Tag: statistics

J Pediatr Endocrinol Metab. 2025 Aug 7. doi: 10.1515/jpem-2025-0137. Online ahead of print.

ABSTRACT

OBJECTIVES: Congenital hypothyroidism (CH) requires early diagnosis to prevent irreversible neurodevelopmental impairments. This study aimed to determine cutoff values for initial capillary thyroid-stimulating hormone (TSH), first venous TSH, and levothyroxine (LT4) dose at 6 months to differentiate between transient and permanent CH.

METHODS: A retrospective analysis was conducted on 289 patients diagnosed with CH at the Pediatric Endocrinology Clinic of the University of Health Sciences, Umraniye Training and Research Hospital, from January 2014 to September 2021. Patients received treatment and were followed for at least 6 months after treatment discontinuation or remained under therapy. Patients were divided into two groups: permanent CH and transient CH. Initial capillary TSH, first venous TSH, and LT4 dose at 6 months were recorded, and cutoff values were determined using ROC analysis.

RESULTS: Of the 289 patients, 179 (62 %) had transient CH and 110 (38 %) had permanent CH. The permanent CH group had significantly higher levels of capillary TSH, first venous TSH, and LT4 dose at 6 months (p<0.001). The cutoff values for predicting transient CH were <23.1 mIU/L for capillary TSH, <64.5 mIU/L for first venous TSH, and <3.6 mcg/kg/day for LT4 dose at 6 months, all statistically significant.

CONCLUSIONS: Initial capillary TSH, first venous TSH, and LT4 dose at 6 months are reliable predictors for distinguishing between transient and permanent CH. These cutoff values provide clinical guidance, especially for early treatment discontinuation in patients with LT4 doses below 3.6 mcg/kg/day, indicating a higher likelihood of transient CH.

PMID:40768246 | DOI:10.1515/jpem-2025-0137

Elife. 2025 Aug 6;14:RP105111. doi: 10.7554/eLife.105111.

ABSTRACT

Biological membranes are complex and dynamic structures with different populations of lipids in their inner and outer leaflets. The Ca²⁺-activated TMEM16 family of membrane proteins plays an important role in collapsing this asymmetric lipid distribution by spontaneously and bidirectionally scrambling phospholipids between the two leaflets, which can initiate signaling and alter the physical properties of the membrane. While evidence shows that lipid scrambling can occur via an open hydrophilic pathway (groove) that spans the membrane, it remains unclear if all family members facilitate lipid movement in this manner. Here, we present a comprehensive computational study of lipid scrambling by all TMEM16 members with experimentally solved structures. We performed coarse-grained molecular dynamics (MD) simulations of 27 structures from five different family members solved under activating and non-activating conditions, and we captured over 700 scrambling events in aggregate. This enabled us to directly compare scrambling rates, mechanisms, and protein-lipid interactions for fungal and mammalian TMEM16s, in both open (Ca²⁺-bound) and closed (Ca²⁺-free) conformations with statistical rigor. We show that all TMEM16 structures thin the membrane and that the majority of scrambling (>90%) occurs at the groove only when TM4 and TM6 have sufficiently separated. Surprisingly, we also observed 60 scrambling events that occurred outside the canonical groove, over 90% of which took place at the dimer-dimer interface in mammalian TMEM16s. This new site suggests an alternative mechanism for lipid scrambling in the absence of an open groove.

PMID:40768244 | DOI:10.7554/eLife.105111

JAMA Surg. 2025 Aug 6. doi: 10.1001/jamasurg.2025.2564. Online ahead of print.

ABSTRACT

IMPORTANCE: How the Intelligent Continuous Expertise Monitoring System, an artificial intelligence tutoring system, might be best optimized for surgical training is unknown.

OBJECTIVE: To determine the effects of artificial intelligence-augmented personalized expert instruction vs intelligent tutoring alone on surgical performance, skill transfer, and affective-cognitive responses.

DESIGN, SETTING, AND PARTICIPANTS: This single-blinded randomized clinical trial was conducted among a volunteer sample of medical students in preparatory, first, or second year without prior use of a virtual reality surgical simulator (NeuroVR) at the McGill Neurosurgical Simulation and Artificial Intelligence Learning Centre in Montreal, Quebec, Canada. Cross-sectional data were collected from March to September 2024, and per-protocol data analysis was conducted in March 2025.

INTERVENTION: During simulated surgical procedures, trainees received 1 of 3 feedback methods. Group 1 received only intelligent tutor instruction (control). The 2 intervention arms included group 2, which received expert feedback in identical words to the intelligent tutor, and group 3, which received artificial intelligence data-informed personalized expert feedback.

MAIN OUTCOMES AND MEASURES: The coprimary outcomes included change in overall surgical performance across practice resections and skill transfer to a complex realistic scenario, measured by artificial intelligence-calculated composite expertise score (range, -1.00 [novice] to 1.00 [expert]). Secondary outcomes included emotional and cognitive demands, measured via questionnaires.

RESULTS: In this randomized clinical trial, the final analysis included 87 medical students (46 [53%] women; mean [SD] age, 22.7 [4.0] years), with 30, 29, and 28 participants in groups 1, 2, and 3, respectively. Group 3 achieved significantly higher scores than group 1 across several trials, including trial 5 (mean difference, 0.26; 95% CI, 0.09-0.43; P = .01) and the realistic task (mean difference, 0.20; 95% CI, 0.06-0.34; P = .02). Group 3 also achieved significantly better scores than the other 2 groups in certain metrics, such as bleeding and injury risk. Emotions and cognitive load demonstrated significant differences.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, personalized expert instruction resulted in enhanced surgical performance and skill transfer compared with intelligent tutor instruction, highlighting the importance of human input and participation in artificial intelligence-based surgical training.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06273579.

PMID:40768205 | DOI:10.1001/jamasurg.2025.2564

Radiol Med. 2025 Aug 6. doi: 10.1007/s11547-025-02069-w. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to compare palliative cTACE, DEB-TACE and DSM-TACE in patients affected by HCC in intermediate BCLC stage in terms of efficacy and patient tolerance.

MATERIALS AND METHODS: Patients treated with palliative TACE were prospectively enrolled in two centers during 9 months. Procedures were performed superselectively in all patients. Inclusion criteria were: HCC diagnosis, intermediate BCLC stage, portal tree patency, preserved hepatic-renal-coagulation functions, palliative procedural aim, follow-up available up to 6-month post-TACE intervention. Exclusion criteria were: previous TACE treatments, alone or in combination with ablation in the same session, ascites, bilirubin > 2mg/dL, age < 18years, bridge to transplant procedural aim, concomitant infectious diseases. Primary endpoint was to compare efficacy and patients tolerance among the 3 different TACE techniques; secondary endpoint was to compare post-procedural complications occurrence.

RESULTS: Seventy patients were included and divided into three groups according to the TACE technique: 24 were treated with cTACE, 25 with DEB-TACE, 21 with DSM-TACE. According to mRECIST criteria at 1-, 3- and 6-month follow-up, DEB-TACE presented better local response rates but without statistically significant differences. Patients treated with DSM-TACE showed significantly better tolerance, considering post-procedural transaminases and INR values together with clinical adverse events occurrence monitored up to 7 days. There were no differences in post-procedural complications and no major complications occurred.

CONCLUSIONS: In this study, in patients with intermediate-stage HCC undergoing palliative treatments, no significant differences emerged comparing cTACE, DEB-TACE and DSM-TACE in terms of procedural efficacy; however, patients treated with DSM-TACE showed significant better procedural tolerance.

PMID:40768186 | DOI:10.1007/s11547-025-02069-w

Radiol Med. 2025 Aug 6. doi: 10.1007/s11547-025-02063-2. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the radiomic phenotype of epicardial adipose tissue (EAT) derived from coronary artery calcium score (CACS) and its predictive value for myocardial ischemia.

MATERIALS AND METHODS: This retrospective study included patients with angina and intermediate-to-high pre-test probability of coronary artery disease who underwent CACS, dynamic CT myocardial perfusion imaging (CT-MPI) and coronary CT angiography (CCTA). All image acquisitions were performed with third generation dual source CT. Radiomic features of EAT derived from CACS were extracted. EAT volume, EAT density, Coronary Artery Disease-Reporting and Data System (CAD-RADS) grades, CACS, and clinical characteristics were recorded. The diagnostic abilities of CT-derived parameters, clinical + CACS model, the EAT radiomic model, and combined model for identification of myocardial ischemia (defined as quantitative myocardial blood flow of less than 100 mL/100 mL/min) were evaluated.

RESULTS: A total of 555 patients from two hospitals were included and divided into training set and external validation set separately. The EAT radiomic model was found to have a larger area under the curve (AUC) (0.840 for training set, 0.838 for validation set) than other CT-derived parameters and the clinical + CACS model for predicting myocardial ischemia (all p < 0.05). The overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of radiomic model in validation set were 65%, 80%, 59%, 41% and 89%, respectively.

CONCLUSION: The EAT radiomic model demonstrated superior diagnostic performance over clinical + CACS model and other CT-derived parameters in discriminating myocardial ischemia with highest sensitivity and NPV. Nevertheless, the PPV of the EAT radiomic model was found to be low.

PMID:40768185 | DOI:10.1007/s11547-025-02063-2

Appl Biochem Biotechnol. 2025 Aug 6. doi: 10.1007/s12010-025-05322-0. Online ahead of print.

ABSTRACT

Hydrothermal processing is known to influence the nutritional and functional properties of cereals; however, its effects on the bioactive metabolite composition of traditional Indian brown rice varieties remain underexplored. In this study, we investigated the impact of hydrothermal treatment on four indigenous rice varieties, Seeraga samba, Kattu ponni, Kuzhiyadichaan, and Poongar, focusing on the compositional changes in lipophilic bioactive compounds. Using GC-MS/MS analysis, we quantified the alterations in fatty acids, phytosterols, triterpenes, and tocopherols before and after processing. Significant varietal responses were also observed. Seeraga samba exhibited a 20.38% increase in total fatty acid post-treatment, whereas Kuzhiyadichaan showed a 13.72% increase in β-sitosterol (p < 0.01). Poongar displayed an 18.92% increase in polyunsaturated fatty acids, whereas Kattu ponni showed a 2.13% increase in squalene content. Notably, vitamin E and γ-tocopherol were detected exclusively in hydrothermally processed Kuzhiyadichaan and Poongar, indicating enhanced micronutrient release. Statistical analysis revealed significant compositional differences (p < 0.05) between the raw and processed samples with distinct clustering patterns. These findings suggest that hydrothermal processing can be strategically optimized to enhance the nutraceutical value of traditional brown rice, thereby offering a promising approach for dietary biofortification and functional food development.

PMID:40768180 | DOI:10.1007/s12010-025-05322-0

Cancer Causes Control. 2025 Aug 6. doi: 10.1007/s10552-025-02039-7. Online ahead of print.

ABSTRACT

PURPOSE: The positive predictive value (PPV) of cervical cancer screening was projected to decrease in the era of human papillomavirus (HPV) vaccination.

METHODS: We conducted a retrospective cohort study at three U.S. healthcare systems during 2010-2018. Females aged 21-38 years with an abnormal cervical cancer screening test result for which colposcopy was guideline-recommended were included. We estimated age-specific PPVs of cervical intraepithelial neoplasia grade 2 or more severe diagnosis (≥ CIN 2) in HPV-vaccinated and unvaccinated females.

RESULTS: The age-specific PPV point estimates were lower in vaccinated versus unvaccinated females in each age group (21-24; 25-29; and 30-38 years), but the difference was statistically significant only among 25-29-year-olds (PPV = 16.4% [95% CI (confidence interval), 14.6-18.4%] and PPV = 19.8% [95% CI 18.5-21.1%], respectively). Among vaccinated 25-29-year-olds, the PPV was lower in those who received their first dose at ≤ 20 versus > 20 years of age (PPV = 12.1% [95% CI 9.5-15.2%] and PPV = 18.8% [95% CI 16.4-21.4%], respectively). Among all age groups combined, the PPV was lower in vaccinated versus unvaccinated females.

CONCLUSIONS: Our findings suggest that among females with a cervical test result recommended for colposcopy, the PPV for ≥ CIN2 was lower in those vaccinated versus unvaccinated, and was relatively lower in those vaccinated at younger ages. Future studies will have greater ability to estimate the impact of vaccination at the recommended age (9-12 years) on the PPV as more recent birth cohorts, who had greater vaccine uptake, age-in to screening eligibility.

PMID:40768171 | DOI:10.1007/s10552-025-02039-7

JAMA Netw Open. 2025 Aug 1;8(8):e2524783. doi: 10.1001/jamanetworkopen.2025.24783.

ABSTRACT

IMPORTANCE: Although the use of pneumococcal conjugate vaccines (PCV) has reduced the overall burden of pneumococcal disease, recent measurements of pneumococcal pneumonia incidence are lacking.

OBJECTIVE: To prospectively quantify the burden of pneumococcal pneumonia and to assess the potential impact of the recently approved adult-specific 21-valent pneumococcal conjugate vaccine (V116).

DESIGN, SETTINGS, AND PARTICIPANTS: This cross-sectional study for prospective active surveillance included adults residing in defined catchment areas in Tennessee and Georgia hospitalized with clinical and radiographical evidence of community-acquired pneumonia (CAP) at 3 hospitals between 2018 and 2022. Data were analyzed from July 2024 to January 2025.

MAIN OUTCOMES AND MEASURES: Pneumococcal etiology was determined using an on-market serotype-agnostic urinary antigen test, serotype-specific urinary antigen detection assays covering 30 serotypes, and routine clinical tests. Overall and age-stratified incidence rates for pneumonia hospitalizations were estimated accounting for the probability of enrollment and hospital market share of enrolling hospitals within the catchment area.

RESULTS: Among 2016 patients hospitalized for CAP, the median (IQR) age was 60.1 (47.0-70.2) years; 726 patients (36.0%) were Black, 81 (4.0%) were Hispanic, and 1209 (60.0%) were White; 1863 patients (92.4%) lived in a community dwelling. A total of 279 patients (13.8%) hospitalized for CAP had evidence of pneumococcal pneumonia, and 198 (9.8%) had detection of serotypes included in V116. The overall estimated annual incidence of hospitalizations for all-cause CAP was 340 per 100 000 adults. The incidence of hospitalizations for pneumococcal CAP and pneumococcal CAP due to serotypes included in V116 was 43 and 30 per 100 000 adults, respectively. The burden of all-cause and pneumococcal CAP was consistently highest among adults age 65 years or older.

CONCLUSIONS AND RELEVANCE: This prospective surveillance study demonstrated a large burden of hospitalizations for CAP among US adults, with the highest burden of disease among adults age 65 years or older. A sizable fraction of CAP was caused by Streptococcus pneumoniae, especially by serotypes included in V116.

PMID:40768150 | DOI:10.1001/jamanetworkopen.2025.24783

JAMA Netw Open. 2025 Aug 1;8(8):e2525222. doi: 10.1001/jamanetworkopen.2025.25222.

ABSTRACT

IMPORTANCE: With acute care utilization and mortality rates increasing among people with opioid use disorder, hospital addiction consult services can provide an important touchpoint for care, potentially leading to improved outcomes.

OBJECTIVE: To study the effectiveness of interprofessional hospital addiction consultation services on postdischarge acute care utilization and mortality.

DESIGN, SETTING, AND PARTICIPANTS: In this pragmatic stepped-wedge cluster randomized implementation and effectiveness (hybrid type 1) clinical trial, 6 New York City public hospitals were randomized to an intervention start date, and outcomes were compared during treatment as usual (TAU) and intervention conditions. Participants included adults with hospitalizations identified in Medicaid claims data between October 2017 and January 2021. Eligible patients had an admission or discharge diagnosis of opioid use disorder or opioid poisoning or adverse effects, were hospitalized at least 1 night in a medical or surgical inpatient unit, and were not receiving medication for opioid use disorder before hospitalization.

INTERVENTION: Hospitals implemented the Consult for Addiction Treatment and Care in Hospitals (CATCH) program, an interprofessional inpatient addiction consult service providing specialty care for substance use disorders, with teams consisting of a medical clinician, social worker or addiction counselor, and peer counselor.

MAIN OUTCOMES AND MEASURES: Acute care utilization (hospitalizations and emergency department [ED] visits) and mortality rates (all-cause deaths, overdose deaths, and opioid-involved overdose deaths) 1 year after hospital discharge. Data for the eligible patients were analyzed July 2023 to September 2024.

RESULTS: In total, 1355 eligible admissions were identified (968 [71.4%] men; mean [SD] age, 46.6 [12.4] years). A majority of patients (835 [61.5%]) had at least 1 subsequent hospitalization or ED visit. There were 113 deaths, including 34 overdose deaths (30.1%), of which 28 (82.4%) involved opioids. ED admissions were lower in the intervention period compared with TAU (incidence rate ratio, 0.79 [95% CI, 0.72-0.88]; P < .001). There were no statistically significant differences between CATCH and TAU periods in numbers of hospitalizations (incidence rate ratio, 0.99 [95% CI, 0.87-1.13]) or mortality (eg, hazard ratio for all-cause death, 1.14 [95% CI, 0.98-1.92]).

CONCLUSIONS AND RELEVANCE: In this prespecified secondary analysis of a cluster randomized clinical trial, postdischarge ED visits decreased with the CATCH program, highlighting the potential of hospital-based addiction consult services to address needs of patients with opioid use. Nonetheless, high rates of acute care utilization and mortality persisted, underscoring the need for comprehensive care strategies that extend beyond the hospital walls, and addressing the complex health and social needs of individuals with opioid use.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03611335.

PMID:40768148 | DOI:10.1001/jamanetworkopen.2025.25222

JAMA Netw Open. 2025 Aug 1;8(8):e2525355. doi: 10.1001/jamanetworkopen.2025.25355.

ABSTRACT

IMPORTANCE: The Cheetah randomized trial demonstrated that changing sterile gloves and instruments before wound closure reduces surgical site infections (SSI) in abdominal surgery. However, its environmental impact remains unclear.

OBJECTIVES: To estimate the global carbon footprint associated with changing sterile gloves and instruments before closure abdominal wound.

DESIGN, SETTING, AND PARTICIPANTS: This decision analytic model compared the carbon footprint of a glove and instrument change intervention against a control (no glove and instrument change). Model parameters were sourced from a large cluster randomized trial conducted in 7 low- and middle-income countries (LMICs) between June 2020 and March 2022, as well as data from stakeholder engagement and existing research. Boundaries included the trial intervention and in-hospital resources used to manage SSI. The analysis was stratified by wound contamination status (clean-contaminated, contaminated-dirty) and country-income classification.

MAIN OUTCOME AND MEASURES: Average per-patient wound-specific carbon footprint, calculated as the sum of the carbon footprint of glove and instrument change and SSI. Sensitivity analyses were based on the lowest and highest possible values for key model parameters: intervention effectiveness, intervention carbon footprint, and SSI carbon footprint. The best-case analysis was based on highest possible intervention effectiveness, lowest possible intervention carbon footprint, highest possible SSI carbon footprint. The worst-case analysis was based on lowest intervention effectiveness, highest intervention carbon footprint, and lowest SSI carbon footprint.

RESULTS: In LMICs, the difference in carbon footprints between the intervention and control groups was 10.97 kg CO2 equivalents (kgCO2e) (scenario range, -2.53 to 33.50 kgCO2e) for clean-contaminated and 22.60 kgCO2e (scenario range, -1.62 to 61.17 kgCO2e) for contaminated-dirty surgeries. In high-income countries, differences were 4.14 kgCO2e (scenario range, -3.38 to 17.95 kgCO2e) and 10.48 kgCO2e (scenario range, -3.06 to 37.62 kgCO2e), respectively. Country-level modeling found the intervention to be consistently associated with a lower wound-specific carbon footprint across all countries.

CONCLUSIONS AND RELEVANCE: In this decision analytic model, sterile glove and instrument change before wound closure was associated with a reduced wound-specific carbon footprint across all country income settings. Alongside clinical and economic benefits, this intervention may support more sustainable surgical care; national associations and governments should consider its adoption to improve outcomes for both patients and the planet.

PMID:40768147 | DOI:10.1001/jamanetworkopen.2025.25355