Tag: statistics

Medicine (Baltimore). 2026 Jun 26;105(26):e49266. doi: 10.1097/MD.0000000000049266.

ABSTRACT

The triglyceride-glucose-Chinese visceral adiposity index (TyG_CVAI) has been validated as an effective predictor of early stroke. However, its predictive efficacy across different glycemic metabolic states remains unexplored. This study utilized data from the China Health and Retirement Longitudinal Study, including 7744 stroke-free participants. Participants were categorized into 3 glycemic groups: diabetes mellitus (DM), prediabetes mellitus (Pre-DM), and normal glucose regulation (NGR). K-means clustering further divided participants into 2 clusters based on TyG_CVAI fluctuations: Cluster 1 (lower TyG_CVAI) and Cluster 2 (higher TyG_CVAI). The primary outcome was the first stroke occurrence. Statistical analyses included Kaplan-Meier survival curves, Cox proportional hazards models, restricted cubic spline analysis, and receiver operating characteristic curve analysis to assess associations between baseline TyG_CVAI and stroke risk. Over 9 years (2011-2020), 540 participants (7.0%) experienced a first stroke. Participants in Cluster 2 (higher TyG_CVAI) exhibited a significantly elevated stroke risk compared to Cluster 1. Kaplan-Meier analysis revealed significant differences in stroke incidence between clusters among Pre-DM, NGR, and the overall population (P < .001), but not in the DM group (P = .071). Cox regression models, adjusted for confounders, confirmed a significant positive correlation between TyG_CVAI and stroke risk in the overall population, Pre-DM, and NGR groups. The hazard ratios and 95% confidence intervals for Cluster 2 versus Cluster 1 were 1.40 (1.15-1.71), 1.42 (1.07-1.88), and 1.68 (1.19-2.36), respectively. In contrast, no significant association was observed in the DM group (P > .1). Restricted cubic spline analysis further supported that higher TyG_CVAI levels correlated with increased stroke risk. Elevated baseline TyG_CVAI is significantly associated with stroke risk in middle-aged and older adults. However, its predictive capacity is attenuated in individuals with diabetes compared to those with normal glycemic metabolism. These findings underscore the importance of considering glycemic status when evaluating TyG_CVAI as a stroke predictor.

PMID:42363562 | DOI:10.1097/MD.0000000000049266

Medicine (Baltimore). 2026 Jun 26;105(26):e49516. doi: 10.1097/MD.0000000000049516.

ABSTRACT

Breast cancer (BC) has the highest cancer incidence and mortality in women worldwide, and the relationship between serum enzymes and BC has been inconsistent in previous observational studies. In this paper, 2-sample Mendelian randomization (MR) is used to clarify the causal relationship between them. The serum enzymes in 216,026 study subjects from Finnish heritage subjects as the exposure data. The BC included 212,402 study subjects in United Kingdom Biobank as the result data. We performed univariable MR with 5 MR methods inverse variance weighted, MR-Egger regression, weighted median, simple mode, and weighted mode and multivariable MR to estimate the effect of serum enzymes independent of BC. Finally, we performed a series of sensitivity analyses as validation of primary MR results. The single nucleotide polymorphisms screened in this study were mostly strong effect instrumental variables. A total of 5 forest plot model results indicate that abnormal serum enzyme levels have a significant causal relationship with BC. MR analysis of different models of abnormal serum enzyme levels gave consistent direction estimates, and their slopes were relatively consistent. Serum enzyme indicators did not consider heterogeneity in the MR results of BC (Cochran Q P value > .05, I 2 < 50%). MR-Egger’s results show that there is no effect of pleiotropy(P ≥ .05, intercepts were close to 0). Sensitivity analysis showed that no significant change in the estimated effect value of abnormal serum enzyme levels was found, indicating the stability of the results. inverse variance weighted model results indicate that BC has no causal effect on abnormal serum enzyme levels (P value > .05). The results of multivariate MR showed that serum enzyme indicators still have a significant direct effect on BC. Our findings suggest that a significant statistical causal association between abnormal serum enzyme levels and the risk of BC. Abnormal serum enzyme levels have important clinical implications and might be used as BC risk.

PMID:42363553 | DOI:10.1097/MD.0000000000049516

Medicine (Baltimore). 2026 Jun 26;105(26):e49310. doi: 10.1097/MD.0000000000049310.

ABSTRACT

Coronavirus disease 2019 (COVID-19) was reported to persist long-term in the brain and leave several long-term neurologic sequelae. However, the causal relationship between COVID-19 and brain aging is still unknown. The genome-wide association study (GWAS) data on COVID-19 phenotypes (susceptibility, hospitalization, and severity), involving a total of 5,779,391 participants, were collected from the COVID-19 Host Genetics Initiative. In addition, GWAS data on longitudinal changes in 15 brain structures, assessed via magnetic resonance imaging across the lifespan, were sourced from the ENIGMA Consortium and involved 15,640 participants. Two-sample Mendelian randomization was conducted to infer the causal relationship between COVID-19 and longitudinal brain changes. Multi-trait GWAS meta-analysis, colocalization, and fine-mapping analyses were performed to identify shared genetic etiologies. H3K27me3 ChIP-seq was used to evaluate the regulatory effect of colocalized loci. Two-step Mendelian randomization was applied to explore potential mediating mechanisms across multi-omics layers, including proteomics, metabolomics, and immunomics. Our results showed that COVID-19 hospitalization (β = -262.405, P = .041) and severity (β = -177.676, P = .049) were genetically associated with atrophied volume of total brain during longitudinal change. This suggests that individuals with advanced COVID-19 may be more susceptible to accelerated global brain aging. Caudate was genetically affected by all COVID-19 phenotypes. Seven variants were shared between advanced COVID-19 and global brain aging. rs117169628 was colocalized between advanced COVID-19 and global brain aging, and exerted an inhibitory effect on CDH15 expression, further strengthening the causality. Six metabolites, 1 protein, and 1 immune trait were identified as potential mediators. Our study indicates that advanced COVID-19 might be genetically associated with accelerated brain aging. Brain health should be paid more attention in long COVID-19.

PMID:42363551 | DOI:10.1097/MD.0000000000049310

Medicine (Baltimore). 2026 Jun 26;105(26):e49486. doi: 10.1097/MD.0000000000049486.

ABSTRACT

It has been proved that lipids have an effect on endometriosis, and the plasma atherosclerosis index (AIP), as a new lipid index, has not been proved to be correlative to endometriosis. The National Health and Nutrition Examination Survey from 1999 to 2006 covered 2405 female. AIP (log10 (triglyceride/high-density lipoprotein cholesterol)) was employed to evaluate the danger of hyperlipidemia. Moreover, the connection between AIP and endometriosis can be further studied by using multivariate logistic regression, restricted cubic spline and subgroup analysis. Totally 2405 female were covered, of whom 182 (7.57%) had endometriosis and 2223 (92.43%) did not have endometriosis (named control). The AIP level in the endometriosis group (0.37) was visibly exceed that in the non-endometriosis group (0.26), and the imparity was statistically meaningful(P < .0001), even when sensitivity analysis was performed, the imparity retained the same. Overall, there was a significant active connection between the AIP and endometriosis (per 1-unit increment in the AIP: OR = 2.624; 95% CI 1.479, 4.657). The consequences of subgroup analysis demonstrated that there was no meaningful interaction between AIP and concrete subgroups (all interaction P < .05). Restricted cubic spline analysisprovide evidence of statistically significant linearity between AIP and endometriosis prevalence. AIP is actively connection with endometriosis in US female. Therefore, by using AIP as a new lipid market indicator, we are expected to offer new ideas and insights into the prevention and treatment of endometriosis.” To further confirm our works, we need larger cohort researches to support the consequences of this research.

PMID:42363550 | DOI:10.1097/MD.0000000000049486

Medicine (Baltimore). 2026 Jun 26;105(26):e49477. doi: 10.1097/MD.0000000000049477.

ABSTRACT

We performed a 2-step Mendelian randomization (MR) study to investigate the associations of Fms-related tyrosine kinase 3 ligand (FLT3L) and phosphate levels with the risk of hypertrophic cardiomyopathy (HCM). Genetic instruments for 75 circulating inflammatory factors were obtained from the NHGRI-EBI GWAS Catalog, while summary statistics for circulating phosphate and HCM were derived from the UK Biobank and FinnGen, respectively. Univariable MR analysis using the inverse-variance weighted method indicated that genetically predicted higher phosphate levels were associated with an increased risk of HCM (OR = 1.36, P = 4.82 × 10-2). Among the inflammatory markers, FLT3L emerged as a significant candidate and showed inverse associations with phosphate levels (β = -0.05, P = 1.70 × 10-9) and HCM (OR = 0.79, P = 4.10 × 10-2). Bidirectional MR analyses did not support a causal effect of phosphate on FLT3L. Mediation analysis suggested that phosphate levels accounted for an estimated 12.05% of the total effect of FLT3L on HCM. Genetic liability to lower FLT3L levels is associated with a higher risk of HCM, and this relationship may be partially mediated through circulating phosphate levels.

PMID:42363547 | DOI:10.1097/MD.0000000000049477

Medicine (Baltimore). 2026 Jun 26;105(26):e49518. doi: 10.1097/MD.0000000000049518.

ABSTRACT

The routine placement of a double-J (DJ) stent before ureteroscopic lithotripsy (URS) remains controversial. This study aims to compare the stone clearance rates between preoperative DJ stent placement and non-placement and to analyze the risk factors associated with residual stones, providing more clinical evidence for preoperative management. A retrospective analysis was conducted on 163 patients who underwent URS for kidney and ureteral stones between April 2023 and October 2024, among which 135 patients met the inclusion criteria. General clinical and perioperative data were collected. The stone clearance rates were compared between the group with preoperative DJ stent placement and the group without DJ stent placement. Univariate and multivariate logistic regression analyses were used to identify risk factors for residual stones after URS. The overall stone clearance rate in patients undergoing URS was 85.19% (115/135). The stone clearance rate in the non-DJ group was 75.51% (37/49), while it was 90.70% (78/86) in the DJ group, showing a statistically significant difference between the 2 groups (P = .017). Univariate regression analysis found that the preoperative DJ stent placement (P = .021) and surgery duration (P = .047) were risk factors for residual stones after URS. Multivariate regression analysis also identified the preoperative DJ stent placement (P = .019) and surgery duration (P = .039) as independent risk factors for residual stones after URS. Preoperative DJ stent placement resulted in a higher stone clearance rate compared to non-placement during URS. The preoperative DJ stent placement and surgery duration were independent risk factors for residual stones after URS.

PMID:42363538 | DOI:10.1097/MD.0000000000049518

Medicine (Baltimore). 2026 Jun 26;105(26):e49526. doi: 10.1097/MD.0000000000049526.

ABSTRACT

The association between early magnesium sulfate administration and outcomes in sepsis remains incompletely understood, particularly in relation to differences in systemic immune-inflammatory status. In this retrospective cohort study using Medical Information Mart for Intensive Care IV (version 3.1), adult critically ill patients with sepsis were included. Systemic immune-inflammation index (SII) was calculated from platelet, neutrophil, and lymphocyte counts obtained within a peri-intensive care unit window (6 hours before to 24 hours after intensive care unit admission). Early magnesium administration was defined as intravenous magnesium sulfate initiated within the same window. The primary outcome was 30-day all-cause mortality. Propensity score matching was performed to balance baseline characteristics. Associations were examined overall and across SII quartiles using stratified multivariable Cox proportional hazards models, with nonlinear relationships explored using restricted cubic splines. Among 12,087 patients, 6039 received early intravenous magnesium. After propensity score matching, 3396 matched pairs were analyzed. Early magnesium administration was associated with lower 30-day mortality overall (15.8% vs 18.3%, P = .007). In stratified analyses, adjusted hazard ratios were 0.66 (95% confidence interval: 0.51-0.87), 0.65 (0.49-0.85), 0.75 (0.59-0.94), and 0.85 (0.70-1.04) across quartiles 1 to 4. Restricted cubic spline analyses showed descriptive attenuation at higher SII values (P for interaction = .208), without evidence of a statistically definitive interaction. Early magnesium administration was associated with lower 30-day mortality in critically ill patients with sepsis. Although formal interaction testing did not reach statistical significance, adjusted hazard ratios showed a descriptive gradient of attenuation across increasing SII quartiles, directionally consistent across sensitivity analyses. These findings are hypothesis-generating and require prospective validation.

PMID:42363536 | DOI:10.1097/MD.0000000000049526

BMC Pharmacol Toxicol. 2026 Jun 26. doi: 10.1186/s40360-026-01177-1. Online ahead of print.

ABSTRACT

BACKGROUND: Methylphenidate is widely prescribed for attention-deficit/hyperactivity disorder, and its use has increased substantially in recent years. Although generally considered safe within therapeutic ranges, supratherapeutic ingestion may result in various systemic adverse effects. This study aimed to evaluate the demographic and clinical characteristics of children presenting with overdose ingestion and to identify potential factors associated with symptom development.

METHODS: We conducted a retrospective review of patients younger than 18 years who presented to a tertiary pediatric emergency department between January 1, 2020, and December 31, 2024, due to overdose ingestion. Demographic characteristics, psychiatric history, ingested dose, mode of exposure, clinical findings, emergency department course, and factors potentially associated with adverse effects were analyzed.

RESULTS: Thirty-two patients were included; 72% were female, and ingestion was intentional in 84%. The mean ingested dose was 5.7 mg/kg. Clinical symptoms developed in 41% of patients. The most frequent findings were tachycardia (38%), mild hypertension (34%), agitation (22%), and seizures (16%). Although most cases were mild and resolved within 12 h of observation, one toddler developed neuropsychiatric manifestations requiring close monitoring with full recovery within 48 h. No statistically significant association was observed between age, sex, gastrointestinal decontamination status, or reported ingested dose and the development of clinical symptoms (p > 0.05).

CONCLUSIONS: Pediatric methylphenidate intoxication is generally mild, but severe neuropsychiatric and cardiovascular effects may occur. Careful clinical monitoring remains essential.

TRIAL REGISTRATION: Not applicable.

PMID:42363304 | DOI:10.1186/s40360-026-01177-1

J Neuroeng Rehabil. 2026 Jun 26. doi: 10.1186/s12984-026-02060-0. Online ahead of print.

ABSTRACT

BACKGROUND: Functional constipation (FCon) involves central nervous system dysregulation, particularly in brain regions responsible for visceral sensation, emotional processing, and autonomic control. Using functional near-infrared spectroscopy (fNIRS), we examined brain activity alterations in FCon patients to elucidate brain-gut interactions.

METHOD: Patients with constipation meeting Rome IV criteria were recruited from Sir Run Run Shaw Hospital, while healthy controls were enrolled from the local community. The cortical regions of interest (ROIs) included the prefrontal cortex (PFC), dorsolateral prefrontal cortex (DLPFC), broca’s area, primary motor cortex (M1), supplementary motor area (SMA)/premotor cortex (PMC), and primary somatosensory cortex (S1). Participants were monitored during resting state and three defecation-related tasks: imagined defecation, simulated defecation and anal sphincter contraction. Functional connectivity (FC) strength and regional brain activation (HbO concentration changes) were compared between groups and across tasks.

RESULT: 64 patients and 64 healthy controls (50% females each) were included. There was no significant difference in average FC between groups (P = 0.757). In both groups, simulated defecation and anal sphincter contraction activated most ROIs more strongly than imagined defecation (P < 0.05). In healthy controls, anal sphincter contraction elicited significantly lower HbO than simulated defecation in the left Broca’s area (P < 0.05); no significant differences between these two tasks were found in the FCon group. No significant between-group differences in HbO were found during any task. During imagined defecation, FCon patients showed a trend toward lower HbO across most ROIs, most notably in the right M1, with comparable levels in the right PFC. During simulated defecation, a similar trend of lower HbO in sensorimotor ROIs was observed alongside numerically higher HbO in the right PFC/DLPFC. During anal sphincter contraction, they showed numerically higher HbO across all ROIs. Progression curves further revealed a linear increasing pattern in FCon patients across tasks, contrasting with task-appropriate modulation in healthy controls.

CONCLUSION: This first fNIRS study reveals task-specific cortical dysregulation in FCon. Although between-group differences were not statistically significant, these trends and dynamic patterns identify sensorimotor and prefrontal cortical targets for future neuromodulation therapies. Trial registration ChiCTR2500104882.

PMID:42363274 | DOI:10.1186/s12984-026-02060-0

Health Qual Life Outcomes. 2026 Jun 26. doi: 10.1186/s12955-026-02573-1. Online ahead of print.

ABSTRACT

PURPOSE: Quality of life (QOL) research in diabetes has long been a concern with many specific instruments being developed, but no scale for diabetes has been developed based on the modular approach. This study aimed to develop and validate the Diabetes Mellitus Scale of the System of Quality of Life Instruments for Chronic Diseases QLICD-DM (V2.0) by a modular approach and mixed methods.

METHODS: The Scale was developed based on procedural decision-making methods and by combining the general module and the specific module. The instrument was used to assess the quality of life of 242 diabetic patients both before and after treatments. Under Classical Test Theory (CTT), the psychometric properties of the scale were assessed with regard to validity, reliability and responsiveness by correlation analyses, structural equation modeling, as well as t-tests. In addition, G-study and D-study in Generalizability Theory (GT) were used to validate the scale further.

RESULTS: The QLICD-DM (V2.0) was developed with a 14-item specific module and a 28-item general module in the final scale. For all domains, Cronbach’s α values were greater than 0.70 with the exception of physical function (0.68), the test-retest reliability correlations r and ICCs were greater than 0.80 with the exception of physical and social function (0.65,0.64). The theoretical construct was supported by correlation analyses and confirmatory factor analysis using structural equation modeling, which demonstrated good construct validity. There were significant differences (P < 0.05) in the domains of physical function, specific module and the total scale before and after treatments. The standardized response means (SRMs) of the physical, psychological, social, and the specific module were 0.36, 0.14, 0.11 and 0.28 respectively. All G-coefficients were all greater than 0.70 with the exception of the physical domain (0.683), further confirming the reliability of the scale further. The overall error was found to be small in the G-study and in the D-study, indicating a high level of accuracy.

CONCLUSION: The QLICD-DM (V2.0) not only integrated characteristics of generic and disease-specific instruments but also demonstrated good reliability, validity, and moderate responsiveness, and it could serve as a quality of life assessment tool for diabetes patients.

PMID:42363272 | DOI:10.1186/s12955-026-02573-1