Abstract Purpose Infertility is associated with considerable psychosocial distress, yet many affected individuals lack formal diagnosis or treatment. The Fertility Quality of Life (FertiQoL) tool is widely used to assess quality of life in infertile populations, while the Patient Health Questionnaire-4 (PHQ-4) is a validated screening tool for anxiety and depression. This study investigated whether FertiQoL could be applied as a screening measure to identify high-risk individuals during in vitro fertilization–embryo transfer (IVF-ET). Methods This study enrolled participants (320 patients with 444 valid responses) between February and July 2023 across 11 assisted reproductive technology institutions in Taiwan. FertiQoL was used to evaluate quality of life, and PHQ-4 was used to screen for anxiety and depression. Associations between the two measures were analyzed, and a decision tree model was applied to identify an optimal FertiQoL cutoff score for risk classification. Results FertiQoL total scores were significantly and negatively correlated with PHQ-4 outcomes (–0.531 for PHQ-2; − 0.525 for GAD-2). A cutoff FertiQoL score of 63.6 provided satisfactory performance in identifying high-risk individuals, demonstrating sensitivities and specificities of 72% and 76% for anxiety (GAD-2), and 81% and 73% for depression (PHQ-2). Conclusions The findings support the clinical utility of FertiQoL as a standardized tool not only for quality of life assessment but also for identifying mental health risks in infertile patients.

We evaluated the renal outcomes and safety of spironolactone added to renin-angiotensin system inhibitors (RASis) among patients with type 2 diabetes (T2D), given its uncertain role alongside RASis, the cornerstone of T2D with renal disease management. In this retrospective study at National Cheng Kung University Hospital (2014-2021), we identified adult T2D patients receiving RASis alone or combined with spironolactone. Propensity score matching between treatment groups was implemented to achieve between-group comparability. The primary outcome was a composite renal outcome (including end-stage renal disease [ESRD], renal transplant, or a ≥ 30% estimated glomerular filtration rate [eGFR] decline). Secondary outcomes included proteinuria, major adverse cardiovascular events, and hyperkalemia. Cox proportional hazard model analyses were adopted to assess the treatment outcomes. 404 PS-matched pairs of RASis-alone and RASis+spironolactone users were included. Adding spironolactone to RASis was associated with increased composite renal event (hazard ratio [95% CI]: 1.27 [1.06-1.51]), persistent eGFR decline ≥ 30% (1.31 [1.09-1.58]), and hyperkalemia (1.57 [1.21-2.04]) risks while associated with a higher likelihood of achieving ≥ 30% proteinuria reduction (HR 1.34 [1.12-1.60]). Having heart failure (HF) was a significant effect modifier, that is, using RASis+spironolactone versus RASis alone was associated with a lower ESRD/renal transplant risk among patients with HF (0.62 [0.38-1.02]) but an increased risk for those without HF (1.32 [0.98-1.78]) (p for interaction = 0.011). Adding spironolactone to RASis might increase renal adverse events and hyperkalemia but reduce proteinuria in T2D patients. Notably, heart failure status significantly modified these associations, underscoring the importance of personalized medicine.

Objective Atosiban has demonstrated effectiveness in improving pregnancy outcomes in patients with recurrent implantation failure (RIF). However, the optimal dosage protocol is yet to be established, and only a few studies have directly compared different regimens. Materials and methods This double-blind, randomized controlled trial recruited 100 patients with RIF undergoing treatment at the Assisted Reproductive Technology Center at National Cheng Kung University Hospital between March 2022 and May 2024. Patients were assigned to receive either a bolus protocol of atosiban (6.75 mg; Group A, n = 50) or an infusion protocol of atosiban (total 37.5 mg; Group B, n = 50) before embryo transfer. Results Although no significant differences were observed, Group B showed a tendency toward higher live birth rates (6.0% vs 20.0%, RR = 3.333; P = 0.071). Other pregnancy outcomes also demonstrated a positive trend, with a notably higher ongoing pregnancy (6.0% vs 20.0%, RR = 3.333; P = 0.071) and a lower miscarriage rate (75.0% vs 33.3%, RR = 0.444; P = 0.054). Subgroup analysis revealed a significant benefit of the infusion protocol in subgroups of patients with high fertility quality of life scores and high-quality embryos (P = 0.039 and 0.048, respectively). Conclusion The atosiban infusion protocol demonstrated a positive trend in pregnancy outcomes among patients with RIF. Further large-scale studies are needed to confirm its effectiveness and establish optimal strategies.

AIMS:Diabetic foot ulcers (DFUs) impose a vast health and economic burden on individuals and healthcare systems globally. We assessed the cost-effectiveness of adding ON101, a novel treatment for accelerating wound healing, to general wound care (GWC) versus GWC alone for DFUs in Singapore, a multi-ethnic country with increasing DFU prevalence in a growing type 2 diabetes population. MATERIALS AND METHODS:A Markov model was utilized to estimate the healthcare costs and quality-adjusted life years (QALYs) over 5 years from a healthcare sector perspective. Model inputs were mainly derived from the Singapore Wound Registry and published literature. The primary outcome was the incremental cost-effectiveness ratio (ICER). Subgroup analyses stratified by clinically important DFU conditions and scenario analyses were conducted to confirm the study's robustness. RESULTS:Compared to GWC alone, adding ON101 yielded greater QALY gained (i.e., 0.15) and lower healthcare costs (i.e., -US$16237) for patients with DFUs. Remarkable cost-savings from the use of ON101 with GWC were observed for patients with complex DFUs, namely ICERs of -US$161 963, -US$181 726 and -US$199 130 per QALY gained for cases with HbA1c ≥ 9%, ulcer duration >6 months and ulcer size >5 cm2, respectively. Scenario analysis comparing ON101 with GWC to negative pressure wound therapy with GWC yielded an ICER of -US$677 243 per QALY gained. CONCLUSIONS:Combining ON101 with GWC versus GWC alone was highly cost-effective for DFUs in Singapore. Also, the economic results for complex DFU cases underscore the value of ON101 in addressing DFU treatment challenges for managing complex cases, offering cost-savings alongside clinical benefits.

AIM:To examine the association between long-term variability in low-density lipoprotein cholesterol (LDL-C) and the development of adverse kidney events among type 2 diabetes patients. METHODS:Kidney events of interest included sustained estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2, 30 % eGFR decline, and composite kidney events. The Cox proportional hazard model was used to assess the association between LDL-C variability and kidney events. RESULTS:A total of 15,444 patents were included (54 % male, mean age of 62.3 years, baseline HbA1c of 7.6 %, and eGFR of 84.2 mL/min/1.73 m2). The risk of kidney events increased with greater LDL-C variability across variability indices, except for that measured by coefficient of variation. Specifically, average real variability had the best predictive performance, with an optimal cut-off value of 19.26 for discriminating patients' risk of a sustained eGFR < 15 mL/min/1.73 m2. A greater effect of lipid variability on kidney event risk was observed among a subset of patients aged < 75 years, with eGFR ≥ 90 mL/min/1.73 m2, or having fewer diabetes-related complications. CONCLUSIONS:An increased risk of adverse kidney events with greater visit-to-visit variability in LDL-C highlights the clinical importance of monitoring both the single-point LDL-C and its stability over time.

Background and ObjectiveApproximately half of lung adenocarcinomas in East Asia harbor epidermal growth factor receptor (EGFR) mutations. EGFR testing followed by tissue-based next-generation sequencing (NGS), upfront tissue-based NGS, and complementary NGS approaches have emerged on the front line to guide personalized therapy. We study the cost effectiveness of exclusionary EGFR testing for Taiwanese patients newly diagnosed with advanced lung adenocarcinoma.MethodsThis economic evaluation was conducted from the perspective of the healthcare sector with a lifetime horizon. Simulated patients were entered into a joint model combining decision trees and partitioned survival models upon diagnosis of advanced lung adenocarcinoma. We compared exclusionary EGFR testing with upfront tissue-based NGS and complementary NGS approaches. The model inputs were derived from regional estimates (prevalence of targetable gene alterations), trials (testing accuracy, survival outcomes, and adverse events), ACT Genomics (testing costs), National Health Insurance payments, retail prices (drug costs), and hospital cohorts (utility values). All costs were made equivalent to 2023 US dollars. An annual discount rate of 3% was applied. We adopted a willingness-to-pay threshold of US$70,000 per quality-adjusted life-year. One-way deterministic and probabilistic analyses were performed.ResultsThe incremental cost-effectiveness ratio of exclusionary EGFR testing versus upfront tissue-based NGS was US$15,521 per quality-adjusted life-year, whereas the incremental net monetary benefit was US$2530. The costs of osimertinib and pembrolizumab were the major determinants. The incremental net monetary benefit of exclusionary EGFR testing versus complementary NGS approach was US$2174, and its major determinants included the true-negative rate of EGFR testing and the prevalence rate of an EGFR mutation. Given the willingness-to-pay thresholds of US$35,000, US$70,000, and US$105,000 (1, 2, and 3 per capita gross domestic product) per quality-adjusted life-year, the probabilities that exclusionary EGFR testing would be cost effective were 79.1%, 95.6%, and 91.2%, respectively.ConclusionsOur analysis suggests that exclusionary EGFR testing is a cost-effective strategy for Taiwanese patients newly diagnosed with advanced lung adenocarcinoma.

Although heterogeneous treatment effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been revealed, the heterogeneous economic value of SGLT2is in real-world type 2 diabetes (T2D) populations with diverse clinical characteristics remains unclear. We conducted subgroup cost-effectiveness analyses of SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP4is) among patients with T2D. A multi-state transition model was used to estimate the incremental cost-effectiveness ratios (ICERs, in USper quality-adjusted life-years [QALYs] gained) and value-based pricing (VBP) among patients with T2D stratified by age, estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), and body mass index (BMI) over 5 years and a Lifetime horizon from a healthcare sector perspective, with both costs and quality-adjusted Life years discounted at 3

OBJECTIVE:To evaluate the real-world effectiveness and dose-response of ON101 , especially for high-risk patients with poor healing outcomes. PATIENTS AND METHODS:ON101 cream, a novel treatment for diabetic foot ulcers (DFUs), modulates the function of macrophages and accelerates the emergence and expansion of anti-inflammatory properties. In this study, 80 and 98 patients with DFU who were treated using ON101 and standard care with adjuvant therapy (denoted as nonuse), respectively, from January 1, 2020, to December 31, 2022, were identified from Taipei Medical University-Shuang Ho Hospital, Taiwan. The primary outcome was a complete healing event within 120 days following treatment initiation. Secondary outcomes included ulcer recurrence, amputation, and all-cause mortality within 1 year of follow-up. Cox proportional hazard model analysis was applied to determine the treatment effect on study outcomes. The dose-response of ON101 on healing outcomes was modeled using a regression analysis. RESULTS:Compared with nonuse, ON101 use significantly increased the complete healing outcome by 79% (HR, 1.79; 95% CI, 1.24 to 2.58), with an average of 1.85 ON101 tubes used per person with healed ulcers. Favorable healing outcomes were consistently shown in the analyses of high-risk patients. The dose-response analysis results suggest 25%, 107%, 33%, and 19% decreases in the ulcer size per additional ON101 tube use for all study patients and those with Wagner grade 1, 2, and 3 ulcers, respectively (all P<.01). CONCLUSION:Promising healing outcomes following ON101 therapy at lower doses among real-world patients with DFU are corroborated, with a potential therapeutic benefit for clinically disadvantaged patients and practical feasibility for use in routine practice.

AIMS:This study aimed to compare the real-world effectiveness of dapagliflozin versus empagliflozin in patients with type 2 diabetes (T2D) and to examine prescribing patterns across specialties. METHODS:We conducted a target trial emulation using multi-institutional electronic health records from January 2016 to August 2023, identifying 2649 new users of dapagliflozin and 2046 of empagliflozin. The primary composite outcome was sustained eGFR decline ≥30 %, end-stage renal disease, heart failure hospitalization, or all-cause mortality. Safety outcomes included acute kidney injury, hypoglycemia, urinary tract infection, and fracture. Inverse probability of treatment weighting (IPTW) was used for confounding adjustment, and Cox regression estimated hazard ratios. RESULTS:After IPTW, 1662 patients remained in each group. No significant differences were found in primary, secondary, or safety outcomes. However, analysis among patients without stable prior ACEI/ARB exposure revealed a higher risk of all-cause mortality with empagliflozin. Dapagliflozin was more often prescribed by cardiologists, while endocrinologists and nephrologists favored empagliflozin. CONCLUSIONS:Dapagliflozin and empagliflozin showed similar cardiorenal and safety outcomes in T2D. However, unstable prior ACEI/ARB use may influence mortality risk with empagliflozin. Prescribing patterns highlight the importance of multidisciplinary care. Further prospective studies are needed.

The restricted mean survival time has been widely used in the field of medical research because of its clear physical and simple clinical interpretation. In this paper, we propose an efficient estimation that incorporates the auxiliary restricted mean survival information into the estimation of the proportional hazard (PH) model. Compared to conventional models that do not incorporate available auxiliary information, the proposed method improves efficiency in estimating regression parameters by utilizing the double empirical likelihood method. We prove that the estimator asymptotically follows a multivariate normal distribution with a covariance matrix that can be consistently estimated. To address scenarios where the PH assumption is violated, we also extended the method to the stratified Cox model. In addition, simulation studies show that the proposed estimators are more efficient than those derived from the conventional partial likelihood approach. A type 2 diabetes dataset is then used to evaluate the risk of antidiabetic drugs and demonstrate the proposed method.

Introduction and Objective: Observational studies showed contradictory results with using SGLT-2 inhibitors and GLP-1 RAs on the risk of dementia in patients with type 2 diabetes. We aimed to evaluate the association between these medications and dementia risk with meta-analysis. Methods: We searched PubMed, EMBASE, and CENTRAL databases up to October 2024, selecting studies that examined the association between SGLT-2 inhibitors or GLP-1 RAs and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in patients with type 2 diabetes. The ROBINS-I tool was used to evaluate the risk of bias in eligible studies. Random-effects meta-analyses with inverse variance weighting were conducted to calculate the pooled HRs with 95% confidence intervals for dementia risk. Subgroup analyses were performed: (1) older patients aged>60 years, (2) studies including a 1-year lag time, and (3) types of active comparator (e.g., DPP4 inhibitors). Results: There was a total of 18 observational studies with 3,008,234 patients included. The use of SGLT-2 inhibitors versus non-use is associated with a decreased risk of all-cause dementia (HR [95% CI]: 0.76 [0.67-0.85]), AD (0.75 [0.61-0.92]), and VD (0.58 [0.44-0.78]). Similarly, the use of GLP-1 RAs versus non-use is associated with a reduced risk of all-cause dementia (HR [95% CI]: 0.77 [0.67-0.89]), and AD (0.42 [0.34-0.50]). A lower risk of all-cause dementia risk was also observed with SGLT-2 inhibitors or GLP-1 RAs treatment in older patients, in studies applying a 1-year lag time and in those using DPP4 inhibitors as an active comparator. Conclusion: The use of SGLT-2 inhibitors and GLP-1 RAs is significantly associated with a lower risk of dementia in patients with type 2 diabetes. However, given the considerable heterogeneity inherent in observational studies, large-scale randomized controlled trials are needed to clarify these findings. C. Cheng: None. T. Nguyen: None. W. St. Peter: Consultant; Fresenius Medical Care. Advisory Panel; GlaxoSmithKline plc, Boehringer-Ingelheim. Consultant; Bayer Pharmaceuticals, Inc. H. Ou: None.

Background Existing studies are mainly focused on overall obesity or specific subpopulations, while the disease burden among patients with different characteristics of obesity progression remains uncertain. Objectives To conduct a descriptive analysis of the contemporary obesity/overweight associated economic burdens stratified by clinically meaningful features associated with obesity. Settings Utilizing Taiwan's 2013 National Health Interview Survey and the 2012-2019 National Health Insurance Research Database. Methods Six groups of adults with obesity and/or obesity-related conditions were targeted, including people receiving bariatric surgery (BS, n = 1679), having metabolic syndrome (MS, n = 1437), having body mass index (BMI) >= 27/30 kg/m(2) with obesity-related comorbidities (ORCs, n = 1428/552), and having BMI >= 27/30 kg/m(2) (n = 3235/1191). Healthcare utilization/expenditures (in 2022 USD) were measured. Results In the first year of follow-up, the BS group incurred the highest healthcare expenditures ($3494/person), followed by the MS group ($2852), the BMI >= 30/27 kg/m(2) with ORCs groups ($2025/$1920), and the BMI >= 30/27 kg/m(2) groups ($1160/$1032). In the years following BS, the prevalence and treatments for hypertension, diabetes, hyperlipidemia, and sleep apnea decreased significantly, and healthcare expenditures remained the lowest among the 6 groups but increased gradually. Heterogeneity of geographic distribution of obesity prevalence was observed. Conclusions Interventions tailored to patient characteristics, especially advanced obesity with high economic burden and obesity-associated geographic disparities, are needed. BS may curtail ORCs/MS, but the gradually increasing expenditures following BS would suggest a need of routine follow-ups. (c) 2025 American Society for Metabolic andBariatric Surgery. Published by Elsevier Inc. All rights are reserved, including those for text anddata mining, AI training, and similar technologies.