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Aims/Introduction Substantial variability in demographic and clinical characteristics exists among patients with type 2 diabetes mellitus, which may impact treatment. This post‐hoc analysis evaluated the efficacy and safety of imeglimin 1,000 mg twice daily (BID) monotherapy in type 2 diabetes mellitus patients according to demographic and clinical characteristics. Materials and Methods Data were pooled from two placebo‐controlled, 24 week, randomized, double‐blind studies in adults with type 2 diabetes mellitus. Outcomes (least squares mean [LSM] change in HbA1c from baseline to week 24, and safety) were analyzed according to subgroups based on demographics, clinical characteristics, and comorbidities. Results The difference in LSM change in HbA1c from baseline to week 24 was statistically significant for imeglimin vs placebo in all patient subgroups analyzed (P < 0.05 each), including demographics (age, body mass index), clinical characteristics (duration of type 2 diabetes mellitus, chronic kidney disease [CKD] stage, and prior medication use) and comorbidities (hypertension, dyslipidemia, risk of hepatic fibrosis and liver function parameter status). A statistically significant separation from placebo in HbA1c was observed at week 4 and maintained through week 24. No new safety concerns were identified with imeglimin in any patient subpopulations. Conclusions The efficacy and safety of imeglimin was demonstrated across patient subgroups, irrespective of baseline demographic and clinical characteristics. Our findings confirm the efficacy and safety of imeglimin across a broad spectrum of patients with type 2 diabetes mellitus. Substantial variability in the demographic and clinical characteristics exists among patients with type 2 diabetes mellitus, which may impact treatment. In this post‐hoc analysis, the efficacy of imeglimin was demonstrated across patient subgroups irrespective of baseline demographic and clinical characteristics, with a statistically significant separation from placebo in HbA1c observed at week 4 and maintained through week 24. No new safety concerns were identified with imeglimin in any patient subpopulations.

Evocalcet is a novel oral calcimimetic drug that has demonstrated similar efficacy to cinacalcet in regulating serum parathyroid hormone (PTH), calcium, and phosphate levels, with fewer upper gastrointestinal tract-related adverse drug reactions (ADRs) in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. We investigated the efficacy and safety of once-daily oral evocalcet under different dialysate calcium concentrations. A post hoc analysis by dialysate calcium concentration (2.5, 2.75, and 3.0 mEq/L) was performed using data from a previous Phase 3 study that included cinacalcet as an active control. Efficacy endpoints were the proportion of patients who achieved the target intact PTH levels of ≥60 and ≤240 pg/mL between Week 28 and Week 30; time-course changes in serum intact PTH; calcium and phosphorus levels, bone turnover markers, and fibroblast growth factor 23 (FGF23) over the 30-week study period. Safety endpoints were overall ADRs and hypocalcemia- and upper gastrointestinal tract-related ADRs. A total of 634 patients were included in the analysis. Levels of intact PTH, calcium, phosphate, bone turnover markers, and FGF23 showed improvement in all sub-groups, irrespective of dialysate calcium concentration. The incidence of upper gastrointestinal tract-related ADRs was significantly lower in the evocalcet group than the cinacalcet group with dialysate calcium concentrations of 2.75 and 3.0 mEq/L ( <0.05 for both concentrations). Evocalcet was effective and safe in regulating the levels of serum intact PTH, calcium, and phosphate in patients with secondary hyperparathyroidism undergoing hemodialysis, irrespective of dialysate calcium concentration.

Efficacy analyses that go beyond the primary outcome of major depressive disorder (MDD) clinical trials and consider clinical relevance, response range, disease severity, and patient subpopulations may inform clinical decision-making. This post hoc analysis assessed clinically relevant outcomes associated with adjunctive cariprazine for MDD. Data from a randomized controlled trial (NCT03738215) of cariprazine 1.5 or 3 mg/d + antidepressant therapy (ADT) versus placebo + ADT were analyzed. Change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed and number of patients achieving thresholds of MADRS response (≥5, ≥10, ≥15, ≥20, and ≥25 points) were determined. MADRS severity shifts were reported as the proportion of patients with no change or worsened severity, 1, ≥1, and ≥2 category improvements. Other efficacy characterizations included improvements in each MADRS item score and MADRS total score improvement across demographic-defined (age, sex, race) patient subgroups, baseline ADT response, and number of prior ADTs. More patients treated with adjunctive cariprazine versus placebo had MADRS total score improvements across all response thresholds and achieved ≥1 MADRS severity category improvement. Adjunctive cariprazine was associated with numerically greater improvements versus placebo in all individual MADRS items, with statistically significant improvements in 7/10 items. Adjunctive cariprazine was also associated with MADRS total score reductions, regardless of patient demographics, baseline ADT response, or number of prior ADTs. Results suggest that adjunctive cariprazine provides clinically meaningful improvements in depressive symptoms, with efficacy ranging across individual depressive symptoms and in diverse subpopulations.

HP-3070, the first asenapine transdermal system (patch), is indicated for adults with schizophrenia. The US Food and Drug Administration recommends analyzing clinical outcome data by using meaningful score difference (MSD) and meaningful score regions (MSRs) to determine what score changes are clinically meaningful to patients. This post hoc analysis aimed to determine the MSD and MSRs in Positive and Negative Syndrome Scale (PANSS) total score from the pivotal phase 3 study of HP-3070. Clinician-Rated Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scores were used as anchors to quantify improvement from baseline to Week 6 in PANSS total score. The following were identified: MSD-change and percentage change in PANSS for ≥50% of responders (CGI-I=1,2) and MSRs-change and percentage change in PANSS by baseline CGI-S for 25th and 75th percentiles of responders. In total, 616 patients were evaluated. The mean (SD) baseline PANSS total score was 96.6 (9.5). MSD of change in PANSS score was -30 points. MSDs of percentage change in PANSS scores were -32% and -46% based on calculations without and with adjustment for the scale's minimum score, respectively. For all responders defined as CGI-I=1 or 2, MSRs of change in PANSS score ranged from -37 to -24. MSRs of percentage change in PANSS score ranged from -39% to -25% without adjustment and -57% to -37% with adjustment. The MSD and MSRs provide an estimate of expected treatment effect on schizophrenia patients in a population and serve as a threshold to identify individual patients with clinically meaningful improvement. These results contribute to the ongoing discussion of what constitutes a clinically meaningful response in patients with an acute episode of schizophrenia and provide an estimate of the expected treatment effect of HP-3070.

Abstract Many scientists learn during training to use analysis of variance (ANOVA) when comparing more than 2 groups, yet the principles and follow-up steps are often not well explained. This overview provides a practical guide for selecting appropriate multiple comparisons tests and for interpreting and presenting data accurately. While not exhaustive, it highlights commonly used approaches, many of which are available in GraphPad Prism, a widely used statistical program among cell and molecular biologists. The authors have no affiliation with Dotmatics, the distributor of GraphPad Prism, and this overview is not intended as an endorsement of the software.

Belimumab, a human monoclonal antibody that works against B-cell activating factor (BAFF), has significantly advanced the management of systemic lupus erythematosus (SLE). Beyond the initial Phase III randomised controlled trials (RCTs) that demonstrated efficacy for belimumab as an add-on to non-biological standard therapy (ST) along with a favourable safety profile, more than 50 post hoc analyses of RCT data have provided additional insights into its clinical utility. These analyses have shown uniformly that belimumab increases the likelihood of achieving meaningful reductions in disease activity, sustained low disease activity, and improved health-related quality of life (HRQoL) outcomes, with more pronounced benefits in serologically active SLE. Studies focusing on organ-specific manifestations revealed that belimumab confers benefits across multiple SLE facets, with prominent effects on musculoskeletal and mucocutaneous symptoms. Along the same lines, post hoc analyses of the BLISS-LN trial demonstrated benefit from belimumab regarding multiple renal outcomes, including reduced renal flare rates, improved glomerular filtration rate, and improved histological findings in repeat kidney biopsies. Long-term extension studies and real-world evidence confirm its durable efficacy and safety, with continued reductions in overall disease activity, glucocorticoid use, and healthcare resource utilisation over several years. By exploring different efficacy endpoints, person-centred outcomes, disease trajectories, and characteristics across organ manifestations, this body of post-marketing evidence has not only enhanced our understanding of belimumab use in SLE but also constitutes a comprehensive framework for future clinical trial design and development of novel therapeutic strategies. The present review summarises key findings of post hoc analyses of RCTs and observational studies of belimumab.

Background The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. Methods This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n  = 121), group 2 (3 to 12 weeks, n  = 113), group 3 (15 weeks, n  = 30), and group 4 (≥ 18 weeks, n  = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. Results Group 4 achieved the highest 5-year OS (82.1%) and DFS (66.0%) rates. Compared with groups 1 and 2, group 4 demonstrated significantly improved OS (adj. P  ≤ 0.001) and improved DFS versus group 1 (HR 0.621, 95% CI 0.443–0.870, adj. P  = 0.017). In the TNT cohort, group 4 was associated with significantly improved OS and DFS compared with group 2 (adj. P  < 0.01), but not with group 3. Additionally, group 4 showed a significantly lower risk of LRR than group 3. In the CRT cohort, group 4 was associated with improved OS compared with group 1 (adj. P  = 0.005); however, this association was not retained in surgical patients. No significant differences in DFS, DM, or LRR were observed across groups in the CRT cohort. Conclusions In TNT cohort, minimum 18 weeks of chemotherapy was associated with improved OS and DFS compared to 3 to 12 weeks. The observed OS benefit of minimum 18 weeks versus no chemotherapy in the CRT cohort was not retained among surgical patients. These findings suggest caution in shortening chemotherapy duration, particularly in high-risk patients treated with TNT, and warrant confirmation in prospective TNT-specific trials. Trial registration The STELLAR trial was registered at ClinicalTrials.gov (identifier: NCT02533271); however, this post hoc analysis was retrospectively conducted.

Long-term treatment with antipsychotic agents is indicated for patients with schizophrenia, but treatment is associated with adverse events (AEs) that contribute to medication discontinuation and nonadherence. Understanding drug safety profiles is critical to avoid unwanted side effects. Cariprazine is a potent dopamine D /D receptor partial agonist that is approved for the treatment of adults with schizophrenia (EU, US) and acute manic/mixed and depressive episodes associated with bipolar I disorder (US). Post hoc analyses were conducted to characterize the safety profile of cariprazine within the recommended 1.5-6 mg/d dose range for schizophrenia; data from 8 short- or long-term clinical trials were analyzed. In the pooled cariprazine-treated safety population (n=2048), the rate of study completion was 52.8%, with withdrawal of consent, insufficient response, and AEs the most common reasons for premature discontinuation. The most commonly reported AEs (>10%) in the overall cariprazine-treatment group were akathisia (14.6%), insomnia (14.0%), and headache (12.1%); most AEs were considered mild (71.0%) or moderate (26.5%). Most akathisia was mild/moderate (97.5%) and >93% of patients remained on treatment; akathisia events were managed by rescue medications (56.3%) or dose reduction (18.3%). The metabolic profile of cariprazine was neutral in patients with short- and long-term exposure; mean weight gain was 1 kg for overall cariprazine, with an AE of weight increased reported for 5.1%. Other AEs of special interest that occurred at >3% for overall cariprazine were extrapyramidal disorder (7.0%), sedation (3.7%), and somnolence (3.1%); prolactin elevation, cognition impairment, sexual dysfunction, suicidality, and QT prolongation occurred at ≤1%. Akathisia, the most common cariprazine-related AE, was mild/moderate and resulted in few study discontinuations; symptoms were well managed and most patients remained on treatment. Results of this analysis indicated that cariprazine in the recommended dose range was safe and generally well tolerated in patients with schizophrenia. Studies registered with ClinicalTrials.gov (NCT00404573, NCT01104779, NCT00694707, NCT01104766, NCT01104792, NCT00839852, and NCT01412060) and EudraCT (2012-005485-36).

Breast cancer is a serious health concern and one of the leading causes of cancer-related deaths among women worldwide. The early diagnosis of breast cancer is crucial for successful treatment and improved patient outcomes. Advanced computational techniques, particularly deep transfer learning have gained considerable attention for their effectiveness in medical image computing. Initially, six transfer learning models with different specifications are trained, validated and tested on the breast ultrasound image dataset. Additionally, a novel hybrid model, DRM-Net, is developed by stacking the top three TL models based on concatenation and flattening of deep dense layers. Various techniques, including image preprocessing, image masking, data augmentation, and hyperparameter tuning, are incorporated to enhance the overall performance of the considered models. The models are thoroughly evaluated using various standard metrics and statistical methods. Furthermore, to ensure transparent decision-making, the proposed model is interpreted using XAI-based class activation mapping (CAM) method with different versions. The proposed DRM-Net model demonstrated superior predictive performance compared to the other six transfer learning models. Among all the models, DRM-Net achieved the highest overall performance, with an accuracy of 96.71%, precision of 96%, recall of 97%, F1-score of 97%, and an AUC value of 99%, respectively. It also outperformed state-of-the-art similar studies in the literature. The experimental results demonstrate the potential utility of the hybrid DRM-Net model in improving the accuracy of breast cancer diagnosis, which could facilitate informed clinical decision-making. The proposed model can also be applied to other diseases where ultrasound imaging is available

Obesity is a major public health concern. Predicting obesity risk from lifestyle data can guide targeted interventions, but current models remain limited. This study first evaluates ensemble learning methods and then combines approaches to improve prediction accuracy and generalizability. Four ensemble techniques—boosting, bagging, stacking, and voting—were tested. Five boosting and five bagging models were constructed alongside voting and stacking models. Hyperparameter tuning optimized performance, and feature importance analysis guided potential feature elemination. In phase two, hybrid stacking and voting models integrated the best-performing boosting and bagging models to enhance predictive capability. Model robustness was ensured through k-fold cross-validation and statistical validation. SHAP (SHapley Additive exPlanations) and LIME (Local Interpretable Model-agnostic Explanations) improved interpretability by analyzing feature contributions. Hybrid stacking and voting models outperformed other ensemble methods, with stacking achieving the best performance (accuracy: 96.88%, precision: 97.01%, and recall: 96.88%). Feature importance analysis identified key predictors, including sex, weight, food habits, and alcohol consumption. The results demonstrated that hybrid ensembles significantly improved obesity risk prediction while preserving interpretability. Integrating multiple ensemble and explainability techniques provides a reliable framework for obesity prediction, supporting clinical decisions and personalized healthcare strategies to mitigate obesity risk.