Category: Statistics

Clin Pharmacokinet. 2026 Jul 26. doi: 10.1007/s40262-026-01685-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Personalizing anti-tumor necrosis factor (TNF) therapy in pediatric Crohn’s disease (CD) remains challenging due to variable drug clearance and response. Identifying pharmacokinetic (PK) and pharmacodynamic (PD) predictors of deep remission could enable precision dosing strategies. The primary aim was to define PK metrics and PD biomarkers associated with deep remission.

METHODS: Patients initiating infliximab or adalimumab were prospectively enrolled from four pediatric centers with longitudinal blood and stool biospecimens collected for one year. Deep remission was defined as a combination of weighted pediatric CD activity index (wPCDAI) < 12.5 and Simple Endoscopic Score-CD < 3. Trough concentrations (cTrough) were measured throughout the study. Drug exposure (area under the curve, AUC) and clearance were estimated using drug-specific population PK models and Bayesian estimation using nonlinear mixed-effects modeling (NONMEM).

RESULTS: Deep remission was achieved in 34/70 (48.6%) with no difference in outcomes between biologics. Infliximab cTrough thresholds associated with deep remission were 33 µg/mL (Week 2), 15 µg/mL (Week 6), and 4.7 µg/mL (Month 3) with Week 6 cTrough targets ranging 15-26 µg/mL depending on the outcome of interest. Higher AUC during induction for both infliximab and adalimumab was associated with deep remission, whereas rapid infliximab clearance at various timepoints was inversely associated with deep remission. Baseline predictors of rapid infliximab clearance included older age, low albumin, and elevations in body mass index, C-reactive protein, soluble CD64, and wPCDAI.

CONCLUSIONS: We identified PK/PD cut-points associated with deep remission and rapid infliximab clearance, providing actionable metrics to individualize induction dosing and optimize maintenance therapy for children starting anti-TNF therapy.

PMID:42503050 | DOI:10.1007/s40262-026-01685-7

Ann Nucl Med. 2026 Jul 26. doi: 10.1007/s12149-026-02266-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) provides a survival advantage in metastatic castration-resistant prostate cancer (mCRPC). However, the physiologically high PSMA-ligand uptake in salivary glands makes these organs susceptible to radiation damage. The aim of this study is to examine the changes occurring in salivary glands after PSMA-RLT and to evaluate their relationship with treatment-related parameters, including cumulative administered activity and number of RLT cycles.

METHOD: The study included 68 mCRPC patients who received 177Lu PSMA-617 treatment. Volume, surface area, density, and PSMA uptake levels were calculated for the parotid and submandibular glands in pre- and post-treatment imaging. Treatment-related changes and their associations with baseline imaging parameters, treatment timing, cumulative administered activity, and number of RLT cycles were statistically analyzed.

FINDINGS: After RLT, parotid glands showed significant decreases in SUVmean, volume, surface area, and PSMA total activity (all p < 0.001), whereas parotid density remained stable. Submandibular glands also demonstrated significant reductions in SUVmean, volume, surface area, PSMA total activity, and CT-derived density (all p < 0.001). In the exploratory correlation analyses, the number of RLT cycles and cumulative administered activity showed weak nominal positive associations with parotid density change; however, these associations did not remain statistically significant after Benjamini-Hochberg false discovery rate correction. BMI was not significantly associated with glandular SUVmean, HU measurements, or post-treatment glandular changes after correction for multiple testing.

CONCLUSION: PSMA-targeted RLT was associated with significant imaging-detectable structural alterations and reductions in PET-derived glandular activity in the major salivary glands. CT-derived density significantly decreased in the submandibular glands, whereas parotid density remained stable. No baseline imaging-, BMI-, time-, or administered activity-related parameter remained significantly associated with post-treatment glandular changes after correction for multiple testing.

PMID:42503048 | DOI:10.1007/s12149-026-02266-1

Ann Nucl Med. 2026 Jul 26. doi: 10.1007/s12149-026-02265-2. Online ahead of print.

ABSTRACT

OBJECTIVES: In this study, we aimed to evaluate the association between liver clearance values obtained from pre-treatment [⁹⁹ᵐTc]mebrofenin hepatobiliary scintigraphy and conventional liver function scores and biochemical parameters, and to perform an exploratory prognostic assessment of whether baseline clearance is associated with post-treatment outcomes, including overall survival, prior to ⁹⁰Y radioembolization. We also compared the functional assessment of the treatment region (based on mebrofenin uptake) with its anatomical CT volume (derived from [⁹⁹ᵐTc]macroaggregated albumin SPECT/CT) to determine the concordance between functional and volumetric data.

METHODS: Pre-treatment [⁹⁹ᵐTc]mebrofenin and [⁹⁹ᵐTc]MAA scintigraphies were performed in 19 patients scheduled to receive Yttrium-90 (⁹⁰Y) microsphere therapy. Mebrofenin clearance was calculated, and its association with biochemical parameters and overall survival was examined. The functional definition of the planned treatment territory was estimated based on mebrofenin uptake, and this was compared with the anatomical volume of the same region on MAA SPECT/CT.

RESULTS: Mebrofenin liver clearance showed significant (p < 0.05) negative correlations with pre- and post-treatment total and direct bilirubin levels and a positive correlation with post-treatment albumin. Clearance also demonstrated a strong inverse correlation with ALBI score (p < 0.05). Among biochemical changes, only the post-treatment change in direct bilirubin was significantly associated with clearance (p < 0.05). Functional and volumetric definitions of the treatment area showed strong correlation (ρ = 0.837, p < 0.001). In five patients with target ratio greater than 50% of liver volume, functional definition was not concordant with volumetric estimates. The difference in clearance values between patients surviving ≤ 6 months and > 6 months did not reach statistical significance. Among liver function scores, Child-Pugh exhibited the strongest, though non-significant, correlation with survival (ρ = – 0.407, p = 0.084).

CONCLUSION: [⁹⁹ᵐTc]mebrofenin scintigraphy correlated with both pre- and post-treatment biochemical liver function parameters. The functional definition of the treatment region assessed by scintigraphy and volumetric definition derived from SPECT/CT were also well concordant. The difference in clearance values between patients surviving ≤ 6 months and > 6 months did not reach statistical significance. Discrepancies between volumetric and functional definitions were observed in patients with extensive target volume (> 50% of liver volume). These preliminary findings suggest that [⁹⁹ᵐTc]mebrofenin scintigraphy may complement anatomical volumetry in the pretreatment assessment of functional liver reserve, but its potential role in individualized dosimetry requires confirmation in larger prospective studies.

PMID:42503047 | DOI:10.1007/s12149-026-02265-2

Water Environ Res. 2026 Jul;98(7):e70493. doi: 10.1002/wer.70493.

ABSTRACT

The Pingyin-Changqing section of the Yellow River serves as an important groundwater recharge area in the lower reaches of the Yellow River, and its groundwater quality safety holds significant importance for the regional ecology and the health of its residents. This study systematically collected groundwater samples from this area, detected concentrations of six heavy metals (Mn, Zn, Ni, Pb, As, and Cd), and comprehensively applied mathematical statistics, spatial mapping analysis, source apportionment, and health risk assessment methods to systematically investigate the characteristics, distribution patterns, source mechanisms, and health risks of groundwater heavy metals in the region. The results indicate that (1) the mean concentrations of heavy metals in groundwater of the study area, in descending order, are Mn > Zn > Ni > Pb > As > Cd; compared against the Class III standard limits of the National Standard for Groundwater Quality, Mn shows the highest exceedance rate, followed by Pb, with exceedance rates of 18% and 5%, respectively; (2) heavy metal concentrations exhibit considerable spatial variability, with Mn exceedance points uniformly distributed in upstream and downstream areas on both banks of the Yellow River, while Pb concentrations demonstrate higher values downstream than upstream, with exceedance points mainly concentrated in the junction of Qihe and Dong’e; (3) sources of groundwater heavy metal pollution are identified as follows: Zn, Ni, and Cd primarily originate from different industrial sources, Pb mainly from traffic sources, As primarily from agricultural sources, and Mn predominantly from natural sources; (4) groundwater ingestion was identified as the dominant exposure pathway. Pb was the major contributor to noncarcinogenic risk, whereas As was the primary contributor to carcinogenic risk. Children exhibited higher noncarcinogenic risk levels than adults, reflecting their greater susceptibility to heavy metal exposure. Although both carcinogenic and noncarcinogenic risks remained within acceptable limits overall, relatively elevated risk values were concentrated at the junction of Changqing, Pingyin, Dong’e, and Qihe. Through the technical route of “pollution identification-spatial mapping-source apportionment-risk assessment,” this study provides a scientific basis for groundwater safety protection in the Yellow River Basin. It is recommended to strengthen dynamic monitoring of Pb pollution and implement comprehensive prevention and control measures in high-risk areas of this region.

PMID:42503035 | DOI:10.1002/wer.70493

Inflamm Bowel Dis. 2026 Jul 26:izag148. doi: 10.1093/ibd/izag148. Online ahead of print.

ABSTRACT

BACKGROUND: Encountering an intra-abdominal abscess during elective surgery for Crohn disease (CD) presents a clinical dilemma. While guidelines often recommend temporary fecal diversion, stomas carry substantial morbidity. Existing literature is heavily confounded by selection bias, obscuring the true safety of bowel reconstruction. This study evaluated the safety of primary anastomosis in the presence of an intraoperative abscess.

METHODS: A retrospective review of patients undergoing ileocecal resection for CD was conducted. To isolate the impact of the abscess and eliminate selection bias, an a priori multivariable logistic regression model and a 1:2 propensity score matched (PSM) analysis were utilized on the subcohort of patients who underwent primary anastomosis. The primary endpoint was the rate of 30-day postoperative complications.

RESULTS: Among the 810 included patients (210 with an intraoperative abscess, 600 without), an abscess significantly increased operative complexity, resulting in higher rates of open conversion (29.3% vs 10.3%, P < .001) and fecal diversion (24.8% vs 6.2%, P < .001). However, multivariable analysis demonstrated that an abscess was not an independent predictor of overall 30-day complications (odds ratio [OR], 1.25; P = .190). Furthermore, in the PSM cohort of 474 patients, rates of anastomotic leak (10.1% vs 11.7%, P = .718), overall complications (41.1% vs 38.0%, P = .571), and severe complications (8.2% vs 10.8%, P = .480) were statistically identical between the abscess and non-abscess groups.

CONCLUSION: While an intraoperative abscess increases operative difficulty, it does not independently compromise anastomotic integrity. Primary anastomosis in an infected field is safe, allowing surgeons to spare appropriately selected patients at experienced centers the profound morbidity of an unnecessary stoma.

PMID:42502992 | DOI:10.1093/ibd/izag148

J Econ Entomol. 2026 Jul 26:toag222. doi: 10.1093/jee/toag222. Online ahead of print.

ABSTRACT

The Asian subterranean termite, Coptotermes gestroi (Wasmann), has never been intercepted in wooden stakes or in‑ground (IG) bait stations in South Florida. We used a large arena to test whether laboratory colonies of C. gestroi could intercept baits placed 3 m apart, following label specifications. In contrast to our field observations, these laboratory colonies readily intercepted baits in 13.1 ± 3.2 d, a rate not statistically different from the Coptotermes formosanus Shiraki (20.5 ± 3.5 d). The cause of this discrepancy between laboratory and field behavior is still under investigation. There were no significant differences in most tunnel‑geometry parameters between C. gestroi and C. formosanus. However, the secondary‑tunnel length distribution differed significantly, with C. gestroi constructing a greater number of shorter secondary tunnels than C. formosanus. Fractal analysis showed that C. formosanus produced more abundant and more complex tunnel networks than C. gestroi. A distinctive behavior in C. gestroi was observed when a tunnel approached within 17.8 ± 6.8 cm of a bait, at which point the tunnel shifted direction toward the bait. GC‑MS analysis and the use of new Plexiglas arena ruled out any involvement of trail‑following pheromones. Follow‑up experiments evaluating light, magnetism, bait odor, temperature gradients, colony age, and substrate type also failed to identify a causal mechanism. Despite clear behavioral evidence of short‑range bait detection, the sensory basis underlying this response in C. gestroi remains unresolved.

PMID:42502990 | DOI:10.1093/jee/toag222

Psychiatr Hung. 2026;41(1):44-52.

ABSTRACT

Between 1985 and 2024, Hungary’s annual suicide rate gradually decreased from approximately 46 per 100000 people to approximately 17 per 100 000 people (i.e., by approximately 63 percent), while the number of patients receiving medication for depression increased twelvefold. Studies confirm that more widespread and effective treatment of depression has played a key role in this significant decline in suicides. There have been two periods of stagnation in the decline in suicide rates over the last 40 years: the first was between 2007 and 2011, while the second has been ongoing since 2019. These two periods were characterized by suboptimal functioning of psychiatric care and reduced access to care. Keywords: Hungary; suicide rate; suicide; antidepressants.

PMID:42502910

Psychiatr Hung. 2026;41(1):25-43.

ABSTRACT

INTRODUCTION: Test anxiety impacts approximately 25-50% of university students’ psychological wellbeing and academic achievement, yet support options remain limited. Despite rising demand for mental health services, many students face barriers in accessing help. Digital mental health interventions (DMHIs) could provide accessible support; however, their effectiveness in alleviating test anxiety has not been systematically evaluated. This review aimed to assess how effectively DMHIs reduce test anxiety in students and to identify key features of these interventions.

METHOD: The protocol was preregistered on OSF (July 21, 2025) and adhered to PRISMA 2020 guidelines. Searches were conducted in PubMed, PsycINFO, Scopus, Web of Science, ERIC, and ClinicalTrials.gov in August 2025. Eligible studies involved higher education students, utilized a DMHI, reported validated test anxiety outcomes, and employed experi mental designs. Risk of bias was assessed using RoB 2 and ROBINS-I tools.

RESULTS: Eight studies with a total of 813 students met inclusion criteria, including six randomized controlled trials. Inter ventions utilized multicomponent, mindfulness-based, or serious game formats delivered through web or app platforms. All studies reported reductions in test anxiety post-intervention; however, only three found statistically significant improvements over controls. Multicomponent programs showed the most consistent benefits. Most studies assessed test anxiety with a bidimensional measure, though emerging models highlight the importance of a multidimensional perspec tive to distinguish components.

CONCLUSION: DMHIs hold promise for reducing test anxiety, especially when integrating cognitive or dialectical behavioral therapy with study skills or mindfulness. Further research, including follow-ups and multidimensional assessments, is essential to establish their full efficacy.

PMID:42502909

Vet Clin Pathol. 2026 Jul 26. doi: 10.1111/vcp.70116. Online ahead of print.

ABSTRACT

BACKGROUND: The edible insect industry, driven by the nutritional and environmental benefits of mealworms, faces increasing challenges from pathogens affecting Tenebrio molitor farming systems. Hemocyte-based health assessments could provide valuable diagnostic insights, yet standardized hemolymph processing protocols and hematological reference intervals (RIs) are currently lacking for this species.

OBJECTIVES: This study aimed to develop practical protocols for hemolymph sampling, refine hemocyte classification, and establish hematological RIs for both larval and adult stages of T. molitor.

METHODS: An optimized tearing method, involving capillary collection of hemolymph from a proleg transected at the femoral-tibial joint, was used to sample healthy individuals. Total and differential hemocyte counts were determined using a hemocytometer and Wright-Giemsa-stained smears, respectively, and from distinct insect populations (n = 41-43 samples per group). Hemolymph was analyzed in pools due to the small size of T. molitor. Transmission electron microscopy was conducted on a multinucleated giant hemocyte (MGH) isolated from a histologic slide. RIs were calculated following American Society for Veterinary Clinical Pathology (ASVCP) guidelines, and life-stage differences were statistically assessed.

RESULTS: Granular cells and plasmatocytes predominated, whereas prohemocytes and oenocytoids were rare. MGHs, newly identified in T. molitor, were characterized as a fifth hemocyte population. Significant life-stage differences were observed, warranting separate RIs for larvae and adults. The established RIs were relatively wide, reflecting natural fluctuations in invertebrate hemolymph volume and the unsexed, age-diverse reference population.

CONCLUSIONS: This report of hematological RIs for T. molitor lays the groundwork for implementing hemocyte-based health surveillance in yellow mealworm beetle farming.

PMID:42502903 | DOI:10.1111/vcp.70116

J Res Adolesc. 2026 Sep;36(3):e70237. doi: 10.1111/jora.70237.

ABSTRACT

Sexually and racially diverse (SD) adolescents experience elevated proximal and distal minority stressors that vary across school, community, and policy contexts. Limited research has examined how access to and use of LGBTQIA+ supportive structures, such as Gender and Sexualities Alliances (GSAs), LGBTQIA+ community centers, and affirming school staff, shape distal minority stress for racially and sexually diverse youth across geographic settings. Using cross-sectional national sample data of SD adolescents from the Adolescent Stress Experiences Over Time Study (ASETS; N = 1076), this study applied binary logistic regression and linear regression to assess how racial identity, urbanicity, and structural access to and use of LGBTQ community centers and school affirmative SD groups are associated with distal sexual minority stress domains (homonegative climate, social marginalization, and intersectional stress), friend social support, and coping skills. Results indicated that GSA presence, regardless of individual participation, was associated with reduced odds of minority stress across all domains, while attending a GSA was further associated with increased use of engagement-oriented coping strategies. Conversely, community center attendance was associated with higher odds of social marginalization, suggesting contextual variability in the protective impacts of community-based supports. Geographic differences in distal minority stress were evident in only one domain, homonegative climate, and rurality was not significantly associated with differences in peer social support or coping. Findings underscore the importance of school-embedded, structurally inclusive supports for reducing minority stress and bolstering resilience among sexually and racially diverse adolescents, and highlight ongoing gaps in support for youth outside urban areas or in restrictive community climates. Future research should examine culturally grounded mechanisms that enhance the effectiveness of supportive structures and ensure inclusivity across racial and geographic contexts.

PMID:42502898 | DOI:10.1111/jora.70237