Tag: statistics

Clin Drug Investig. 2025 Oct 12. doi: 10.1007/s40261-025-01494-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Lazertinib, a potent and irreversible third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has shown promising efficacy and favorable tolerability in EGFR-mutated non-small cell lung cancer (NSCLC). On the basis of in vitro findings, lazertinib is primarily metabolized by glutathione conjugation via glutathione-S-transferase mu 1 (GSTM1), occurring via enzymatic activity of GST or non-enzymatic processes, as well as through cytochrome P450 3A4. Here, we report the effect of GSTM1 on lazertinib pharmacokinetics (PK) using clinical evaluations.

METHODS: The effect of GSTM1 on lazertinib PK was evaluated in multiple phase 1 pharmacology studies. Clinical studies (NCT03556436, NCT04410081, and NCT05076877) involving healthy adult participants given lazertinib were analyzed on the basis of GSTM1 genotype (null [i.e., no expression] or non-null [i.e., expression]).

RESULTS: In a clinical study where participants were genotyped and analyzed to determine the association of lazertinib plasma maximum concentration (C_max) and area under curve (AUC) with a panel of genes known to affect PK, GSTM1 genotype showed a statistically significant association with AUC. Compared with null GSTM1 participants, non-null GSTM1 participants had relatively lower plasma exposure owing to increased GSTM1-mediated clearance. The mean single-dose and steady-state plasma C_max and AUC of lazertinib was 1.1- to 1.8-fold and 1.4- to 2.2-fold higher in null GSTM1 participants, respectively. The safety profiles of lazertinib were generally comparable across null and non-null GSTM1 participants.

CONCLUSIONS: Overall, GSTM1 status affected lazertinib PK in healthy participants and hence further research is warranted to determine the magnitude of PK differences and whether they are clinically meaningful in the NSCLC patient population intended to be treated with lazertinib.

PMID:41076618 | DOI:10.1007/s40261-025-01494-z

Obes Surg. 2025 Oct 12. doi: 10.1007/s11695-025-08305-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Bariatric surgery (BS) is an effective and durable long-term treatment for severe obesity, yet less than 1% of eligible patients undergo surgery. Thus, we explored the perceptions and experiences of patients with obesity seeking BS prior to obtaining a referral for surgery.

METHODS: A survey was prospectively administered to patients who were referred to our institution from March 25, 2023, to May 28, 2024. Questions assessed patients’ initial exposure to BS, perceptions of its safety and efficacy, who initiated referral discussions, and whether patients would have considered surgery earlier if prompted by their healthcare provider. Statistical analyses included Chi-square test. Qualitative analysis using thematic analysis was conducted for free-text responses.

RESULTS: Out of 327 patients invited, 118 completed the survey (36.1%). The majority of participants (57.9%) initiated discussions about BS with their provider, and 79.7% would have considered BS sooner if approached earlier. Respondents had considered BS for 3.8 years on average (standard deviation = 5.3). The most important contributions of BS for patients were “improved health” (94.1%) and “improved appearance” (31.6%). The most commonly reported barriers to obtaining a referral included cost (55.1%), followed by safety (45.8%) and efficacy (33.1%) concerns.

DISCUSSION: Our findings underscore the importance of proactive and early engagement between providers and patients regarding BS referrals. Addressing safety and efficacy concerns through comprehensive patient education by providers may improve BS referral rates by removing patients’ perceived barriers to care. Financial concerns remain a significant barrier to BS utilization and should be further investigated and addressed.

PMID:41076616 | DOI:10.1007/s11695-025-08305-6

Plant Foods Hum Nutr. 2025 Oct 12;80(4):170. doi: 10.1007/s11130-025-01401-z.

ABSTRACT

Chia seeds (Salvia hispanica L.) have attracted interest for their potential health benefits, yet their overall effectiveness remains uncertain due to limited high-quality evidence and heterogeneity across studies. This umbrella review critically synthesizes data from systematic reviews and meta-analyses of randomized controlled trials (RCTs) to evaluate the effects of chia supplementation on key health outcomes. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science. Eligible studies assessed outcomes including blood pressure, lipid profiles, inflammation, and anthropometric measures. Methodological quality was evaluated using AMSTAR-2, and certainty of evidence was graded using GRADE. Meta-analyses were performed using Comprehensive Meta-Analysis (CMA) software v3.7, with Hedges’ g and 95% confidence intervals (CI); significance was set at P < 0.05. Eight meta-analyses involving approximately 2,500 participants were included. Chia supplementation resulted in significant reductions in diastolic blood pressure (g = -0.550; 95% CI: -0.718 to -0.382), systolic blood pressure (g = -0.119; 95% CI: -0.228 to -0.010), total cholesterol (g = -0.300), LDL-C (g = -0.300), triglycerides (g = -0.200), waist circumference (g = -0.289), and C-reactive protein (g = -0.165). However, a small reduction in HDL-C was also observed (g = -0.093). Overall, chia supplementation may offer modest but statistically significant benefits for improving blood pressure, lipid profiles, inflammation, and central obesity. The certainty of evidence, based on GRADE assessments, ranged from moderate to low for most outcomes. .

PMID:41076614 | DOI:10.1007/s11130-025-01401-z

J Robot Surg. 2025 Oct 12;19(1):682. doi: 10.1007/s11701-025-02888-z.

ABSTRACT

With waiting lists for elective surgery at an all-time high in the NHS, achieving safe, effective and efficient surgery has become paramount. “HIT lists” (high intensity theatre lists) have gained popularity and have successfully been implemented in institutions within the NHS to improve productivity across specialties with a view to achieving waiting list reduction. Achieving efficiency through meticulous planning and parallel processing has been shown to be effective in urology but has yet to be reported in the context of (robotic) general surgery. With 75,000 cholecystectomies performed in the UK on an annual basis, the issue of high throughput for this procedure is of particular relevance. Here, we report the successful application of HIT principles in the context of an NHS hospital, for the first time using a single team and a single theatre, performing up to 10 robotic cholecystectomies during a standard working day and hereafter being referred to as an “stHIT list”. We increased theatre utilisation by up to 100% with a significant potential overall increase in income in the context of a tariff-based reimbursement framework compared to a standard 5 case laparoscopic list.

PMID:41076601 | DOI:10.1007/s11701-025-02888-z

JAMA. 2025 Oct 12. doi: 10.1001/jama.2025.18572. Online ahead of print.

NO ABSTRACT

PMID:41076589 | DOI:10.1001/jama.2025.18572

Blood Coagul Fibrinolysis. 2025 Oct 13. doi: 10.1097/MBC.0000000000001389. Online ahead of print.

ABSTRACT

Thrombophilia is influenced by genetic variants, such as Factor V Leiden (FVL) and the prothrombin G20210A mutation. In clinical settings, assessing numerous genetic factors can lead to diagnostic errors and unnecessary treatments. This meta-analysis examines gene variants associated with thrombosis in the Iranian population, where their role in thrombotic disorders remains underexplored. A systematic literature search was performed across PubMed, Scopus, and Web of Science, targeting case-control studies published up to July 2025. Studies were included if they evaluated thrombophilia-related polymorphisms in Iranian patients with various thrombotic conditions, such as recurrent pregnancy loss (RPL), venous thromboembolism (VTE), or deep vein thrombosis (DVT). Advanced statistical analyses, including random-effects models, fixed-effects models, and Bayesian meta-analysis, were used to compute odds ratios (ORs) and 95% confidence intervals (CIs). From 36 studies encompassing over 14 000 participants, significant associations emerged. For RPL, FVL G1691A heterozygote (OR: 1.998, 95% CI: 1.02-3.88), methylenetetrahydrofolate reductase (MTHFR) C677T heterozygote (OR: 1.77, 95% CI: 1.31-2.39), MTHFR A1298C heterozygote (OR: 3.10, 95% CI: 1.33-7.20) and homozygote (OR: 1.69, 95% CI: 1.05-2.70), prothrombin G20210A heterozygote (OR: 2.435, 95% CI: 1.09-5.39) and homozygote (OR: 0.487, 95% CI: 0.40-0.58), plasminogen activator inhibitor-1 (PAI-1) polymorphisms, factor V (FV) A4070G, FV 5279A/G, factor XIII (FXIII) Val34Leu, and integrin subunit beta-3 (ITGB3)1565T/C were linked to elevated RPL risk. Additionally, FVL G1691A heterozygote (OR: 5.25, 95% CI: 2.39-11.54) was associated with higher VTE risk, while MTHFR C677T heterozygote (OR: 1.404, 95% CI: 1.030-1.914) increased DVT risk. These ethnicity-specific findings highlight critical genetic risk factors for thrombotic disorders in Iranians, potentially guiding precise diagnostics and personalized interventions.

PMID:41076578 | DOI:10.1097/MBC.0000000000001389

Hematol Oncol. 2025 Nov;43(6):e70146. doi: 10.1002/hon.70146.

ABSTRACT

The use of low-dose PD-1 inhibitors may offer a promising treatment strategy for patients with refractory Hodgkin lymphoma. This approach has the potential to mitigate the financial toxicity commonly associated with immune checkpoint inhibitors while also reducing the likelihood of severe adverse events. The aim of this study was to further investigate the efficacy and safety of nivolumab (nivo) at a 40 mg dose (LD group) within NCT03343665 clinical trial framework and to compare these results to the standard-dose therapy (SD group) using a propensity score matching approach. This study included 62 patients in each group. Median follow up was 63 (11-87) and 73 months (20-107) in the LD and SD group, respectively. The overall response rate and complete response was 68% and 39% versus. 70% and 39%, respectively. Five-year PFS was 26.8% (95% CI 17.8-40.7) and 22.1% (95% CI 12-40.6), p = 0.77, and 5-year OS 95.7% (95% CI: 90-100) and 93.3% (95% CI: 87-99), p = 0.33. The PFS was not statistically different regarding the prior treatment and key clinical factors. In the LD group the median dose of nivo was 0.58 mg/kg (0.35-0.91). There was no statistically significant difference based on dose per body weight in terms of survival. No differences were observed in the incidence of any AEs (69% vs. 77%) and 3-4 AEs (6% vs. 13%). Nivolumab therapy at a dose of 40 mg demonstrates comparable efficacy and safety to the standard dose of 3 mg/kg in patients with r/r cHL.

PMID:41076560 | DOI:10.1002/hon.70146

Brain Behav. 2025 Oct;15(10):e70958. doi: 10.1002/brb3.70958.

ABSTRACT

OBJECTIVE: To develop and validate a machine learning (ML)-based predictive model for intensive care unit (ICU) readmission in patients with cerebral infarction using neurophysiological and clinical data from the MIMIC-IV database.

METHODS: A retrospective cohort of 3,348 patients diagnosed with cerebral infarction was identified from the MIMIC-IV database. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression analysis. Various ML models, including Decision Tree, K-Nearest Neighbors, LightGBM, Naïve Bayes, Random Forest, Support Vector Machine, and XGBoost, were developed and evaluated based on model performance metrics.

RESULTS: The logistic regression model achieved the highest area under the receiver operating characteristic curve (AUC) of 0.682 (95% CI: 0.630-0.733). Significant predictors of ICU readmission included peptic ulcer disease, glucocorticoid use, potassium levels, and red blood cell count.

CONCLUSIONS: This study demonstrates that ML models can effectively predict ICU readmission in CI patients. Logistic regression provides a clinically interpretable approach for risk stratification.

PMID:41076549 | DOI:10.1002/brb3.70958

J Health Popul Nutr. 2025 Oct 11;44(1):357. doi: 10.1186/s41043-025-00945-9.

ABSTRACT

BACKGROUND: Global health risk factors contribute significantly to mortality and morbidity worldwide, with diverse impacts across socio-economic groups. This study developed a composite index for health risk factors and subdomains, including nutrition, environmental risks, and non-communicable diseases, across 100 countries stratified by human development index (HDI) from 2015 to 2019. The index tracks disparities, trends, and associations with human development, aiding in resource allocation and informed policy-making for reducing health risks and improving global health outcomes.

METHODS: A panel dataset comprising 100 countries, categorized into four HDI groups, was analyzed for the period 2015 to 2019. Health indicators were selected to construct a Health Risk Factors Index based on the World Health Organization’s Global Reference List 2018. The development of the composite index and its sub-domains followed the United Nations Development Programme’s methodology for data normalization, utilized Principal Component Analysis to determine weights, and employed the inverse normalized Euclidean distance formula for aggregation. Spearman’s rank correlation was used to examine the relationships between the composite Health Risk Factors Index, its sub-indices, and the HDI.

RESULTS: The study revealed that very high HDI countries excelled in the Health Risk Factors Index and sub-indices for nutrition and environmental risks, indicating lower health risks. While low and medium HDI groups performed better in the non-communicable diseases index. Singapore achieved the highest health risk factors index scores in 2015 and 2019. A strong positive correlation was observed between HDI with composite and sub-indices of health risk factors and a negative correlation with sub-index of noncommunicable disease during 2015-2019.

CONCLUSION: The study highlights significant disparities in health risk factors across HDI groups, underscoring the need for tailored interventions. In general, very high and high HDI countries require focused efforts on noncommunicable disease-related health risk factors, while low and medium HDI countries should prioritize nutrition and environmental risks. Composite indices like the health risk factor index facilitate benchmarking and policy development, promoting accountability and targeted strategies for global health improvement.

PMID:41076528 | DOI:10.1186/s41043-025-00945-9

BMC Pulm Med. 2025 Oct 11;25(1):466. doi: 10.1186/s12890-025-03860-1.

ABSTRACT

BACKGROUND: Pulmonary eosinophilic syndromes (PES) are a heterogeneous group of respiratory disorders characterized by eosinophilic infiltration of lung tissues and/or elevated eosinophil counts in peripheral blood. Accurate diagnosis and understanding of PES are crucial for effective management, especially in underrepresented regions such as Saudi Arabia.

OBJECTIVES: To evaluate the clinical, radiological, and biomarker profiles of PES in a Saudi Arabian cohort and to identify factors associated with disease presentation and severity.

METHODS: This retrospective case-control study included 95 patients diagnosed with PES at Mouwasat Hospital, Jubail, Eastern Province, Saudi Arabia, from January 2023 to January 2024. Clinical data, laboratory findings (including eosinophil counts, IgE, and FeNO levels), pulmonary function tests, and radiological imaging were analyzed. Statistical analysis was performed using SPSS, with descriptive and inferential methods to assess associations.

RESULTS: The cohort had a mean age of 40.5 ± 12.9 years, with a majority being male (65.3%) and Saudi nationals (87%). Elevated eosinophil counts and FeNO levels were significantly associated with PES (p < 0.05). Patients exhibited characteristic radiological patterns such as ground-glass opacities and consolidations. Pulmonary function tests showed reduced FEV₁ and small airway impairment in cases versus controls (p = 0.027). The study observed strong correlations between eosinophilia, airway obstruction, and higher BMI. Smoking was associated with increased symptom severity.

CONCLUSIONS: The study underscores the distinct clinical, radiological, and biomarker features of PES in the included population. Integrating multi-modal assessments can improve diagnostic accuracy. These findings emphasize the importance of standardized pathways for PES diagnosis, especially in regions with potential underdiagnosis, and highlight the need for increased awareness among healthcare professionals.

PMID:41076527 | DOI:10.1186/s12890-025-03860-1