Category: Statistics

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4041-4047. doi: 10.3760/cma.j.cn112137-20250405-00836.

ABSTRACT

Objective: To explore the effectiveness and safety of anlotinib combination regimens in patients with previously immunotherapy treated advanced non-small cell lung cancer (NSCLC). Methods: This study retrospectively included 85 patients with previously immunotherapy treated advanced NSCLC who received anlotinib combination regimens or single-agent chemotherapy in the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023. The observation group was consisted of 43 patients who received anlotinib combination regimens, and the control group was consisted of 42 patients who received single-agent chemotherapy. Observation group received anlotinib combined with chemotherapy and anlotinib combined with immunotherapy, while control group received single-agent chemotherapy. The follow-up period ended on May 25, 2024. The baseline characteristics, recent effectiveness, prognosis, and adverse reactions were compared between the observation group and the control group. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences. Results: In observation group, there were 29 males and 14 females with a median age [M (Q₁, Q₃)] of 63 (27, 73) years; in control group, there were 27 males and 15 females, with a median age of 64 (28, 73) years. Objective response rates for the observation group and control group were 23.3% (10/43) and 14.3% (6/42), respectively, with no statistically significant difference (P=0.290). Disease control rates were 83.7% (36/43) and 57.1% (24/42) for the observation and the control groups, respectively, with a statistically significant difference (P=0.007). The median follow-up duration for the observation group and the control group was 14.2 and 9.6 months, respectively. Prognosis results indicated that the median PFS for the observation group and the control group were 6.1 (95%CI: 2.41-9.79) and 2.9 months (95%CI: 2.59-3.21), respectively. The observation group was significantly higher than the control group (P=0.009). The median OS were 15.5 (95%CI: 8.99-22.01) and 10.3 months (95%CI: 7.87-12.74), respectively. The observation group was also significantly higher than the control group (P=0.016). Safety analysis results exhibited that the incidence of adverse reactions of different grades in the observation group and control groups were 88.4% (38/43) and 81.0% (34/42), respectively; The grade ≥3 adverse reactions occurred in 41.9% (18/43) and 33.3% (14/42), respectively, with no statistically significant difference (both P>0.05). The grade≥3 adverse reactions were controlled through dose adjustment and symptomatic treatment. Conclusion: In patients with previously immunotherapy treated advanced NSCLC, anlotinib combination regimens demonstrates preliminary efficacy and tolerable safety profile compared to single-agent chemotherapy.

PMID:41320658 | DOI:10.3760/cma.j.cn112137-20250405-00836

Tissue Barriers. 2025 Nov 30:2585246. doi: 10.1080/21688370.2025.2585246. Online ahead of print.

ABSTRACT

The placenta possesses several structural and immunological barriers against viral infections, the SARS-CoV-2 detection in placental tissues has raised concerns regarding possible alternative viral entry mechanisms beyond the canonical ACE2/TMPRSS2-mediated pathway. In this context, the present study evaluated the immunohistochemical expression patterns of ADAM17, Cathepsin L, Clathrin, ACE-2, Furin, NRP-1, and TMPRSS2-molecules involved in SARS-CoV-2 placental entry pathways – as well as the detection of viral RNA by RT-qPCR in paraffin-embedded samples. The study included 75 paraffin-embedded placental samples (decidua and villi) collected after spontaneous placental delivery at birth from patients who tested positive for COVID-19 (COVID-19 Group), and 19 paraffin-embedded control placental samples collected prior to the COVID-19 pandemic (NON-COVID-19 Group). A statistically significant reduction in NRP-1 expression was observed in the COVID-19 group decidua (p < 0.001), including in RT-qPCR – positive samples (p = 0.001), regardless of comorbidities or underlying conditions. A statistically significant reduction in Clathrin expression was also found in the decidual samples of the COVID-19 group and in RT-qPCR – positive samples (p = 0.05and 0.013, respectively), while Cathepsin L expression was significantly increased in the placental villi of the COVID-19 group (p < 0.001) and in RT-qPCR – positive samples (p = 0.005). These findings may contribute to a better understanding of the mechanisms underlying SARS-CoV-2 interaction with the placenta, possibly through auxiliary and/or endocytic entry pathways, and may support future investigations into the impact of these alterations in the context of maternal SARS-CoV-2 infection.

PMID:41319265 | DOI:10.1080/21688370.2025.2585246

Endocrinol Diabetes Metab. 2026 Jan;9(1):e70129. doi: 10.1002/edm2.70129.

ABSTRACT

OBJECTIVE: Postoperative hypocalcemia and hypoparathyroidism are common complications after thyroidectomy, often impairing quality of life (QoL). This study investigates the impact of preoperative calcium and magnesium supplementation on postoperative QoL and hypocalcemia in patients undergoing total thyroidectomy for symptomatic nodular goitre or Graves’ disease.

METHODS: A total of 62 patients undergoing thyroidectomy for benign thyroid diseases were randomised into two groups. The intervention group (IG, n = 31) received 500 mg calcium carbonate thrice daily and 300 mg magnesium carbonate once daily for 2 weeks preoperatively, while the control group (CG, n = 31) received no supplementation. Laboratory parameters (Ca, Mg, PTH, 25-OH-Vitamin D) were measured at study enrolment (T₁), preoperatively (T₂), immediately postoperatively (T₃) and 6 weeks post-discharge (T₄). QoL was assessed using EQ-5D and ThyPro39de questionnaires.

RESULTS: QoL significantly improved postoperatively in both groups. Patients with Graves’ disease in the IG reported earlier QoL improvements immediately post-surgery (T₃). Postoperative hypocalcemia occurred in 19.4% of IG patients and 25% of CG patients, with hypoparathyroidism in 16% and 23%, respectively. The IG demonstrated higher postoperative calcium levels and fewer hypocalcemia symptoms, especially in Graves’ disease patients (not significant). Vitamin D deficiency was prevalent (66.7%) but showed no correlation with hypocalcemia.

DISCUSSION: Preoperative calcium and magnesium supplementation might have positive effects on postoperative QoL, especially in Graves’ disease patients, and may reduce hypocalcemia symptoms. This simple, inexpensive and low-risk intervention may be beneficial in the preoperative setting prior to thyroidectomy. Although the observed effect did not reach statistical significance, it could still be of clinical relevance. The additional benefit of preoperative magnesium supplementation seems to be of minor significance, while the effect of pre-existing vitamin D deficiency remains uncertain.

PMID:41319240 | DOI:10.1002/edm2.70129

Clin Transl Sci. 2025 Dec;18(12):e70412. doi: 10.1111/cts.70412.

ABSTRACT

Proteomics can identify pharmacodynamic (PD) biomarkers by detecting protein changes in response to drug treatment, providing insights into drug mechanism and biological effects. In this study, we profiled over 7000 plasma proteins to identify potential PD biomarkers for the interleukin-5 (IL-5) inhibitors mepolizumab and reslizumab, which are approved for treating eosinophilic asthma. We used longitudinal plasma samples from healthy participants treated with a single dose of mepolizumab (n = 8, 24 mg) or reslizumab (n = 8, 0.8 mg/kg), or placebo (n = 8) to identify differentially expressed proteins. We then characterized PD biomarker candidates by their magnitude of response, area under the effect curve (AUEC), dose-response, variability, and replication of response at a lower dose for mepolizumab (n = 8, 12 mg) or reslizumab (n = 8, 0.4 mg/kg) compared to placebo. Eosinophil major basic protein (EMBP) and proteoglycan-3 (PRG3) were differentially expressed in response to mepolizumab and reslizumab, respectively, achieving Bonferroni-adjusted statistical significance (p-value < 6.86E-06) and nominal significance (p-value < 5.0E-05) with the other IL-5 inhibitor. EMBP showed a > 20% fold change difference with mepolizumab (24 mg) versus placebo at peak time, and PRG3 demonstrated a > 20% fold change with reslizumab (0.8 mg/kg) versus placebo at peak time. Both proteins had significant AUEC with both drug doses, with EMBP AUEC only significant (absolute AUEC high > low dose) at the higher mepolizumab dose. Both biomarkers showed dose-response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL-5 inhibitors, warranting further validation for early phase trials and biosimilar development programs.

PMID:41319239 | DOI:10.1111/cts.70412

J Diabetes Investig. 2025 Nov 30. doi: 10.1111/jdi.70205. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyperglycemia or diabetes mellitus (DM) is a well-known risk factor for pancreatic cancer, but it is uncertain whether well-controlled glycemic status can affect the pancreatic cancer incidence rate.

METHODS: This study used 2,993,519 individuals who underwent four consecutive national annual health screenings between 2009 and 2013. The study participants were divided into three groups: nondiabetes mellitus (non-DM), new-onset DM, and known DM. Each group was further subcategorized based on the fasting blood glucose (FBG) levels and use of antidiabetic medication: well-controlled (<100 mg/dL), moderately controlled (100-125), or poorly controlled (>126).

RESULTS: During a median follow-up of 6.3 years, the incidence rate of pancreatic cancer in the non-DM group significantly increased in the moderately controlled group compared with that in the well-controlled group, regardless of whether the FBG level was recently or initially elevated. However, no dose-response relationship was observed between glucose control status and pancreatic cancer incidence, although the incidence of pancreatic cancer in the new DM and known DM groups was generally higher than that in the non-DM group.

CONCLUSION: The pancreatic cancer incidence rate in the non-DM group significantly increased in the poorly controlled group. These findings suggest that in populations without DM, maintaining optimal glucose control may be associated with a lower risk of developing pancreatic cancer.

PMID:41319229 | DOI:10.1111/jdi.70205

Biostatistics. 2024 Dec 31;26(1):kxaf045. doi: 10.1093/biostatistics/kxaf045.

ABSTRACT

A key objective in vaccine studies is to evaluate vaccine-induced immunogenicity and determine whether participants have mounted a response to the vaccine. Cellular immune responses are essential for assessing vaccine-induced immunogenicity, and single-cell assays, such as intracellular cytokine staining (ICS) and B-cell phenotyping (BCP), are commonly employed to profile individual immune cell phenotypes and the cytokines they produce after stimulation. In this article, we introduce a novel statistical framework for identifying vaccine responders using ICS data collected before and after vaccination. This framework incorporates paired control data to account for potential unintended variations between assay runs, such as batch effects, that could lead to misclassification of participants as vaccine responders or non-responders. To formally integrate paired control data for accounting for assay variation across different time points (ie before and after vaccination), our proposed framework calculates and reports two $ P $-values, both adjusting for paired control data but in distinct ways: (i) the maximally adjusted $ P $-value, which applies the most conservative adjustment to the unadjusted $ P $-value, ensuring validity over all plausible batch effects consistent with the paired control samples’ data, and (ii) the minimally adjusted $ P $-value, which imposes only the minimal adjustment to the unadjusted $ P $-value, such that the adjusted $ P $-value cannot be falsified by the paired control samples’ data. Minimally and maximally adjusted $ P $-values offer a balanced approach to managing Type I error rates and statistical power in the presence of batch effects. We apply this framework to analyze ICS data collected at baseline and 4 wks post-vaccination from the COVID-19 Prevention Network (CoVPN) 3008 study. Our analysis helps address two clinical questions: (i) which participants exhibited evidence of an incident Omicron infection between baseline and 4 wks after receiving the final dose of the primary vaccination series, and (ii) which participants showed vaccine-induced T cell responses against the Omicron BA.4/5 Spike protein.

PMID:41319224 | DOI:10.1093/biostatistics/kxaf045

Biostatistics. 2024 Dec 31;26(1):kxaf043. doi: 10.1093/biostatistics/kxaf043.

ABSTRACT

Nonlinear causal effects are prevalent in many research scenarios involving continuous exposures, and instrumental variables (IVs) can be employed to investigate such effects, particularly in the presence of unmeasured confounders. However, common IV methods for nonlinear effect analysis, such as IV regression or the control-function method, have inherent limitations, leading to either low statistical power or potentially misleading conclusions. In this work, we propose an alternative IV framework for nonlinear effect analysis, which has recently emerged in genetic epidemiology and addresses many of the drawbacks of existing IV methods. The proposed IV framework consists of up to three key “S” elements: (i) the Stratification approach, which constructs multiple strata that are sub-samples of the population in which the IV core assumptions remain valid, (ii) the Scalar-on-function model and Scalar-on-scalar model, which connect local stratum-specific information to global effect estimation, and (iii) the Sum-of-single-effects method for effect estimation. This framework enables study of the effect function while avoiding unnecessary model assumptions. In particular, it facilitates the identification of change points or threshold values in causal effects. Through a wide variety of simulations, we demonstrate that our framework outperforms other representative nonlinear IV methods in predicting the effect shape when the instrument is weak and can accurately estimate the effect function as well as identify the change point and predict its value under various structural model and effect shape scenarios. We further apply our framework to assess the nonlinear effect of alcohol consumption on systolic blood pressure using a genetic instrument (ie Mendelian randomization) with UK Biobank data. Our analysis detects a threshold beyond which alcohol intake exhibits a clear causal effect on the outcome. Our results are consistent with published medical guidelines.

PMID:41319223 | DOI:10.1093/biostatistics/kxaf043

Cancer Med. 2025 Dec;14(23):e71392. doi: 10.1002/cam4.71392.

ABSTRACT

BACKGROUND: The method of lymph node (LN) irradiation for locally advanced esophageal squamous cell carcinoma (LA-ESCC) is still a topic of debate. We investigated the efficacy, toxicity, and rate of out-of-field LNs in irradiation across different target areas in patients with LA-ESCC undergoing neoadjuvant chemoradiotherapy (nCRT).

METHODS: We retrospectively reviewed patient records from June 2017 to August 2022 and divided patients into elective nodal irradiation (ENI) and involved-field irradiation (IFI) groups. The differences in hematological and non-hematological toxicities of the out-of-field LNs were analyzed between the two groups. The log-rank test was used to evaluate the Kaplan-Meier curves for overall and progression-free survival.

RESULTS: Among the 306 included patients, 202 (66.0%) received ENI and 104 (34.0%) received IFI. At the 3-year follow-up, the survival rate did not differ significantly between the groups (p > 0.05). Although the occurrence of radiation-induced pneumonia did not differ (p > 0.05), the incidence of radiation-induced esophagitis and the degree of leukopenia differed significantly (p < 0.05). While the average heart irradiation dose or heart V₂₀, V₃₀, and V₄₀ did not differ significantly (p > 0.05), we observed significant differences in the clinical target volume, average lung irradiation dose, and lung V₂₀, V₃₀, and V₄₀ (p < 0.05). Among all patients, 29 cases (9.5%) experienced out-of-field LNs with 26 (93.1%) in abdominal LNs, whereas only 3 cases (6.9%) with out-of-field LNs were in the upper esophagus. There was no statistical significance between out-of-field LNs and LN irradiation methods (p = 0.724).

CONCLUSIONS: Under similar prognostic conditions, IFI resulted in mild toxicity compared to ENI. Therefore, for patients with ESCC undergoing nCRT, IFI is the preferred irradiation approach for the lymphatic drainage area.

PMID:41319202 | DOI:10.1002/cam4.71392

Brain Behav. 2025 Dec;15(12):e70873. doi: 10.1002/brb3.70873.

ABSTRACT

AIM: This study was conducted to investigate the effects of positive psychotherapy-based education on pain, psychological resilience, and mental well-being after lumbar canal stenosis surgery.

MATERIALS AND METHODS: A randomized controlled experimental study was conducted with 66 participants (33 control, 33 experimental) at the Brain and Neurosurgery Department of Medical Center X between March 2025 and July 2025. The control group received no intervention, while the experimental group received 8 weeks of psychoeducation based on positive psychotherapy. Pretests were administered to the control and experimental groups in March 2025. The training of the experimental group was administered between April 2025 and May 2025. Data collection tools included the Descriptive Characteristics Form, Pain Scale, Brief Resilience Scale, and Mental Well-Being Scale. It was determined that the data showed normal distribution, and parametric tests were used in the analyses. Chi-square and Fisher’s exact tests were used to compare the descriptive characteristics of the patients in the experimental and control groups. A t-test was applied to the dependent and independent groups to determine the effect of the training.

FINDINGS: In the study, no statistically significant difference was found in the comparison of the pretest pain, psychological resilience, and mental well-being scales of the control and experimental groups (p = 0.259, p = 0.177, p = 0.428). In the study, a statistically significant difference was found in the comparison of the posttest pain, psychological resilience, and mental well-being scales of the control and experimental groups (p = 0.001). In the study, a statistically significant difference was found in the pretest-posttest pain, psychological resilience and mental well-being scale total score averages of the experimental group (p = 0.001).

CONCLUSION AND RECOMMENDATIONS: Positive psychotherapy-based education was effective in reducing pain and increasing psychological resilience, and mental well-being in patients after lumbar spinal stenosis surgery. Based on these findings, positive psychotherapy-based education can be recommended as an adjunct to pharmacological treatment for not only physical but also psychological recovery.

PMID:41319196 | DOI:10.1002/brb3.70873

Med Educ Online. 2025 Dec 31;30(1):2592434. doi: 10.1080/10872981.2025.2592434. Epub 2025 Nov 30.

ABSTRACT

Medical career preferences are in focus because the future medical workforce should align with society’s needs. The study investigated how medical students’ perceptions of the attractiveness of various clinical and non-clinical career options evolved as they approached the end of medical school, and which factors might influence their career choices. This was a cross-sectional online survey of medical students who completed the master’s program in spring 2025 in different medical education tracks at different Swiss universities. The survey included both Likert-scaled and open-ended questions. Flow diagrams were used to depict changes in attractiveness throughout medical school. Network visualization mapped the connections between the most important career determinants. Regression analysis assessed the factors associated with career preferences. Among 364 medical students included, the most attractive careers at the end of medical school were the specialized disciplines of inpatient care (37%) and outpatient care (20%). These specialties were preferred due to interest in surgery or specialization. During the master’s program, attractiveness of general practice, specialized outpatient care, and specialized inpatient care increased while the attractiveness of outpatient gynecology/pediatrics and inpatient general internal medicine decreased. Career characteristics perceived to be the most important determinants of career choice were primarily performing medical activities, part-time work, and relationships with patients. The most prevalent factors favoring career decisions were experience during the elective year (91%) and clinical courses with patient contact during the studies (70%). Students who found a career more attractive during their studies were more likely to prefer that career at the end of medical school. Career preferences at the end of medical school were associated with specific factors. Among these factors, the most significant was the perceived attractiveness of the career during medical education. This emphasizes the importance of medical education in shaping students’ dynamic and multifaceted career decisions.

PMID:41319195 | DOI:10.1080/10872981.2025.2592434