Category: Statistics

Rheumatol Int. 2025 Sep 6;45(9):220. doi: 10.1007/s00296-025-05977-2.

ABSTRACT

Familial Mediterranean Fever (FMF) is frequently diagnosed during reproductive ages, but its impact on pregnancy remains unclear. We aimed to evaluate maternal and neonatal outcomes in FMF pregnancies by comparing before and after diagnosis periods as well as with healthy controls, and to identify predictors of adverse outcomes. This retrospective, cross-sectional study included 215 pregnancies (129 before and 86 after FMF diagnosis) from 81 women with FMF and 94 pregnancies from 42 healthy controls. Demographic data, disease characteristics, medications, and genetic mutations were recorded. Maternal and neonatal outcomes were compared, and multivariate logistic regression was used to identify predictors of adverse maternal outcomes. After FMF diagnosis, live birth occurred in 69 cases (80.2%), miscarriage in 15 (17.4%), and stillbirth in 2 (2.3%). In contrast, before diagnosis, live birth occurred in 104 cases (80.6%), miscarriage in 17 (13.4%), and stillbirth in 7 (5.4%). Among pregnancies after diagnosis, cesarean section was more frequent (38 cases, 53.5% vs. 29 cases, 25.9%, p < 0.001), as well as adverse maternal outcomes (58 cases, 67.4% vs. 63 cases, 48.8%, p = 0.007), compared to before diagnosis. Compared with controls, FMF patients showed no significant differences in maternal or neonatal outcomes. Among 86 pregnancies after diagnosis, colchicine was used in 66 (76.7%), and FMF flares were reported in 22 cases (31.9%) among pregnancies resulting in live birth, most commonly during the second trimester. Logistic regression identified older maternal age (OR 1.12, 95% CI: 1.02-1.25, p = 0.02) and disease flares before pregnancy (OR 6.96, 95% CI: 1.40-34.58, p = 0.02) as independent predictors of adverse maternal outcomes. Maternal and neonatal outcomes in FMF pregnancies were comparable to those in controls. Advanced maternal age and disease activity before conception were identified as independent predictors of adverse maternal outcomes.

PMID:40913658 | DOI:10.1007/s00296-025-05977-2

Arch Gynecol Obstet. 2025 Sep 6. doi: 10.1007/s00404-025-08159-4. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by reproductive and endocrine abnormalities.

OBJECTIVE: The present study aimed to assess the effect of oral contraceptive pills (OCPs) and vitamin D3 on sexual dysfunction in women with PCOS and vitamin D3 deficiency.

MATERIALS AND METHODS: This randomized double-blind placebo-controlled clinical trial was conducted in Iran between January and April 2019. The Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI) questionnaires were filled out for all participants and their serum levels of vitamin D3 were measured. Women with PCOS and vitamin D3 deficiency were divided into 2 equal groups (A and B) with a table of random numbers (n = 35/ each). Both groups were given vitamin D3 (50,000 IU/w) for 12 week. The case group was given low-dose OCP for 3 months and a similar placebo was given to the control group. Vitamin D3 level and sexual function were assessed in both groups at 3 and 6 months after taking OCP.

RESULTS: There was no statistically significant difference between the two groups in demographic characteristic such as weight (69.54 ± 10.34 vs 70.17 ± 10.60, P = 0.803). Both groups treated with vitamin D3 exhibited increased sexual function scores at the beginning of the study (P = 0.03) and 3 months (P = 0.01) after taking OCP. Examination of sexual function variables showed that sexual desire in the control group was greater than in the OCP-treated group at 3 (P = 0.009) and 6 (P = 0.01) months after entering the study.

CONCLUSION: The results of the study showed that the score of women’s sexual performance increased in all areas, especially in the area of sexual desire, with the use of vitamin D3. The simultaneous use of OCP with vitamin D3 to improve sexual performance in these women had no significant difference with the use of vitamin D3 alone. According to the research findings, it is recommended that vitamin D3 supplementation can be used to increase the quality of life and improve sexual function in PCOS women.

PMID:40913650 | DOI:10.1007/s00404-025-08159-4

J Gastroenterol. 2025 Sep 6. doi: 10.1007/s00535-025-02294-0. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.

METHODS: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.

RESULTS: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55-1.17) and 0.55 for PFS (95% CI 0.38-0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42-1.29) and 0.79 for PFS (95% CI 0.42-1.49).

CONCLUSIONS: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.

PMID:40913639 | DOI:10.1007/s00535-025-02294-0

Eur J Orthop Surg Traumatol. 2025 Sep 6;35(1):381. doi: 10.1007/s00590-025-04472-5.

ABSTRACT

PURPOSE: To identify factors that contribute to the speed of angular correction in skeletally immature patients with genu varum treated with paraphyseal tension band plates, hypothesizing that screw length and divergence, severity of deformity, and underlying pathology influence the rate and speed of genu varum correction.

METHODS: Fifty-three patients (38 males, 15 females) undergoing genu varum correction were included; a total of 138 physes (64 distal femur, 74 proximal tibia) were assessed. The median age at surgery was 37.83 ± 34.27 months (24.37-188.60), and the median follow-up was 11.03 ± 4.9 months (3.17-23). The severity of the deformity, the relative screw length, correction speed (degree per month), and initial screw divergence were calculated for comparison.

RESULTS: Patients close to skeletal maturity showed faster correction speed. Patients with genu varum secondary to metabolic disease had the slowest correction speed (0.76° per month), while there was no clinically significant difference with different etiologies. The distal femur showed a lower correction speed than that of proximal tibia in genu varum. The correction rate was negatively correlated with the relative screw length in genu varum deformity (linear regression coefficient: – 2.39; P < 0.01). The initial screw divergence had no statistically significant impact on the correction speed (P = 0.97).

CONCLUSION: Screw length is an important parameter affecting the rate of genu varum correction with GG using paraphyseal tension band plates.

PMID:40913637 | DOI:10.1007/s00590-025-04472-5

Eur Radiol. 2025 Sep 6. doi: 10.1007/s00330-025-11986-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Contrast extravasation on imaging studies is a clinical surrogate for bleeding severity. However, the prognostic relevance of this imaging sign needs to be evaluated. The aim of this study was to analyze the impact of contrast extravasation defined by computed tomography (CT) and angiography on massive transfusion and 30-day mortality in patients with acute bleeding undergoing transarterial embolization (TAE).

MATERIALS AND METHODS: A mixed cohort of patients with acute bleeding requiring treatment with TAE between 2018 and 2022 was retrospectively evaluated. All patients underwent triphasic CT to localize the source of bleeding and to calculate extravasation volumes in the arterial and portal venous phases. The bleeding rate k was calculated from the CT images.

RESULTS: A total of 128 patients (79 male, 61.7%) with a mean age of 67.4 years (range 21-95 years) and an all-cause 30-day mortality rate of 34.4% were included in the present analysis. A moderate positive correlation was identified between transfused packed red blood cell units and bleeding rate k (r = 0.33, p < 0.001). However, no correlation was found between transfused packed red blood cell units and arterial and portal venous extravasation volume. In multivariable logistic regression analysis, bleeding rate k was identified as an independent prognostic factor for massive transfusion (OR 25.77, 95% CI 1.35-493.61, p = 0.031, area under the receiver operating characteristic curve (AUROC) of the model: 0.847) and 30-day mortality (OR 25.04, 95% CI 2.29-273.42, p = 0.008, AUROC of the model: 0.781).

CONCLUSION: CT-defined bleeding rate, k, is a prognostic factor for massive transfusion and 30-day mortality in patients with acute bleeding undergoing TAE and may be superior to the volume of contrast extravasation volume alone. Further studies are needed to confirm this finding.

KEY POINTS: Question Does contrast media extravasation on CT have a prognostic role in patients with acute bleeding? Findings Bleeding rate, k, was identified as an independent prognostic factor for massive transfusion (OR 25.77) and 30-day mortality (OR 25.04). Clinical relevance Diagnostic triphasic CT can be used to provide prognostic information of patients with acute bleeding.

PMID:40913621 | DOI:10.1007/s00330-025-11986-3

Spec Care Dentist. 2025 Sep-Oct;45(5):e70097. doi: 10.1111/scd.70097.

ABSTRACT

AIMS: Systematically review the literature to answer the focused question: “What is the best way to facilitate pain communication for patients with intellectual disabilities (ID) in dental care?”

METHODS: A systematic search strategy was conducted in five databases and gray literature. Studies evaluating pain communication in dental care for patients with ID were included. The risk of bias was assessed according to the Meta-Analysis of Statistics Assessment and Review Instrument.

RESULTS: A total of 1525 studies were screened, and after applying exclusion criteria, 10 articles remained. The included studies were published between 2003 and 2021, with sample sizes ranging from 28 to 270 participants with developmental disabilities. The Dental Discomfort Questionnaire (DDQ) was the most commonly used tool in the studies. Most studies showed a low risk of bias.

CONCLUSION: The DDQ is the most validated tool for assessing dental pain in individuals with ID, though evidence in adults is limited. Other tools provide useful behavioral cues but may not clearly differentiate pain from discomfort or anxiety. The absence of a gold standard underscores the need for context-appropriate tool selection and clinician training to interpret nonverbal pain, enhancing diagnostic accuracy and promoting equitable care.

PMID:40913592 | DOI:10.1111/scd.70097

Curr Med Res Opin. 2025 Sep 6:1-15. doi: 10.1080/03007995.2025.2558140. Online ahead of print.

ABSTRACT

OBJECTIVES: In ENGAGE, patients with major depressive disorder (MDD) demonstrated improvements in patient-reported depression and life engagement while taking adjunctive brexpiprazole. This analysis aimed to further characterize patient perspectives on the effects of adjunctive brexpiprazole, using patient diary data from ENGAGE, and describe development of a ‘word of the day’ activity.

METHODS: Prior to ENGAGE, word lists describing a ‘good,’ ‘average,’ and ‘bad’ day with depression were generated from semi-structured interviews with patients with MDD. ENGAGE (ClinicalTrials.gov identifier: NCT04830215) was an 8-week, phase 4, single-arm, open-label study of adjunctive brexpiprazole 0.5-2 mg/day in patients with MDD and inadequate response to antidepressant treatment. Patient diaries were completed periodically at home, comprising the Patient Global Impression – Severity of illness (PGI-S), Patient Global Impression – Improvement (PGI-I), and a ‘word of the day’ activity in which patients selected one word to describe how they felt that day. This analysis evaluated mean change in PGI-S scores (mixed model for repeated measures), mean PGI-I scores (descriptive statistics), PGI-S response and PGI-S sustained response (Kaplan-Meier), PGI-I response (normal approximation), and ‘word of the day’ (descriptive statistics).

RESULTS: In the interviews, 20 patients used 132 words to describe living with depression. Five words of each valence (positive, neutral, negative) were selected for ENGAGE. 122 patients were enrolled in ENGAGE; 120 had evaluable diary data. PGI-S score improved from baseline to week 8 (least squares mean change [standard error]: -1.5 [0.2]; nominal p < 0.001; effect size: 1.04). PGI-I scores at week 8 indicated “minimal improvement” to “much improvement” (mean [standard deviation]: 2.6 [1.1]). At week 8, rates of PGI-S response, sustained PGI-S response, and PGI-I response were 86.0% (95% confidence interval: 77.1, 92.8), 67.9% (54.5, 80.6), and 47.1% (38.1, 56.0), respectively. On ‘word of the day,’ the proportion of positive and neutral words increased from baseline to week 8, and the proportion of negative words decreased.

CONCLUSIONS: Patient-reported diary data revealed early and sustained improvements in depressive symptom severity during 8 weeks of adjunctive brexpiprazole treatment. ‘Word of the day’ may be an effective qualitative tool for future trials.

PMID:40913583 | DOI:10.1080/03007995.2025.2558140

Expert Opin Drug Deliv. 2025 Sep 6. doi: 10.1080/17425247.2025.2556979. Online ahead of print.

ABSTRACT

INTRODUCTION: The potential of nanomedicine in alleviating different disorders is immense, but its clinical translation rate is severely debilitated, despite promising preclinical study outcomes. For therapeutically successful targeted delivery of nanomedicines, it is crucial to understand why well-designed nanomedicines often fail during clinical trials.

AREAS COVERED: This review comprehensively explores the multifactorial reasons behind the poor clinical success rate of nanomedicines, including pathophysiological complexity, limitations in statistical analysis, inadequate animal models, variability in the EPR effect, and manufacturing challenges. Special focus is placed on the misinterpretation and misuse of statistical tools in preclinical studies, which significantly reduces data interpretation and clinical predictability. The review is based on an in-depth literature survey of recent advances and failures in nanomedicine translation, with an emphasis on incorporating simulation models and synthesized data to overcome the challenges of statistics.

EXPERT OPINION: Addressing translational gaps requires a multidisciplinary approach, refined preclinical models, robust statistical frameworks, and adaptive clinical designs that are essential. Innovative tools, such as CTGAN and personalized trial strategies, can bridge the preclinical-clinical divide. To realize the full potential of nanomedicine, it is crucial to resolve foundational issues in experimental design, data interpretation, analytical frameworks, and regulatory compliance.

PMID:40913551 | DOI:10.1080/17425247.2025.2556979

Int J Stroke. 2025 Sep 6:17474930251380184. doi: 10.1177/17474930251380184. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on the role of herpes-zoster (shingles) vaccination in reducing stroke risk is inconsistent and limited, particularly concerning intracerebral hemorrhage (ICH). We aimed to examine the association between zoster live vaccine (ZVL) and overall stroke, as well as its main subtypes.

METHODS: We conducted a population-based nested case-control study using the database of Israel’s largest healthcare provider. The underlying cohort consisted of individuals aged 50 years or older, regardless of prior stroke status, from 2015 to 2022, with follow-up through June 2023. Stroke cases diagnosed during follow-up were matched with controls based on age, sex, population sector, and index date. ZVL exposure was defined as the prior filling of a prescription of the vaccine.

RESULTS: Among 37,027 matched case-control pairs, ZVL was associated with significantly reduced odds of stroke, with an adjusted OR of 0.65 (95% CI, 0.58-0.72) for overall stroke, 0.65 (95% CI, 0.58-0.73) for ischemic stroke, and 0.64 (95% CI, 0.47-0.89) for ICH. The protective association with overall stroke decreased as time since vaccination increased; adjusted OR of 0.56 (0.48-0.65) within the first 2.5 years, 0.71 (95% CI, 0.58-0.87) after 2.5 to 5 years, and 0.81 (95% CI, 0.65-1.01) after 5 years. The association between ZVL and stroke was modified by age and sex, with a stronger association in individuals younger than 65 years (P for interaction = 0.004) and males (P for interaction = 0.031).

CONCLUSIONS: ZVL is associated with a reduced risk of both ischemic stroke and ICH. The protective association appears to decrease over time and to be stronger in males and younger individuals.

PMID:40913529 | DOI:10.1177/17474930251380184

Epileptic Disord. 2025 Sep 6. doi: 10.1002/epd2.70101. Online ahead of print.

ABSTRACT

OBJECTIVE: Despite pharmacological advances in epilepsy treatment, one-third of patients remain pharmacoresistant and may require surgery. Despite extensive literature on epilepsy surgery, studies with follow-ups longer than 5 years are rare. Our goal was to analyze the outcomes of patients undergoing epilepsy surgery at our center, with a minimum follow-up of 15 years.

METHODS: This was a retrospective study of prospectively collected data. We used the Engel classification to assess seizure freedom, performed univariate descriptive analysis of the variables of interest, and applied appropriate correlation tests for nominal and categorical variables, with statistical significance set at 0.05.

RESULTS: We included 160 patients with a minimum follow-up of 15 years. A total of 105 (70%) patients underwent resective surgeries, the most common being lesionectomy (46.7%), followed by anterior temporal lobectomy with amygdalectomy (21.9%). Among resective surgeries, 73.6% used intraoperative ECOG. Most surgeries were in the temporal lobe (68.8%), and mesial sclerosis was the most frequent etiology (33.8%), followed by long-term epilepsy-associated tumors (LEAT) (25.6%). Seizure freedom at 15 years was achieved by 57.5% of patients, and most of the remaining patients (63.2%) had rare disabling seizures. The majority (65%) discontinued at least one ASM. Temporal surgeries (χ²(1) = 8.444, p < 0.05), left-sided surgeries (χ²(1) = 6.436, p = 0.04), mesial sclerosis (χ²(1) = 50.870, p = 0.024), and the use of intraoperative ECOG (χ²(1) = 23.235, p < 0.001) were associated with a better prognosis. No differences in outcome were found between the different temporal lobe surgeries (Fisher’s exact test value = 0.859, p = 0.659).

SIGNIFICANCE: Appropriate referral to a refractory epilepsy center permits a multidisciplinary approach that can result in long-term seizure freedom for most patients undergoing surgery, especially for left-temporal lobe surgeries performed with the aid of intraoperative monitoring techniques.

PMID:40913513 | DOI:10.1002/epd2.70101