Category: Statistics

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

Eur J Dent Educ. 2025 Sep 6. doi: 10.1111/eje.70038. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Working in a dental private practice is an investment that requires many skills in management, including the management of the dental office and staff recruitment. The objective of our study was to identify the need for continuing training in dental practice management among dental students at the end of their training.

METHODS: A descriptive cross-sectional study was conducted among students at the end of their course at the Faculty of Dentistry of Casablanca using an anonymous questionnaire. The questionnaire included 7 general questions, 15 questions on the liberal installation, and 7 questions on the financing of the dental office. Data were entered and statistically analysed using SPSS software at the epidemiology and research laboratory of the faculty.

RESULTS: 3% of students were able to answer correctly to the questions on the types of possible contracts for staff. 88.7% of students do not know dental practice management software, and 93.2% do not know which software to use to communicate with prosthetists. 88% of participants express a need for training in the running of their practice. To complete their knowledge, 70.7% of students expressed their interest in workshops, and 66.2% in guided lessons.

CONCLUSION: To address the identified training needs, the organisation of additional scientific events, such as congresses, seminars, and workshops, is proposed within the faculty, in collaboration with the Order Council and other institutional stakeholders.

PMID:40913502 | DOI:10.1111/eje.70038

Australas Psychiatry. 2025 Sep 6:10398562251375269. doi: 10.1177/10398562251375269. Online ahead of print.

ABSTRACT

ObjectivesThere is limited research on entry to aged residential care (ARC) in people living with young-onset dementia (YOD). Most people with YOD eventually require ARC, often in facilities designed for older adults. This study aimed to investigate the time to ARC admission in a previously identified YOD cohort and their health outcomes before and after ARC admission.Methods60 YOD participants (diagnosed in Waikato, New Zealand between 2014 and 2016) were retrospectively followed over a median of 5.4 years, using routinely collected health data (interRAI and mortality data). Survival analysis assessed the ARC admissions time, considering age, gender, ethnicity, and dementia type. McNemar’s/McNemar-Bowker tests were conducted to compare health outcomes before and after ARC admission.Results32 participants required ARC, with a median admission time of 4.5 years post-diagnosis. No significant effects were detected for age at diagnosis, gender, ethnicity (Māori vs non-Māori), or dementia type (Alzheimer’s vs non-Alzheimer’s disease) on ARC admission time. Significant health improvements were observed post-admission regarding health stability (CHESS), smoking, physical activity, and hospitalisations.ConclusionsWell-being improvements after ARC admission are encouraging and align with the New Zealand Aged Care Association (NZACA) report. However, the small sample size warrants further research to confirm these findings.

PMID:40913498 | DOI:10.1177/10398562251375269