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OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.
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OBJECTIVE：To provide evidence-based reference for c linical drug selection and decision by rapidly evaluating the effectiveness，safety and economy of treprostinil in the treatment of pulmonary arterial hypertension （PAH）. METHODS ：Retrieved from Chinese and English database such as PubMed ，Embase，Web of Science ，the Cochrane Library ，Epistemonikos，HTA database（University of York ），CNKI and Wanfang databases ，included the health technology assessment （HTA）report，systematic/ Meta-analysis and pharmacoeconomic evaluation of treprostinil compared with placebo or other drugs in the treatment of PAH. The search time limit is from the construction of the database to May 1st，2020. HTA checklist ，AMSTA and CHEERS were applied to evaluate the quali ty of the literatures about HTA ，systematic review/Meta-analysis analysis a nd pharmacoecono mic evaluation and the inclusion studies was analyazed by descriptive summary. RESULTS：A total of 18 literatures were included ，involving 1 HTA report ，12 systematic review/Meta-analysis ，5 pharma- coeconomic studies. The analysis results of effectiven- ess mail： showed that compared with placebo ，treprostinil could signifi- cantly increase 6-MWD while decrease Borg dyspnea score of PAH p atients（P＜0.05），but had no significant effect on mortality，the rate of clinical deterioration ，WHO functional grading ，the rate of hospitalization ，mPAP，PVR，cardiac index and mRAP（P＞0.05）. In addition ，compared with placebo combined with endothelin receptor antagonist and/or phosphodiesterase inhibitors，oral administration of treprostinil combined with endothelin receptor antagonist and/or phosphodiesterase inhibitors could extend 6-MWD significantly. Compared with riociguat ，treprostinil could significantly reduce Borg dyspnea score of patients. The analysis results of safety displayed that ，although the incidence of drug withdrawal due to can ’t tolerate ADR increased in patients receiving treprostinil ，there was no significant difference in the incidence of serious adverse events compared with placebo or other treatments，and it was better tolerated when administered by inhalation or intravenous injection. The analysis results of pharmacoeconomic studies showed that ICER of treprostinil was higher than the willingness payment threshold ，although the willingness payment threshold was different in different countries and different payers. CONCLUSIONS ：Treprostinil treatment is effective for PAH. Patients may stop taking it due to can ’t tolerate ADR ，but the risk of serious adverse events are not increase. Although the price is high ，it is still an important alternative for PAH patients with clinical progress or poor prognosis.
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OBJECTIVE@#To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.@*METHODS@#The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.@*RESULTS@#In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.@*CONCLUSIONS@#CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
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Humans , Adrenergic beta-Antagonists , Chromatography, Liquid , Coronary Artery Disease , Cytochrome P-450 CYP2D6 , Genotype , Metoprolol , Tandem Mass SpectrometryABSTRACT
OBJECTIVE:To provide reference for the establishment of work mode of automatic dispensing system in large-scale integrated pharmacy. METHODS:Introducing the establishment and optimization situation of the automatic pharmacy dispensing system in the outpatient pharmacy of our hospital,changes of related deployment indexes before and after optimization were compared,and the main measures for improving the work efficiency of automatic dispensing system were explored. RE-SULTS:Based on setting and regularly adjusting stored drug varieties,numbers of occupied tracks and unbundled drug factors,de-signing deployment operation mode that the system automatically dispensing preparations to immediate-dispensing and pre-dispens-ing windows,establishing operational specifications and management refinement,the outpatient pharmacy had established automat-ic dispensing system with prescription deployment number more than 12000 pieces/d and optimized work mode. Compared with be-fore optimization,host,auxiliary and smart cabinet varieties were increased in the case of the same number of total staff,immedi-ate-dispensing windows were increased and pre-dispensing windows were decreased. Proportion of full-automatically-dispensed pre-scriptions was increased (up from 41.18% to 48.32%) in the case of total prescription increasing in peak hours,and numbers of hourly prescription deployment were increased in both immediate-dispensing and pre-dispensing windows. Average time to wait for medicine of patients was shortened(down from 5.63 min to 5.18 min),supplemental medicine error and inner errors rate of deploy-ment (down from 0.48% to 0.44%) were decreased (P<0.05). CONCLUSIONS:The established automatic dispensing system mode can meet the needs of prescription deployment in large-scale integrated outpatient pharmacy,and improve the work efficiency by continually optimization.
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OBJECTIVE:To explore the ways and methods for pharmacists to participate in community pharmaceutical care, and to provide reference for guaranteeing safe use of drugs in the elderly. METHODS:Questionnaire survey about medication situa-tions and pharmaceutical care demands was conducted among the elderly randomly selected from some communities of Guangzhou Yuexiu District and Liwan District. The investigation data was analyzed statistically. RESULTS:Totally 300 questionnaires were sent out,and 283 were recycled with effective recovery rate of 94.33%. Among respondents,64.66% geriatric people had a high school education or above and 87.99% elderly people enjoyed medical insurance for urban residents;the major health problems of the elderly were chronic diseases like hypertension,osteoporosis,hyperlipidemia,diabetes. 55.48% interviewees preferred to pur-chasing drugs from governmental hospitals and 40.28% interviewees used to purchase drugs from community hospitals;in terms of understanding of drug information,72.08% interviewees tended to consult doctors about drug use but only 12.72% intervieweestended to consult hospital pharmacists about drug use. Interviewees often took various kinds of drugs,there were 72.44%interview-ees taking drugs according to the doctor's advice. 44.88%interviewees accustomed to storing drugs at discretion. 68.20%interview-ees deemed that the responsibilities of the pharmacists were drug dispensing,but only 28.27% interviewees thought that pharma-cists could provide medication guidance and consultation;in terms of community pharmaceutical care,interviewee had much great-er demands to daily care and rational drug use of lectures. CONCLUSION:Geriatric people take many different drugs to treat their diseases in those communities,there are many problems that are not conducive to safe drug use. Those reflected urgent need for community pharmaceutical care,and then higher requirements are put forward for the professional quality of pharmacists.
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Immunomagnetic separation (IMS) was coupled with fluorescent microspheres lateral flow assay (FM-LFA) for rapid detection of S.choleraesuis in this study.The target bacteria were firstly enriched from sample by immunomagnetic beads (IMBs),then eluted by heat treatment and detected by fluorescent microspheres lateral flow test strip.The IMBs was labeled with 30 μg/mg antibody,and the capture efficiency was greater than 90％ against 102-106 CFU/mL of S.choleraesuis with great specificity.The immunofluorescent microspheres were prepared by coupling 300 μg of 11 D8-D4 monoclonal antibody with 1 mg of fluorescent microspheres at pH 6.Monoclonal antibody 5F11-B11 (2.0 mg/mL) and donkey anti-mouse IgG (1.0 mg/mL) were sprayed on nitrocellulose membrane as test line and control line,respectively.The FM-LFA based on IMS was used to detect S.choleraesuis in PBS and milk.The limits of detection in PBS buffer and milk were 1.5×105 CFU/mL and 7.6×105 CFU/mL respectively,which were 10 and 200 times lower than that of traditional fluorescent microspheres lateral flow assay,respectively.The results showed that the method,which could enrich S.choleraesuis in milk effectively,could avoid matrix interference and improve the detection sensitivity,thus had a good application prospect.
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A method for quantitative detection of florfenicol by colloidal gold lateral flow immunoassay was developed.The experimental conditions including pH value, concentrations of antibody in the process of conjugation between the colloidal gold and antibody, amount of gold-labeled antibody, concentration of the antigen sprayed on test lines (T line), and detection time were optimized.With a colloidal gold strip reader, the signal intensity of T lines and control lines (C line) on lateral flow strips was recorded.The T/C ratio of negative control and positive samples was defined as B0 and Bx, and the standard curve was established by plotting the Bx/B0 ratio against the concentration of florfenicol.This assay showed a good linear range from 0.1 to 1.5 ng/mL with the limit of detection of 0.08 ng/mL, while the result could be obtained within 15 min.The result showed that this quantitative method was convenient and rapid, and could be used in screening a large amount of samples on site.
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OBJECTIVE:To explore the genome-wide methylation differences between coronary heart disease (CHD) patients and healthy volunteers,and to investigate the relationsip of DNA methylation with CHD from epigenetics. METHODS:In case-control study,subjects were divided into CHD group(50 cases)and health control group(50 cases). DNA of 2 groups were sequenced with methylated DNA immunoprecipitation sequencing technology. The genome-wide methylation differences were analyzed and compared between 2 groups. RESULTS:The number of methylation peak in CHD group was higher than health group,with statistical signfi-cance(P<0.05). The methylation peak mainly distributed in 5'UTR,Intron functional elements. The number of reads in AQP1,SHB and other gene promoters in CHD group were lower than health group,and its methylation level decreased. The number of reads in GRK5 and serveal gene promoters on chrX in CHD group were higher than helath group,and its methylation level increased,with sta-tistical significance(P<0.01). CONCLUSIONS:The genome-wide methylation level of CHD patients are higher than those of healthy volunteers. The occurence of CHD is possibly associated with the change of methylation level of related gene promoters.
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OBJECTIVE: To study the hospital infections caused by ESBLs-producing Escherichia coli and Kalispell.METHODS: Bacterial drug resistance of 460 stains of ESBLs-producing Escherichia coli and Kalispell pneumonia and the application of antibiotics in our hospital in 2005 were analyzed retrospectively.RESULTS: The infections caused by ESBLs-producing Escherichia coli and Kalispell pneumonia were more often found in department of respiratory diseases,ICU and neurosurgery patients,which were treated empirically predominantly with levofloxacin,followed by cefoperazone/sulbactam,but were treated mostly by carbapenems,levofloxacin,cefoperazone/sulbactam after the drug susceptibility test results were obtained.The drug combination was characterized predominantly by combined use of two kinds,at most 6 kinds in combination.CONCLUSION: In most of the cases the medication for infections caused by ESBLs-producing Escherichia coli and Kalispell pneumonia is effective and reasonable.However,in a few cases the application of antibiotics is irrational and nonstandard,which should be given fully attention.
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OBJECTIVE:To study the potential of three kinds of Chinese medicines in combination with Ceftriaxone in inducing endotoxin release from Klebsiella for references of combined use of Chinese medicines and western medicines in the treatment of severe infections.METHODS:The amount of endotoxin released from Klebsiella after being treated in vitro by Ceftriaxone(high,medium and low concentrations)alone or in combination with 3 antibacterial Chinese medicines for 4 hours was compared.RESULTS:The amount of endotoxin released by Klebsiella in low concentration of Ceftriaxone either alone or in combination with Chinese medicines were the maximum but minimum in high concentration Ceftriaxone group.The amount of endotoxin released in low concentration group was larger than in blank group(without antibacterial treatment),and that released amount in Shuanghuanglian plus Ceftriaxone group was less than in Ceftriaxone alone group.CONCLUSION:Low concentration of Ceftriaxone can induce Klebsiella to release endotoxin,while Shuanghuanglian can reduce Ceftriaxone-induced release of endotoxin.
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OBJECTIVE:To explore the suitable clinical service mode for pharmacists in China.METHODS:A questionnaire was designed and a random sample of 170 people were selected from 2 hospitalized patients,doctors,nurses and pharmacists,the results were analyzed using statistical method.RESULTS:There was a general lack of knowledge about clinical pharmaceutical service,higher demands on participation of pharmacists in clinical work were made,and present situation was less than satisfied.CONCLUSION:Clinical service mode of patients first and rational drug use foremost should be established,Chinese pharmacists should improve their knowledge construction and clinical service capability.
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OBJECTIVE: To standardize and simplify the drug receving and preparing model. METHODS: Reasonable pharamcy inventory parameters were set up based on our experience; second order drug storeroom dynamic inventory system was designed and applied, and the indexes of drug storeroom inventory and workload of the new and the old models were reported and analyzed. RESULTS: The new warning system provided an optimal inventory, and in which the incidences of overstock or stock shortage, the frequency of daily drug receving, drug kinds and the time used with checking stock and filling receipt were all significantly less than in the traditional model. CONCLUSION: Due to the second order drug storeroom dynamic inventory warning system, the drug receiving was more scientific, the drug stock amount was reduced and the drug receiving time was saved, and the mangament level of hospital drug storeroom inventory was enhanced.
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100MIC.The endotoxin could be released more and more with the time.CONCLUSION:It is reasonable to choose antibiotics to refer to the characteristics of the endotoxin release by germs.