Evaluation of Potential Racial Disparities in CYP2C19-Guided P2Y12 Inhibitor Prescribing After Percutaneous Coronary Intervention.

Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y12 inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from 9 sites that performed clinical CYP2C19 genotyping after PCI were included. Alternative therapy (e.g., prasugrel or ticagrelor) was recommended for CYP2C19 no-function allele carriers, in whom clopidogrel is predicted to be less effective. The primary outcome was choice of P2Y12 inhibitor (clopidogrel vs. alternative therapy) based on genotype. Of 3,342 patients included, 2,448 (73%) were White, and 659 (20%) were Black. More Black than White patients had a no-function allele (34.3% vs. 29.7%, P = 0.024). At hospital discharge following PCI, 44.2% of Black and 44.0% of White no-function allele carriers were prescribed alternative therapy. At the time of the last follow-up within 12 months, numerically fewer Black (51.8%) than White (56.7%) no-function allele carriers were prescribed alternative therapy (P = 0.190). However, the difference was not significant after accounting for other factors associated with P2Y12 inhibitor selection (odds ratio 0.79, 95% confidence interval 0.58-1.08). Alternative therapy use did not differ between Black (14.3%) and White (16.7%) patients without a no-function allele (P = 0.232). Among real-world patients who received CYP2C19 testing after PCI, P2Y12 inhibitor prescribing rates did not differ between Black and White patients. Our data suggest an absence of racial disparity in genotype-guided antiplatelet prescribing among patients receiving CYP2C19 testing.

Assessment of the relationship between subclinical hypothyroidism and blood lipid profile: reliable or not?

BACKGROUND: The relationship between subclinical hypothyroidism (SCH) and blood lipid metabolism is controversial. This study is intended to evaluate the relationship between SCH and blood lipid profiles using well defined diagnostic criteria. METHODS: Data from 11,512 physical examinees in our hospital who had finished two tests with an interval of at least 3 months were analyzed, including 685 cases of SCH as stipulated in this study. In addition to common physical examination indicators, other parameters such as thyroid function indices and blood lipids were measured twice with an interval of at least 3 months. Subjects were diagnosed with SCH only when their levels of TT3, TT4, FT3 and FT4 were normal and TSH levels were increased on both tests, which meant these subjects were in a state of SCH for at least 3 months. The results of blood lipids for the second time were analyzed. RESULTS: Statistically significant differences were found in age, sex, BMI, hemoglobin, total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), and BFP between the SCH and control groups (P < 0.001). However, there were no statistically significant differences in age, sex, blood pressure, blood lipids, blood glucose or BMI between patients with mild SCH and those with severe SCH (P > 0.05). After balancing the age and sex ratio, no factors were confirmed to be statistically significant independent factors of SCH. None of the parameters showed statistically significant differences between patients with mild SCH and those with severe SCH (P > 0.05). CONCLUSION: After defining rigorous criteria for the diagnosis of SCH, no definite association between SCH and TC, LDL-C or HDL-C was confirmed in this study. SCH may have no relationship to the most concerning blood lipid profile.

Individualized assessment of risk and overall survival in patients newly diagnosed with primary osseous spinal neoplasms with synchronous distant metastasis.

Background: The prognosis of patients with primary osseous spinal neoplasms (POSNs) presented with distant metastases (DMs) is still poor. This study aimed to evaluate the independent risk and prognostic factors in this population and then develop two web-based models to predict the probability of DM in patients with POSNs and the overall survival (OS) rate of patients with DM. Methods: The data of patients with POSNs diagnosed between 2004 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistics regression analyses were used to study the risk factors of DM. Based on independent DM-related variables, we developed a diagnostic nomogram to estimate the risk of DM in patients with POSNs. Among all patients with POSNs, those who had synchronous DM were included in the prognostic cohort for investigating the prognostic factors by using Cox regression analysis, and then a nomogram incorporating predictors was developed to predict the OS of patients with POSNs with DM. Kaplan-Meier (K-M) survival analysis was conducted to study the survival difference. In addition, validation of these nomograms were performed by using receiver operating characteristic (ROC) curves, the area under curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: A total of 1345 patients with POSNs were included in the study, of which 238 cases (17.70%) had synchronous DM at the initial diagnosis. K-M survival analysis and multivariate Cox regression analysis showed that patients with DM had poorer prognosis. Grade, T stage, N stage, and histological type were found to be significantly associated with DM in patients with POSNs. Age, surgery, and histological type were identified as independent prognostic factors of patients with POSNs with DM. Subsequently, two nomograms and their online versions (https://yxyx.shinyapps.io/RiskofDMin/ and https://yxyx.shinyapps.io/SurvivalPOSNs/) were developed. The results of ROC curves, calibration curves, DCA, and K-M survival analysis together showed the excellent predictive accuracy and clinical utility of these newly proposed nomograms. Conclusion: We developed two well-validated nomograms to accurately quantify the probability of DM in patients with POSNs and predict the OS rate in patients with DM, which were expected to be useful tools to facilitate individualized clinical management of these patients.

Tunable, Low-Cost, Multi-Channel, Broadband Liquid Crystal Shutter for Fluorescence Imaging in Widefield Microscopy.

Bistable liquid crystal (LC) shutters have attracted much interest due to their low energy consumption and fast response time. In this paper, we demonstrate an electrically tunable/switchable biostable LC light shutter in biological optics through a three-step easy-assembly, inexpensive, multi-channel shutter. The liquid crystal exhibits tunable transparency (100% to 10% compared to the initial light intensity) under different voltages (0 V to 90 V), indicating its tunable potential. By using biomedical images, the response time, resolution, and light intensity changes of the LC under different voltages in three common fluorescence wavelengths are displayed intuitively. Particularly, the shutter's performance in tumor images under the near-infrared band shows its application potential in biomedical imaging fields.

Surveillance of long-term environmental elements and PM2.5 health risk assessment in Yangtze River Delta, China, from 2016 to 2020.

PM2.5 metal pollution significantly harms human health. The air quality in Wuxi is poor, especially in winter, and long-term monitoring of PM2.5 elements comprising has not been performed previously. In the present study, 420 PM2.5 samples were collected from January 2016 to December 2020. Eleven elements, including Al, Mn, Ni, Cr, As, Cd, Sb, Hg, Pb, Se, and Tl, were analyzed by inductively coupled plasma mass spectrometry. The mean PM2.5 level was 56.1 ± 31.0 µg/m3, with a tendency of yearly decreasing and a significant seasonal distribution variation. The concentration of 11 elements in the PM2.5 samples was 0.38 ± 0.33 µg/m3. Al was the highest element with a range of 37.5-2148 ng/m3. Meanwhile, the spatial distribution differences were compared by literatures review. Based on the Crystal Ball model, health risks were assessed dynamically using Monte Carlo uncertainty analysis. After 10,000 simulations, the mean value of the hazard index for nine elements was 0.743, and Mn contributed the most to the hazard index among elements, with a correlation of 0.3464. The average carcinogenic risk was 1.01 × 10-5, which indicated that the non-carcinogenic and carcinogenic risks were within the acceptable range. However, considerable attention should be paid to the potential health risks associated with long-term Al, Mn, and As exposure. This study provides detailed data on local atmospheric pollution characteristics, helps identify potential risk elements, and contributes to the development of effective regional air quality management.

A randomized, cross-over trial of metoprolol succinate formulations to evaluate PK and PD end points for therapeutic equivalence.

There are limited comparison data throughout the dosing interval for generic versus brand metoprolol extended-release (ER) tablets. We compared the pharmacokinetics (PKs) and pharmacodynamics of brand name versus two generic formulations (drugs 1 and 2) of metoprolol ER tablets with different time to maximum concentration (Tmax ) in adults with hypertension. Participants were randomized to equal drug doses (50-150 mg/day) administered in one of two sequences (brand-drug1-brand-drug2 or brand-drug2-brand-drug1) and completed 24-h PK, digital heart rate (HR), ambulatory blood pressure (BP), and HR studies after taking each formulation for greater than or equal to 7 days. Metoprolol concentrations were determined by liquid chromatography tandem mass spectrometry, with noncompartmental analysis performed to obtain PK parameters in Phoenix WinNonlin. Heart rate variability (HRV) low-to-high frequency ratio was determined per quartile over the 24-h period. Thirty-six participants completed studies with the brand name and at least one generic product. Among 30 participants on the 50 mg dose, the primary PK end points of area under the concentration-time curve and Cmax were similar between products; Tmax was 6.1 ± 3.6 for the brand versus 3.5 ± 4.9 for drug 1 (p = 0.019) and 9.6 ± 3.2 for drug 2 (p < 0.001). Among all 36 participants, 24-h BPs and HRs were similar between products. Mean 24-h HRV low-to-high ratio was also similar for drug 1 (2.04 ± 1.35), drug 2 (1.86 ± 1.35), and brand (2.04 ± 1.77), but was more sustained over time for the brand versus drug 1 (drug × quartile interaction p = 0.017). Differences in Tmax between metoprolol ER products following repeated doses may have implications for drug effects on autonomic balance over the dosing interval.

Potential trade-off between water consumption and water quality: life cycle assessment of nonaqueous solvent dyeing.

Fashion industry consumes over 60% of global fibers and attracts increasing attentions due to its environmentally polluting supply chain. In addition to natural fibers cultivation, wet processes of textile manufacturing are also important contributors to water-related impacts due to their large freshwater consumption and the production of chemicals containing wastewater. Despite of efforts made in improving efficiency of water use and wastewater treatment in textile industry, innovative 'water-free' technologies, such as nonaqueous dyeing technology using organic solvent, have been developed and demonstrated to reduce water consumption significantly. However, the potential impact on water quality by organic solvents induced in supply chain of this emerging technology remains unassessed, posing an unknown risk of its promotion. Hence, in the present study, a comprehensive life cycle assessment is applied to evaluate its full environmental impacts, including those on ecosystem and human health caused by decamethylcyclopentasiloxane (D5) as the solvent used. Further, the nonaqueous dyeing system is compared with traditional aqueous dyeing technology from both environmental and economic perspectives. Results indicate that nonaqueous dyeing system is advanced in most of environment categories except for abiotic depletion potential (ADP) and Ecotoxicity. However, scenarios analysis reveal that these findings are influenced by the loss fraction of D5 during the solvent recovery process. It is suggested that the loss fraction should be controlled below 2% o.w.f. for the nonaqueous dyeing technology to be advanced throughout all environmental categories. Nonaqueous D5 dyeing could reduce water consumption by 61.30%-79.95% and greenhouse gas emissions by 43.70% compared to the traditional system, delivering a promising contribution to China's 2060 carbon neutrality ambition. Sensitivity and uncertainty analyses are also conducted to investigate the effects of the key parameters (incl. inventory data and USEtox model inputs) and demonstrate the robustness of our assessment.

Drinking water elements constituent profiles and health risk assessment in Wuxi, China.

Water elements pollution has attracted public attention globally. Wuxi is located in East China, and its water source, Taihu Lake, has been severely polluted since 2007. Studies of elemental pollution profiles have yet to be conducted in this area. In this study, 56 water samples were collected in 2018, and 33 elements were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that the levels of 33 elements ranged from 1.35 × 10-3 µg/L(Tl) to 101 mg/L(Ca), with Sr, Al, Fe, B, Ti, Ba, and Zn levels being relatively higher. A comprehensive literature review showed spatial distribution of conspicuous elements in drinking water worldwide. Meanwhile, Monte Carlo simulations were applied to evaluate exposure health risks. The total hazard index(HI) for 14 non-carcinogens and the average incremental lifetime cancer risk (ILCR) of As and Pb exposure through drinking water were found acceptable. Sensitivity analyses suggested that Sb and As in the drinking water represent an increasing risk to human health. The results of this study provide key data on local metal pollution characteristics, help identify potential risk factors, and contribute to the development of effective environmental management policies for Taihu Lake.

Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes.

BACKGROUND: The incidence of thyroid cancer in black Americans is significantly lower than that in white Americans, and the impact of race on the prognosis of thyroid cancer remains controversial. The purpose of this study was to determine the risk factors for survival in black and white patients and to compare the survival of differentiated thyroid carcinoma subtypes between these two races. We further investigated the association of lymph node and distant metastases with races. METHODS: This is a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A total of 70,346 cases were included in our study. Patients' demographics and cancer- and treatment-related characteristics were compared between the black and white Americans using chi-square and Fisher's exact tests. For multivariate analysis, Cox proportional hazards regression were used to assess the association between potential risk factors and the survival in black and white patients. RESULT: Black Americans had a worse overall survival than white Americans (HR = 1.127, P = 0.002). While disease-specific survival (DSS) was comparable, the risk factors for DSS were different between white and black Americans. Black Americans had less lymph node metastasis of classical variant papillary thyroid carcinoma (CPTC, OR = 0.476, P < 0.001) and follicular variant papillary thyroid carcinoma (FVPTC, OR = 0.522, P < 0.001), but not follicular thyroid carcinoma (FTC). However, black Americans with FVPTC, but not CPTC or FTC, had a higher potential of distant metastasis (OR = 1.715, P = 0.026). Furthermore, only white patients with tumor > 2 cm and lymph node metastasis benefited from radioactive iodine. CONCLUSIONS: The risk factors for DSS were significantly different in white and black patients. The impact of race should be considered in treatment strategy for thyroid cancer.

Blood pressure response to metoprolol and chlorthalidone in European and African Americans with hypertension.

Despite the availability of many antihypertensive drug classes, half of patients with hypertension have uncontrolled blood pressure (BP). The authors sought to assess the effect of age on BP response in European American and African American patients with hypertension. Clinic BP from the PEAR2 (Pharmacogenomics Evaluation of Antihypertensive Responses 2) study was used to estimate BP responses from baseline following sequential treatment with metoprolol 100 mg twice daily and chlorthalidone 25 mg daily for 8 to 9 weeks each, with a minimum 4-week washout between treatments. BP responses to both drugs were compared in 159 European Americans and 119 African Americans by age with adjustment for baseline BP and sex. European Americans younger than 50 years responded better to metoprolol than chlorthalidone (diastolic BP: -9.6 ± 8.0 vs -5.9 ± 6.8 mm Hg, adjusted P = .003), whereas patients 50 years and older responded better to chlorthalidone than metoprolol (systolic BP: -18.7 ± 13.8 vs -13.6 ± 14.8 mm Hg, adjusted P = .008). African Americans younger than 50 years responded similarly to both drugs, whereas those 50 years and older responded better to chlorthalidone than metoprolol (-17.0 ± 13.2/-9.6 ± 7.5 vs -7.0 ± 18.6/-6.7 ± 9.3 mm Hg, adjusted P<.0001/.008). Therefore, age should be considered when selecting antihypertensive therapy in European and African American populations with hypertension.

CD4 Lymphocyte Enumeration and Hemoglobin Assessment Aid for Priority Decisions: A Multisite Evaluation of the BD FACSPresto™ System.

BACKGROUND: The BD FACSPresto™ system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. METHODS: Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur™ system, and for Hb, using the Sysmex® KX-21N™ analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. RESULTS: For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96-1.05 and R2 ≥0.96; Hb slopes were ≥1.00 and R2 ≥0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. CONCLUSION: The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems.

[Research Progress on Risk Assessment of Secondary Transmission of Imported Malaria].

In 2015, WHO issued the Global Technical Strategy for Malaria 2016-2030, which sets the target of reducing global malaria incidence and mortality rates by at least 90% by 2030. Although many countries have successfully achieved malaria elimination, they are facing the risk of imported malaria. In China, despite the acceleration of malaria elimination, imported malaria has become a potential threat to achieving complete malaria elimination. This paper reviews the worldwide research progress on risk assessment of secondary transmission of imported malaria, in the aim of providing reference for risk assessment of imported malaria and preventing secondary transmission in China.

Potential risk assessment of polybrominated diphenyl ethers (PBDEs) by consuming animal-derived foods collected from interior areas of China.

Polybrominated diphenyl ethers (PBDEs) are one class of brominated flame retardants (BFRs). Although studies have reported the occurrence of PBDEs in freshwater fish species from several locations, to our best knowledge, there was no comprehensive data on PBDEs in foods of animal origin, such as pork, egg, and milk samples from interior areas of China, where pork and eggs are the major constituents of diet. The levels of PBDEs (BDE-28, 47, 99, 100, 153, 154, and 183) were determined in samples of animal-derived foods widely consumed by the population of Hubei in east-central China and the middle reaches of the Yangtze River. Two hundred six samples of animal-derived foods were randomly acquired in 17 sites of Hubei in 2010. The highest medium concentration of ∑7PBDEs was found in chicken eggs (0.191 ng/g wet weight (ww)), followed by duck eggs (0.176 ng/g ww), pork (0.050 ng/g ww), carps (0.047 ng/g ww), and cow milk (0.013 ng/g ww). The estimated dietary intake of Σ7PBDEs for a standard adult of 60 kg body weight based on medium and 95th percentile concentrations with consumption of animal-derived foods in Hubei province were 157.5 and 1960.3 pg/kg body weight/day, respectively. Chicken eggs (65.9 %) and pork (23.4 %) were the largest contributors to dietary intake of ∑7PBDEs through animal-derived foods. The same PBDE sources were exposed in Hubei province via principal component analysis (PCA), and the particular congener profile in samples of animal-derived foods revealed the possible exposure history of octa-BDEs and penta-BDEs in the local region. The large margins of exposure (MOE) calculated following the European Food Safety Authority (EFSA) approach for three important congeners, BDE-47, BDE-99, and BDE-153, indicated that the estimated dietary exposures were unlikely to be a significant health concern to in Hubei.

Social determinants of health and depression: a preliminary investigation from rural China.

BACKGROUND: In the last several years, research related to social determinants of health (SDH) has begun to resonate in the medical, behavioral, social and political sciences arena. The aim of the present study was to explore the relationship between SDH and depression, and to provide new evidences and clues for depression control and prevention. METHODOLOGY/PRINCIPAL FINDINGS: This research was a cross-sectional survey executed door to door from October 2006 to April 2008, with a sample of 3,738 individuals aged 18 and older in rural China. The three variables of SDH were socioeconomic status (years of schooling and self-reported economic status of family), social cohesion and negative life events. Demographic variables and self-perceived physical health were taken as potential confounders. The cross-table analysis showed that variations in levels of depression were associated with variations in SDH, and logistic regression analysis confirmed the association even after adjusting for potential confounding variables. CONCLUSIONS: Although there were some limitations, the current study provides initial evidence of the importance of SDH in depression. Findings indicate that social inequity and the role of policy action emphasized by SDH should be considered high priorities when addressing the issue of depression. In addition, cell-to-society and pill-to-policy approaches should be encouraged in the future.