized in detail.

RESULTS: 2877 citations were identified and screened, with 228 studies reviewed as full text. 56% of these studies were conducted within China or North America. The studies identified 113 biomarkers. Most common biomarkers studied were troponin I, IL-6, platelets, and ALT. The studies exhibited considerable variation, reflecting the diverse range of investigated biomarkers and the absence of standardized statistical validation for the biomarkers.

CONCLUSIONS: Numerous biomarkers have been evaluated in the literature, but none have been studied to impact clinical practice. There is significant variation in the methodology and statistical validation. There is a need for further research to identify clinically relevant biomarkers for heat related illnesses.

PMID:40524268 | DOI:10.1017/dmp.2025.10069

Clin Epigenetics. 2025 Jun 16;17(1):103. doi: 10.1186/s13148-025-01912-1.

ABSTRACT

BACKGROUND: Cancer remains a serious public health problem impeding gains in life expectancy. Epigenetic clocks, derived from sets of DNA methylation CpGs and mathematical algorithms, have demonstrated a remarkable ability to indicate biological aging and age-related health risks. Dunedin(P)ace(o)f(A)ging(m)ethylation is a single-timepoint DNA methylation clock. It is an aging speedometer rather than a state measure. The association between the DunedinPoAm-measured pace of biological aging and cancer risk based on a nationally non-institutionalized sample remains to be elucidated. Physical activity, a modifiable lifestyle factor, is associated with delayed biological aging and lower risks of developing cancer. We hypothesized that DunedinPoAm-measured pace of biological aging is positively associated with cancer risk, and physical activity moderates this association.

RESULTS: In total, 2,529 participants aged 50 or older from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 were included. Weighted logistic regression calculating odds ratios (OR) and 95% confidence intervals (CI) showed that when scaled per 1-SD increase, DunedinPoAm was positively associated with cancer risk (OR, 95% CI) (1.21, 1.05-1.39) in the crude model and adjusted for age and sex (1.19, 1.01-1.40). Individuals of high DunedinPoAm tertile had a 68% (95% CI 1.16-2.43) increase in cancer risk compared with the low tertile (P trend < 0.001). As hypothesized, effect modification by physical activity was significant (P interaction = 0.013). The association was apparent in physically inactive participants (1.52, 1.16-2.00), whereas insignificant in physically active individuals (1.08, 0.89-1.32). Exploratory interaction analyses for other covariates showed significant effect modification by age (> 65 years, 1.38, 1.08-1.77 vs 50-65 years, 1.00, 0.79-1.27).

CONCLUSION: The study supported the hypothesis by demonstrating a positive association between the DunedinPoAm-measured pace of biological aging and cancer risk and a modulating role of physical activity. Physically inactive individuals or participants over 65 years showed increased susceptibility to this association. These findings suggest that incorporating the DunedinPoAm-measured pace of biological aging into cancer screening strategies may benefit those with physically inactive lifestyles and older individuals. Whether physical activity can mitigate the increased risk of cancer in individuals with a faster pace of biological aging needs to be validated in further interventional cohort studies.

PMID:40524240 | DOI:10.1186/s13148-025-01912-1

Cancer Metab. 2025 Jun 16;13(1):30. doi: 10.1186/s40170-025-00388-0.

ABSTRACT

BACKGROUND: Colon cancer is strongly influenced by lifestyle factors. Sociodemographic factors like sex and socioeconomic position (SEP) might modulate the relationship between lifestyle and colon cancer risk. Metabolomics offers potential to uncover biological mechanisms linking lifestyle and colon cancer.

METHODS: Lifestyle and untargeted metabolomic data were available from a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 1,067 colon cancer cases and 1,067 controls matched on age, sex, study centre, and blood collection time. Serum samples were analyzed using liquid chromatography-mass spectrometry. The Healthy Lifestyle Index (HLI) score was derived from smoking habits, alcohol intake, body mass index (BMI), physical activity, and diet. Penalised regression was applied in controls to derive metabolic signatures for the HLI and the lifestyle components. Associations of lifestyle factors and the metabolic signatures with colon cancer risk were estimated in conditional logistic regression models, overall and by sex and SEP.

RESULTS: The HLI score was inversely associated with colon cancer risk, with an odds ratio (OR) per 1-standard deviation (SD) increment equal to 0.79; 95% CI: 0.71, 0.87. The metabolic signature of HLI, comprising 130 features, was moderately correlated with HLI (r = 0.59; 94% CI: 0.56, 0.61), and was inversely associated with colon cancer risk (OR = 0.86; 95% CI: 0.78, 0.95). After adjustment for the HLI score, the association of the metabolic signature of HLI and colon cancer risk was null (OR = 1.00, 95% CI 0.88, 1.13). Associations of lifestyle factors and the metabolic signature with colon cancer risk were consistently stronger for men than for women and did not differ by SEP.

CONCLUSIONS: In this study across seven European countries, healthy lifestyle was inversely associated with colon cancer risk, with stronger associations in men than women and no differences across SEP. However, the serum metabolic signatures after adjustment for lifestyle factors were not found to be associated with colon cancer risk, suggesting that lifestyle impacts colon cancer through mechanisms not captured by the signatures.

PMID:40524238 | DOI:10.1186/s40170-025-00388-0

J Orthop Surg Res. 2025 Jun 16;20(1):592. doi: 10.1186/s13018-025-06009-2.

ABSTRACT

BACKGROUND: Magnetically controlled intramedullary lengthening nails offer a fully internal approach to limb lengthening, avoiding complications associated with external fixators such as pin site infections and soft tissue transfixation. While their use in adults is well-documented, evidence regarding their safety and efficacy in adolescents and young adults remains limited.

METHODS: This retrospective cohort study evaluated the clinical and radiological outcomes of 24 limb lengthening procedures performed in 18 adolescent and young adult patients between 2022 and 2024 using PRECICE^® intramedullary lengthening nails. Patients aged ≤ 18 years with a minimum of 9 months follow-up were included. Lengthening parameters, regenerate morphology, complication rates, and inter-group comparisons were analyzed.

RESULTS: A total of 24 long bone segments (femur, tibia, and humerus) underwent lengthening in 19 sessions. The mean follow-up period was 18.8 months. The average length gained was 45.7 ± 10.5 mm, with a distraction rate of 1.0 ± 0.1 mm/day. Complications requiring return to the operating room occurred in 16% of cases, while 5.3% had minor unresolved issues at treatment completion. Radiographic analysis revealed favorable regenerate morphology, and no case showed regenerate insufficiency. Statistical comparison revealed a significantly higher distraction rate in femoral versus tibial lengthenings (p = 0.036).

CONCLUSIONS: Fully internal limb lengthening using magnetically controlled nails is a safe and effective option for adolescents and young adults, with a low rate of complications and high-quality regenerate formation. These findings support broader adoption of internal lengthening in younger patients, particularly in centers with trained teams and appropriate patient selection.

PMID:40524232 | DOI:10.1186/s13018-025-06009-2

Diabetol Metab Syndr. 2025 Jun 16;17(1):219. doi: 10.1186/s13098-025-01756-y.

ABSTRACT

BACKGROUND: As the immune response product to food antigens, food-specific serum immunoglobulin G reactivity (FSsIgGR) has been reported the clinical relevance to metabolic disorders, but its connections to metabolic dysfunction-associated fatty liver disease (MAFLD) remain underexplored, particularly within Chinese populations. Understanding this association could facilitate personal diet modification for MAFLD treatment. We investigated the association between FSsIgGR and MAFLD and the mediating roles of plasma glucose markers, specifically fasting blood glucose (FPG) and hemoglobin A1c (HbA1c).

METHODS: This study utilized data from the Second Medical Center of the Chinese PLA General Hospital from 2017 to 2021, to analyze the relationships between FSsIgGR and MAFLD in 25,928 participants. Using a robust sampling method and adjusting for various covariates, we explored both linear and nonlinear associations using linear regression models, restricted cubic splines (RCS), subgroup analysis, and sensitivity analysis. Furthermore, mediation analyses were conducted to evaluate the role of plasma glucose markers, such as FPG and HbA1c, in these relationships.

RESULTS: The overall prevalence of FSsIgGR-positive and MAFLD was 60.8% and 53.5%, respectively, with a mean age of 49.6 ± 9.7 years (68.8% male). Both the quantity and level of FSsIgGR exhibited negatively linear associations with MAFLD (OR 0.98, 95% CI 0.96-0.99, P = 0.041; OR 0.99, 95% CI 0.97-0.99, P = 0.044), even after adjusting for multiple covariates. Sensitivity analyses supported the robustness of these findings. Of note, subgroup analysis showed that FSsIgGR still was negatively associated with MAFLD patients without Type 2 diabetes (OR 0.98, 95% CI 0.95-0.99) or insulin resistance (OR 0.97, 95% CI 0.94-0.99), while that statistical significance of associations disappears in MAFLD patients with Type 2 diabetes or insulin resistance. Furthermore, plasma glucose markers, particularly FPG, significantly mediated the relationship between FSsIgGR and MAFLD, with indirect effects estimated at 15.5% (P = 0.0002).

CONCLUSIONS: These findings indicated FSsIgGR was linked to a reduced risk of MAFLD, particularly MAFLD without Type 2 diabetes or insulin resistance, and plasma glucose mediated that process. Further research is needed to elucidate the mechanism underlying that association, expecting to provide reference for personalized diet of MAFLD patients.

PMID:40524225 | DOI:10.1186/s13098-025-01756-y

Orphanet J Rare Dis. 2025 Jun 16;20(1):309. doi: 10.1186/s13023-025-03750-z.

ABSTRACT

Precision treatments for monogenic epilepsies, i.e. treatments that can at least partially reverse the biochemical consequences of a pathogenic gene variant, have been gradually emerging over the years. To date, however, information on the efficacy of these treatments is mostly based on case-reports and retrospective studies. As a result, utilisation of precision treatments often lack consistency and a pre-defined outcome monitoring plan. N-of-1 strategies in clinical care are pre-defined, individually tailored, repeated challenge-withdrawal therapeutic trials designed to assess the value of a treatment of interest for an individual. Despite their potential to improve clinical decision-making, N-of-1 strategies have been hampered by limited guidance on their implementation and lack of consensus on oversight procedures. To improve treatment selection for rare monogenic epilepsies, the PINPOINT initiative (Precision Treatments In MoNogenic EPilepsies: Observational Registry And N-of-1 Trial Recommendations) was set up as a collaborative effort within the European Reference Network for Rare and Complex Epilepsies. PINPOINT aims to develop recommendations for the design of N-of-1 strategies with off-label precision treatments for monogenic epilepsies. Using available N-of-1 trial manuals, different components of N-of-1 design were tailored to the context of epilepsy and oversight procedures were outlined. These efforts resulted in this guidance document-or blueprint for N-of-1 strategies for monogenic epilepsies in clinical care. This blueprint defines the characteristics of treatments and patients that would be suitable for N-of-1 strategies. Key principles for outcome measure selection, period duration and statistical analysis are defined. Consideration is given to interim assessment rules, which establish whether proceeding onto an additional treatment cycle is likely to provide significant advantages. Procedures for ethical oversight are proposed. This blueprint for N-of-1 strategies can be used as a basis for master protocols to optimise individualised clinical care in a standardised and consistent manner. We are confident that this document will provide physicians with the building blocks needed to elevate precision treatments for rare monogenic epilepsies out of their current landscape of inadequate evidence.

PMID:40524218 | DOI:10.1186/s13023-025-03750-z

Biol Sex Differ. 2025 Jun 16;16(1):42. doi: 10.1186/s13293-025-00729-0.

ABSTRACT

BACKGROUND: Takotsubo Syndrome (TTS) is an acute form of heart failure that disproportionately impacts post-menopausal women. The brain-heart connection is considered a pathway for TTS pathophysiology leading to investigations of the role of psychological, psychosocial, and personality factors in TTS.

OBJECTIVES: We compare psychosocial characteristics among a subset of individuals with confirmed TTS and those who had symptoms adjudicated as non-TTS in our online Takotsubo registry (n = 104). We also evaluate differences in TTS clinical characteristics among those with and without symptoms of PTSD and depression.

METHODS: The Smidt Heart Institute Takotsubo registry enrolls individuals with a history of TTS sourced through physician referrals, medical records review, peer- and self-referrals. Psychosocial characteristics were assessed using questionnaires validated in acute coronary syndrome populations. Hedge’s g effect sizes were computed to compare differences in perceived stress, depression symptoms, and post-traumatic stress disorder (PTSD) symptoms relative to TTS status.

RESULTS: Compared to participants confirmed to be non-TTS, those with adjudication-confirmed TTS had worse mean psychosocial scores (indicative of worse psychosocial characteristics). After adjusting for age at event, BMI, race, and smoking status, the Hedge’s g effect size for depressive symptoms was moderate [0.60 (-0.03, 1.22)] while effect sizes for other psychosocial measures were minimal (Trait anxiety: [0.01 (-0.58, 0.60)], PTSD symptoms [0.13 (-0.46, 0.73)], perceived stress [0.06 (-0.53, 0.65)]. Effect sizes were relatively lower following adjustment, largely driven by participants’ age at first event. Individuals with elevated PTSD symptoms were significantly younger at their first TTS event compared to those with minimal or no symptoms (54 ± 8 vs. 61 ± 10; p = 0.005). QTc was relatively longer among individuals with elevated PTSD symptoms (483 ± 40 msec vs. 465 ± 32 msec; p = 0.08) and elevated depressive symptoms (481 ± 33 msec vs. 464 ± 36 msec; p = 0.07), although the differences were not statistically significant.

CONCLUSIONS: Psychosocial characteristics including PTSD, depression, and stress are common among women with TTS, and age at the time of TTS event is a potentially important moderator of this relationship. We did not find Trait-anxiety or early childhood trauma to be associated with TTS in our cohort.

PMID:40524204 | DOI:10.1186/s13293-025-00729-0

Thromb J. 2025 Jun 16;23(1):65. doi: 10.1186/s12959-025-00756-2.

ABSTRACT

BACKGROUND: Worldwide, the diagnosis and treatment of immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) remain a major and ongoing challenge in hematology. Emerging clinical evidences suggest serum mineral elements are associated with ITP or HSP, but the causal relationship between them is still unclear.

AIMS: Conducting a two-sample, bidirectional Mendelian randomization (MR) study to evaluate the causal association between serum mineral elements including zinc, copper, magnesium, iron and calcium with ITP and HSP.

METHODS: In this two-sample, bidirectional MR study, summary statistics data of genome-wide association studies (GWAS) on exposures including zinc, copper, iron, magnesium and calcium were extracted from the MRC-Integrative Epidemiology Unit (MRC-IEU). The GWAS data on study outcomes, including ITP and HSP, were obtained from the FinnGen consortium. MR-Egger intercept and MR-PRESSO global test were utilized to assess the heterogeneity and horizontal pleiotropic of instrumental variables (IVs) between the exposures and outcomes, respectively. Inverse variance weighted (IVW) test was used as the primary analysis method to evaluate the causal between serum mineral elements with the risk of ITP and HSP, and weighted-median, weighted model, MR steiger, MR-PRESSO and radial MR were used as auxiliary analysis methods, moreover, the odds ratio (OR) and 95% confidence interval (CI) were calculated. Reverse MR analysis was also conducted. Leave-one-out test was further to conduct whether the association between serum mineral elements and the risk of ITP and HSP remain robust.

RESULTS: No significant horizontal pleiotropy and heterogeneity between individuals IVs was found after MR-Egger and MR-PRESSO global test. Genetically predicted that high copper (OR = 0.768, 95%CI: 0.628-0.937) and magnesium (OR = 0.314, 95%CI: 0.112-0.884) concentrations may reduce the risk of ITP and HSP, respectively. High calcium concentration may increase the risk of HSP (OR = 1.823, 95%CI: 1.226-2.712). There was no significant evidence to support a causal association between iron, zinc, magnesium, and calcium with the risk of ITP, or between iron, copper, and zinc and the risk of HSP (all P > 0.005). Moreover, no reverse causal associations between five serum mineral elements with the risk of ITP and HSP were found (all P > 0.05), suggesting the causal associations between serum mineral elements with ITP and HSP were not bidirectional. In addition, consistent results were obtained by multiple sensitivity analyses, indicating the associations of serum mineral elements with the risk of ITP and HSP relatively robust.

CONCLUSION: In this MR study, we discovered genetically predicted that elevated serum levels of copper and magnesium decreased the risk of ITP and HSP, respectively, and elevated levels of serum calcium increased the risk of HSP. However, no reverse causal association was found between serum mineral elements with the risk of ITP and HSP.

PMID:40524203 | DOI:10.1186/s12959-025-00756-2

Nutr J. 2025 Jun 16;24(1):91. doi: 10.1186/s12937-025-01159-9.

ABSTRACT

BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide, with acute coronary syndrome (ACS) being particularly fatal. Percutaneous coronary intervention (PCI) is a key treatment for ACS; however, major adverse cardiovascular events (MACE) frequently occur postoperatively. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been proposed as an emerging risk factor for cardiovascular disease. This study aims to systematically evaluate TMAO’s predictive value for MACE post-PCI and explore its dose-response relationship.

METHODS: A comprehensive literature search was conducted in four databases (PubMed, Web of Science, Embase, and the Cochrane Library), including retrospective or prospective cohort studies involving patients undergoing PCI. The primary outcome was MACE, and the secondary outcome was all-cause mortality. A dose-response analysis was conducted using a restricted cubic spline model to explore potential nonlinear associations between TMAO levels and outcomes. Heterogeneity was assessed using the Cochrane Q test and the I² statistic. Subgroup analysis and meta-regression were performed to identify sources of heterogeneity.

RESULTS: Eleven studies (comprising 13 independent cohorts) with 11,279 participants were included. Pooled analysis showed a significant association between elevated plasma TMAO levels and an increased risk of MACE after PCI (HR: 1.99, 95%CI: 1.68-2.35, 95%PI: 1.64-2.40, I² = 0%, p < 0.00001). Similarly, elevated plasma TMAO levels were significantly associated with an increased risk of all-cause mortality after PCI (HR: 1.76, 95%CI: 1.32-2.35, 95%PI: 0.79-3.90, I² = 65.1%, p < 0.00001). The dose-response analysis did not reveal a nonlinear relationship between TMAO and MACE or all-cause mortality. The linear model showed that each 1 µmol/L increase in plasma TMAO was associated with an 8.95% increased hazard of MACE (HR = 1.0895, 95%CI: 1.03-1.15), while all-cause mortality increased by 4% (HR = 1.04, 95%CI: 0.99-1.09).

CONCLUSIONS: This study demonstrates that elevated plasma TMAO levels are significantly associated with an increased risk of MACE and all-cause mortality after PCI, with a dose-dependent effect on MACE risk. As a potential biomarker, TMAO may be used to predict the risk of adverse cardiovascular events after PCI, and future studies should further validate its clinical utility.

REGISTRATION: PROSPERO CRD42024557486.

PMID:40524200 | DOI:10.1186/s12937-025-01159-9