CYP2C19＊2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome

Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function （LOF） and gain of function （GOF） genotype,adenosine 5＇-diphosphate （ADP）-channel platelet inhibition rate （PIR） tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results：High on-treatment platelet reactivity （HTPR） prevalence defined by PIR 〈30% by TEG in ADP-channel was 32.76% （38/116）.With respect to the normal wild type,CYP2C 19＊2,and ＊3 LOF alleles,and ＊ 17 GOF alleles,patients were classified into three metabolism phenotypes：41.38% were extensive metabolizers （EMs）,56.90% were intermediate metabolizers （IMs）,and 1.72% were poor metabolizers （PMs）.Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of ＊2,＊3,and ＊ 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen （17.24%） ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions：Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.

Determinants and Equity Evaluation for Health Expenditure Among Patients with Rare Diseases in China

Background： China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity. Methods： Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket （OOP） health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve. Results： Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female （P = 0.048）, over 50 years of age （P = 0.062）, high-income group （P = 0.021）, hospitalization （P- 0.000）, and reimbursement ratio （RR） （P = 0.000） were positively correlated with total health expenditure. Diseases not needing long-term treatment （P = 0.000） was negatively correlated with total health expenditure. Over 50 years of age （P = 0.065）, high-income group （P = 0.018）, hospitalization （P = 0.000） and having Urban Employee Basic Medical Insurance （UEBMI） （P - 0.022） were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education （P = 0.044 and P = 0.08 l） and reimbursement ratio （P = 0.078） were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively. Conclusions： OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people.

Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity

Objective： To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboe- lastography （TEG）. Methods： One hundred and eighty patients with acute coronary syndrome （ACS） treated with clopJdogrel and aspJdn were included and platelet function was assessed by TEG. Five selected P2RY12 single nu- cleotide polymorphisms （SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934）, which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs （ 2, 3, 17） were geno- typed and possible haplotypes were analyzed. Results： The high on-treatment platelet reactivity （HTPR） prevalence defined by a platelet inhibition rate 〈30% by TEG in adenosine diphosphate （ADP）-channel was 69 （38.33%）. Six common haplotypes were inferred from four of the selected P2RY12 SNPs （denoted H0 to H5） according to the linkage disequilibrium R square （except for rs2046934）. Haplotype H1 showed a significantly lower incidence of HTPR than the reference haplotype （H0） in the total study population while haplotypes H1 and H2 showed significantly lower incidences of HTPR than H0 in the nonsmoker subgroup after adjusting for CYP2Clg effects and demographic characteristics. rs2046934 （T744C） did not show any significant association with HTPR. Conclusions： The combination of common P2RY12 variations including regulatory regions rather than rs2046934 （T744C） that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

Domestic trends in malaria research and development in China and its global influence

Background:Though many countries,including China,are moving towards malaria elimination,malaria remains a major global health threat.Due to the spread of antimalarial drug resistance and the need for innovative medical products during the elimination phase,further research and development(R&D)of innovative tools in both epidemic and elimination areas is needed.This study aims to identify the trends and gaps in malaria R&D in China,and aims to offer suggestions on how China can be more effectively involved in global malaria R&D.Methods:Quantitative analysis was carried out by collecting data on Chinese malaria-related research programmes between 1985 and 2014,invention patents in China from 1985 to 2014,and articles published by Chinese researchers in PubMed and Chinese databases from 2005 to 2014.All data were screened and extracted for numerical analysis and were categorized into basic sciences,drug/drug resistance,immunology/vaccines,or diagnostics/detection for chronological and subgroup comparisons.Results:The number of malaria R&D activities have shown a trend of increase during the past 30 years,however these activities have fluctuated within the past few years.During the past 10 years,R&D on drug/drug resistance accounted for the highest percentages of research programmes(32.4%),articles(55.0%in PubMed and 50.6%in Chinese databases)and patents(45.5%).However,these R&D activities were mainly related to artemisinin.R&D on immunology/vaccines has been a continuous interest for China’s public entities,but the focus remains on basic science.R&D in the area of high-efficiency diagnostics has been rarely seen or reported in China.Conclusions:China has long been devoted to malaria R&D in multiple areas,including drugs,drug resistance,immunology and vaccines.R&D on diagnostics has received significantly less attention,however,it should also be an area where China can make a contribution.More focus on malaria R&D is needed,especially in the area of diagnostics,if China would like to contribute in a more significant way to global malaria control and elimination.