Category: Statistics

J Therm Biol. 2026 Jun 29;140:104529. doi: 10.1016/j.jtherbio.2026.104529. Online ahead of print.

ABSTRACT

OBJECTIVES: Topical menthol is increasingly used as a perceptual cooling strategy during exercise, yet its ergogenic potential and underlying mechanisms remain unclear. Unlike previous route-mixed meta-analyses, this systematic review and three-level meta-analysis specifically examined the effects of acute topical menthol application on exercise performance alongside perceptual and physiological responses.

DESIGN: Meta-analysis.

METHODS: Six databases were searched from inception to March 2026. Randomized or controlled trials examining acute topical menthol application during exercise were included. Risk of bias was assessed using RoB-2. Three-level meta-analyses accounted for dependence among multiple outcomes. Prespecified moderators included sex, training status, environmental condition, application method, application site, and exercise modality. Sensitivity analyses addressed outliers and influential cases.

RESULTS: Sixteen studies involving 191 participants were included. Topical menthol produced a small but significant improvement in exercise performance (g = 0.27, p = 0.02). Thermal sensation (g = -0.74) and perceived exertion (g = -0.35) were reduced, with a small improvement in thermal comfort (g = 0.34), whereas core body temperature was unchanged. Performance benefits were most evident in aerobic endurance tasks, following rub-on application methods, and under temperate conditions, whereas effects in hot environments (≥30 °C) were smaller and not statistically significant. Several subgroup findings were sensitive to influential observations and should be interpreted cautiously.

CONCLUSIONS: Acute topical menthol may provide a small ergogenic benefit primarily through perceptual cooling rather than physiological heat strain. Effects appear context dependent and most relevant for endurance exercise. Further well-controlled studies are needed to clarify optimal application strategies and environmental conditions.

PMID:42385298 | DOI:10.1016/j.jtherbio.2026.104529

Public Health. 2026 Jul 1;258:106404. doi: 10.1016/j.puhe.2026.106404. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary health challenges currently facing the United States (U.S.) and many other countries around the world are largely due to patients with chronic conditions, which act either independently or synergistically. The current study assesses the ability of the Ecological Framework of Population Health to predict U.S. county-level prevalences of eight common chronic conditions.

STUDY DESIGN: Analytic analysis of population-level surveillance data METHODS: This study utilizes several U.S. county-level datasets representing over 30 predictive variables of the ecological framework, a model that includes measures of culture, politics, policy, socioeconomics, lifestyle behaviors, and both chronic condition risk factors and diagnoses. A non-linear artificial intelligence statistical approach was used to assess the ability of these variables (i.e., features) to predict the prevalence of eight leading chronic conditions at the U.S. county-level.

RESULTS: Artificial intelligence models demonstrated good to excellent performances in the independent test set (0.73 < R² < 0.96) in predicting U.S. county-level prevalence of chronic conditions. Findings indicate that upstream domains (culture, politics, policy and environment) explain substantial variance in the prevalence of chronic conditions before downstream domains (behavior and risk) are introduced.

CONCLUSIONS: Despite a significant amount of attention given to the health challenges associated with chronic conditions, little progress has been made in reversing trends. The findings presented here propose a new approach to this complex issue that focuses on the forcing factors that lie upstream from health behaviors to improve downstream health outcomes.

PMID:42385291 | DOI:10.1016/j.puhe.2026.106404

Seizure. 2026 Jun 2;140:193-203. doi: 10.1016/j.seizure.2026.05.031. Online ahead of print.

ABSTRACT

BACKGROUND: Oxcarbazepine (OXC) is widely used in focal epilepsy but is frequently limited by tolerability issues, particularly neurovestibular and sedative adverse events. Switching to eslicarbazepine acetate (ESL) has emerged in clinical practice as a pragmatic strategy to improve tolerability, although the available evidence remains fragmented and predominantly observational.

MATERIAL AND METHODS: We conducted a systematic review and single-arm meta-analysis of studies reporting outcomes after switching from OXC to ESL in patients with focal epilepsy. PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched from inception to December 2025. Random-effects models were used to estimate pooled proportions for effectiveness and tolerability outcomes. Heterogeneity was assessed using the I² statistic.

RESULTS: Seven studies comprising 312 patients were included. Pooled treatment retention was 74.0% (95% CI: 45.9-90.5; I²=79.2%). Resolution of OXC-related adverse events was observed in 53.1% of patients (95% CI: 12.3-90.1; I²=87.3%), although estimates showed substantial variability across studies. Somnolence improvement was reported in 28.2% (95% CI: 4.3-77.4%). The pooled response rate (≥50% seizure reduction) was 22.1% (95% CI: 6.4-53.9), while seizure freedom was achieved in 14.2% (95% CI: 4.5-37.2). Treatment discontinuation occurred in 15.0% of patients (95% CI: 7.2-28.6).

CONCLUSION: Switching from OXC to ESL may represent a pragmatic strategy for patients with OXC-related intolerance, particularly when treatment retention and tolerability are prioritized. However, the observational nature of the available evidence, together with substantial heterogeneity and wide confidence intervals, limits the precision and generalizability of pooled estimates.

PMID:42385282 | DOI:10.1016/j.seizure.2026.05.031

Eur J Radiol. 2026 Jun 28;203:113038. doi: 10.1016/j.ejrad.2026.113038. Online ahead of print.

ABSTRACT

Here, we establish a co-clinical computed tomography (CT) radiomics pipeline for the identification of candidate imaging biomarkers in RAS-mutant metastatic colorectal cancer (mCRC). Orthotopic KRAS-mutant xenograft models (LOVO-Luc2 (N = 52) and SW480-Luc2 (N = 52)) were treated with standard-of-care regimens (FOLFOX, bevacizumab, or combination) and longitudinally imaged by CT (N = 104 tumour scans, N = 156 liver scans collected over 4 timepoints). Radiomic features derived from primary tumour and liver parenchyma were assessed as biomarkers of treatment sensitivity and early metastatic disease. Pre-treatment CT-radiomics identified baseline radiomic correlates of treatment sensitivity in the LOVO-Luc2 model (0.716), with first-order statistical features (Median, 10percentile) significantly associated with therapy outcome. Texture-based liver radiomic features enabled prediction of metastases earlier than visual CT assessment (AUROC = 0.871). The most predictive features, GLSZM Gray Level Non-Uniformity, GLRLM Run Length Non-Uniformity Normalized, and GLDM Small Dependence Emphasis, were significantly associated with metastatic burden and survival in a clinical CRC cohort (N = 41), indicating species conservation and translational relevance. Collectively, these data demonstrate that preclinical CT radiomics can identify quantitative imaging features associated with treatment sensitivity and early metastatic progression, supporting translational potential.

PMID:42385277 | DOI:10.1016/j.ejrad.2026.113038

Theriogenology. 2026 Jun 30;265:118056. doi: 10.1016/j.theriogenology.2026.118056. Online ahead of print.

ABSTRACT

This study aimed to investigate the potential role of 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) in steroidogenesis and its possible involvement in germ cell development and meiotic initiation in ducks. Primordial germ cells (PGCs) were isolated from duck embryos and characterized by epithelioid adherent morphology, with more than 90% of cells showing positive expression of c-kit. Functional analyses indicated that overexpression of 17β-HSD3 was associated with increased PGC proliferation (48 h, P < 0.05; 72 h, P < 0.01) and reduced apoptosis (P < 0.0001). In addition, 17β-HSD3 overexpression was correlated with a numerical increase in AKR1D1 expression (P > 0.05) and a significant decrease in P450scc expression (P < 0.001). Retinoic acid (RA) treatment (0.25-1 μM) showed a tendency toward cell cycle progression, as reflected by a decrease in the G0/G1 phase population and an increase in S phase cells, although these changes did not reach statistical significance (P > 0.05). Furthermore, RA exposure was significantly associated with increased expression of 17β-HSD3, Cvh, and Stra8, and decreased expression of pluripotency-associated genes Itga6 and Sox2 (P < 0.001 or P < 0.0001), suggesting molecular changes consistent with meiotic entry. Collectively, these results suggest that 17β-HSD3 may be involved in the modulation of steroidogenesis-related gene expression in duck germ cells and is associated with germ cell proliferation and meiotic initiation. This study provides preliminary evidence that may contribute to the understanding of molecular mechanisms underlying avian germ cell development and reproductive regulation in poultry.

PMID:42385267 | DOI:10.1016/j.theriogenology.2026.118056

Neurosurg Focus. 2026 Jul 1;61(1):E4. doi: 10.3171/2026.3.FOCUS2617.

ABSTRACT

OBJECTIVE: The aim of this study was to determine the risks of reoperations for adjacent segment disease (ASD) and all causes between 1-level cervical disc arthroplasty (CDA) and 1-level anterior cervical discectomy and fusion (ACDF) and 2-level CDA and 2-level ACDF using meta-analysis. This study was specifically designed to address several key methodological limitations of prior meta-analyses, including cohort duplication, short follow-up duration, non-level-matched pooling of 1-level and 2-level procedures, and exclusion of international randomized controlled trials (RCTs).

METHODS: Using PRISMA guidelines, the authors performed a thorough search of the PubMed, Embase, and Scopus databases from January 2012 through November 2025. Studies were restricted to FDA investigational device exemption (IDE) trials and international RCTs with > 5 years of follow-up. Direct pairwise meta-analyses were conducted, and odds ratios and standard errors were calculated for outcomes. Random-effects pooling was performed, and between-study heterogeneity was assessed using Cochran’s Q statistic and the I2 statistic.

RESULTS: A total of 1756 studies were identified from the databases with 199 studies available for full review. Sixteen studies were selected for the analysis. For ASD reoperations in 13 studies, the authors found that 1-level CDA was associated with an approximately 55% lower odds of reoperation for ASD compared with 1-level ACDF (OR 0.45, 95% CI 0.29-0.69; p < 0.001). For 2-level CDA, there was a 49% lower chance of having an ASD reoperation compared with 2-level ACDF (OR 0.51, 95% CI 0.30-0.87; p = 0.013). Similarly, in 14 studies, there was a statistically significant reduction in the odds of all-cause reoperations in 1-level CDA compared with ACDF (OR 0.58, 95% CI 0.42-0.80; p = 0.001) while for 2-level CDAs there was a 52% lower chance of all-cause reoperations compared with 2-level ACDFs (OR 0.48, 95% CI 0.32-0.72; p < 0.001).

CONCLUSIONS: In this comprehensive, level-matched meta-analysis of FDA IDE studies and international RCTs in which we addressed several key methodological limitations of prior meta-analyses, we found that 1-level and 2-level CDAs were associated with a consistent reduction in reoperation risks compared with ACDF for ASD and all-cause reoperations with a mean 7-year follow-up. Future investigations leveraging large, prospective registries will be essential to determine the generalizability of IDE studies and international RCTs to the broader clinical populations.

PMID:42385252 | DOI:10.3171/2026.3.FOCUS2617

Neurosurg Focus. 2026 Jul 1;61(1):E3. doi: 10.3171/2026.3.FOCUS251150.

ABSTRACT

OBJECTIVE: The aim of this study was to determine if there is a difference in reoperations for adjacent segment disease (ASD) and all-cause reoperations between 1-level and contiguous 2-level cervical disc arthroplasty (CDA).

METHODS: A retrospective cohort study was conducted on patients (18-60 years of age) with cervical degenerative disc disease who underwent a primary 1-level or 2-level CDA using data from a national spine registry. Cox proportional hazards regression was used to evaluate reoperations for all-cause risks. Hazard ratios (HRs) and 95% confidence intervals are presented; a p value < 0.05 was the significance threshold.

RESULTS: The cohort consisted of 650 patients with 1-level CDA and 159 patients with 2-level CDA. The mean overall observational follow-up was 6.2 years (SD 4.3 years) for 1-level CDA and 4.2 years (SD 3.1 years) for 2-level CDA. The 5-year incidence of ASD reoperations was higher in 1-level CDA (4.7%, 95% CI 2.8%-6.6%) compared to 2-level CDA (1.1%, 95% CI 0.0%-3.15%). In Cox regression analysis, there was no statistical difference in all-cause reoperations between 1-level CDA and 2-level CDA (HR 0.93, 95% CI 0.44-1.94; p = 0.84). Few events in 2-level ASD reoperations allowed determination of hazard ratio.

CONCLUSIONS: This study is the first large real-world analysis outside of investigational device exemption trials to show no significant difference in all-cause reoperation rates between 1-level and 2-level CDA. Notably, the 5-year incidence of ASD-related reoperations was substantially higher following 1-level CDA compared with 2-level CDA. The reason for this discrepancy remains unclear. One possibility is surgeon selection bias-where an adjacent degenerative level may be left untreated during a 1-level CDA under the assumption that motion preservation would protect against adjacent segment deterioration. Alternatively, the higher ASD rate may simply reflect the natural history of cervical spondylosis rather than device effect. Further investigation is needed to determine the true drivers of this observation.

PMID:42385245 | DOI:10.3171/2026.3.FOCUS251150

Neurosurg Focus. 2026 Jul 1;61(1):E9. doi: 10.3171/2026.3.FOCUS251207.

ABSTRACT

OBJECTIVE: Anterior cervical disc arthroplasty offers theoretical advantages over fusion such as quicker recovery and decreased biomechanical stress at adjacent levels. However, anterior cervical discectomy and fusion (ACDF) may be beneficial for patients with dynamic instability or advanced spondylosis. In patients with multilevel cervical degenerative disc disease, anterior cervical hybrid arthroplasty-fusion (ACHAF) constructs may allow for personalized approaches, addressing level-specific pathology while offering other theoretical advantages such as requiring a shorter anterior plate (if utilized), potentially reducing complications and risk of dysphagia. The authors aimed to evaluate radiographic outcomes and early safety of ACHAF compared with ACDF.

METHODS: This is a single-center retrospective study of patients who underwent 2- or 3-level ACHAF or ACDF between January 2021 and May 2025 by the senior author. In the ACHAF group, arthroplasty was performed at the most cephalad level. Radiographic parameters (C2-7 lordosis, C2-7 sagittal vertical axis [cSVA], and Cobb angle and height of the disc immediately proximal to the construct) were assessed preoperatively and at 6 months postoperatively. Clinical outcomes included length of stay and rates of return to the emergency department (ED) within 90 days, complications, dysphagia at 6 months postoperatively, and reoperation during the study period.

RESULTS: A total of 66 patients met the study criteria: 23 underwent ACHAF and 43 underwent ACDF (mean age 57.9 years). There was no difference in change of C2-7 lordosis or cSVA. The ACHAF group exhibited a decreased adjacent disc Cobb angle and increased disc height postoperatively, whereas the ACDF group exhibited an increased disc Cobb angle and decreased disc height (p < 0.001). Dysphagia at 6 months was more frequent in ACDF patients (32.6% vs 8.7%, p = 0.04). There was no significant difference in reoperation rates during the study period. Complications (p = 0.29) were more common in the ACDF group, and return to ED was more frequent in the ACHAF group (p = 0.71), although these did not meet statistical significance. There was no difference in rates of discharge on postoperative day 1 (p > 0.99).

CONCLUSIONS: ACHAF constructs possibly reduce stress on the proximal unoperated motion segment due to adjacent load sharing from the arthroplasty. Furthermore, dysphagia at 6 months postoperatively was less prevalent in the ACHAF group. Additional studies are needed to determine if ACHAF is associated with differences in patient-reported outcomes or long-term differences in rates of dysphagia or reoperation.

PMID:42385243 | DOI:10.3171/2026.3.FOCUS251207

Neurosurg Focus. 2026 Jul 1;61(1):E12. doi: 10.3171/2026.3.FOCUS2624.

ABSTRACT

OBJECTIVE: The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial.

METHODS: This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35-80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations.

RESULTS: One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329).

CONCLUSIONS: Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

PMID:42385242 | DOI:10.3171/2026.3.FOCUS2624

Stat Med. 2026 Jul;45(15-17):e70647. doi: 10.1002/sim.70647.

ABSTRACT

Dependent censoring, common in medical studies with informative dropout, invalidates standard Cox regression by violating the independent censoring assumption. While copula-based methods offer flexible dependence modeling, their parametric extensions face identifiability barriers. We address this problem through a novel fully identifiable parametric model that synergizes double-Cox marginal structures with copula dependence, which is called the copula-double-Cox model. Using Weibull or generalized exponential (GenExp) distributions, the double-Cox model links both scale and shape parameters to covariates via Cox-type regressions. This structure accommodates non-proportional hazards while containing the standard Cox model as a special case. We establish identifiability under dependent censoring and derive consistent estimators for baseline parameters, regression coefficients, and copula association. Simulations confirm robustness to association structure misspecification and over-parameterization. Estimation accuracy is supported by asymptotic theory and standard error evaluation via the observed information matrix. Finally, we illustrate the proposed approach through a real-world application to a dataset on monoclonal gammopathy of undetermined significance (MGUS), highlighting its practical relevance. The results show that our method provides an interpretable characterization of covariate effects on both failure time and censoring time through its double-Cox structure. An open-source R implementation of the copula-double-Cox model is provided on GitHub.

PMID:42385224 | DOI:10.1002/sim.70647