Racial and social inequities in medication use: A review of articles responding to the Journal of Managed Care + Specialty Pharmacy's Call to Action.

This article provides a summary of Viewpoint and Research articles responding to the 2020 Journal of Managed Care + Specialty Pharmacy Call to Action to address racial and social inequities in medication use. We find great heterogeneity in terms of topic, clinical condition examined, and health disparity addressed. Common recommendations across Viewpoint articles include the need to increase racial and ethnic diversity in clinical trial participants, the need to address drug affordability and health insurance literacy, and the need to incentivize providers and plans to participate in diversity initiatives, such as the better capture of information on social determinants of health (SDOH) in claims data to be able to address SDOH needs. Across research articles, we also find a large range of approaches and study designs, spanning from randomized controlled trials to surveys to observational studies. These articles identify disparities in which minoritized beneficiaries are shown to be less likely to receive medications and vaccines, as well as less likely to be adherent to medications, across a variety of conditions. Finally, we discuss Healthy People 2030 as a potential framework for future health disparity researchers.

Comprehensive analysis of PSMG3 in pan-cancer and validation of its role in hepatocellular carcinoma.

BACKGROUND: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC). METHODS: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines. RESULTS: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells. CONCLUSION: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.

Examining Health Inequities in A1C Control over Time across Individual, Geospatial, and Geopolitical Factors among Adults with Type 2 Diabetes: Analyses of a Sample from One Commercial Insurer in a Southern State.

INTRODUCTION: Type 2 diabetes impacts millions and poor maintenance of diabetes can lead to preventable complications, which is why achieving and maintaining target A1C levels is critical. Thus, we aimed to examine inequities in A1C over time, place, and individual characteristics, given known inequities across these indicators and the need to provide continued surveillance. METHODS: Secondary de-identified data from medical claims from a single payer in Texas was merged with population health data. Generalized Estimating Equations were utilized to assess multiple years of data examining the likelihood of having non-target (>7% and ≥7%, two slightly different cut points based on different sources) and separately uncontrolled (>9%) A1C. Adults in Texas, with a Type 2 Diabetes (T2D) flag and with A1C reported in first quarter of the year using data from 2016 and 2019 were included in analyses. RESULTS: Approximately 50% had A1Cs within target ranges (<7% and ≤7%), with 50% considered having non-target (>7% and ≥7%) A1Cs; with 83% within the controlled ranges (≤9%) as compared to approximately 17% having uncontrolled (>9%) A1Cs. The likelihood of non-target A1C was higher among those individuals residing in rural (vs urban) areas (P < .0001); similar for the likelihood of reporting uncontrolled A1C, where those in rural areas were more likely to report uncontrolled A1C (P < .0001). In adjusted analysis, ACA enrollees in 2016 were approx. 5% more likely (OR = 1.049, 95% CI = 1.002-1.099) to have non-target A1C (≥7%) compared to 2019; in contrast non-ACA enrollees were approx. 4% more likely to have non-target A1C (≥7%) in 2019 compared to 2016 (OR = 1.039, 95% CI = 1.001-1.079). In adjusted analysis, ACA enrollees in 2016 were 9% more likely (OR = 1.093, 95% CI = 1.025-1.164) to have uncontrolled A1C compared to 2019; whereas there was no significant change among non-ACA enrollees. CONCLUSIONS: This study can inform health care interactions in diabetes care settings and help health policy makers explore strategies to reduce health inequities among patients with diabetes. Key partners should consider interventions to aid those enrolled in ACA plans, those in rural and border areas, and who may have coexisting health inequities.

Pharmacological Prescribing and Satisfaction with Pain Treatment Among Non-Hispanic Black Men with Chronic Pain.

Introduction: Pharmacological strategies are often central to chronic pain management; however, pain treatment among non-Hispanic Black men may differ because of their disease profiles and healthcare interactions. However, less is known about pain medication prescribing and patients' satisfaction with pain treatment and management among non-Hispanic Black men with self-reported chronic pain. Purpose: This study assessed factors associated with non-Hispanic Black men being prescribed/recommended narcotics/opioids for chronic pain and their satisfaction with pain treatment/management. Methods: Data were analyzed from 286 non-Hispanic Black men with chronic pain who completed an internet-delivered questionnaire. Participants were recruited nationwide using a Qualtrics web-based panel. Logistic regression was used to identify factors associated with being prescribed/recommended narcotics/opioids for pain management treatment. Then, ordinary least squares regression was used to identify factors associated with their satisfaction level with the pain treatment/management received. Results: On average, participants were 56.2 years old and 48.3% were prescribed/recommended narcotics/opioids for chronic pain. Men with more chronic conditions (Odds Ratio [OR] = 0.57, P = 0.043) and depression/anxiety disorders (OR = 0.53, P = 0.029) were less likely to be prescribed/recommended narcotics/opioids. Men who were more educated (OR = 2.09, P = 0.044), reported more frequent chronic pain (OR = 1.28, P = 0.007), and were allowed to participate more in decisions about their pain treatment/management (OR = 1.11, P = 0.029) were more likely to be prescribed/recommended narcotics/opioids. On average, men with more frequent chronic pain (B = -0.25, P = 0.015) and pain problems (B = -0.16, P = 0.009) were less satisfied with their pain treatment/management. Men who were allowed to participate more in decisions about their pain treatment/management reported higher satisfaction with their pain treatment/management (B = 0.55, P < 0.001). Conclusion: Playing an active role in pain management can improve non-Hispanic Black men's satisfaction with pain treatment/management. This study illustrates the importance of patient-centered approaches and inclusive patient-provider interactions to improve chronic pain management.

Dietary consumption trend and its correlation with global cancer burden: A quantitative and comprehensive analysis from 1990 to 2019.

OBJECTIVE: The aim of this study was to estimate the effect of dietary consumption on cancer burden and formulate an effective solution. METHODS: Dietary consumption, number of cancer deaths, disability-adjusted life years, and corresponding age-standardized rates were extracted from the Global Burden of Disease Study 2019. The annual percentage change was used to quantify the temporal trends in cancer burden and dietary consumption. Age, sex, location, and sociodemographic index were stratified to further analyze the discrepancy in cancer burden attributable to dietary intake. RESULTS: Five cancers (breast, colon and rectal, tracheal, bronchus and lung, esophageal, and stomach) were documented to be associated with dietary consumption in the Global Burden of Disease database. The age-standardized death rate and age-standardized disability-adjusted life years rate in 2019 were 7.56 and 1168.77 per 100 000 population, respectively. For most cancers, the age-standardized death rate and age-standardized disability-adjusted life years rate displayed a decreasing tendency, with annual percentage change varying from -3.60 to -0.29 and from -3.64 to -0.03 from 1990 to 2019, respectively. The age-standardized death rate and age-standardized standardized disability-adjusted life years rate were higher in men than in women (9.68 vs 5.79 and 213.16 vs 129.18, respectively). In addition, the diet-related cancer burden in higher sociodemographic index regions exceeded that in lower sociodemographic index regions. CONCLUSION: Dietary consumption has a considerable influence on cancer burden, among which colon and rectal cancer burden account for the largest proportion. Increasing the intake of whole grains, milk, fiber, calcium, vegetables, and fruits and reducing the consumption of processed meat and sodium are instrumental in lowering the disease burden of cancer. The quantitative analysis of dietary consumption would provide a more detailed reference for diet-related decision makers and raise awareness of healthy dietary habits in diet management departments, food production enterprises, and the general public.

Group-based trajectory analysis identifies varying diabetes-related cost trajectories among type 2 diabetes patients in Texas: an empirical study using commercial insurance.

BACKGROUND: The trend of Type 2 diabetes-related costs over 4 years could be classified into different groups. Patient demographics, clinical factors (e.g., A1C, short- and long-term complications), and rurality could be associated with different trends of cost. Study objectives are to: (1) understand the trajectories of cost in different groups; (2) investigate the relationship between cost and key factors in each cost trajectory group; and (3) assess significant factors associated with different cost trajectories. METHODS: Commercial claims data in Texas from 2016 to 2019 were provided by a large commercial insurer and were analyzed using group-based trajectory analysis, longitudinal analysis of cost, and logistic regression analyses of different trends of cost. RESULTS: Five groups of distinct trends of Type 2 diabetes-related cost were identified. Close to 20% of patients had an increasing cost trend over the 4 years. High A1C values, diabetes complications, and other comorbidities were significantly associated with higher Type 2 diabetes costs and higher chances of increasing trend over time. Rurality was significantly associated with higher chances of increasing trend over time. CONCLUSIONS: Group-based trajectory analysis revealed distinct patient groups with increased cost and stable cost at low, medium, and high levels in the 4-year period. The significant associations found between the trend of cost and A1C, complications, and rurality have important policy and program implications for potentially improving health outcomes and constraining healthcare costs.

Factors associated with higher hemoglobin A1c and type 2 diabetes-related costs: Secondary data analysis of adults 18 to 64 in Texas with commercial insurance.

OBJECTIVE: This study will identify factors associated with higher hemoglobin A1c (A1c) values and diabetes-related costs among commercially insured adults in Texas diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: This secondary data analysis was based on claims data from commercially insured individuals 18-64 years of age residing in Texas with diagnosed type 2 diabetes during the 2018-2019 study period. The final analysis sample after all the exclusions consisted of 34,992 individuals. Measures included hemoglobin A1c, diabetes-related costs, Charlson Comorbidity Index, diabetes-related complications, rurality and other socioeconomic characteristics. Longitudinal A1c measurements were modeled using age, sex, rurality, comorbidity, and diabetes-related complications in generalized linear longitudinal regression models adjusting the observation time, which was one of the 8 quarters in 2018 and 2019. The diabetes-related costs were similarly modeled in both univariable and multivariable generalized linear longitudinal regression models adjusting the observation time by calendar quarters and covariates. RESULTS: The median A1c value was 7, and the median quarterly diabetes-related cost was $120. A positive statistically significant relationship (p = < .0001) was found between A1c levels and diabetes-related costs, although this trend slowed down as A1c levels exceeded 8.0%. Higher A1c values were associated with being male, having diabetes-related complications, and living in rural areas. Higher costs were associated with higher A1c values, older age, and higher Charlson Comorbidity Index scores. CONCLUSION: The study adds updated analyses of the interrelationships among demographic and geographic factors, clinical indicators, and health-related costs, reinforcing the role of higher A1c values and complications as diabetes-related cost drivers.

The lead time and geographical variations of Baidu Search Index in the early warning of COVID-19.

Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of "COVID-19 epidemic", "Novel Coronavirus" and "COVID-19" can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0-28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5-8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1-3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70-0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase.

Factors Associated With In-Hospital Death Among Pneumonia Patients in US Hospitals From 2016~2019.

BACKGROUND: Pneumonia is one of the leading causes of hospital admission in the United States with a global health burden of about 6.8 million hospitalizations and 1.1 million deaths in patients over 65 years old in 2015. This study aimed to identify possible patient and hospital-related risk factors for in-hospital pneumonia death across US hospitals. METHODS: The National Inpatient Sample (NIS) was used to identify nationwide pneumonia patients (n=374 766, weighted n=1 873 828) from 2016 to 2019. We examined the characteristics of the study sample and their association with in-hospital death. Multivariate survey logistic regression models were used to identify risk factors. RESULTS: During the study periods, in-hospital death rates continuously decreased (2.45% in 2016 to 2.19% in 2019). Descriptive statistics showed that patient and hospital factors had varied in-hospital death rates. Survey logistic regression results suggested that male, very low income, non-Medicare, government hospitals, rural hospitals, and specific hospital regions were associated with higher in-hospital death rates than their reference groups. CONCLUSION: Socioeconomic factors, including income and insurance, are associated with pneumonia mortality. Census region, hospital ownership, and rural location are also related to in-hospital mortality. Such findings in underserved, impoverished, and rural areas to identify possible health disparities.

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations.

Randomized controlled trials are considered the 'gold standard' to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.

The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression.

The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes HDAC5/p16INK4a was studied in GC cells, and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP). Additionally, the role of the miR-4256/HDAC5/p16INK4a axis in GC was studied using in vitro and in vivo experiments. Finally, the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments. miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues; in vitro and in vivo results showed that miR-4256 promoted GC growth and progression. Mechanistically, miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells, and then restrained the expression of p16INK4a through the epigenetic modulation of HDAC5 at the p16INK4a promoter. Furthermore, miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells. Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16INK4a axis, which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.

Effectiveness of the Program to Encourage Active, Rewarding Lives (PEARLS) to reduce depression: a multi-state evaluation.

Introduction: An estimated 15% of community-dwelling older adults have depressive symptoms in the U.S. The Program to Encourage Active, Rewarding Lives (PEARLS) is an evidence-based program for managing late-life depression. PEARLS is a home/community-based collaborative care model delivered by community-based organizations to improve access to quality depression care. Trained staff actively screen for depression to improve recognition, teach problem-solving and activity planning skills for self-management, and connect participants to other supports and services as needed. Methods: This study examined 2015-2021 data from 1,155 PEARLS participants across four states to assess PEARLS effectiveness to reduce depressive symptoms. The clinical outcomes were measured by the self-reported PHQ-9 instrument to assess changes in depressive symptoms scored as depression-related severity, clinical remission, and clinical response. A generalized estimating equation (GEE) model was fitted to examine changes in composite PHQ-9 scores from baseline to the final session. The model adjusted for participants' age, gender, race/ethnicity, education level, income level, marital status, number of chronic conditions, and number of PEARLS sessions attended. Cox proportional hazards regression models were conducted to estimate the hazard ratio for improvement of depressive symptoms (i.e., remission or response), while adjusting for the covariates. Results: PHQ-9 scale scores significantly improved from baseline to their final sessions (mean difference = -5.67, SEM = 0.16, p < 0.001). About 35% of participants achieved remission with PHQ-9 score < 5. Compared to participants with mild depression, patients with moderate depression (HR = 0.43, 95%CI = 0.35-0.55), moderately severe depression (HR = 0.28, 95%CI = 0.21-0.38), and severe depression (HR = 0.22 95%CI = 0.14-0.34) were less likely to experience clinical remission with PHQ-9 score < 5, while adjusting for the covariates. About 73% achieved remission based on no longer having one or both cardinal symptoms. Compared to participants with mild depression, patients with moderate depression (HR = 0.66, 95%CI = 0.56-0.78), moderately severe depression (HR = 0.46, 95%CI = 0.38-0.56), and severe depression (HR = 0.38, 95%CI = 0.29-0.51) were less likely to experience clinical remission, while adjusting for the covariates. Nearly 49% of participants had a clinical response or a ≥ 50% decrease in PHQ-9 scores over time. There were no differences between the severity of depression groups based on the time to clinical response. Discussion: Findings confirm that PEARLS is an effective program to improve depressive symptoms among older adults in diverse real-world community settings and can be a more accessible option for depressive older adults who are traditionally underserved by clinical care.

Cyclocarya paliurus leaves extracts alleviate metabolic phenotypes in Chinese T2DM patients by modulating gut microbiota and metabolites: a clinical randomized controlled trial.

Objective: We aimed to investigate the effect of Cyclocarya paliurus leaves extracts (CP) on glucose and blood lipid metabolism and its relationship with intestinal flora in type 2 diabetes mellitus (T2DM) patients. Methods: In this open-label, 84-day randomized controlled trial, a total of 38 T2DM patients were randomly assigned to the CP group or the Glipizide group (G group) in a 2:1 ratio. T2DM-associated metabolic phenotypes, gut microbiota and metabolites including short-chain fatty acids (SCFAs) and bile acids (BAs) were detected. Results: At the end of intervention, CP, like Glipizide, significantly improved HbA1c level and other glucose metabolism parameters (fasting plasma glucose (FBG), 2-hour post-meal blood glucose (2hPBG), the area under curve of oral glucose tolerance test glucose (OGTT glucose AUC)). Moreover, CP also resulted in the significant improvement in the levels of blood lipid and blood pressure. Notably, the improvement in blood lipid(triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c)) and blood pressure (diastolic blood pressure (DBP)) was significantly greater in the CP group compared with the G group. Furthermore, the liver and kidney function parameters did not significantly change in both CP group and the G group over the 84-day period. Additionally, the enrichment of potentially beneficial bacteria (Faecalibacterium and Akkermansia), SCFAs and unconjugated BAs and the depletion of potential pathogenic bacteria (Prevotella_9) and conjugated BAs were observed in the CP group, while the abundances of the gut microbial were kept stable in the G group after intervention. Conclusion: CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than glipizide by regulating gut microbiota and metabolites in T2DM patients, with no significant effects on liver and kidney function.

Efficacy and safety of vedolizumab in the treatment of patients with inflammatory bowel disease: A systematic review and meta­analysis of randomized controlled trials.

Few studies have thoroughly assessed the efficacy and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD). Therefore, this systematic review and meta-analysis was performed to further evaluate this association. PubMed, Embase, and the Cochrane databases were searched until April 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of VDZ in the treatment of IBD were included. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome using a random effects model. A total of 12 RCTs, including 4,865 patients, met the inclusion criteria. In the induction phase, VDZ was more effective than placebo for patients with ulcerative colitis and Crohn's disease (CD) in clinical remission (RR=2.09; 95% CI=1.66-2.62) and clinical response (RR=1.54; 95% CI=1.34-1.78). In the maintenance therapy group, VDZ reached higher clinical remission (RR=1.98; 95% CI=1.58-2.49) and clinical response (RR=1.78; 95% CI=1.40-2.26) rates compared with the placebo group. VDZ particularly improved clinical remission (RR=2.07; 95% CI=1.48-2.89) and clinical response (RR=1.84; 95% CI=1.54-2.21) in patients with TNF antagonist failure. In terms of corticosteroid-free remission, VDZ was also more effective than placebo in patients with IBD (RR=1.98; 95% CI=1.51-2.59). In Crohn's patients, VDZ was more effective than placebo in terms of mucosal healing (RR=1.78; 95% CI=1.27-2.51). With respect to adverse events, VDZ significantly reduced the risk of IBD exacerbation compared with the placebo (RR=0.60; 95% CI=0.39-0.93; P=0.023). However, when compared with the placebo, VDZ increased the risk of nasopharyngitis in patients with CD (RR=1.77; 95% CI=1.01-3.10; P=0.045). No significant differences in other adverse events were observed. Although there might be underlying risk, such as selection bias, in the present study it can be safely concluded that VDZ is a safe and effective biological agent for IBD, particularly for patients with TNF antagonist failure.

Identification of Cuproptosis-Related Genes in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, the precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) is found. However, the relationship between NAFLD and cuproptosis remains unclear. We analyzed three public datasets (GSE89632, GSE130970, and GSE135251) to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed a series of bioinformatics analyses to explore the relationship between NAFLD and cuproptosis-related genes. Finally, 6 high-fat diet- (HFD-) induced NAFLD C57BL/6J mouse models were established to carry out transcriptome analysis. The results of gene set variation analysis (GSVA) revealed that the cuproptosis pathway was abnormally activated to a certain degree (p = 0.035 in GSE89632, p = 0.016 in GSE130970, p = 0.22 in GSE135251), and the principal component analysis (PCA) of the cuproptosis-related genes showed that the NAFLD group separated from the control group, with the first two principal components accounting for 58.63%-74.88% of the variation. Among three datasets, two cuproptosis-related genes (DLD and PDHB, p < 0.01 or 0.001) were stably upregulated in NAFLD. Additionally, both DLD (AUC = 0.786-0.856) and PDHB (AUC = 0.771-0.836) had favorable diagnostic properties, and the multivariate logistics regression model further improved the diagnostic properties (AUC = 0.839-0.889). NADH, flavin adenine dinucleotide, and glycine targeted DLD, and pyruvic acid and NADH targeted PDHB in the DrugBank database. The DLD and PDHB were also associated with clinical pathology, especially with steatosis (DLD, p = 0.0013-0.025; PDHB, p = 0.002-0.0026) and NAFLD activity score (DLD, p = 0.004-0.02; PDHB, p = 0.003-0.031). What is more, DLD and PDHB were correlated with stromal score (DLD, R = 0.38, p < 0.001; PDHB, R = 0.31, p < 0.001) and immune score (DLD, R = 0.26, p < 0.001; PDHB, R = 0.27, p < 0.001) in NAFLD. Furthermore, Dld and Pdhb were also significantly upregulated in the NAFLD mouse model. In conclusion, cuproptosis pathways, especially DLD and PDHB, could be potential candidate genes for NAFLD diagnostic and therapeutic options.

Disease burden of prostate cancer from 2014 to 2019 in the United States: estimation from the Global Burden of Disease Study 2019 and Medical Expenditure Panel Survey.

OBJECTIVES: The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS: The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS: For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS: From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics.

Avelumab Maintenance Treatment After First-line Chemotherapy in Advanced Urothelial Carcinoma-A Cost-Effectiveness Analysis.

BACKGROUND: Recently, a clinical trial (NCT02603432) showed that avelumab maintenance treatment, post first-line chemotherapy, can significantly prolong the overall survival of patients with advanced urothelial carcinoma (UC), however, the treatment was very expensive. This study aimed to determine the cost-effectiveness of avelumab maintenance therapy in advanced or metastatic UC from the US taxpayer perspective. METHODS: Based on the data of the JAVELIN Bladder 100 clinical trial (NCT02603432), a Markov multi-state model was constructed to investigate the costs and clinical outcomes of avelumab maintenance after platinum-based chemotherapy versus best supportive care (BSC) for advanced or metastatic UC. Parameters of the model came from the 2020 Average Sales Price Drug Pricing Files and published literature. The main outputs were costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Robustness was tested by deterministic and probabilistic sensitivity analyses. The analysis was stratified to include both the overall population and a subset of programmed death-ligand 1 (PD-L1)-positive patients. RESULTS: Avelumab maintenance therapy was estimated to generate an additional 0.26 QALYs (1.46 vs. 1.20 QALYs) and costs $183,271 ($278,323 vs. $95,052) more compared to BSC alone in the overall population, yielding an ICER of $699,065/QALY. For the PD-L1-positive population, avelumab produced a 0.42 increase in QALYs (1.74 vs. 1.32 QALYs) and raised costs to $223,238 ($320,355 vs. $97,117), resulting in an ICER of $521,850/QALY for this population. Both ICERs were above the willingness-to-pay (WTP) threshold of $200,000/QALY. Sensitivity analyses manifested that the model was robust. CONCLUSION: From the perspective of the US taxpayer, avelumab maintenance therapy is considered cost-ineffective for patients with advanced or metastatic UC at a WTP threshold of $200,000/QALY in the overall population as well as in PD-L1-positive population.

Physicians' interest in different strategies for supporting pain -management and opioid prescribing: A cross-sectional study.

OBJECTIVE: The purpose of this study was to explore physicians' attitudes toward different strategies for supporting pain management and opioid prescribing and to identify factors related to their attitudes toward the support strategies. Design/setting/participants/measures: This preliminary cross-sectional study collected and analyzed online survey responses from physicians in Texas and Minnesota (N = 69) between December 2017 and February 2018. Primary outcomes were physicians' interest in online continuing medical education (CME), mHealth patient monitoring system, and short, non-CME YouTube informational briefs about pain management and opioid prescribing. Multiple logistic regression models were used to examine the associations between physicians' characteristics, attitudes, training, experience, practice setting, and their interest in three different support strategies. RESULTS: About 51-58 percent of physicians indicated moderate-to-extreme interest in online CME (54 percent), mHealth monitoring (58 percent), and short, non-CME YouTube informational briefs (51 percent). Physicians, who practiced in a medium or large practice setting, were less likely to be interested in online CME or short, non-CME YouTube informational briefs. Physicians who prescribed a small number of Schedule II opioids were more likely to be interested in short, non-CME YouTube informational briefs and mHealth monitoring. CONCLUSIONS: Findings suggest that physicians may have different preferences in strategies for supporting their pain management and opioid prescribing practices. Future studies are needed to better understand the mechanisms underlying physicians' interest in different support strategies.

High Prevalence of Hyperuricemia and Associated Factors among Zhuang Adults: A Cross-Sectional Study Based on the Ethnic Minority Population Cohort in the Southwestern China.

The highest prevalence of hyperuricemia was found in Zhuang minority adults in two national surveys in China, with only 1% Zhuang study subjects. However, the prevalence of hyperuricemia and the associated factors in Zhuang adults have not been well-addressed. A cross-sectional study was conducted to explore the prevalence of hyperuricemia and the common comorbidities, and the associated factors in Zhuang adults based on the Guangxi Ethnic Minority Population Cohort. Among 11,175 Zhuang adults aged 35-74 years, the age- and sex-standardized prevalence rate was 18.1% for hyperuricemia and 1.1% for gout. The standardized prevalence rate and awareness rate were 31.6% and 32.3%, respectively, for hypertension, and were 5.1% and 48.2%, respectively, for diabetes. High education level, history of coronary heart disease (CHD), hypertension, being a current drinker, high body mass index (BMI), central obesity, hyper-triglyceride (hyper-TG), hyper-total cholesterol (hyper-TC), hypo-high density lipoprotein cholesterol (hypo-HDL-C), and abnormal aspartate aminotransferase (AST) were risk factors, while smoking and diabetes were protective factors of hyperuricemia in males. Older age, being single/divorced, having a high education level, hypertension, drinking tea, high BMI, central obesity, hyper-TG, hyper-TC, hypo-HDL-C, and abnormal alanine aminotransferase (ALT) were risk factors in females. The high prevalence of hyperuricemia but low prevalence of gout and common comorbidities in Zhuang adults may be due to a lag effect of lifestyle changes. Health education and health management should be strengthened to prevent the progression of comorbidities, considering the lag effect and low awareness rate.