Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.

Evidence-based assessment of proton-pump inhibitors in Helicobacter pylori eradication: A systematic review

Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.

Proton-pump inhibitor-induced hypomagnesemia: Current research and proposed mechanisms

Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective,controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the feld of PPIH and the proposed mechanisms of this effect.

A Pharmacist-Led Medication Use Evaluation of Proton-Pump Inhibitors

Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine annual clinic cost-savings per prescription. Design： The study was conducted as a prospective, medication use evaluation. Using an electronic medical record system at a clinic, reports generated all patients receiving PP1 therapy from January 2013-June 2015. Patients were encouraged to participate in a PPI discontinuation trial through a pharmacist-led educational session. Participants were followed-up three months post enrollment to assess their quality of life through a survey assessing severity and frequency of symptoms. Participants unable to maintain symptom control after the intervention were referred back to their primary care physician for further evaluation. Results： Of one hundred participants, 25% （n = 25） were able to discontinue the use of PPI by lifestyle modifications, 43% （n = 43） refused to discontinue PP1 therapy and lifestyle changes due to the severity of their symptoms, 17% （n = 17） switched to over-the-counter H2 receptor antagonist daily to control their symptoms, 9% （n = 9） used PPIs only as needed, and 6% （n = 6） of participants were dropped from the study after three failed communication attempts. The clinic saved approximately $11 thousand annually for every one prescription of PPI＇s. Conclusions： Discontinuation of PPI or step-down therapy was possible for patients with mild-moderate GERD （Gastroesophageal Reflux Disease） symptoms when mediated by pharmacist counseling and follow-up. Also, the annual PPI expenditure at this clinic will decrease due to participant＇s discontinuation of therapy.

Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis

AIM:To investigate the preventive effects of low-dose proton-pump inhibitors(PPIs) for upper gastrointestinal bleeding(UGIB) in end-stage renal disease.METHODS:This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013.We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs(control group).RESULTS:During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years.The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo.Bleeding occurred in only two patients in the PPI group(2.5/1000 person-years) and in 39 patients in the control group(19.2/1000 person-years).Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group(log-rank test, P < 0.001).Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB.After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group(HR = 13.7, 95%CI:1.8-101.6; P = 0.011).CONCLUSION:The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

288家医院质子泵抑制剂注射剂脱包调剂现状及对药品质量的影响分析

目的探讨质子泵抑制剂(PPIs)注射剂的医院脱包(脱去硬纸盒外包装)调剂现状及其对药品质量的影响。方法比较2010年版、2015年版、2020年版《中国药典》及国家药品监督管理局(NMPA)、美国食品和药物管理局(FDA)、欧洲药品管理局(EMA)官网药品说明书中PPIs注射剂贮藏条件的差异。通过问卷星设计并向全国30个省(96个市)的288家三级、二级、二级以下医院发放调查问卷,调查PPIs注射剂在医院的脱包贮藏现状。观察注射用奥美拉唑钠光照后的颜色变化,采用高效液相色谱-质谱法测定脱包后在光照下奥美拉唑的含量。结果《中国药典》要求PPIs应在遮光或凉暗处贮藏,国内上市的PPIs注射剂要求遮光贮藏的药品说明书占90.59%,要求避光贮藏的占9.41%,其中注射用奥美拉唑钠原研药规定脱包后在一般室内光照条件下有效期不超过24 h;FDA和EMA的奥美拉唑钠和艾司奥美拉唑钠注射剂药品说明书均要求现用现脱包。共回收问卷408份,有效问卷356份,有效回收率为87.25%。其中,三级医院最多(占68.54%),被调查人员主要为药师(占64.89%),76.69%的工作年限超过10年,仅48.03%接受过遮光药品贮藏管理培训。PPIs注射剂在药房、运输、病区环节脱包的分别占43.75%,52.78%,79.86%,脱包后未遮光贮藏的分别占35.71%,82.24%,77.83%;脱包后使用时长主要为3~5 d(占45.14%)。注射用奥美拉唑钠脱包后在一般室内光照条件下24 h内表面变黄,随光照时间的延长逐渐加深;连续光照30 d,奥美拉唑浓度的RSD为6.67%(>5%),光照16 d的含量较光照1 d减少了12.30%。结论在医院药品流通各环节中,PPIs注射剂提前脱包且脱包后未遮光贮藏的情况普遍存在,导致药品含量降低。建议相关部门应制订PPIs注射剂的脱包管理制度,要求现用现脱包,脱包后遮光贮藏。

质子泵抑制剂对非小细胞肺癌免疫检查点抑制剂疗效的影响

目的探讨质子泵抑制剂(PPIs)对接受免疫检查点抑制剂(ICIs)治疗的非小细胞肺癌(NSCLC)患者疗效的影响。方法选择2020年1月至2022年10月就诊于郑州大学第一附属医院的NSCLC患者200例为研究对象,根据入组前30d是否有PPIs服药史(至少连续服用7 d)将其随机分为抑酸组和非抑酸组,每组100例,两组患者均根据病情需要接受ICIs抗肿瘤治疗。收集患者性别、年龄、吸烟史、肺癌家族史、病理及临床数据、治疗方案等基线数据。自患者接受ICIs治疗开始随访12个月,比较两组疗效、无病生存率、总生存率和药物不良反应发生情况。结果非抑酸组总有效率(72.00%)高于抑酸组(53.00%)(P<0.05)。多因素COX回归显示,服用PPIs可显著降低NSCLC患者随访期间的无病生存率(HR:0.428,95%CI:0.282~0.650)和总生存率(HR:0.538,95%CI:0.304~0.953)。两组患者经ICIs治疗后主要不良反应发生率比较,差异均无统计学意义(P>0.05)。结论服用PPIs可能对ICIs治疗NSCLC的疗效产生负面影响,并可能导致患者预后不良。

紧密型帮扶驻点药师干预对Ⅰ类切口手术质子泵抑制剂应用的影响

目的研究3种Ⅰ类切口手术中,紧密型帮扶驻点药师干预质子泵抑制剂(PPIs)注射剂的应用效果。方法选取2020年1月至12月乐昌市人民医院收治的160例外科住院患者为对照组,2021年1月至12月收治的160例外科住院患者为干预组。对照组采取常规的管理方式,干预组采用紧密型帮扶驻点药师干预的管理模式。对两组PPIs用药情况及不合理用药情况进行分析。结果干预组PPIs注射液使用率为37.5%,低于对照组的77.5%,差异有统计学意义(P<0.05)。干预组的PPIs注射液不合理使用率为30.6%,低于对照组的50.0%,差异有统计学意义(P<0.05)。干预组的PPIs注射剂用药天数为(2.06±2.80)d,少于对照组的(4.78±3.38)d,差异有统计学意义(P<0.05)。结论对外科3种Ⅰ类切口手术PPIs注射剂的使用,紧密型帮扶药师通过药学干预促进PPIs注射剂合理用药取得满意效果。

静脉用质子泵抑制剂使用合理性分析及院内管控

目的:探讨我院静脉用质子泵抑制剂(PPIs)使用的合理性。方法:收集2022年度我院使用PPI的病例,共226份病历资料符合要求。结果:进入季度使用金额排名前五名次数最多的PPIs依次是注射用艾司奥美拉唑、注射用艾普拉唑、注射用雷贝拉唑、注射用奥美拉唑;病历不合理率为64.16%,无适应证用药53例(36.55%),用法用量不适宜46例(31.72%),疗程不适宜21例(14.48%),遴选药品不适宜17例(11.72%),联合用药不适宜5例(3.45%),溶媒不适宜3例(2.07%)。结论:对PPI使用不合理的现象需要加强重点品种管控,提升医师的合理用药水平,促进合理用药。

住院患者质子泵抑制剂的使用情况分析

目的分析近年来四川省医学科学院·四川省人民医院住院患者质子泵抑制剂(PPIs)使用情况,为临床PPIs的合理使用提供参考。方法收集医院住院信息管理系统中2019—2023年住院患者使用PPIs相关数据信息,包含药物名称、规格、剂型、使用数量和金额等;依据世界卫生组织推荐的限定日剂量(DDD)、用药数量和金额、用药频度(DDDs)和限定日费用(DDC)等药物经济学指标,对相关数据进行统计分析。结果医院住院患者PPIs的使用量呈逐年下降趋势,且使用金额及金额占比均呈逐年下降趋势,其中雷贝拉唑(口服)、兰索拉唑(口服)与艾司奥美拉唑(注射)分别占据DDDs和使用金额的前3位。用药金额与用药人数同步性呈逐年变好趋势,B/A值为1.00的品种占比从2019年的0升至2021年的25%,再到2023年的75%。结论医院住院患者PPIs使用基本合理,用量较大的雷贝拉唑(口服)、兰索拉唑(口服)和艾司奥美拉唑(注射)是目前抑酸剂的一线用药。

外科手术患者围术期使用质子泵抑制剂预防应激性溃疡的合理性分析

目的:分析外科手术患者围术期使用质子泵抑制剂预防应激性溃疡的合理性。方法:回顾性分析2019年9月—2022年8月于南京医科大学第二附属医院外科行手术并于围术期应用质子泵抑制剂的1 640例患者的临床资料,统计各科室患者围术期质子泵抑制剂预防应激性溃疡的不合理用药情况。结果:1 640例患者中,质子泵抑制剂预防应激性溃疡的不合理用药发生率为76.65%(1 257/1 640),用药指征不合理例数最多,占85.28%(1 027/1 257)。结论:该院外科手术患者围术期使用质子泵抑制剂预防应激性溃疡存在不合理情况,以用药指征不合理为主,相关部门需制定相关干预措施,规范外科围术期质子泵抑制剂的使用。

24h pH-阻抗监测对胃食管反流病患者治疗反应性的预测价值

目的探讨24 h pH-阻抗监测对胃食管反流病(gastroesophageal reflux disease,GERD)患者治疗反应性的预测价值。方法选取2020年12月—2022年11月成都市第三人民医院接受治疗的286例具有典型反流症状的GERD患者作为研究对象,所有患者均接受质子泵抑制剂(proton pump inhibitors,PPI)治疗,2个月后根据治疗效果,将患者分为有效组和无效组。对比2组患者的日常生活习惯、高分辨率测压结果、24 h pH-阻抗监测结果、症状及量表评分。采用多因素logistic回归分析筛选治疗反应影响因素,构建预测模型,绘制ROC曲线分析其预测价值。结果治疗2个月后,有效组纳入184例,无效组纳入102例。有效组治疗前食管下括约肌(low esophageal sphincter,LES)长度以及LES静息压均低于无效组(P<0.10),远端潜伏期(distal latency,DL)及远端收缩积分(distal contractile integral,DCI)均高于无效组(P<0.10),有效组患者治疗前的酸暴露时间(acid exposure time,AET)≥6%、总反流发作次数、DeMeester评分均低于无效组(P<0.10);有效组反流后吞咽诱发的蠕动波(post-reflux swallow-induced peristaltic wave,PSPW)指数≥61%比例、平均夜间基线阻抗(mean nocturnal baseline impedance,MNBI)值≥2292Ω比例高于无效组(P<0.10)。多因素logistic回归分析显示,LES静息压(OR=0.738)、DL(OR=3.643)、DCI(OR=1.124)及24 h pH-阻抗监测综合预测(OR=1.940)水平均可影响GERD治疗反应性(P<0.10)。ROC曲线分析显示,24 h pH-阻抗监测的综合预测水平(AUC=0.969,特异度=90.2%,敏感度=91.3%)高于其他影响因素。结论24 h pH-阻抗监测的相关参数可高度预测典型的GERD患者对采用PPI后的治疗反应。

康复新液联合PPI治疗反流性食管炎的疗效及安全性Meta分析

目的纳入系统评价康复新液联合质子泵抑制剂(Proton pump inhibitor,PPI)治疗反流性食管炎(Reflux esophagitis,RE)相较于单独使用PPI的疗效和安全性评价。方法以康复新液、反流性食管炎、反流性食道炎、KangFuXin、reflux esophagitis等为检索词在CNKI、WanFang Data、VIP、Embase、Web of Science、PubMed和The Cochrane Library数据库检索康复新液联合PPI治疗RE的随机对照研究,采用RevMan 5.4软件进行Meta分析。结果共纳入25项研究,统计分析结果显示康复新液联合PPI治疗RE较单独PPI治疗能显著提高临床有效率(95%CI:1.15,1.24)、胃镜下有效率(95%CI:1.14,1.22),血清胃泌素(95%CI:1.15,2.03)和胃动素的分泌(95%CI:0.96,1.39),降低复发率(95%CI:0.20,0.61),且不会增高不良反应发生率(95%CI:0.33~0.79),此外,不同PPI种类以及患者年龄高低对临床有效率无显著影响,而不同内镜下诊断标准对内镜下有效率也无显著影响。结论康复新液联合PPI治疗RE较单独PPI治疗能取得更好的疗效且减少疾病复发,并不会额外造成不良反应的发生。

带量采购政策下口服质子泵抑制剂在宣武医院的应用分析

目的:分析带量采购奥美拉唑肠溶胶囊对其他4个口服质子泵抑制剂(Proton Pump Inhibitors,PPIs)使用的影响及其处方合理性,探讨带量采购政策执行过程中存在的问题,促进临床合理用药和优化带量采购政策。方法:采用药物经济学方法,根据实施集采1年PPIs使用情况分析门诊药物奥美拉唑带量采购实施前后口服PPIs的销售数量、销售金额、用药频度(DDDs)和日均费用(DDC)、仿制药替代率、PPIs构成比、日剂量、排序比等指标变化情况。结果:奥美拉唑肠溶胶囊带量采购后使原用药奥美拉唑肠溶片的DDDs降低,同时也对其他抑酸药的使用产生影响,不同品规使用结构有变化,集采后奥美拉唑DDDs排序第二,代替了集采前兰索拉唑的排序。雷贝拉唑DDDs仍居首位,艾司奥美拉唑DDDs保持第三。PPIs的DDC整体下降,奥美拉唑的排序比B/A>1,集采药品带来的经济效益与社会效益同步化。就双倍标准日剂量的占比而言,奥美拉唑和雷贝拉唑增加而兰索拉唑减少。肾科PPIs消耗量下降,主要与奥美拉唑的用量减少、法莫替丁使用量增加相关。此外,仍有13.87%的奥美拉唑处方被认为是超说明书用药,需加强监管。结论:实施集采后,口服PPIs实现量增价减的同时还存在一些亟待解决的问题,比如日剂量并非是最低有效剂量、肾科对集采药品接受度不高、超说明书用药等,这些问题影响了政策正面作用的发挥,应加强精细管理促进集采药品合理使用。

PPIs与重症缺血性脑卒中患者短期、长期死亡风险的关联:基于MIMIC-Ⅲ数据库的回顾性队列研究

目的 研究质子泵抑制剂(PPIs)的使用与重症缺血性脑卒中患者短期、长期死亡风险的关联。方法 基于美国重症监护医学信息数据库Ⅲ(MIMIC-Ⅲ),纳入年龄≥18岁、首次入住重症监护病房(ICU)并诊断为缺血性脑卒中的患者。根据住院期间是否使用过PPIs(泮托拉唑、兰索拉唑和奥美拉唑),将患者分为PPIs组和非PPIs组。对比2组基线数据后,采用Kaplan-Meier生存曲线和Cox比例风险回归模型分析使用PPIs与重症缺血性脑卒中患者ICU死亡风险、30 d死亡风险、90 d死亡风险的关联。结果 共纳入1 015例患者,其中PPIs组402例,非PPIs组613例。基线资料显示,重症缺血性脑卒中患者的ICU死亡率、30 d死亡率、90 d死亡率分别为15.37%,13.60%,20.10%。Kaplan-Meier生存曲线表明,相对于非PPIs组,PPIs组的ICU死亡风险较低(P=0.002)。Cox比例风险回归模型在调整多个变量后的结果显示,PPIs组相对于非PPIs组的ICU死亡风险比为0.671 9 [95%CI(0.478 8,0.942 8),P=0.021],但2组患者30 d和90 d的死亡风险差异均无统计学意义(P> 0.05)。结论 重症缺血性脑卒中患者中,使用PPIs可能会有效降低患者的ICU死亡风险,但对患者的30 d死亡风险和90 d死亡风险没有改善作用。

社区居民长期服用质子泵抑制剂和处方精简的现状及影响因素研究

背景质子泵抑制剂(PPI)长期服用的潜在风险和潜在不合理用药问题逐渐得到重视。PPI处方精简已得到广泛认同,我国社区居民中长期服用PPI的情况及进行PPI处方精简的意愿尚不明确。目的了解社区居民长期服用PPI及PPI处方精简的现状,探讨其影响因素并提出改进措施。方法于2018年4月—2020年1月对在北京市西城区什刹海社区卫生服务中心就诊长期服用PPI的389例居民进行调查,通过社区电子健康信息系统和电话问卷调查收集居民一般情况、PPI使用情况、是否同时使用非甾体类抗炎药(NSAIDs)和/或抗血小板药物、合并慢性疾病情况、用药数量、是否可开展PPI精简处方、多重用药情况等。通过电话问卷调查2020年6—12月仍长期服用PPI的92例居民对PPI长期服用的认知和处方精简态度。对可开展处方精简居民连续服用PPI时间>6个月的影响因素采用多因素Logistic回归分析。结果本次调查排除拒绝回答或无法联系、未连续服用PPI的患者后,最终318例长期服用PPI的居民纳入研究,平均年龄(63.9±12.5)岁,女性占61.0%,合并慢性疾病的数量平均为(3.3±1.4)种,用药数量平均为(6.1±3.3)种。可开展PPI处方精简的居民231例(72.6%)。PPI的处方指征中预防NSAIDs和抗血小板药物消化道损伤最多[202例(63.5%)]。多因素Logistic回归分析显示:居民的年龄(OR=1.044,95%CI=1.016~1.073)、用药数量(OR=1.175,95%CI=1.009~1.376)是连续服用PPI>6个月的影响因素(P<0.05)。2020年6—12月仍长期服用PPI且可开展处方精简的居民中82.6%(76/92)知晓药物使用适应证,70.7%(65/92)不了解长期服用PPI的潜在不良反应,71.7%(66/92)的愿意在全科医生的帮助下精简PPI处方,对于处方精简的主要担心是症状反复。结论社区卫生服务机构长期服用PPI居民的年龄较大、女性居多,多重用药比例高;应关注年龄大、用药数量较多居民使用PPI药物的情况,需加强对PPI长期服用潜在风险的宣教;长期服用PPI的居民对PPI处方精简的态度积极,但需加强对PPI长期用药管理。

基于MIMIC-Ⅳ数据库分析PPIs与AECOPD患者预后相关性的回顾性队列研究

目的探讨质子泵抑制剂(PPIs)的使用与慢性阻塞性肺疾病急性加重期(AECOPD)患者短期、长期预后关系。方法回顾性收集MIMIC-Ⅳ数据库中2008年1月—2019年12月入住重症监护病房(ICU)的AECOPD患者临床资料。根据在ICU治疗期间是否使用PPIs,将患者分别纳入PPIs组和非PPIs组。比较2组患者一般情况,并使用Kaplan-Meier法绘制生存曲线,分别比较2组在28 d、90 d生存率的差异。采用Cox比例风险回归模型分析PPIs使用情况与患者28 d、90 d死亡风险的关联。结果共纳入447例患者,其中PPIs组358例,非PPIs组89例。PPIs组28 d死亡率、90 d死亡率分别为15.64%、23.46%,均低于非PPIs组的31.46%、40.45%(P<0.05)。Kaplan-Meier曲线分析结果显示,PPIs组28 d、90 d生存率均高于非PPIs组(P<0.001)。Cox比例风险回归模型分析结果表明,在校正所有纳入变量后,与非PPIs组比较,PPIs组28 d、90 d死亡风险比分别为0.58[95%CI(0.35,0.94),P=0.030]、0.63[95%CI(0.41,0.96),P=0.022]。结论AECOPD患者使用PPIs可能会降低其28 d、90 d死亡风险。

注射用奥美拉唑钠致低钠血症1例分析

目的分析注射用奥美拉唑钠致低钠血症不良反应及其代谢基因型和与三唑类抗真菌药相互作用,为临床安全使用质子泵抑制剂提供参考。方法报道1例80岁感染侵袭性肺曲霉菌病患者,分析其用药后致低钠血症原因。结果患者CYP2C19慢代谢型且联合三唑类抗真菌药物,低钠血症可能与注射用奥美拉唑钠有关,怀疑为注射用奥美拉唑钠导致的不良反应。结论临床发现难治性低钠血症时需考虑质子泵抑制剂引起的可能性。对于CYP2C19慢代谢型患者,质子泵抑制剂与肝药酶抑制剂应谨慎合并使用。

Impact of Proton-pump Inhibitors on the Pharmacodynamic Effect and Clinical Outcomes in Patients Receiving Dual Antiplatelet Therapy after Percutaneous Coronary Intervention： A Propensity Score Analysis

Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much uncertainty in clinical practice.We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention （PCI） in a long-term follow-up study.Methods：A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy （DAPT） at a single center from January 2013 to December 2013 were enrolled.Adenosine diphosphate （ADP）-induced platelet aggregation inhibition was measured by modified thromboelastography （mTEG） in 5042 patients.Propensity score matching （PSM） was applied to control differing baseline factors.Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events （MACCEs）,as well as individual events,including all-cause death,myocardial infarction,unplanned target vessel revascularization,stent thrombosis,and stroke.Results：Among the whole cohort,27.2% were prescribed PPIs.The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users （42.0 ± 30.9% vs.46.4 ± 31.4%,t =4.435,P 〈 0.001）.Concomitant PPI use was not associated with increased MACCE through 2-year follow-up （12.7% vs.12.5%,x2 =0.086,P =0.769）.Other endpoints showed no significant differences after multivariate adjustment,regardless of PSM.Conclusion：In this large cohort of real-world patients,the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.