Tag: statistics

JAMA Otolaryngol Head Neck Surg. 2026 Jul 2. doi: 10.1001/jamaoto.2026.1749. Online ahead of print.

ABSTRACT

IMPORTANCE: Squamous cell carcinomas of the oral cavity (OCSCC), oropharynx (OPSCC), hypopharynx (HPSCC), and larynx (LSCC) are the most common forms of head and neck cancer globally. Epidemiological studies have identified variations in blood trace metal concentrations as potential risk factors for the development of these cancers, but these studies are susceptible to multiple biases.

OBJECTIVE: To determine if variations in genetically predicted blood manganese are associated with risk of OCSCC, OPSCC, HPSCC, and LSCC.

DESIGN, SETTING, AND PARTICIPANTS: This population-based 2-sample cis-mendelian randomization study used a genetic instrument for blood manganese derived from a meta-analysis of 3 individual-level genome-wide association study datasets of 6564 Scandinavian participants. Genetic associations for the development of the specified cancers were obtained from a nonoverlapping, multi-ancestral meta-analysis that combined individual-level genome-wide association study datasets comprising 38 857 healthy controls, 5596 case patients with OCSCC, 2212 case patients with human papillomavirus (HPV)-positive OPSCC, 1473 case patients with HPV-negative OPSCC, 898 case patients with HPSCC, and 4409 case patients with LSCC.

EXPOSURES: Increases in genetically predicted whole blood manganese concentration proxied by a genetic instrument including 2 cis-variants (single-nucleotide variants) selected due to their known functions in regulating manganese metabolism.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the risk of OCSCC, OPSCC (HPV positive and HPV negative), HPSCC, and LSCC, evaluated by estimating the odds ratio (OR) and 95% CI of each outcome per 1-SD increase in whole blood manganese concentration after rank-based inverse normalization transformation.

RESULTS: Genetically predicted higher blood manganese was found to have a statistically significant association with increased risk of OCSCC (OR, 1.25; 95% CI, 1.10-1.43; P < .001) and HPV-positive OPSCC (OR, 1.23; 95% CI, 1.04-1.45; P = .02). Associations between blood manganese and HPV-negative OPSCC (OR, 1.20; 95% CI, 0.95-1.50; P = .13), HPSCC (OR, 1.25; 95% CI, 0.75-2.07; P = .39), and LSCC (OR, 1.10; 95% CI, 0.92-1.32; P = .28) were directionally concordant but not statistically significant.

CONCLUSIONS AND RELEVANCE: This cis-mendelian randomization study demonstrates statistically significant associations between higher blood manganese concentrations and risk of OCSCC and HPV-positive OPSCC. Further work should aim to establish the pathophysiological mechanisms underlying this association to inform potential public health strategies for the prevention of these cancers.

PMID:42390852 | DOI:10.1001/jamaoto.2026.1749

JAMA Oncol. 2026 Jul 2. doi: 10.1001/jamaoncol.2026.2157. Online ahead of print.

ABSTRACT

IMPORTANCE: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis remains suboptimal, with inadequate early-stage detection. α-Fetoprotein (AFP) demonstrates insufficient sensitivity. Circulating methylated septin 9 (SEPT9) has shown diagnostic promise.

OBJECTIVE: To determine whether methylated SEPT9 improves detection of HCC when combined with AFP in patients with cirrhosis undergoing surveillance.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective, cross-sectional, diagnostic accuracy study, patients with cirrhosis undergoing routine HCC surveillance with ultrasonography and AFP were enrolled at 2 French academic centers from February 2018 through October 2024. HCC was diagnosed per international guidelines with centralized radiologic review, blinded to methylated SEPT9 results. Data were analyzed from October 2025 to January 2026.

EXPOSURES: Plasma methylated SEPT9 was analyzed from 3 independent plasma aliquots and classified by number of positive replicates (single-positive, double-positive, or triple-positive). Serum AFP was evaluated at a threshold of 20 ng/mL. Biomarkers were evaluated individually and in combination using disjunction logic (tier 1; maximizing sensitivity) or conjunction logic (tier 2; maximizing specificity).

MAIN OUTCOMES AND MEASURES: The primary outcome was the presence of HCC at enrollment. The primary end point was comparison of the area under the receiver operating characteristic curve (AUROC) between methylated SEPT9 and AFP. Secondary end points included diagnostic performance stratified by Barcelona Clinic Liver Cancer (BCLC) stage.

RESULTS: Among 574 participants, 414 (72.1%) were male, and the median (IQR) age was 63 (57-70) years. A total of 118 had HCC, including 51 (43.2%) with BCLC stage 0-A. Methylated SEPT9 outperformed AFP (AUROC: 0.79 [95% CI, 0.74-0.84] vs 0.71 [95% CI, 0.66-0.76], respectively; P = .002; posterior probability of superiority >99.8%). Tier 1a (at least single-positive methylated SEPT9 or AFP >20 ng/mL) achieved 87.8% (95% CI, 81.6-93.5) sensitivity and a negative likelihood ratio of 0.2 (95% CI, 0.1-0.3). Among 64 HCC cases missed by AFP, tier 1a recovered 50 (78%). For BCLC 0-A disease, tier 1a sensitivity was 74.5% (95% CI, 62.2-86.5) vs 23.5% (95% CI, 12.5-35.8) for AFP, 3.2-fold increase. Tier 2 (triple-positive methylated SEPT9 and AFP >20 ng/mL) achieved 99.6% (95% CI, 98.9-100) specificity, a positive likelihood ratio of 76.0 (95% CI, 26.9-181.0), and a diagnostic odds ratio of 112.1 (95% CI, 37.8-294.7).

CONCLUSIONS AND RELEVANCE: In this diagnostic study, combining methylated SEPT9 with AFP substantially improved HCC detection in patients with cirrhosis, particularly for early-stage disease amenable to curative treatment. Prospective studies are needed to determine whether improved detection translates into survival benefit.

PMID:42390849 | DOI:10.1001/jamaoncol.2026.2157

Ther Innov Regul Sci. 2026 Jul 2. doi: 10.1007/s43441-026-01007-w. Online ahead of print.

ABSTRACT

QTLs aim to ensure that the impact of risks on critical quality aspects of the trial remains within an acceptable range. Action limits can serve as an effective mechanism for the early detection of potential risks, emphasizing the importance of continuous, real-time data monitoring throughout the course of a clinical trial. A breach of an action limit constitutes an early warning of a potential negative impact on trial quality, which could subsequently affect statistical analyses. This paper presents practical examples to elucidate common characteristics of QTL parameters, thresholds, and their associated action limits.

PMID:42390815 | DOI:10.1007/s43441-026-01007-w

Cancer Causes Control. 2026 Jul 2;37(7):119. doi: 10.1007/s10552-026-02204-6.

ABSTRACT

PURPOSE: Mailed stool-based fecal immunochemical testing (FIT) can improve colorectal cancer (CRC) screening rates. We aim to determine whether enhancing communications with evidence-based behavioral economics principles in mailed FIT kits further improves screening rates.

METHODS: This study focused predominantly on Medicare patients at average-risk for colon cancer who were not up-to-date on CRC screening. Patients were randomly assigned to one of two interventions: original communication (a series of standard communications, including a pre-mailing letter, FIT kit and letter, and reminders via text or robo-call); or enhanced communication (the same sequence, but incorporating behavioral economics principles to encourage FIT completion). We compared the rate of FIT tests completed at 90 days and factors associated with completion.

RESULTS: 4,070 patients were included. Within 90 days, 27% of all patients successfully completed the FIT test: 28.1% of patients receiving the enhanced communication had FIT test completed compared to 25.5% of patients receiving the original communication. The adjusted risk difference for obtaining patients’ FIT tests within 90 days was 2.2% (95% CI = -0.4%, 4.9%) for the enhanced communication outreach compared to the original communication (p = 0.094). Younger participants and patients experiencing greater area-level deprivation were less likely to complete the screening.

CONCLUSION: The FIT test screening rate in the enhanced communication group was not statistically different from the original communication group. Using evidence-based behavioral economics principles in mailed FIT communications did not markedly improve the rate of CRC screening, but mailed FIT remains a key, cost-effective tool for reaching unscreened individuals.

PMID:42390812 | DOI:10.1007/s10552-026-02204-6

Surg Endosc. 2026 Jul 2. doi: 10.1007/s00464-026-13049-0. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the comparative effectiveness of extended totally extraperitoneal plasty Rives-Stoppa retromuscular repair (eTEP-RS) and open Rives-Stoppa retromuscular repair (Open-RS) in patients undergoing ventral hernia repair.

METHODS: Clinical data from 850 patients were collected in a prospectively maintained database and retrospectively evaluated. 153 patients undergoing eTEP-RS were compared to 154 selected patients undergoing Open-RS (from the period prior to implementation of eTEP-RS at our university medical center). Short-term perioperative outcomes as well as long-term recurrence rate and quality of life by Carolina Comfort Scale (QoL) were evaluated. Results are shown as median (interquartile range).

RESULTS: Our learning curve phase (first 60 eTEP-RS cases) was compared to eTEP-RS from the steady-state phase (cases 61-153). Significant differences with regard to operation time and perioperative complications were observed indicating a relevant learning curve in the procedure. The eTEP-RS cases from the steady-state cohort were compared to the Open-RS cases. After propensity score matching, 83 eTEP-RS cases were compared to 83 Open-RS cases. While operation time was longer (Open-RS: 135 min (95-161); eTEP-RS: 160 min (126-192); i = 0.004), length of stay was shorter in the eTEP-RS cohort (Open-RS: 7 days (6-9); eTEP-RS: 4 days (3-5); p < 0.001) and postoperative pain was lower on postoperative days 2 and 3. Perioperative complications, hernia recurrence rates, and long-term QoL were not different between the two cohorts.

CONCLUSION: eTEP Rives-Stoppa repair offered superior short-term outcomes compared to open Rives-Stoppa repair in suitable patients with medium-sized ventral hernia and selected patients with large ventral hernia. Given the short follow-up period, no statistically significant differences could be observed regarding the long-term outcomes recurrence rate and QoL. Future long-term multicenter studies are necessary to evaluate long-term efficacy.

PMID:42390803 | DOI:10.1007/s00464-026-13049-0

Updates Surg. 2026 Jul 2. doi: 10.1007/s13304-026-02754-z. Online ahead of print.

ABSTRACT

We aimed to determine the effectiveness of the newly developed CANP score in determining prognosis by comparing it with the HALP score and the Modified HALP score in patients with complicated and uncomplicated acute appendicitis. After getting ethical approval and using the hospital data network, we retrospectively analyzed the demographic data, laboratory parameters, and pathology results of 80 female and 100 male patients aged from 15 to 95 years, who underwent surgery for acute appendicitis in the last two years. They were divided into patients with complicated and uncomplicated acute appendicitis. The HALP, Modified HALP, and CANP scores were compared by using statistical methods. According to the area under the ROC curve (AUC), the highest accuracy was found in the CANP score with an AUC of 0.980 (CI: 0.963-0.997), the sensitivity of 85.3%, and specificity of 97.3%. The AUC for M-HALP score was low as 0.322 (CI: 0.211-0.434), showing limited diagnostic value with a sensitivity of 26.5% and specificity of 58.9%. The AUC for the HALP score was the lowest, at 0.244 (CI: 0.161-0.328), with a sensitivity of 29.4% and specificity of 32.2%. Statistical significance was reported as p < 0.001. We showed that the CANP score, with a significantly higher AUC value and along with a higher sensitivity and specificity when compared to the HALP and M-HALP scores, was the most powerful discriminative parameter for predicting the complicated acute appendicitis, so it can be used as a more reliable scoring system in infectious diseases.

PMID:42390782 | DOI:10.1007/s13304-026-02754-z

Carbon Balance Manag. 2026 Jul 2. doi: 10.1186/s13021-026-00479-5. Online ahead of print.

ABSTRACT

Rising anthropogenic carbon emissions are a major driver of climate change and pose a critical challenge to global sustainable development. As a rapidly advancing technology, artificial intelligence (AI) has shown strong potential to enhance carbon emissions management. This review provides a critical and comprehensive synthesis of recent advances in AI-enabled approaches for carbon emissions monitoring, prediction, and reduction. For monitoring, it explores the integration of satellite remote sensing, sensor networks, and machine learning (ML) algorithms, which can improve multi-scale, high-resolution, and near-real-time monitoring capabilities. For prediction, it categorizes prediction models into three groups, namely deep learning (DL), ensemble learning, and statistical learning, to facilitate the selection of appropriate technical approaches based on varying data characteristics and prediction requirements. For reduction, it examines the practical effectiveness of AI in industrial process optimization, energy structure transformation, transportation scheduling and management, construction energy efficiency improvement, and carbon capture, utilization, and storage (CCUS). We further reveal core challenges and potential solutions across the data layer, model layer, and application layer in AI deployment, including data availability and quality, model generalization and interpretability, and engineering and governance barriers that hinder the translation of AI methods into real-world applications. Furthermore, future research directions are discussed to promote the development of more reliable and scalable AI methods that can better support decision-making and practical governance in carbon emissions management. Overall, distinct from previous reviews that mainly focus on single tasks, specific model types, or sectoral applications, this review represents, to our knowledge, one of the first review-level attempts to develop a policy-relevant and interdisciplinary AI framework for carbon emissions management across the full process of monitoring, prediction, and reduction. By integrating unified evaluation metrics, evidence matrices, deployment-constraint analysis, and a technology readiness level (TRL)-based assessment, this framework links methodological performance, application readiness, and governance needs. It provides an integrated methodological foundation for fine-grained emissions sensing, predictive analysis, and emissions reduction decision support, while supporting quantifiable, verifiable, and actionable carbon balance and management.

PMID:42390761 | DOI:10.1186/s13021-026-00479-5

Can J Public Health. 2026 Jul 2. doi: 10.17269/s41997-026-01226-6. Online ahead of print.

ABSTRACT

OBJECTIVES: This study examined temporal trends in co-infection associated with sexually transmitted and blood-borne infections (STBBIs) in Ontario and assessed associations with behavioural, social, and structural determinants within a syndemic framework.

METHODS: A retrospective, population-based approach was used to analyse 269,814 positive test records for chlamydia, gonorrhea, syphilis, and HIV from Ontario’s public health notifiable diseases database across seven Public Health Units (PHUs) between 2013 and 2023. Co-infection was defined as ≥ 2 STBBIs diagnosed within 14 days. Descriptive statistics, Chi-square, and multivariable logistic regression were used to identify behavioural, social, and structural predictors of co-infection. Area-level marginalization was assessed using ON-Marg indices.

RESULTS: STBBI rates steadily increased across all PHUs over the study period, with Toronto, Northwestern, and Thunder Bay District showing the highest burden. Co-infections accounted for 5.71% of infection episodes and increased significantly over time, with a 10.20% annual increase estimated using negative binomial regression (p = 0.010). Male and transgender individuals had higher odds ratios of co-infection compared to females. Behavioural factors (anonymous sex, multiple partners, condomless sex, substance use) and social vulnerabilities (underhoused/homeless, survival sex, sex work) were associated with co-infection. ON-Marg dimensions in housing, material resources, and racialized populations were also associated with higher co-infection rates while age/labour force marginalization showed an inverse relationship.

CONCLUSION: The findings provide evidence consistent with syndemic patterns among STBBIs in Ontario, shaped by behavioural, social, and structural inequities. Integrated, equity-focused interventions and improved integration of co-infection data within disease surveillance systems may support more effective prevention strategies as co-infection rates rise.

PMID:42390728 | DOI:10.17269/s41997-026-01226-6

Dig Dis Sci. 2026 Jul 2. doi: 10.1007/s10620-026-10087-5. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Patients increasingly use the internet and artificial intelligence chatbots to obtain health information, yet the readability, quality, understandability, and actionability of AI-generated gastrointestinal patient education remain unclear. This study compared gastrointestinal patient education from a professional society website with content generated by ChatGPT using validated health literacy instruments.

METHODS: In this cross-sectional comparative study, 50 gastrointestinal patient education topics from the American Gastroenterological Association patient information website were paired with ChatGPT-generated responses using standardized prompts. Readability was assessed using the Flesch-Kincaid Grade Level, quality of treatment information was evaluated using the DISCERN instrument, and understandability and actionability were assessed using the Patient Education Materials Assessment Tool; scoring was performed by two blinded reviewers. Paired t tests were used to compare mean scores between sources, and intraclass correlation coefficients (ICCs) were used to assess interrater reliability between reviewers.

RESULTS: Fifty paired topics were analyzed. The mean Flesch-Kincaid Grade Level was higher for ChatGPT than GI website materials (10.33 ± 1.5 vs 8.72 ± 1.7; mean difference, 1.61; P < .001). Differences in DISCERN scores (63.5 ± 5.7 vs 64.3 ± 5.4; mean difference, – 0.8), PEMAT understandability (87.9% ± 6.9% vs 86.5% ± 7.8%; mean difference, 1.4%; P = .33), and PEMAT actionability (78.6% ± 9.8% vs 77.9% ± 10.2%; mean difference, 0.6%; P = .73) were not statistically significant. Inter-rater reliability was excellent across all measures, with intraclass correlation coefficients of 0.97 (95% CI, 0.95-0.99) for PEMAT understandability, 0.96 (95% CI, 0.94-0.98) for PEMAT actionability, and 0.99 (95% CI, 0.98-0.99) for DISCERN.

CONCLUSION: ChatGPT-generated gastrointestinal patient education demonstrated similar quality, understandability, and actionability compared with professional society materials but was written at a significantly higher reading level. Improving readability may enhance accessibility and support the safe integration of AI-generated patient education.

PMID:42390721 | DOI:10.1007/s10620-026-10087-5

Ophthalmic Physiol Opt. 2026 Jul 2. doi: 10.1007/s44402-026-00114-3. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to determine the duration of mesopic light conditions in natural environments.

METHODS: Illuminance levels were measured at three outdoor locations (a city terrace, a forest and a shadowy park) during different seasons using a calibrated high-spec lux meter with a sensitivity threshold of 0.01 lux. Measurements were recorded from 1 h before sunset until complete darkness to capture the transition from photopic to mesopic (<40 lux) and scotopic (<0.1 lux) conditions. The duration and onset of mesopic light were analysed across locations and seasons to identify site-specific variations.

RESULTS: A gradual decline in illumination was seen from photopic light at 1 h before sunset down to mesopic and scotopic levels. Among the three measured locations, the shadowy park transitioned to mesopic conditions 15-20 min earlier than the terrace or forest. However, despite these differences in onset, the duration of the mesopic period remained consistent, lasting approximately 25-30 min across all locations during the different seasons.

CONCLUSIONS: In natural outdoor environments, mesopic light exposure during sunset represents a relatively brief and consistent transition period of approximately 25-30 min. These findings provide objective field-based baseline data on the temporal dynamics of mesopic illumination. While the present study did not assess refractive development or myopia status, the quantified environmental parameters may inform future research integrating wearable light sensors and refractive outcomes.

PMID:42390705 | DOI:10.1007/s44402-026-00114-3