Tag: statistics

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):361. doi: 10.1007/s00068-025-03034-y.

ABSTRACT

BACKGROUND: In trauma research, the complexity of patient presentations, variability across clinical environments, and diversity in outcomes often introduce substantial uncertainty into the interpretation of findings. Sensitivity analysis (SA) is a vital methodological tool for examining the stability and reliability of research conclusions by testing how they respond to changes in analytical methods, model structures, unmeasured confounding, and foundational assumptions.

METHODS: A literature review was conducted to provide an overview of current knowledge and updates on the application of sensitivity analysis in trauma research. A search was performed in PubMed and Google Scholar for studies conducted in humans and published in English between May 2000 and May 2025.

RESULTS: This review explored the crucial role that SA plays in trauma studies, outlining key techniques, including addressing missing data through multiple or single imputation, evaluating protocol noncompliance, adjusting for baseline imbalances, validating statistical assumptions, and conducting subgroup analyses. These strategies are particularly relevant in trauma research, where data fragmentation, wide population variability, and ethical challenges are common. Drawing on landmark trauma studies including PROMPTT, PROPPR, PATCH-Trauma, PAMPer, and recent neural network applications, we demonstrated how SA can be utilized to evaluate model accuracy, determine variable importance, and assess the consistency of treatment effects.

CONCLUSION: Although the implementation of SA in trauma research remains uneven across the field, establishing SA as a standard element of study design and reporting is vital. Doing so not only bolsters the transparency and trustworthiness of analytical results but also enhances the reproducibility and applicability of findings, ultimately supporting more robust and clinically meaningful advancements in trauma care.

PMID:41410935 | DOI:10.1007/s00068-025-03034-y

JAMA Otolaryngol Head Neck Surg. 2025 Dec 18. doi: 10.1001/jamaoto.2025.4573. Online ahead of print.

ABSTRACT

IMPORTANCE: Numerous phase 2 trials have evaluated the efficacy of neoadjuvant immune checkpoint inhibition (ICI) for mucosal head and neck squamous cell carcinoma (HNSCC), using some degree of pathologic treatment response as a primary or secondary end point. However, whether pathologic treatment response is a meaningful surrogate end point for survival has yet to be determined.

OBJECTIVE: To systematically assess the association between pathologic treatment response and overall survival (OS) and disease-free survival (DFS) after neoadjuvant ICI.

DATA SOURCES: A systematic search of the PubMed, OVID Medline, Embase, CINAHL, and Cochrane databases was performed from January 1, 2000, through May 31, 2025.

STUDY SELECTION: Peer-reviewed studies investigating neoadjuvant ICI for the treatment of mucosal HNSCC in patients 18 years and older were identified. Full-length English-language articles that presented pathologic treatment response and survival data (OS and/or DFS) and any association between the 2 were included.

DATA EXTRACTION AND SYNTHESIS: Three blinded reviewers independently extracted study characteristics, pathologic treatment response data, and survival data, including hazard ratios (HRs) and CIs when available, according to PRISMA guideline. Data were compiled for statistical analysis to calculate DFS, OS, and HRs using a random-effects model. The I2 index was used to report data heterogeneity.

MAIN OUTCOMES AND MEASURES: HRs for the association of pathologic treatment response with DFS and OS.

RESULTS: Eleven trials involving 451 patients met inclusion criteria, with 368 patients included in this meta-analysis. Nine nonrandomized and 2 randomized studies were included, including 7 cohort studies, 2 randomized clinical trials, and 2 retrospective cohort studies, each with a different neoadjuvant ICI regimen. Pooled analysis demonstrated that overall (primary tumor plus lymph node) partial pathologic response (PPR; ≤50% residual viable tumor; HR, 0.53; 95% CI, 0.28-0.97; I2 = 2.1%) and major pathologic response (MPR; ≤10% residual viable tumor; HR, 0.34; 95% CI, 0.12-0.93; I2 = 0.0%) were both associated with improved DFS up to 2 years. PPR and MPR were not associated with improved OS. Nine of 11 studies were at low risk of bias.

CONCLUSIONS AND RELEVANCE: Study findings suggest that overall PPR and MPR are associated with improved DFS. These data provide additional support for the potential use of pathologic treatment response as a surrogate for DFS after neoadjuvant ICI in resectable mucosal HNSCC.

PMID:41410931 | DOI:10.1001/jamaoto.2025.4573

JAMA Oncol. 2025 Dec 18. doi: 10.1001/jamaoncol.2025.5376. Online ahead of print.

ABSTRACT

IMPORTANCE: Molecular analyses of biospecimens collected from study participants are essential for identifying biomarkers that can tailor treatments to specific subsets of patients who are most likely to benefit. Sharing of data and biospecimens from clinical trials enables personalized, patient-centric use of cancer therapies and accelerates the development of new treatments.

OBJECTIVE: To describe obstacles to sharing data and biospecimens and to propose strategies to enhance access and collaboration.

EVIDENCE REVIEW: This is a Special Communication authored by 53 academic investigators and patient representatives from the breast cancer community with extensive experience in conducting clinical and translational research. The article also evaluates the impact of biomarker research on specifying responsive subpopulations in the 29 registrational clinical trials that have led to approval of a new drug for treatment of breast cancer between 2017 and 2024.

FINDINGS: Clinical trial participants are increasingly asked to provide tissue and/or body fluid biospecimens for biomarker research that is typically controlled by the sponsoring pharmaceutical company, but published biomarker studies are rare. Among 29 breast cancer registrational studies reported in the past 8 years, none resulted in biomarker research that restricted a drug’s approved indication. Herein, strategies to maximize the value of clinical data and biospecimens contributed by participants are proposed, thereby supporting the shared goals of the pharmaceutical industry and academia to improve patient care. These strategies include (1) establishing coleadership structures involving academia and patients in clinical trial design and conduct, (2) ensuring that informed consent forms state that data and biospecimens will be shared with academia for future research, (3) requiring the sharing of clinical data as a condition for regulatory approval, and (4) enabling access to biospecimens and translational research data for independent studies on biomarkers that may indicate drug efficacy and toxicity.

CONCLUSIONS AND RELEVANCE: Data and biospecimen sharing from registrational trials has been suboptimal. Improving clinical data, biospecimens, and biospecimens’ related data sharing requires concrete actions and a multidimensional stakeholder approach to accelerate the impact of clinical cancer research on the quality of patient care.

PMID:41410930 | DOI:10.1001/jamaoncol.2025.5376

Rev Colomb Obstet Ginecol. 2025 Sep 30;76(3). doi: 10.18597/rcog.4318.

ABSTRACT

OBJETIVO: describir la prevalencia del uso de juguetes eróticos en mujeres, caracterizar los dispositivos más usados y su efecto sobre la puntuación en el índice de función sexual femenina. Materiales y métodos: estudio de corte transversal multicéntrico, con análisis descriptivo. Se incluyeron mujeres mayores de 18 años con pareja estable, residentes en Colombia. Las participantes se reclutaron de la consulta externa ginecológica de clínicas privadas de alta complejidad, en 21 ciudades del país, entre 2019 y 2024. Se realizó un muestreo aleatorio simple. Se midieron variables sociodemográficas, orientación sexual, uso de juguetes eróticos, puntuación del índice de función sexual femenina global y por dominio, tipo de dispositivos utilizados, uso individual o con pareja. Análisis descriptivo.

RESULTADOS: se incluyeron 1.759 mujeres, de las cuales 1.280 utilizaron juguetes sexuales para una prevalencia de uso del 72,76 %. Las mujeres homosexuales utilizaron más frecuentemente los juguetes que las heterosexuales. La puntuación media del índice de función sexual femenina en las usuarias de juguetes sexuales fue de 29,55 (DE ± 9,12) y de las no usuarias fue de 27,43 (DE ± 8,59). El dominio de mayor puntuación fue el orgasmo (4,97 ± 1,29), seguido del dominio del deseo (4,95 ± 1,68), (p = 0,027). El dildo (53,49 %) y el vibrador (48,15 %) fueron los juguetes más utilizados.

CONCLUSIONES: el uso de juguetes sexuales entre las mujeres colombianas es una práctica común, por lo cual su uso debe ser indagado en la consulta ginecológica. Se requieren estudios que evalúen la salud sexual y reproductiva de las mujeres usuarias de juguetes sexuales.

PMID:41410884 | DOI:10.18597/rcog.4318

Obes Surg. 2025 Dec 18. doi: 10.1007/s11695-025-08428-w. Online ahead of print.

ABSTRACT

BACKGROUND: Sleeve gastrectomy (SG) is the most commonly performed metabolic and bariatric surgery, yet literature on long-term outcomes, including weight loss durability and safety, remains limited.

METHODS: This retrospective cohort study examined patients from 3 bariatric centers of excellence undergoing SG from 2010 to 2014 to allow for 10 years of follow-up period. Baseline characteristics, annual weight and body mass index (BMI), obesity-related medical conditions resolution and recurrence, and complications were documented. Statistical methods included paired t-test, Kaplan-Meier curve, and multivariate regression.

RESULTS: A total of 830 patients (73.3% female, mean age 45.6 ± 11.6, mean preoperative BMI 45.6 ± 7.8 kg/m² ) were included, with a median follow-up period of 9.8 years. Patients achieved a maximum percentage total weight loss (%TWL) of 29.0 ± 9.7 at 24 months postoperatively (p < 0.001). Resolution rates for type 2 diabetes (T2DM), hypertension (HTN), hyperlipidemia (HLD), and obstructive sleep apnea (OSA) were 58.7%, 45.0%, 41.4%, and 65.8%, respectively, with recurrence rates of 5.4%, 10.4%, 6.9%, and 1.4%. Suboptimal clinical response (< 20% TWL) occurred in 15.8% of patients. 63.9% and 57.5% of the cohort experienced recurrent weight gain of > 10% and > 20% from postoperative nadir weight; T2DM (p = 0.02) and adherence to follow-up (≥ 5 postoperative visits) (p < 0.001) were significantly associated with weight gain of > 20%. Complications occurred in 10.0% (early) and 19.8% (late) of patients. 10.1% of the cohort required revisional surgery by the end of the study period.

CONCLUSION: Overall, SG demonstrates relatively favorable long-term outcomes, but the notable rates of recurrent weight gain raise concern regarding its durability.

KEY POINTS: Sleeve gastrectomy resulted in significant weight loss, with a peak at 24 months. 57.5-63.9% of the cohort had recurrent weight gain; 10.1% required revision surgery. SG counseling must include long-term outcomes and potential need for revision.

PMID:41410827 | DOI:10.1007/s11695-025-08428-w

Biol Trace Elem Res. 2025 Dec 18. doi: 10.1007/s12011-025-04949-8. Online ahead of print.

ABSTRACT

Unexplained recurrent spontaneous abortion (URSA) is a prevalent reproductive issue but its etiology remains obscure. Male exposure to environmental chemicals is suggested to elevate URSA risk in female partners. Herein, a case-control design set out to investigate associations between metal levels in human seminal plasma with URSA risk, plus to determine evidence of mediating effects by oxidative stress. Levels of 15 metal elements and oxidative stress marker malondialdehyde (MDA) in seminal plasma were measured in 125 male spouses of URSA cases compared to 108 male partners of women with successful pregnancy outcomes. The associations of single or mixed metals on URSA risk were analyzed using logistic regression and Bayesian kernel machine regression (BKMR), respectively. BKMR analyses reveal a joint effect of metal co-exposures on URSA risk. Through multiple statistical approaches, titanium (Ti), cadmium (Cd) or magnesium (Mg) were major contributors to metal mixtures elevating URSA risk. MDA was significantly and positively associated with URSA risk. Mediation analysis shows that the associations of Ti, Cd or Mg with URSA risk appear to be mediated by MDA at rates of 23.30%, 16.26% or 34.48%, respectively. In vitro experiments confirmed the seminal plasma relevant dose Ti, Cd or Mg exposure induced male mouse spermatocyte-derived GC-2 cells oxidative stress. Metal mixtures in seminal plasma are associated with increased URSA risk in female spouses, with Ti, Cd or Mg being significant contributors, potentially via oxidative stress, providing further insights into URSA etiology.

PMID:41410821 | DOI:10.1007/s12011-025-04949-8

Mol Neurobiol. 2025 Dec 18;63(1):308. doi: 10.1007/s12035-025-05628-4.

ABSTRACT

Epilepsy is a complex neural disorder that has an impact on over 50 million people around the world. Even though there are environmental factors that can be attributed to its occurrence, this disorder can also be associated with genetics. This work aimed to evaluate some known polymorphisms-CYP3A4*1B (rs2740574) and SLC6A11 (rs2304725). This case-control study consisted of 105 clinically diagnosed cases of epilepsy and 140 healthy controls. Genetic analysis was conducted using SYBR Green-based qRT-PCR with allele-specific primers. The relation of various genotypes with the risk of developing epilepsy was tested using logistic regression models. Stratified analyses were achieved based on the type of epilepsy, age of onset, and response to antiepileptic medication. Some participants were tested for gene expression analysis. Both polymorphisms were statistically associated with increased risk of developing epilepsy as the CYP3A4*1B GG genotype had a risk of 3.54-fold increase (95% CI: 1.35-9.27, p = 0.010) and the SLC6A11 TT genotype had an increase of risk by 3.00-fold (95% CI: 1.15-7.81, p = 0.024). The G-T allele combination of variant alleles conferred an even greater association (OR = 2.87, 95% CI: 1.78-4.62, p < 0.001). The association was found to be higher for generalized and early-onset epilepsy compared with focal and late-onset forms. The CYP3A4*1B GG genotype was significantly associated with drug resistance (OR = 4.44, 95% CI: 1.28-15.41, p = 0.019). Measurement of transcript expression showed a decrease of CYP3A4 and increased SLC6A11 with the variant genotypes. Genetic variants of CYP3A4*1B and SLC6A11 are relevant markers of sustained risk of acquiring epilepsy for the Iraqis population.

PMID:41410815 | DOI:10.1007/s12035-025-05628-4

Proc Natl Acad Sci U S A. 2025 Dec 23;122(51):e2523012122. doi: 10.1073/pnas.2523012122. Epub 2025 Dec 18.

ABSTRACT

Like human decision-making under real-world constraints, artificial neural networks may balance free exploration in parameter space with task-relevant adaptation. In this study, we identify consistent signatures of criticality during neural network training and provide theoretical evidence that such scaling behavior arises naturally from information-driven self-organization: a dynamic balance between the maximum entropy principle that promotes unbiased exploration and mutual information constraint that relates updates with task objective. We numerically demonstrate that the power-law exponent of updates remains stable throughout training, supporting the presence of self-organized criticality. Furthermore, we show that the loss landscape exhibits exponential ruggedness under small perturbations, transitioning to power-law ruggedness at larger scales, in the absence of mini-batch noise, indicating an intrinsic geometric landscape. We also observe a power-law distribution in the intervals between large updates, indicating an intermittent learning process. Together, these findings suggest that neural network learning reflects a nonequilibrium process governed by the fundamental trade-off between randomness and relevance, highlighting its dynamic nature and offering insights into the interpretability of AI systems.

PMID:41410766 | DOI:10.1073/pnas.2523012122

Eur J Appl Physiol. 2025 Dec 18. doi: 10.1007/s00421-025-06095-4. Online ahead of print.

ABSTRACT

PURPOSE: Fatigue can exacerbate gait abnormalities in unilateral transtibial amputees (TTA), but specific changes in walking patterns and compensatory strategies under fatigue remain unclear. This study aimed to investigate gait alterations in unilateral TTA following a fatigue-inducing protocol.

METHODS: Ten male unilateral TTA and ten age-matched able-bodied controls underwent three-dimensional gait analysis at self-selected speed under non-fatigued and fatigued conditions. Spatiotemporal parameters, joint kinematics, and ground reaction forces were measured. Two-way ANOVA was used for statistical comparisons.

RESULTS: Within the TTA group, the residual limb demonstrated a shorter stance phase (62.3 ± 2.4% vs. 65.1 ± 1.4%) and single support (34.7 ± 1.9% vs. 37.1 ± 2.8%), but greater step length (38.27 ± 2.49% vs. 35.76 ± 1.92%), peak hip flexion(35.0 ± 5.6° vs. 28.6 ± 3.0°) and knee flexion(67.3 ± 7.2° vs. 56.4 ± 5.6°) than the intact limb. Fatigue further increased step length (37.42 ± 2.41% vs. 36.61 ± 2.63%) and hip flexion (33.2 ± 5.3° vs. 30.5 ± 5.3°), while reducing hip extension (10.9 ± 4.8° vs. 12.8 ± 4.2°) and hip horizontal range of motion (17.5 ± 6.0° vs. 19.5 ± 6.6°). Compared to controls, TTA group had longer stride time (1.15 ± 0.04s vs. 1.08 ± 0.08s) and greater hip horizontal range of motion (18.5 ± 6.4° vs. 12.5 ± 3.0°), but lower cadence (105.1 ± 4.1 steps/min vs. 111.6 ± 8.1 steps/min).

CONCLUSION: Fatigue amplifies pre-existing gait asymmetries in unilateral TTA and elicits compensatory strategies, including increased reliance on the intact limb and greater proximal joint mobility. Targeted interventions to enhance residual limb function and hip flexor strength and endurance may help reduce fatigue-related asymmetry and fall risk.

PMID:41410758 | DOI:10.1007/s00421-025-06095-4

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):363. doi: 10.1007/s00068-025-03042-y.

ABSTRACT

PURPOSE: Post-traumatic pulmonary embolism (PE) may develop directly in the lungs, termed “de novo” pulmonary embolism (DNPE). Severe chest trauma has been identified as a potential risk factor for DNPE due to localized inflammation, occult vascular injury, and low-flow states (venous stasis). The primary outcome was to examine the association between DNPE and chest trauma, while the secondary outcome was to characterize patients in the DNPE group.

METHODS: We conducted a retrospective cohort study of patients with trauma aged ≥ 15 years admitted to Songklanagarind Hospital, a level 1 trauma center, from 2013 to 2023. All patients diagnosed with post-traumatic PE were reviewed for clinical parameters, imaging findings, and treatments. Patients without ultrasonographic evaluation for DVT were excluded.

RESULTS: Among 43,908 patients with trauma, PE was diagnosed in 78 (0.18%). After excluding four patients without DVT assessment, 74 patients remained. Of these, 49 (66%) were diagnosed with DNPE and 25 (34%) with PE + DVT. Compared with patients with PE + DVT (32%), patients with DNPE (38.8%) showed no significant difference in the incidence of chest trauma (p = 0.567). The location of PE significantly differed (p = 0.005) between the groups, with DNPE showing more peripheral involvement (79.6%) and PE + DVT showing more central emboli (52%). No patient in the DNPE group underwent pulmonary thromboembolectomy.

CONCLUSION: DNPE is more common among patients with trauma, but its association with chest trauma was not statistically significant. DNPE may result from undetected pelvic DVT or other mechanisms requiring further investigation.

PMID:41410754 | DOI:10.1007/s00068-025-03042-y