Search Results (30)

Crossover trials are specifically designed to evaluate treatment effects within individual participants through within-subject comparisons. In a standard AB/BA crossover trial, participants are randomly allocated to one of two treatment sequences: either the AB sequence (where patients receive treatment A first and then cross over to treatment B after a washout period) or the BA sequence (where patients receive B first and then cross over to A after a washout period). Asymptotic and approximate unconditional test procedures, based on two Wald-type statistics, the likelihood ratio statistic, and the score test statistic for the odds ratio (OR), are developed to evaluate the equality of treatment effects in this trial design. Additionally, confidence intervals for OR are constructed, accompanied by an approximate sample size calculation methodology to control the interval width at a pre-specified precision. Empirical analyses demonstrate that asymptotic test procedures exhibit robust performance in moderate to large sample sizes, though they occasionally yield unsatisfactory type I error rates when the sample size is small. In such cases, approximate unconditional test procedures emerge as a rigorous alternative. All proposed confidence intervals achieve satisfactory coverage probabilities, and the approximate sample size estimation method demonstrates high accuracy, as evidenced by empirical coverage probabilities aligning closely with pre-specified confidence levels under estimated sample sizes. To validate practical utility, two real examples are used to illustrate the proposed methodologies. Full article

We evaluated inflammatory markers among 389 surgically confirmed endometriosis cases and 505 controls from the Women’s Health Study: From Adolescence to Adulthood (A2A) cohort. Participants reported dysmenorrhea, acyclic pelvic pain, dyspareunia, and pain with bowel movements. Using multiplex assays, we measured their levels of plasma interleukin (IL)-1β, -6, -8, -10, and -16, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and -4, thymus and activation-regulated chemokine (TARC), and interferon gamma-induced protein (IP)-10. For each symptom, we computed biomarker-level geometric means (GMs) with 95% confidence intervals (95% CI) using multivariate linear regression among the endometriosis cases and controls, with interactions with case/control status tested using Wald statistics. Among the controls, those with dyspareunia had lower levels of IL-8 (GM_present = 4.64 [95% CI = 4.41–4.89] pg/mL vs. GM_absent = 4.99 [95% CI = 4.82–5.17] pg/mL; p = 0.02), and the IL-8 levels were lower for controls reporting pain with bowel movements (GM_present = 4.66 [95% CI = 4.43–4.89] vs. GM_absent = 4.96 [95% CI = 4.82–5.11] pg/mL, p = 0.03). No significant associations between pelvic pain symptoms and inflammatory markers were observed among the endometriosis cases; however, the relationship between inflammatory marker levels and pain experience varied by analgesic use at blood draw. Dyspareunia and pain with bowel movements were associated with inflammatory markers among the controls, while the associations between pelvic pain symptoms and inflammatory markers among the endometriosis cases differed by analgesic use. Full article

Introduction and objective: Assessment of α-synuclein (αSyn) seed amplification assays (αSyn-SAA) accuracy in distinguishing Parkinson’s disease (PD) from controls using cerebrospinal fluid (CSF), blood, skin, extracellular vesicles (ECV), saliva, olfactory mucosa (OM), gastrointestinal tract (GIT), and submandibular gland (SMG). Methodology: PubMed was searched for articles from 2010 to January 2025. The quality assessment used robvis. Diagnostic values with a 95% confidence interval (CI) were obtained. Z-test, Wald CI, and ANOVA were performed. Diagnostic odds ratio (DOR) was used. Results: αSyn-SAAs showed strong diagnostic performance in distinguishing PD from controls across various tissue and fluid types. Overall, αSyn-SAAs demonstrated high sensitivity (86%) and specificity (92%). Among all biomatrices, CSF, skin, blood, and ECV yielded the highest diagnostic accuracy, with sensitivity and specificity approaching or exceeding 90%. In contrast, saliva, oral mucosa, and gastrointestinal tract samples showed more modest sensitivity, though specificity remained relatively high. ECV, CSF, skin, and blood matrices also demonstrated the highest DOR, supporting their potential clinical utility. Conclusions: ECV and blood warrant priority in αSyn-SAA for high accuracy and minimal invasiveness, while GIT, OM, and oral samples show limited utility; saliva and SMG need refinement. Full article

Closed frequent itemsets (CFIs) play a crucial role in frequent pattern mining by providing a compact and complete representation of all frequent itemsets (FIs). This study systematically explores the theoretical properties of CFIs by revisiting closure operators and their fundamental definitions. A series of formal properties and rigorous proofs are presented to improve the theoretical understanding of CFIs. Furthermore, we propose confidence interval-based closed frequent itemsets (CICFIs) by integrating frequent pattern mining with probability theory. To evaluate the stability, three classical confidence interval (CI) estimation methods of relative support (rsup) based on the Wald CI, the Wilson CI, and the Clopper–Pearson CI are introduced. Extensive experiments on both an illustrative example and two real datasets are conducted to validate the theoretical properties. The results demonstrate that CICFIs effectively enhance the robustness and interpretability of frequent pattern mining under uncertainty. These contributions not only reinforce the solid theoretical foundation of CFIs but also provide practical insights for the development of more efficient algorithms in frequent pattern mining. Full article

This paper investigates the construction of confidence intervals for multiple change points in linear regression models. First, we detect multiple change points by performing variable selection on blocks of the input sequence; second, we re-estimate their exact locations in a refinement step. Specifically, we exploit an orthogonal greedy algorithm to recover the number of change points consistently in the cutting stage, and employ the sup-Wald-type test statistic to determine the locations of multiple change points in the refinement stage. Based on a two-stage procedure, we propose bootstrapping the estimated centered error sequence, which can accommodate unknown magnitudes of changes and ensure the asymptotic validity of the proposed bootstrapping method. This enables us to construct confidence intervals using the empirical distribution of the resampled data. The proposed method is illustrated with simulations and real data examples. Full article

Background: Immune checkpoint inhibitors (ICIs), either alone or in combination with platinum-based chemotherapy, are effective in the first-line treatment of metastatic, non-oncogene-addicted, non-small cell lung cancer (NSCLC). However, when NSCLC patients progress, the efficacy of available treatment options is limited. Methods: We undertook a meta-analysis that compared combination regimens with the current standard of care. Only randomized controlled trials (RCTs) were included (endpoint, overall survival [OS]). Our analysis used an artificial intelligence software program that reconstructs individual patient data from Kaplan–Meier curves. Hazard ratio (HR) with 95% confidence interval (CI) was the main parameter. Heterogeneity was based on Wald’s test and likelihood ratio test. Results: Five RCTs were included, whose experimental arms included five different combinations. In our analysis, these combination regimes showed no OS benefit compared to chemotherapy (HR = 1.066, 95%CI, 0.9311 to 1.221; p = 0.35). Among the five control arms, cross-trial heterogeneity was remarkably low (likelihood ratio test = 3.76 on 4 df, p = 0.40; Wald test = 3.83 on 4 df, p = 0.40. Discussion: In conclusion, five new second-line combination treatments for patients with NSCLC were not found to determine any benefit in terms of OS in comparison with the current standard of care. Full article

(1) Background: Large language models (LLMs) are revolutionising various scientific fields by providing advanced support tools. However, the effectiveness of these applications depends on extensive, up-to-date databases to ensure certainty and predictive power. Transparency about information sources in Medicine remains a significant issue. (2) Methods: To evaluate Google Gemini’s accuracy and reproducibility in endodontic diagnosis and treatment, 60 questions were designed based on the European Society of Endodontology Position Statements. Thirty questions were randomly selected and answered using Gemini during April 2023. Two endodontic experts independently scored the answers using a 3-point Likert scale. Discrepancies were resolved by a third expert. The relative frequency and absolute percentage of responses were detailed. Accuracy was assessed using the Wald binomial method, and repeatability was assessed using percentage agreement, Brennan and Prediger’s coefficient, Conger’s generalised kappa, Fleiss’ kappa, Gwet’s AC, and Krippendorff’s alpha, all with 95% confidence intervals. Statistical analysis was performed using STATA software. (3) Results: A total of 900 answers were generated. The percentage of correct answers varied from 0% to 100% per question. Overall accuracy was 37.11% with a 95% confidence interval of 34.02–40.32%; (4) Conclusions: Gemini is not currently designed for medical use and therefore needs to be used with caution when considered for this purpose. Full article

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189–0.969) and GP17 (OR = 0.709, 95%CI = 0.504–0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95%  CI  = 1.384–3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95%  CI =1.008–1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95%  CI  = 1.003–1.261) and GP24 (OR = 1.222, 95%  CI  = 1.046–1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95%  CI  = 1.048–1.537) and GP15 (OR = 1.297, 95%  CI = 1.072–1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms. Full article

Background: Risk factors for severe dengue manifestations have been attributed to various factors, including specific serotypes, sex, and age. Mexico has seen the re-emergence of DENV-3, which has not circulated in a decade. Objective: To describe dengue serotypes by age, sex, and their association with disease severity in dengue-positive serum samples from epidemiological surveillance system units. Materials and Methods: A descriptive analysis was conducted to evaluate the frequency of dengue severity by sex, age, disease quarter, geographical location, and dengue virus serotypes. The study was conducted using laboratory samples from confirmed dengue cases through RT-qPCR from the epidemiological surveillance laboratory network of the Mexican Social Security Institute, Mexico. Simple frequencies and proportions were calculated using the z-test for proportional differences between groups. Bivariate analysis with adjusted Chi2 was performed, and binary logistic regression models were constructed using the forward Wald method considering the model’s predictive capacity. The measure of association was the odds ratio, with 95% confidence intervals. Statistical significance was set to an alpha level of <0.05. Results: In 2023, 10,441 samples were processed for dengue RT-qPCR at the IMSS, with a predominance of serotype DENV-3 (64.4%). The samples were mostly from women (52.0%) and outpatient cases (63.3%). The distribution of dengue severity showed significant variations by age, with a lower proportion of severe cases in young children and a higher proportion in the 5- to 14-year-old group. Hospitalizations increased significantly with severity. Warm regions had more cases overall and severity. Cases were most frequent from July to September. While DENV-2 was associated with severity, DENV-4 was not. Binary regression identified higher risk in women, age extremes, and DENV-2, with an overall predictive model of 58.5%. Conclusions: Women, age groups at the extremes of life, and the DENV-2 serotype presented severe risk of dengue in a population with social security in Mexico during 2023. Full article

This article presents Bayesian estimation methods applied to the gamma zero-truncated Poisson (GZTP) and the complementary gamma zero-truncated Poisson (CGZTP) distributions, encompassing both one-parameter and two-parameter models. These distributions are notably flexible and useful for modeling lifetime data. In the one-parameter model case, the Jeffreys prior is mathematically derived. The use of informative and noninformative priors, combined with the random walk Metropolis algorithm within a Bayesian framework, generates samples from the posterior distributions. Bayesian estimators’ effectiveness is examined through extensive simulation studies, in comparison with the maximum likelihood method. Results indicate that Bayesian estimators provide more precise parameter estimates, even with smaller sample sizes. Furthermore, the study and comparison of the coverage probabilities (CPs) and average lengths (ALs) of the credible intervals with those from Wald intervals suggest that Bayesian credible intervals typically yield shorter ALs and higher CPs, thereby demonstrating the effectiveness of Bayesian inference in the context of GZTP and CGZTP distributions. Lastly, Bayesian inference is applied to real data. Full article

The use of multivitamins has become widespread globally, yet there is a scarcity of studies investigating their impact on resin composite restorations. This study aimed to evaluate the effect of an effervescent multivitamin tablet on micro-hybrid dental resin composites’ surface roughness and color. Fifty disc-shaped samples (8 × 2 mm, shade A2; n = 10) were prepared and polished using five different micro-hybrid resin composites (Pergamon, Dentac, Turkey; Estelite Posterior, Tokuyama, Japan; Geanial Anterior, GC, Japan; Charisma Opal, Kulzer, Germany; Beautifil II, Shofu, USA). Samples were immersed in 200 mL water to one effervescent multivitamin tablet (Redoxon Triple Action, Bayer) at 24 °C for 2 min a day in 24 h intervals for 30 days. All samples’ surface roughness (Ra) and ΔE(L*a*b) measurements were recorded at the beginning and end of the 30 days. The Wald chi-square and a two-way ANOVA were used for statistical analysis (significance level p < 0.05). The resin composite type and exposure to the multivitamin had a statistically significant effect on Ra values (p < 0.05). The resin composite type had a statistically significant effect on ΔE values, likely due to the higher mean value of BII (p = 0.040). The surface roughness and color of resin composites can be affected by multivitamins with a pH value of 3.0. Therefore, it is important to consider the patient’s routine vitamin intake during resin composite selection. Additional research is required to explore the properties of different dental restorative materials. Full article

The inverse Gaussian distribution, known for its flexible shape, is widely used across various applications. Existing confidence intervals for the mean parameter, such as profile likelihood, reparametrized profile likelihood, and Wald-type reparametrized profile likelihood with observed Fisher information intervals, are generally effective. However, our simulation study identifies scenarios where the coverage probability falls below the nominal confidence level. Wald-type intervals are widely used in statistics and have a symmetry property. We mathematically derive the Wald-type profile likelihood (WPL) interval and the Wald-type reparametrized profile likelihood with expected Fisher information (WRPLE) interval and compare their performance to existing methods. Our results indicate that the WRPLE interval outperforms others in terms of coverage probability, while the WPL typically yields the shortest interval. Additionally, we apply these proposed intervals to a real dataset, demonstrating their potential applicability to other datasets that follow the IG distribution. Full article

Thyroid dysfunction stands as the most prevalent endocrine disorder in individuals with Down syndrome, particularly showcasing both clinical and subclinical hypothyroidism. TSH and FT4 blood values serve as common diagnostic and treatment adjustment markers. In Down syndrome (DS), hormone values may deviate from those observed in the general population, which may lead to overdiagnosis and consequent iatrogenesis of subclinical hypothyroidism. The objective of this study was to analyze the appropriateness of the replacement therapeutic approach by identifying the TSH and FT4 values that can be considered normal in these patients. Methods: A cross-sectional study was conducted in 503 subjects with DS of both sexes and without age limit drawn from the Health Program for individuals with DS in Valencia (Spain) from February 1993 to November 2021. The exclusion criteria included hyperthyroidism, nodules, tumors, or individuals under treatment with drugs influencing iodine metabolism. The normality of data distribution was assessed using the Shapiro–Wilk test. Outliers were detected using the Reed’s criterion. Hormone values were estimated using quantile regression models for the 2.5th and 97.5th percentiles. Results: The normal values identified were 0.88–11.25 mIU/L for TSH and 0.71–1.63 ng/dL for FT4. The Wald test indicated no significant differences in the reference intervals based on age or sex. Conclusion: The establishment of these values, which, in people with DS, can be considered unique, is of great importance, allowing a watchful waiting attitude to be maintained before starting replacement therapy that is unnecessarily or adjusting medication in diagnosed cases. Full article

Background and Objectives: The prevalence of chronic kidney disease (CKD) is approximately 10% of the population in many countries. CKD progresses to end-stage renal disease (ESRD), resulting in adverse outcomes, prolonged hospitalization, and increased healthcare costs. Therefore, reducing CKD progression to ESRD is recognized as an important health issue. Materials and Methods: Data from the study participants with stage 3 to stage 5 CKD (n = 7668) were collected from the National Health Insurance (NHI) program in Taiwan (1 November 2014 to 31 December 2020). CKD patients who had ingested or not ingested N-acetylcysteine (NAC) for three years were divided into the study group (NAC users; n = 165) and the control group (NAC non-users; n = 165) to explore whether NAC use could alleviate CKD progression and reduce the risks associated with hemodialysis in CKD patients. Results: The levels of serum creatinine (SCr) and estimated globular filtration rate (eGFR) were nearly unchanged and/or slightly changed in NAC users, but the SCr levels were slightly increased, and the eGFR levels were significantly decreased in NAC non-users at the six-month interval during the three years. A statistical difference was observed between the two groups for both levels from 12 months to 36 months. The incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users (4.8% vs. 12.7%, Wald test = 5.947, p = 0.015, OR = 34.9). These results indicated that NAC use may improve renal function of CKD patients by modulating SCr and eGFR and, in turn, reducing the risk of hemodialysis. Conclusions: We investigated whether NAC could be used to reduce CKD progression to ESRD. For the three-year retrospective study, the incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users via modulating SCr and eGRF levels. NAC use might be a useful clinical approach for reducing CKD progression to ESRD. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitations, occurring mainly in the small airways. Weakness in the respiratory muscles contributes to dyspnea and a decreased exercise capacity in COPD patients. This study aimed to investigate the effectiveness of home-based inspiratory muscle training (IMT) on small airway function and symptoms in COPD patients. This research adopted a non-randomized controlled-study quasi-experimental design. The IMT program consisted of two 15 min sessions·d⁻¹, 5 d·wk⁻¹, with 40% of the maximal inspiratory pressure (PI_max) on each participant’s assessment results and lasted for 12 weeks. Small airway function was assessed using plethysmography at baseline and after 12 weeks. The modified British Medical Research Council (mMRC), COPD assessment test (CAT), PI_max, and 6 min walking distance (6MWD) were recorded at baseline as well as four, eight, and twelve weeks. Twenty-three participants with at least moderate COPD were enrolled in IMT (n = 16) or in the control group (n = 7) in this study. The study participants were mostly male (82.6%), and the average age was 68.29 ± 10.87 years, with a mean body mass index (BMI) of 23.54 ± 4.79. After 12 weeks, the ratios of the first second of forced expiration to the forced vital capacity (FEV₁/FVC%) (B coefficient [95% Wald confidence interval] of 5.21 [0.46 to 9.96], p = 0.032), forced expiratory flow (FEF_25–75%) (0.20 [0.04 to 0.35] L/s, p = 0.012), and FEF_50% (0.26 [0.08 to 0.43] L/s, p = 0.004) in the IMT group were significantly better than in the control group. The IMT group showed significantly lower CAT scores at week 8 (−5.50 [−10.31 to −0.695] scores, p = 0.025) than the control group. The mMRC grade, CAT score, PI_max, and 6MWD were significantly improved compared to their values at baseline in the IMT group. Home-based IMT effectively improved post-bronchodilator small airway function and disease-associated symptoms in COPD patients. Full article