Bidirectional association between NAFLD and gallstone disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Growing evidence indicates an association between NAFLD and gallstone disease (GD), while some does not support this. The aim of this meta-analysis was to evaluate the bidirectional association between NAFLD and GD. RESEARCH DESIGN AND METHODS: Five electronic databases were searched from inception to May 2022. The association was analyzed based on the odds ratio (OR) and 95% confidence interval (CI) with Reviewer Manager 5.3. RESULTS: Ten studies involving 284,512 participants met the criteria for GD predicting the onset of NAFLD. GD patients had a higher incidence of NAFLD (OR:1.48, CI:1.32-1.65, p < 0.00001), especially the incidence of moderate-to-severe NAFLD (OR:1.63; CI:1.40-1.79), with females at a higher risk (OR: 1.84; CI: 1.48-2.29). The inverse association was explored in eight studies involving 326,922 participants. The GD incidence in NAFLD patients was higher (OR:1.71, CI:1.63-1.79, p < 0.00001) and may increase due to female sex (OR: 4.18; CI: 1.21-14.37) and high BMI (OR: 1.80; CI: 1.36-2.56), compared with the non-NAFLD group. Besides, this bidirectional association was also confirmed in the Chinese population. CONCLUSIONS: The findings supported positive concurrent and bidirectional relationships between NAFLD and GD. Therefore, clinicians may alert the possibility of NAFLD in patients with GD and vice versa.

Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China.

INTRODUCTION: The main research purpose is to compare the long-term cost-effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. METHODS: Cost-utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high-dose comparison in the SUSTAIN-7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. RESULTS: Main analysis (SEMA vs. DULA) revealed a mean difference in quality-adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost-utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost-utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost-effective, taking DULA as a reference. CONCLUSION: After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost-effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost-utility analysis. However, there is still scope to reduce the annual cost of SEMA further.

Robust Prediction of Prognosis and Immunotherapy Response for Bladder Cancer through Machine Learning Algorithm.

The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort of 9824 patients. Twelve FRGs were selected through machine learning algorithm to construct the prognosis model. Significantly differential survival outcomes (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.55−2.82, p < 0.0001) were observed between patients with high and low ferroptosis scores in the TCGA cohort, which was also verified in the E-MTAB-4321 cohort (HR = 4.71, 95% CI: 1.58−14.03, p < 0.0001), the GSE31684 cohort (HR = 1.76, 95% CI: 1.08−2.87, p = 0.02), and the pan-cancer cohort (HR = 1.15, 95% CI: 1.07−1.24, p < 0.0001). Tumor immunity-related pathways, including the IL-17 signaling pathway and JAK-STAT signaling pathway, were found to be associated with the ferroptosis score in BCa through a functional enrichment analysis. Further verification in the IMvigor210 cohort revealed the BCa patients with high ferroptosis scores tended to have worse survival outcome after receiving tumor immunotherapy. Significantly different ferroptosis scores could also be found between BCa patients with different reactions to treatment with immune checkpoint inhibitors.

Cost-Utility Analysis of Once-Weekly Semaglutide, Dulaglutide, and Exenatide for Type 2 Diabetes Patients Receiving Metformin-Based Background Therapy in China.

Introduction: The substantial financial burden associated with type 2 diabetes (T2D) over a lifetime cannot be neglected. Therefore, the objective of this study was to evaluate the pharmacoeconomic value of three once-weekly GLP-1 RAs, namely subcutaneous semaglutide (sc. SEMA), dulaglutide (DULA), and extended-release exenatide (e-r EXEN), in treating patients with T2D that cannot be controlled with metformin-based background therapy, and to find a suitable price reduction for non-cost-effective medications, to provide reasonable recommendations to the administration for adjusting drug prices. Methods: The baseline characteristics of the simulation patient cohort were sourced from a comprehensive meta-analysis synthesizing 453 trials evaluating 21 hypoglycemic agents from nine categories of drugs. The UKPDS OM2 was applied to project the long-term effectiveness and costs from a Chinese health care provider's perspective. After cost-utility analysis, the reasonable price adjustment of non-cost-effective options was explored via binary search. Uncertainty was measured by means of sensitivity analysis. Results: After a 40-year simulation, the sc. SEMA, DULA, and e-r EXEN groups yielded 9.6315, 9.5968, and 9.5895 quality-adjusted life years (QALYs), respectively. In terms of expenditure, the total costs for the sc. SEMA, DULA, and e-r EXEN groups were $42012.47, $24931.27, and $40264.80, respectively. DULA was dominant over e-r EXEN due to the higher QALYs and lower total costs. The ICURs of sc. SEMA vs. DULA and sc. SEMA vs. e-r EXEN were $492994.72/QALY and $41622.69/QALY (ICUR > λ), respectively, indicating that sc. SEMA was not more cost-effective than DULA or e-r EXEN. The INMB and absolute NMB yielded the same conclusions which were robust to one-way, scenario, and probabilistic sensitivity analyses. After several assumptions in the binary search, sc. SEMA and e-r EXEN appear to become cost-effective when their annual costs are decreased by 57.67% and 70.34%, respectively, with DULA as a counterpart. Conclusion: From the cost-utility analysis, DULA appears to be the most cost-effective option among sc. SEMA, DULA, and e-r EXEN for the treatment of patients with T2D receiving metformin-based background therapy. With a 57.67% or 70.34% reduction in cost, sc. SEMA or e-r EXEN, respectively, would become as cost-effective as DULA in China.