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Jie-Ying Wan, Li-Zhen Yang Division of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Li-Zhen Yang, Tel +86-15618690375, Email dryanginsh@sina.comPurpose: The correlation between liver enzymes and blood glucose in diabetes mellitus remains unclear. The purpose of present three-year retrospective study was to explore the association between liver enzymes and glycemia in type 2 diabetes mellitus (T2DM).Patients and Methods: 2046 participants (non-fatty liver, n=1253; fatty liver, n=793) with T2DM were included in our study. For all these patients, related basic clinical information, biochemical parameters and liver ultrasonic data were collected. The effects of liver enzymes on blood glucose levels were analysed by linear and binary logistic regression models.Results: In the comparative analyses between groups, gamma-glutamyltransferase (GGT) and serum alkaline phosphatase (AKP) levels increased with glycosylated haemoglobin A1c (HbA1c) concentration, but alanine aminotransferase and aspartate aminotransferase did not show the same trend. Adjusted for possible confounding factors, the linear regression models indicated the strong positive correlations between Log10 AKP, Log10 GGT and three blood glucose parameters (fasting glucose, postprandial glucose, and HbA1c) (all P< 0.01). And such correlations were more significant in the subgroups of fatty liver. Multivariate binary logistic regression showed that the ORs increased by 1.01 times higher per Log10 AKP unit in the highest blood glucose tertile (P< 0.01).Conclusion: GGT and especially AKP can aggravate hyperglycemia in T2DM patients, which provides new clues for the research and treatment of T2DM.Keywords: liver enzymes, fasting blood glucose, postprandial blood glucose, HbA1c, T2DM

OBJECTIVES: This study described the prevalence and characteristics of financial difficulty acquiring food and its relation to nutritional biomarkers in older disabled women. METHODS: Baseline data were analyzed from the Women's Health and Aging Study, a population-based survey of 1002 community-dwelling, disabled women 65 years and older from Baltimore, Md. RESULTS: Minority women (49.5%) were more likely than White women (13.4%) to report financial difficulty acquiring food (odds ratio [OR] = 6.2, 95% confidence interval [CI] = 4.5, 8.6). Of the women reporting financial difficulty acquiring food, only 19.3% received food stamps and fewer than 7% participated in food assistance programs. Women reporting financial difficulty acquiring food had higher levels of psychologic depression than women not reporting such difficulty. Greater likelihood of financial difficulty acquiring food was associated with poorer quality of life and physical performance among White women and with more medical conditions among minority women. Finally, anemia (hemoglobin < 120 g/L) was associated with financial difficulty acquiring food (age-adjusted OR = 2.9, 95% CI = 1.9, 4.3). CONCLUSIONS: Financial difficulty acquiring food was common, and receipt of nutritional services was rare, in community-dwelling, older disabled women. Nutrition assistance programs for the elderly should reexamine their effectiveness in preventing nutritional deficits in older disabled women. [ABSTRACT FROM AUTHOR]

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPs FMT ) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R -/- ) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microlens arrays (MLAs) with a tunable imaging ability are core components of advanced micro-optical systems. Nevertheless, tunable MLAs generally suffer from high power consumption, an undeformable rigid body, large and complex systems, or limited focal length tunability. The combination of reconfigurable smart materials with MLAs may lead to distinct advantages including programmable deformation, remote manipulation, and multimodal tunability. However, unlike photopolymers that permit flexible structuring, the fabrication of tunable MLAs and compound eyes (CEs) based on transparent smart materials is still rare. In this work, we report reconfigurable MLAs that enable tunable imaging based on shape memory polymers (SMPs). The smart MLAs with closely packed 200 × 200 microlenses (40.0 μm in size) are fabricated via a combined technology that involves wet etching-assisted femtosecond laser direct writing of MLA templates on quartz, soft lithography for MLA duplication using SMPs, and the mechanical heat setting for programmable reconfiguration. By stretching or squeezing the shape memory MLAs at the transition temperature (80 °C), the size, profiles, and spatial distributions of the microlenses can be programmed. When the MLA is stretched from 0 to 120% (area ratio), the focal length is increased from 116 to 283 μm. As a proof of concept, reconfigurable MLAs and a 3D CE with a tunable field of view (FOV, 160-0°) have been demonstrated in which the thermally triggered shape memory deformation has been employed for tunable imaging. The reconfigurable MLAs and CEs with a tunable focal length and adjustable FOV may hold great promise for developing smart micro-optical systems.

Background: Evidence is sparse on the effects of Medicare medication therapy management (MTM) on racial/ethnic disparities in medication adherence among patients with Alzheimer's disease and related dementias., Objectives: This study examined the Medicare MTM program's effects on racial/ethnic disparities in the adherence to antidementia medications among patients with Alzheimer's disease and related dementias., Methods: This is a retrospective analysis of 100% of 2010-2017 Medicare Parts A, B, and D data linked to Area Health Resources Files. The study outcome was nonadherence to antidementia medications, and intervention was defined as new MTM enrollment in 2017. Propensity score matching was conducted to create intervention and comparison groups with comparable characteristics. A difference-in-differences model was employed with logistic regression, including interaction terms of dummy variables for the intervention group and racial/ethnic minorities., Results: Unadjusted comparisons revealed that Black, Hispanic, and Asian/Pacific Islander patients were more likely to be nonadherent than non-Hispanic White (White) patients in 2016. Differences in odds of nonadherence between Black and White patients among the intervention group were lower in 2017 than in 2016 by 27% (odds ratios [OR]: 0.73, 95% confidence interval [CI]: 0.65-0.82). A similar lowering was seen between Hispanic and White patients by 26% (OR: 0.74, 95% CI: 0.63-0.87). MTM enrollment was associated with reduced disparities in nonadherence for Black-White patients of 33% (OR: 0.67, 95% CI: 0.57-0.78) and Hispanic-White patients of 19% (OR: 0.81, 95% CI: 0.67-0.99)., Discussion: The Medicare MTM program was associated with lower disparities in adherence to antidementia medications between Black and White patients, and between Hispanic and White patients in the population with Alzheimer's disease and related dementias., Conclusions: Expanding the MTM program may particularly benefit racial/ethnic minorities in Alzheimer's disease and related dementia care., Competing Interests: The authors list the following conflicts of interest: Xiaobei Dong, Chi Chun Steve Tsang, Jim Y. Wan, Christopher K. Finch, Jack W. Tsao, Jamie A. Browning, Joseph Garuccio, Rose Zeng: None; Marie A. Chisholm-Burns: Received funding from Carlos and Marguerite Mason Trust; Junling Wang: Received funding from AbbVie, Curo, Bristol Myers Squibb, Pfizer, and Pharmaceutical Research and Manufacturers of America (PhRMA), and serves on the Health Outcomes Research Advisor Committee of the PhRMA Foundation., (© 2024 The Authors. Published by Elsevier Inc.)

Objective: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes., Design: Systematic review and network meta-analysis., Data Sources: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023., Eligibility Criteria for Selecting Studies: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible., Results: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A 1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A 1c concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration., Conclusions: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A 1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events., Systematic Review Registration: PROSPERO CRD42022342845., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, and Beijing University of Chinese Medicine High-level Talent Start-up Research Project; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g) -1 ·min -1 ; ci1 group: (181.7±29.3) ml·(100 g) -1 ·min -1 ; ci2 group: (158.8±39.2) ml·(100 g) -1 ·min -1 ; ci3 group: (123.1±27.2) ml·(100 g) -1 ·min -1 ; F =14.02, P <0.001]. The renal cortical RBF was moderately negatively correlated with the ci score ( r =-0.644, P <0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95% CI : 0.772-0.950) and 0.680 (95% CI : 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein ( P =0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95% CI : 0.673-0.889) and 0.900 (95% CI : 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

Objective: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups., Methods: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA., Results: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals., Conclusions: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Literature on 30-day readmission in adults with sickle cell disease (SCD) is limited. This study examined the overall and age-stratified rates, risk factors, and healthcare resource utilization associated with 30-day readmission in this population., Methods: Using the Nationwide Readmissions Database, a retrospective cohort study was conducted to identify adult patients (aged ≥ 18) with SCD in 2016. Patients were stratified by age and followed for 30 days to assess readmission following an index discharge. The primary outcome was 30-day unplanned all-cause readmission. Secondary outcomes included index hospitalization costs and readmission outcomes (e.g., time to readmission, readmission costs, and readmission lengths of stay). Separate generalized linear mixed models estimated the adjusted odds ratios (aORs) for associations of readmission with patient and hospital characteristics, overall and by age., Results: Of 15,167 adults with SCD, 2,863 (18.9%) experienced readmission. Both the rates and odds of readmission decreased with increasing age. The SCD complications vaso-occlusive crisis and end-stage renal disease (ESRD) were significantly associated with increased likelihood of readmission (p < 0.05). Age-stratified analyses demonstrated that diagnosis of depression significantly increased risk of readmission among patients aged 18-to-29 years (aOR = 1.537, 95%CI: 1.215-1.945) but not among patients of other ages. All secondary outcomes significantly differed by age (p < 0.05)., Conclusion: This study demonstrates that patients with SCD are at very high risk of 30-day readmission and that younger adults and those with vaso-occlusive crisis and ESRD are among those at highest risk. Multifaceted, age-specific interventions targeting individuals with SCD on disease management are needed to prevent readmissions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Medicare Part D Star Ratings are instrumental in shaping healthcare quality improvement efforts. However, the calculation metrics for medication performance measures for this program have been associated with racial/ethnic disparities. In this study, we aimed to explore whether an alternative program, named Star Plus by us that included all medication performance measures developed by Pharmacy Quality Alliance and applicable to our study population, would reduce such disparities among Medicare beneficiaries with diabetes, hypertension, and/or hyperlipidemia., Method: We conducted an analysis of a 10% random sample of Medicare A/B/D claims linked to the Area Health Resources File. Multivariate logistic regressions with minority dummy variables were used to examine racial/ethnic disparities in measure calculations of Star Ratings and Star Plus, respectively., Results: Adjusted results indicated that relative to non-Hispanic Whites (Whites), racial/ethnic minorities had significantly lower odds of being included in the Star Ratings measure calculations: the odds ratios (ORs) for Blacks, Hispanics, Asians, and Others were 0.68 (95% confidence interval [CI] = 0.66-0.71), 0.73 (CI = 0.69-0.78), 0.88 (CI = 0.82-0.93), and 0.92 (CI = 0.88-0.97), respectively. In contrast, every beneficiary in the sample was included in Star Plus. Further, racial/ethnic minorities had significantly higher increase in the odds of being included in measure calculation in Star Plus than Star Ratings. The ORs for Blacks, Hispanics, Asians, and Others were 1.47 (CI = 1.41-1.52), 1.37 (CI = 1.29-1.45), 1.14 (CI = 1.07-1.22), and 1.09 (CI = 1.03-1.14), respectively., Conclusions: Our study demonstrated that racial/ethnic disparities may be eliminated by including additional medication performance measures to Star Ratings.

Purpose: To determine how telehealth has influenced outcomes in high-risk obstetrics patients during the Coronavirus disease 2019 (COVID-19) pandemic., Methods: A retrospective chart review was conducted to identify patterns in both telehealth and in-person clinic visits among patients of a Maternal Fetal Medicine (MFM) department from the onset of the COVID-19 pandemic from March 2020 until October 2021. For the descriptive analysis, p -values were calculated using Wilcoxon rank sum for continuous variables and chi-square or Fisher exact (where cell n  < 5) for categorical variables. Variables of interest were then tested for their univariate association with telehealth utilization using logistic regression. Variables found to meet the criterion of p  < 0.2 in the univariate case were introduced into a multivariable logistic model with a backward elimination for determining variable retention. We aimed to analyze whether telehealth visits significantly impacted pregnancy outcomes., Results: Four hundred nineteen high-risk patients visited the clinic via in-person and/or telehealth appointments during the study period: 320 patients without telehealth visits and 99 patients with telehealth visits. Care provided by telehealth visits was not found to be related to self-reported race ( p  = 0.81), maternal body mass index ( p  = 1.0), or maternal age ( p  = 0.53). Patients with private insurance were more likely to have telehealth visits than patients with public insurance (79.9% vs. 65.5%, p  < 0.01). In univariate logistic analyses, patients with diagnoses of anxiety ( p  < 0.01), asthma ( p  = 0.03), and depression ( p  < 0.01), at the time care was established, were more likely to have telehealth visits. Those patients with telehealth visits did not have any statistical differences in mode of delivery ( p  = 0.2) or pregnancy outcomes ( p  = 0.12), including fetal demise, preterm delivery, or delivery at term as compared with patients with all in-office visits. In multivariable analysis, patient conditions of anxiety ( p  < 0.01), maternal obesity ( p  < 0.01), and twin pregnancy ( p  = 0.04) were associated with higher rates of telehealth visits., Conclusion: Patients with certain pregnancy complications elected to have more telehealth visits. Patients with private insurance were more likely to have telehealth visits than patients with public insurance. There are benefits for patients with certain pregnancy complications to incorporate telehealth visits in addition to regularly scheduled in-person clinic visits and may be suitable in a post-pandemic setting as well. Further research in this field is needed to better understand the impact of implementing telehealth in high-risk obstetrics patients., Competing Interests: No competing financial interests exist., (© Margie A. Rayford et al., 2023; Published by Mary Ann Liebert, Inc.)

The Medicare Parts C and D Star Ratings system was established to improve care quality in Medicare. Previous studies reported racial/ethnic disparities in the calculation of medication adherence measures of Star Ratings in patients with diabetes, hypertension, and hyperlipidemia. This study aimed to identify possible racial/ethnic disparities in the calculation of adherence measures of Medicare Part D Star Ratings among patients with Alzheimer's disease and related dementias (ADRD) and diabetes, hypertension, or hyperlipidemia. This retrospective study analyzed the 2017 Medicare data and Area Health Resources Files. Non-Hispanic White (White) patients were compared to Black, Hispanic, Asian/Pacific Islander (Asian), and other patients on their likelihood of being included in the calculation of adherence measures for diabetes, hypertension, and/or hyperlipidemia. To adjust for the individual/community characteristics, logistic regression was used when the outcome is the inclusion in the calculation of one adherence measure; multinomial regression was used when examining the inclusion in the calculation of multiple adherence measures. Analyzing the data of 1438,076 Medicare beneficiaries with ADRD, this study found that Black (adjusted odds ratio, or OR = 0.79, 95% confidence interval, or 95% CI = 0.73-0.84) and Hispanic (OR = 0.82, 95% CI = 0.75-0.89) patients were less likely than White patients to be included in the calculation of adherence measure for diabetes medications. Further, Black patients were less likely to be included in the calculation of the adherence measure for hypertension medications than White patients (OR = 0.81, 95% CI = 0.78-0.84). All minorities were less likely to be included in calculating the adherence measure for hyperlipidemia medications than Whites. The ORs for Black, Hispanic, and Asian patients were 0.57 (95% CI = 0.55-0.58), 0.69 (95% CI = 0.64-0.74), and 0.83 (95% CI = 0.76-0.91), respectively. Minority patients were generally likely to be included in the measure calculation of fewer measures than White patients. Racial/ethnic disparities were observed in the calculation of Star Ratings measures among patients with ADRD and diabetes, hypertension, and/or hyperlipidemia. Future studies should explore possible causes of and solutions to these disparities., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Equity and effectiveness of the medication therapy management (MTM) program in Medicare has been a policy focus since its inception. The objective of this study was to evaluate the cost-effectiveness of the Medicare MTM program in improving medication utilization quality across racial and ethnic groups., Methods: This study analyzed 2017 Medicare data linked to the Area Health Recourses File. A propensity score was used to match MTM enrollees and nonenrollees, and an incremental cost-effectiveness ratio between the 2 groups was calculated. Effectiveness was measured as the proportion of appropriate medication utilization based on medication utilization measures developed by Pharmacy Quality Alliance. Net monetary benefits were compared across racial and ethnic groups at various societal willingness-to-pay (WTP) thresholds. The 95% confidence intervals were obtained by nonparametric bootstrapping., Results: MTM dominated non-MTM among the total sample (N = 699 992), as MTM enrollees had lower healthcare costs ($31 135.89 vs $32 696.69) and higher proportions of appropriate medication utilization (87.47% vs 85.31%) than nonenrollees. MTM enrollees had both lower medication costs ($10 681.21 vs $11 003.08) and medical costs ($20 454.68 vs $21 693.61) compared with nonenrollees. The cost-effectiveness of MTM was higher among Black patients than White patients across the WTP thresholds. For instance, at a WTP of $3006 per percentage point increase in effectiveness, the net monetary benefit for Black patients was greater than White patients by $2334.57 (95% confidence interval $1606.53-$3028.85)., Conclusions: MTM is cost-effective in improving medication utilization quality among Medicare beneficiaries and can potentially reduce disparities between Black and White patients. Expansion of the current MTM program could maximize these benefits., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Racial/ethnic disparities have been found in prior literature examining enrolment in Medicare medication therapy management programs. However, those studies were based on various eligibility scenarios because enrolment data were unavailable. This study tested for potential disparities in enrolment using actual MTM enrolment data., Methods: Medicare Parts A&B claims, Medication Therapy Management Data Files, and the Area Health Resources File from 2013 to 2014 and 2016 to 2017 were analysed in this retrospective analysis. An adjusted logistic regression compared odds of enrolment between racial/ethnic minorities and non-Hispanic Whites (Whites) in the total sample and subpopulations with diabetes, hypertension, or hyperlipidaemia. Trends in disparities were analysed by including interaction terms in regressions between dummy variables for race/ethnic minority groups and period 2016-2017., Key Findings: Disparities in MTM enrolment were detected between Blacks and Whites with diabetes in 2013-2014 (Odds Ratio = 0.78, 95% Confidence Interval = 0.75-0.81). This disparity improved from 2013-2014 to 2016-2017 for Blacks (Odds Ratio=1.08, 95% Confidence Interval = 1.04-1.11) but persisted in 2016-2017 (Odds Ratio = 0.84, 95% Confidence Interval = 0.81-0.87). A disparity was identified between Blacks and Whites with hypertension in 2013-2014 (Odds Ratio = 0.92, 95% Confidence Interval = 0.89-0.95) but not in 2016-2017. Enrolment for all groups, however, declined between periods. For example, in the total sample, the odds of enrolment declined from 2013-2014 to 2016-2017 by 22% (Odds Ratio=0.78, 95% Confidence Interval=0.75-0.81)., Conclusions: Racial disparities in MTM enrolment were found between Blacks and Whites among Medicare beneficiaries with diabetes in both periods and among individuals with hypertension in 2013-2014. As overall enrolment fell between periods, concerns about program enrolment remain., Competing Interests: Joseph Garuccio: None. Chi Chun Steve Tsang: None. Jim Y. Wan: None. Ya Chen Tina Shih: Received consulting fees, travel, and accommodations for serving on a grants review panel for Pfizer Inc and an advisory board for AstraZeneca in 2019. Marie A. Chisholm-Burns: Received funding from Carlos and Marguerite Mason Trust. Samuel Dagogo-Jack: Led clinical trials for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk, Inc., received consulting fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck & Co. Inc., and Sanofi, and has equity interests in Jana Care, Inc. and Aerami Therapeutics. William C. Cushman: Received grant funding from Eli Lilly. Xiaobei Dong: None. Jamie Browning: None. Rose Zeng: None. Junling Wang: Received funding from AbbVie, Curo, Bristol Myers Squibb, Pfizer, and Pharmaceutical Research and Manufacturers of America (PhRMA), and serves on the Heath Outcomes Research Advisor Committee of the PhRMA Foundation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Medicare Part D medication therapy management (MTM) program has positive effects on medication and health service utilization. However, little is known about its utilization, much less so about the use among racial and ethnic minorities., Objective: To examine MTM service utilization among older Medicare beneficiaries and to identify any racial and ethnic disparity patterns., Methods: A retrospective cross-sectional analysis of 2017 Medicare administrative data, linked to the Area Health Resources Files. Fourteen outcomes related to MTM service nature, initiation, quantity, and delivery were examined using logistic, negative binomial, and Cox proportional hazards regression models., Results: Racial and ethnic disparities were found with varying patterns across outcomes. For example, compared with White patients, the odds of opting out of MTM were 8% higher for Black patients (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.03-1.14), 57% higher for Hispanic patients (OR = 1.57, 95% CI = 1.42-1.72), and 57% higher for Asian patients (OR = 1.57, 95% CI = 1.33-1.85). The odds of continuing MTM from the previous years were 12% lower for Black patients (OR = 0.88, 95% CI = 0.86-0.90) and 3% lower for other patients (OR = 0.97, 95% CI = 0.95-0.99). In addition, the probability of being offered a comprehensive medication review (CMR) after MTM enrollment was 9% lower for Hispanic patients (hazard ratio [HR] = 0.91, 95% CI = 0.85-0.97), 9% lower for Asian patients (HR = 0.91, 95% CI = 0.87-0.94), and 3% lower for other patients (HR = 0.97, 95% CI = 0.95-0.99). Hispanic and Asian patients were more likely to have someone other than themselves receive a CMR., Conclusions: Racial and ethnic disparities in MTM service utilization were identified. Although the disparities in specific utilization outcomes vary across racial/ethnic groups, it is evident that these disparities exist and may result in vulnerable communities not fully benefiting from the MTM services. Causes of the disparities should be explored to inform future reform of the Medicare Part D MTM program., Competing Interests: Xiaobei Dong: None. Chi Chun Steve Tsang: None. Jamie A. Browning: None. Joseph Garuccio: None. Jim Y. Wan: None. Ya Chen Tina Shih: None. Marie A. Chisholm-Burns: Received funding from Carlos and Marguerite Mason Trust. Samuel Dagogo-Jack: Led clinical trials for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk, Inc., received consulting fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck & Co. Inc., and Sanofi, and has equity interests in Jana Care, Inc. and Aerami Therapeutics. William C. Cushman: Received grant funding from Eli Lilly. Junling Wang: Received funding from AbbVie, Curo, Bristol Myers Squibb, Pfizer, and Pharmaceutical Research and Manufacturers of America (PhRMA), and serves on Heath Outcomes Research Advisor Committee of the PhRMA Foundation., (© 2023 The Authors.)

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia - Shigella , which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.

This study aimed to determine intra-observer and inter-observer reliability of the Mayo Elbow Performance Score (MEPS). Patients undergoing elbow surgery completed a MEPS questionnaire initially and another 2-3 weeks later. During the second interview, patients completed the Oxford Elbow Score (OES) for comparison. Intraclass correlation coefficients (ICC) and Pearson correlation coefficients (PCC) > 0.80 indicated substantial agreement. In 42 patients who had elbow surgery, the average MEPS score initially was 78 (range, 5-100, SD 22.4) and 77 (range, 5-100, SD 21.5) at second interview. The average normalized OES score was 79 (range, 17-100, SD 23.6). The ICC for MEPS scores at the two time points was 0.90, and the PCC between the MEPS and OES scores was 0.87, indicating substantial agreement. The MEPS has strong intra-observer reliability at different time points and strong inter-observer reliability when compared with the OES, validating the MEPS as an outcome measure of elbow surgery. (Journal of Surgical Orthopaedic Advances 31(4):229-232, 2022).

Ethnopharmacological Relevance: Essential oils (EO) are volatile compounds obtained from different parts of natural plants, and have been used in national, traditional and folk medicine to treat various health problems all over the world. Records indicate that in history, herbal medicines rich in EO have been widely used for the treatment of CVDs in many countries, such as China., Aim of the Study: This review focused on the traditional application and modern pharmacological mechanisms of herbal medicine EO against CVDs in preclinical and clinical trials through multi-targets synergy. Besides, the EO and anti-CVDs drugs were compared, and the broad application of EO was explained from the properties of drugs and aromatic administration routes., Materials and Methods: Information about EO and CVDs was collected from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The obtained data sets were sequentially arranged for better understanding of EO' potential., Results: The study showed that EO had significant application in CVDs at different countries or regions since ancient times. Aiming at the complex pathological mechanisms of CVDs, including intracellular calcium overload, oxidative stress, inflammation, vascular endothelial cell injury and dysfunction and dyslipidemia, we summarized the roles of EO on CVDs in preclinical and clinical through multi-targets intervention. Besides, EO had the dual properties of drug and excipients. And aromatherapy was one of the complementary therapies to improve CVDs., Conclusions: This paper reviewed the EO on traditional treatment, preclinical mechanism and clinical application of CVDs. As important sources of traditional medicines, EO' remarkable efficacy had been confirmed in comprehensive literature reports, which showed that EO had great medicinal potential., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Previous analysis of policy scenarios reported potential disparities in eligibility in the Medicare Medication Therapy Management (MTM) program. With recently released MTM data, this study aimed to determine if racial/ethnic disparities exist in MTM enrollment among Medicare beneficiaries with Alzheimer's disease and related dementias (ADRD)., Methods: Medicare claims/records (from 2013-2014 and 2016-2017) linked to the Area Health Resources File were examined. Included individuals were patients with ADRD and diabetes, hypertension or hyperlipidemia. The proportions of MTM enrollment were compared between non-Hispanic White (White) patients and racial/ethnic minority groups in descriptive analysis. Racial/ethnic disparities were then examined using a logistic regression adjusting for patient and community characteristics. Disparities across study periods were compared by estimating a logistic regression model with interaction terms between dummy variables for each racial/ethnic minority group and 2016-2017., Results: In unadjusted analyses, minorities had higher enrollment proportions than Whites. In 2016-2017, for example, enrollment percentages for Whites, Blacks, Hispanics, Asian/Pacific Islanders (Asians) and Others were respectively 14.44%, 16.71%, 19.83%, 16.66%, and 17.78%. In adjusted analyses, Blacks had lower enrollment odds than Whites within all cohorts. In the entire study sample in 2016-2017, for example, Blacks with ADRD had 9% lower odds of MTM enrollment (odds ratio 0.91, 95% confidence interval [CI] = 0.86-0.97) than Whites. These disparities decreased over time among the ADRD sample and all sub-groups. The interaction term between Blacks and 2016-2017, for instance, indicated that disparities were lowered by 11% (odds ratio 1.11, 95% CI = 1.05-1.16) across study periods among those with ADRD., Conclusions: Blacks with ADRD, and diabetes, hypertension or hyperlipidemia have lower likelihood of MTM enrollment than Whites. Racial disparities were reduced over time but not eliminated.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis. Therefore, this review summarizes the pharmacological effects of AS for the treatment of AD and AD-complications for the first time. AS contains many effective components, such as ligustilide, z-ligustilide, n -butylidenephthalide, α-pinene, p -cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B 12 , folic acid, arginine, and oleic acid, which can improve the symptoms of AD. Besides, this review focuses on the safety and toxicity evaluation of AS, which provides a basis for its application. This review will provide further support for the research on AD and the application of medicine-food herb AS in a healthy lifestyle in the future.

Obesity-prone (OP) individuals have a significant predisposition to obesity and diabetes. Previously, we have found that OP individuals, despite being normal in weight and BMI, have already exhibited diabetes-related DNA methylation signatures. However, the underlying mechanisms remain obscure. Here we determined the effects of gut microbiota on DNA methylation and investigated the underlying mechanism from microbial-derived short-chain fatty acids (SCFAs). Diabetes-related DNA methylation loci were screened and validated in a new OP cohort. Moreover, the OP group was revealed to have distinct gut microbiota compositions, and fecal microbiota transplantation (FMT) demonstrated the role of gut microbiota in inducing diabetes-related DNA methylations and glucolipid disorders. UPLC-ESI-MS/MS analysis indicated a significantly lower level of total fecal SCFAs in the OP group. The gut microbiota from OP subjects yielded markedly decreased total SCFAs, while notably enriched propionate. Additionally, propionate was also identified by variable importance in projection (VIP) score as the most symbolic SCFAs of the OP group. Further cellular experiments verified that propionate could induce hypermethylation at locus cg26345888 and subsequently inhibit the expression of the target gene DAB1, which was crucially associated with clinical vitamin D deficiency and thus may affect the development and progression of diabetes. In conclusion, our study revealed that gut microbiota-derived propionate induces specific DNA methylation, thus predisposing OP individuals to diabetes. The findings partially illuminate the mechanisms of diabetes susceptibility in OP populations, implying gut microbiota and SCFAs may serve as promising targets both for clinical treatment and medication development of diabetes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To provide a comprehensive introduction of mediastinal hematoma., Background: Mediastinal hematoma is a rare complication that is usually not considered in the differential diagnosis of chest pain after cardiac catheterization., Methods: From January 1, 2006, to December 31, 2013, at Fuwai Hospital, 126,265 patients underwent coronary angiography (CAG); 121,215 of them underwent CAG via the radial artery. Ultimately, 10 patients with mediastinal hematoma due to cardiac catheterization were included. Patients' clinical characteristics, diagnosis, treatment, and prognosis were retrospectively analyzed., Results: The incidences of mediastinal hematoma in cardiac catheterization and transradial cardiac catheterization were 0.79‱ and 0.74‱, respectively. A super slide hydrophilic guidewire was used in all 10 patients with mediastinal hematoma. These patients felt chest pain and dyspnea during/after the procedure, and computed tomography (CT) was used to diagnose mediastinal hematoma. Among them, two patients had a neck hematoma. The post-procedural hemoglobin level decreased substantially in all patients. Antiplatelet therapy was discontinued for 8-20 days in three patients without stents implanted, and then only oral aspirin was prescribed. Aspirin was transiently discontinued for 2 days in one patient undergoing percutaneous coronary intervention. The others continued taking dual antiplatelet drugs. Two patients received blood transfusion. There was no case of stent thrombosis, and surgery was not indicated for any patient. No complication was observed after discharge during the 9.0 ± 2.5-year follow-up., Conclusion: CT should be performed as early as possible in patients with suspected mediastinal hematoma. The prognosis of mediastinal hematoma is usually good with early diagnosis and suitable therapy., (© 2022 Wiley Periodicals LLC.)

Planar cell polarity (PCP) signaling regulates several polarization events during development of ommatidia in the Drosophila eye, including directing chirality by polarizing a cell fate choice and determining the direction and extent of ommatidial rotation. The pksple isoform of the PCP protein Prickle is known to participate in the R3/R4 cell fate decision, but the control of other polarization events and the potential contributions of the three Pk isoforms have not been clarified. Here, by characterizing expression and subcellular localization of individual isoforms together with re-analyzing isoform specific phenotypes, we show that the R3/R4 fate decision, its coordination with rotation direction, and completion of rotation to a final ±90° rotation angle are separable polarization decisions with distinct Pk isoform requirements and contributions. Both pksple and pkpk can enforce robust R3/R4 fate decisions, but only pksple can correctly orient them along the dorsal-ventral axis. In contrast, pksple and pkpk can fully and interchangeably sustain coordination of rotation direction and rotation to completion. We propose that expression dynamics and competitive interactions determine isoform participation in these processes. We propose that the selective requirement for pksple to orient the R3/R4 decision and their interchangeability for coordination and completion of rotation reflects their previously described differential interaction with the Fat/Dachsous system which is known to be required for orientation of R3/R4 decisions but not for coordination or completion of rotation., Competing Interests: The authors have declared that no competing interests exist.

Background: Alzheimer's Disease (AD) is the mostcommon cause of dementia, a neurological disorder characterized by memory loss and judgment impairment. Hyperlipidemia, a commonly co-occurring condition, should be treated to prevent associated complications. Medication adherence may be difficult for individuals with AD due to the complexity of AD management. Comprehensive Medication Reviews (CMRs), a required component of Medicare Part D Medication Therapy Management (MTM), have been shown to improve medication adherence. However, many MTM programs do not target AD. Additionally, racial/ethnic disparities in MTM eligibility have been revealed. Thus, this study examined the effects of CMR receipt on reducing racial/ethnic disparities in the likelihood of nonadherence to hyperlipidemia medications (statins) among the AD population., Methods: This retrospective study used 2015-2017 Medicare data linked to the Area Health Resources Files. The likelihood of nonadherence to statin medications across racial/ethnic groups was compared between propensity-score-matched CMR recipients and non-recipients in a ratio of 1 to 3. A difference-in-differences method was utilized to determine racial/ethnic disparity patterns using a logistic regression by including interaction terms between dummy variables for CMR receipt and each racial/ethnic minority group (non-Hispanic Whites, or Whites, as reference)., Results: The study included 623,400 Medicare beneficiaries. Blacks and Hispanics had higher statin nonadherence than Whites: Compared to Whites, Blacks' nonadherence rate was 4.53% higher among CMR recipients and 7.35% higher among non-recipients; Hispanics' nonadherence rate was 2.69% higher among CMR recipients and 7.38% higher among non-recipients. Differences in racial/ethnic disparities between CMR recipients and non-recipients were significant for each minority group (p < 0.05) except Others. The difference between Whites and Hispanics in the odds of statin nonadherence was 11% lower among CMR recipients compared to non-recipients (OR = 0.89; 95% Confidence Interval = 0.85-0.94 for the interaction term between dummy variables for CMR and Hispanics). Interaction terms between dummy variables for CMR and other racial/ethnic minorities were not significant., Conclusions: Receiving a CMR was associated with a disparity reduction in nonadherence to statin medications between Hispanics and Whites among patients with AD. Strategies need to be explored to increase the number of MTM programs that target AD and promote CMR completion., (© 2022. The Author(s).)

In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MS n ) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans -resveratrol-4'- O -glucuronide (M2'), trans -resveratrol-3- O -glucoside-4'- O -glucuronide (M3), trans -resveratrol-3- O -glucoside-5- O -glucuronide (M3'), trans -resveratrol-3-sulfate (M4) and trans -resveratrol-4'-sulfate (M4'). Additionally, the metabolic pathways of TRG in monkeys and dogs were proposed. There were also species differences of metabolism of TRG between monkeys and dogs.

Many studies have evaluated factors that influence the course of the COVID-19 pandemic in different countries. This multicountry study assessed the influence of democracy and other factors on the case fatality rate of COVID-19 during the early stage of the pandemic. We accessed the World Health Organization, World Bank, and the Democracy Index 2019 databases for data from the 148 countries. Multiple analyses were conducted to examine the association between the Democracy Index and case fatality rate of COVID-19. Within 148 countries, the percentage of the population aged 65 years and above (p = 0.0193), and health expenditure as a percentage of GDP (p = 0.0237) were positively associated with countries' case fatality rates. By contrast, hospital beds per capita helped to reduce the case fatality rates. In particular, the Democracy Index was positively associated with case fatality rates in a subgroup of 47 high-income countries. This study suggests that enhancing the health system with increased hospital beds and healthcare workforce per capita should reduce case fatality rate. The findings suggest that a higher Democracy Index is associated with more deaths from COVID-19 at the early stage of the pandemic, possibly due to the decreased ability of the government., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Balloon-expandable valves (BEV) and self-expanding valves (SEV) for transcatheter aortic valve replacement (TAVR) have shown promising results in Western populations. Herein, we comparatively evaluated their hemodynamics and early clinical outcomes in a Chinese population., Methods: One hundred seventy-eight patients with symptomatic aortic stenosis who had undergone transfemoral TAVR using SEV (n=153; Venus-A, 97; VitaFlow, 56) or BEV (n=25; Sapien3) from September 2020 to April 2021 were retrospectively enrolled, and 25 pairs were propensity-score matched for 10 baseline variables. The primary study outcomes were aortic valve hemodynamics and postoperative complications at discharge and 3-month follow-up., Results: TAVR was successful in all patients. Compared with SEV group, the BEV group had similarly distributed baseline characteristics, procedural time, hospital stay, new pacemaker implantation, and paravalvular regurgitation grade. We also observed that the BEV group had lower rates of balloon pre-dilation (60% vs. 92%, P=0.018), post-dilation (0 vs. 20%, P=0.050) and second valve implantation (0 vs. 24%, P=0.022); higher mean transaortic gradient (14.3±6.1 vs. 10.8±4.9, P=0.030) and proportion of patients with elevated gradients (20% vs. 0, P=0.050) at discharge; and similar rehospitalization, mean transaortic gradient, new pacemaker implantation, and paravalvular regurgitation grade than the SEV group at the 3-month follow-up. There were no deaths in either group. However, the proportion of patients with elevated gradients in SEV group was higher at 3 months than before discharge (24% vs. 0, P=0.022)., Conclusions: BEV and SEV for transfemoral TAVR appear comparably safe and effective, with high device success and favorable 3-month clinical outcomes. However, the transaortic gradient and new pacemaker implantation in the SEV group increased during follow-up, warranting larger studies with longer-term follow-up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6637/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To measure the survival among comparable neonates with CDH supported with and without ECLS., Summary of Background Data: Despite widespread use in the management of newborns with CDH, ECLS has not been consistently associated with improved survival., Methods: A retrospective cohort study was performed using ECLS-eligible CDH Study Group registry patients born between 2007 and 2019. The primary outcome was in-hospital mortality. Neonates who did and did not receive ECLS were matched based on variables affecting risk for the primary outcome. Iterative propensity score-matched, survival (Cox regression and Kaplan-Meier), and center effects analyses were performed to examine the association of ECLS use and mortality., Results: Of 5855 ECLS-eligible CDH patients, 1701 (29.1%) received ECLS. "High-risk" patients were best defined as those with a lowest achievable first-day arterial partial pressure of CO2 of ≥60 mm Hg. After propensity score matching, mortality was higher with ECLS (47.8% vs 21.8%, odds ratio 3.3, 95% confidence interval 2.7-4.0, hazard ratio 2.3, P < 0.0001). For the subgroup of high-risk patients, there was lower mortality observed with ECLS (64.2% vs 84.4%, odds ratio 0.33, 95% confidence interval 0.17-0.65, hazard ratio 0.33, P = 0.001). This survival advantage was persistent using multiple matching approaches. However, this ECLS survival advantage was found to occur primarily at high CDH volume centers that offer frequent ECLS for the high-risk subgroup., Conclusions: Use of ECLS is associated with excess mortality for low- and intermediate-risk neonates with CDH. It is associated with a significant survival advantage among high-risk infants, and this advantage is strongly influenced by center CDH volume and ECLS experience., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Drug-drug interactions (DDIs) cause many preventable hospitalizations and admissions. Efforts have been made to raise DDI awareness and reduce DDI occurrence; for example, Medicare Part D Star Ratings, a health plan quality assessment program, included a DDI measure. Previous research reported racial and ethnic disparities in health services utilization and that racial and ethnic minorities, compared with non-Hispanic whites (whites), may be less likely to be targeted for a similar measure, a Star Ratings adherence measure for diabetes medications., Objective: This study aimed to investigate whether any racial and ethnic disparities are associated with the DDI measure in Part D Star Ratings among Medicare populations with diabetes, hypertension, and hyperlipidemia., Methods: This cross-sectional study analyzed a 2017 Medicare Part D data sample, including 3,960,813 beneficiaries. Because the inclusion in the denominator of the Star Ratings DDI measure was determined by the use of a list of target medications, the likelihood of using a listed target medication was compared between racial and ethnic minorities and whites. Individuals with diabetes, hypertension, and hyperlipidemia were included in the analysis owing to the high prevalence of these conditions. Patient- and community-level characteristics were adjusted by logistic regression., Results: Of the entire study sample, 26.2% used a target medication. Compared with whites, most racial and ethnic minorities were less likely to use a target medication. For example, among individuals with diabetes, blacks, Hispanics, Asians/Pacific Islanders, and others had, respectively, 14% (odds ratio 0.86 [95% CI 0.84-0.88]), 5% (0.95 [0.93-0.98]), 12% (0.88 [0.84-0.92]), and 10% (0.90 [0.87-0.93]) lower odds compared with whites. Findings were similar among hypertension and hyperlipidemia cohorts, except that Hispanics had similar odds of use as whites., Conclusion: Most racial and ethnic minorities may have lower likelihood of being targeted for the DDI measure compared with whites. Future studies should examine whether these disparities affect health outcomes and devise new DDI measures for racial and ethnic minorities., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Accumulating knowledge has been achieved on DNA methylation participating in numerous cellular processes and multiple human diseases; however, few studies have addressed the pleiotropic role of DNA methylation in Chinese herbal medicine (CHM). CHM has been used worldwide for the prevention and treatment of multiple diseases. Newly developed epigenetic techniques have brought great opportunities for the development of CHM. In this review, we summarize the DNA methylation studies and portray the pleiotropic role of DNA methylation in CHM. DNA methylation serves as a mediator participating in plant responses to environmental factors, and thus affecting CHM medicinal plants growth and bioactive compound biosynthesis which are vital for therapeutic effects. Furthermore, DNA methylation helps to uncover the pharmaceutical mechanisms of CHM formulae, herbs, and herbal-derived compounds. It also provides scientific validation for constitution theory and other essential issues of CHM. This newly developed field of DNA methylation is up-and-coming to address many complicated scientific questions of CHM; it thus not only promotes disease treatment but also facilitates health maintenance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer (WHH) declared past co-authorships with several of the authors (CZW, JYW, HY, CSY) to the handling editor., (Copyright © 2021 Guo, Ma, Wang, Wan, Yao and Yuan.)

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus . A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus , whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus ., Competing Interests: The authors declare that they have no competing interests., (© 2021 Wan et al.)

Data from the early stage of a novel infectious disease outbreak provide vital information in risk assessment, prediction, and precise disease management. Since the first reported case of COVID-19, the pattern of the novel coronavirus transmission in Wuhan has become the interest of researchers in epidemiology and public health. To thoroughly map the mechanism of viral spreading, we used the patterns of data at the early onset of COVID-19 from seven countries to estimate the time lag between peak days of cases and deaths. This study compared these data with those of Wuhan and estimated the natural history of disease across the infected population and the time lag. The findings suggest that comparative analyses of data from different regions and countries reveal the differences between peaks of cases and deaths caused by COVID-19 and the incomplete and underestimated cases in Wuhan. Different countries may show different patterns of cases peak days, deaths peak days, and peak periods. Error in the early COVID-19 statistics in Brazil was identified. This study provides sound evidence for policymakers to understand the local circumstances in diagnosing the health of a population and propose precise and timely public health interventions to control and prevent infectious diseases.

Background: There has been a lack of evidence on whether there are racial and ethnic disparities in medication nonadherence among individuals receiving comprehensive medication review (CMR), a required component of the Medicare Part D medication therapy management (MTM) services., Objectives: To explore racial/ethnic disparities in medication nonadherence among older MTM enrollees who received a CMR and to determine how much the identified disparities can be explained by observed characteristics., Methods: The retrospective study used 100% of the 2017 Medicare claims, including MTM data. Linked Area Health Resources Files provided community characteristics. Nonadherence was defined as proportion of days covered <80%, and was measured for diabetes, hypertension, and hyperlipidemia medications. Racial/ethnic disparities were examined by logistic regressions that included racial/ethnic minority dummy variables. A nonlinear Blinder-Oaxaca decomposition method was applied to decompose the identified disparities., Results: Compared with non-Hispanic Whites (Whites), Blacks were respectively 39% (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.33-1.45), 27% (OR = 1.27, 95% CI = 1.22-1.32), and 43% (OR = 1.43, 95% CI = 1.39-1.47) more likely to be nonadherent to diabetes, hypertension, and hyperlipidemia medications; Hispanics were 20% (OR = 1.20, 95% CI = 1.14-1.27) more likely to be nonadherent to hyperlipidemia medications. The total portion of disparity explained was 13.42%, 7.66%, 14.87%, and 10.69% respectively for disparities in Black-White (B-W) diabetes, B-W hypertension, B-W hyperlipidemia, and Hispanic-White hyperlipidemia. The top three contributors were the proportion of married-couple families, census region, and male gender., Conclusions: A lower level of community affluence and social support, regional variations, and a lower proportion of males in Blacks and Hispanics may contribute to the disparities in medication nonadherence. The large unexplained portion of the disparity attests that nonadherence is a complex issue. The Medicare MTM program needs to implement measures to reduce disparities in medication adherence.

Background: Substantial research has documented inequalities between US minorities and whites in meeting the eligibility criteria for the Medicare Part D medication therapy management (MTM) program. Even though the Centers for Medicare & Medicaid Services attempted to relax the eligibility criteria, a critical barrier to effective MTM reform is a lack of stronger evidence about the effects of MTM on minorities' health outcomes., Objective: To examine the effects of comprehensive medication review (CMR), an MTM core component, on racial and ethnic disparities in adherence to diabetes, hypertension, and hyperlipidemia medications among Medicare beneficiaries aged ≥65 years., Methods: This study used full-year 2017 Medicare Parts A, B, and D claims data, including MTM data, linked to the Area Health Resources Files. Racial and ethnic disparities in nonadherence to diabetes, hypertension, and hyperlipidemia medications were compared between CMR recipients and nonrecipients matched by their propensity scores. To determine the changes in racial and ethnic disparities after receiving CMR, a difference-in-differences framework was applied, by including in logistic regression analyses interaction terms between dummy variables for CMR receipt and each racial or ethnic minority group., Results: Compared with CMR nonrecipients, CMR recipients had significantly lower racial and ethnic disparities across the 3 outcome measures, with the exception of the difference between whites and blacks in nonadherence to diabetes medications. For example, compared with CMR nonrecipients, among CMR recipients the differences in the odds of nonadherence to hypertension medications were reduced, respectively, by 8% (95% confidence interval [CI], 0.88-0.96) between whites and blacks; by 18% (95% CI, 0.78-0.86) between whites and Hispanics; by 16% (95% CI, 0.77-0.91) between whites and Asians; and by 9% (95% CI, 0.85-0.98) between whites and other racial and ethnic groups., Conclusion: Receiving a CMR reduced the racial and ethnic disparities in adherence to diabetes, hypertension, and hyperlipidemia medications among Medicare beneficiaries aged ≥65 years. These findings provide critical empirical evidence that may inform the future design of the Medicare Part D MTM program, which is valuable for improving pharmacotherapy outcomes and could further realize its potential when additional people from racial and ethnic minorities are enrolled., (Copyright © 2021 by Engage Healthcare Communications, LLC.)

Objective: Older patients with Alzheimer's disease (AD) are challenged with adhering to complex medication regimens. We examined effects of Comprehensive Medication Review (CMR), a required Medicare Part D Medication Therapy Management (MTM) program component, on medication adherence among AD patients., Methods: This retrospective study analyzed 100% of 2016-2017 Medicare claims covering the entire United States, linked to Area Health Resources Files. Medicare beneficiaries aged ≥65 years were included. Propensity score matching identified comparable intervention and comparison groups with the intervention defined as receiving a CMR in 2017. A difference-in-differences analysis included in multivariate logistic regressions an interaction term between CMR receipt and year 2017. The outcome measured was nonadherence to diabetes, hypertension and hyperlipidemia medications, with nonadherence defined as proportion of days covered <80% for study medications., Results: Unadjusted comparisons indicated the proportion of nonadherence for intervention group members decreased from 2016 to 2017 but increased for the comparison group. In adjusted analyses, reduction in medication nonadherence among the intervention group remained higher: odds ratios for the interaction term were 0.62 (95% confidence interval [CI] = 0.54-0.71), 0.54 (95% CI = 0.50-0.58) and 0.50 (95% CI = 0.47-0.53) respectively for diabetes, hypertension and hyperlipidemia medications. This suggests that the likelihood of nonadherence in the intervention group was respectively reduced by 38%, 46% and 50% more than the comparison group., Conclusions: CMR was found to reduce nonadherence to diabetes, hypertension and hyperlipidemia medications among older Medicare beneficiaries with AD. This provides evidence that the MTM program is effective for a population with unique medication compliance challenges.

Background: Previous literature reported racial/ethnic disparities in the measure assessment of diabetes medication adherence in the Medicare Part D Star Ratings program., Objective: This study examined the likelihood of inclusion in measure calculation across racial/ethnic groups for adherence metrics in Part D Star Ratings among individuals with diabetes, hypertension, and/or hyperlipidemia., Methods: This was a retrospective cross sectional analysis of a 10% random sample of 2017 Medicare claims linked to Area Health Resources Files. Inclusion in measure calculation was determined based on inclusion/exclusion criteria in adherence metrics for adherence medications for diabetes, hypertension, and hyperlipidemia in Part D Star Ratings developed by the Pharmacy Quality Alliance. Logistic regression and multinomial logistic regression were used to adjust for patient/community characteristics., Results: The study sample size was 2 707 216. Compared to Non-Hispanic White (White) beneficiaries, minorities were more likely to be excluded from measure calculation among individuals with 1 condition. For example, among individuals with hypertension, compared to White individuals, the adjusted odds ratios for exclusion for Black, Hispanic, Asian/Pacific Islander and other individuals were 1.46 (95% confidence interval, or CI = 1.42-1.50), 1.38 (95% CI = 1.33-1.43), 1.28 (95% CI = 1.21-1.35), and 1.08 (95% CI = 1.02-1.15), respectively. Among individuals with more than 1 chronic condition, minorities were more likely to be included in fewer calculations for medication adherence measures. For example, among individuals with all 3 conditions, the adjusted relative risk ratios for Black, compared to White, beneficiaries for being included in 0, 1, and 2 measures, versus all 3 measures, were 2.14 (95% CI = 1.99-2.30), 1.49 (95% CI = 1.41-1.56), 1.20 (95% CI = 1.18-1.23), respectively., Conclusions: Compared to White beneficiaries, racial/ethnic minorities are more likely to be excluded from the calculation for adherence measures among individuals with diabetes, hypertension, and/or hyperlipidemia. Future studies should examine whether such disparities exacerbate existing racial/ethnic disparities in health outcomes and devise solutions for these disparities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The gut microbiota exists throughout the full life cycle of the human body, and it has been proven to have extensive impacts on health and disease. Accumulating evidence demonstrates that the interplay between gut microbiota and host epigenetics plays a multifaceted role in health maintenance and disease prevention. Intestinal microflora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification. Moreover, epigenetic factors can serve as mediators to coordinate gut microbiota within the host. Aiming to dissect this interplay mechanism, the present review summarizes the research profile of gut microbiota and epigenetics in detail, and further interprets the biofunctions of this interplay, especially the regulation of intestinal inflammation, the improvement of metabolic disturbances, and the inhibition of colitis events. This review provides new insights into the interplay of epigenetics and gut microbiota, and attempts to reveal the mysteries of health maintenance and disease prevention from this new perspective.