Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy最新文献

英文中文

Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation 心房颤动患者急性缺血性卒中后口服抗凝的起始时间

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-07 DOI: 10.1002/phar.2345

M. Smythe, D. Parker, Candice L. Garwood, A. Cuker, S. Messé

Patients with atrial fibrillation (AF) who suffer an acute ischemic stroke are at risk for both hemorrhagic transformation and recurrent ischemic stroke in the acute post‐stroke period. Oral anticoagulants are recommended for secondary stroke prevention in patients with AF. The optimal time to initiate anticoagulant therapy after acute ischemic stroke in patients with AF is uncertain. There is concern that early initiation increases the risk of hemorrhagic transformation, whereas delayed initiation leaves the patient at risk for recurrent ischemic stroke. In this article, we provide a review of the risk of hemorrhagic transformation of acute ischemic stroke as well as review the literature and major guidelines addressing the timing of anticoagulation initiation after an acute ischemic stroke in patients with AF. Relevant articles published from 1990 to the present were identified using the PubMed and Embase databases. The majority of available literature is observational data. Large ischemic lesions, cerebral microbleeds, thrombolytic therapy, and other clinical factors may increase the risk of hemorrhagic transformation of an acute ischemic stroke. Parenteral anticoagulation within 48 hours is associated with an increased risk of hemorrhagic transformation and is not recommended. Insufficient data exist to support the safety of routine oral anticoagulant (direct oral anticoagulants or warfarin) initiation within 48 hours of an acute ischemic stroke. Direct oral anticoagulant initiation within 2 days of an acute ischemic stroke is associated with a 5% rate of hemorrhagic transformation. Infarct size and presence of hemorrhage are important factors in identifying the optimal time to initiation and should guide decisions when available. A recommended framework for patient decision making is provided. Randomized controlled trials in this area are needed to identify the optimal timing of anticoagulation initiation, and such trials are under way.

急性缺血性卒中心房颤动(AF)患者在急性卒中后有出血转化和复发性缺血性卒中的风险。口服抗凝药物被推荐用于房颤患者的二级卒中预防。房颤患者急性缺血性卒中后开始抗凝治疗的最佳时间尚不确定。人们担心早期开始会增加出血性转化的风险，而延迟开始则会使患者处于复发性缺血性卒中的风险中。在本文中，我们回顾了急性缺血性卒中出血转化的风险，并回顾了AF患者急性缺血性卒中后抗凝起始时间的文献和主要指南。从1990年至今发表的相关文章通过PubMed和Embase数据库进行了识别。大多数可用的文献都是观测数据。大的缺血性病变、脑微出血、溶栓治疗和其他临床因素可能增加急性缺血性脑卒中出血转化的风险。48小时内静脉抗凝与出血转化的风险增加有关，不建议使用。目前还没有足够的数据支持急性缺血性卒中后48小时内常规口服抗凝剂(直接口服抗凝剂或华法林)的安全性。急性缺血性中风后2天内直接口服抗凝剂可使出血转化率降低5%。梗死面积和出血的存在是确定最佳起始时间的重要因素，并应在可行的情况下指导决策。为患者决策提供了一个推荐的框架。需要在这一领域进行随机对照试验，以确定抗凝起始的最佳时机，此类试验正在进行中。

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引用次数: 14

Evaluation of Patients with Heart Failure to Determine Eligibility for Treatment with Sacubitril/Valsartan: Insights from a Veterans Administration Healthcare System 评估心力衰竭患者是否有资格接受苏比里尔/缬沙坦治疗:来自退伍军人管理局医疗保健系统的见解

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2328

Jamie Han, F. Chung, Q. Nguyen, F. V. Mody, C. Jackevicius

Despite evidence that supports the use of sacubitril/valsartan – the first angiotensin II receptor blocker–neprilysin inhibitor – for mortality reduction in patients with heart failure (HF), it remains underprescribed. The objective of this study was to evaluate eligibility for initiation of sacubitril/valsartan treatment in patients with HF within the largest Veterans Administration healthcare system in the United States.

尽管有证据支持使用苏比里尔/缬沙坦(第一种血管紧张素II受体阻滞剂-奈普利素抑制剂)来降低心力衰竭(HF)患者的死亡率，但其处方仍然不足。本研究的目的是在美国最大的退伍军人管理局医疗保健系统中评估HF患者开始使用苏比里尔/缬沙坦治疗的资格。

引用次数: 9

Compassionate Use of Cefiderocol in the Treatment of an Intraabdominal Infection Due to Multidrug-Resistant Pseudomonas aeruginosa: A Case Report. 在治疗耐多药性铜绿假单胞菌引起的腹腔感染时同情使用头孢羟氨苄：病例报告。

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 Epub Date: 2019-10-22 DOI: 10.1002/phar.2334

Ryan W Stevens, Megan Clancy

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections often represent a therapeutic challenge requiring utilization of older, more toxic antibiotics, or new agents with limited data. Once susceptibility to β-lactam and fluoroquinolone antibiotics has been lost, other therapeutic options such as aminoglycoside or polymyxin antibiotics carry significant adverse effects such as nephrotoxicity, neurotoxicity, and ototoxicity. A novel cephalosporin, cefiderocol, lacks gram-positive and anaerobic activity but offers broad coverage of gram-negative bacteria, including P. aeruginosa. A unique catechol side chain gives it activity as a siderophore, thereby increasing bacterial uptake and decreasing efflux. Additionally, cefiderocol is stable against a wide array of β-lactamases. Despite these promising characteristics, there are minimal data currently available in the literature detailing the use of cefiderocol in the treatment of MDR P. aeruginosa infections. We present a case of a 46-year-old man who developed an MDR P. aeruginosa intraabdominal infection where serious and life-threatening toxicities to aminoglycosides and polymyxin antibiotics led to the utilization of cefiderocol on compassionate use approval. The isolate was susceptible to cefiderocol, and the patient was treated for 28 days of therapy. He demonstrated clinical and radiographic resolution of his infection and was discharged to home.

耐多药（MDR）铜绿假单胞菌感染通常是一种治疗难题，需要使用毒性更大的老抗生素或数据有限的新药。一旦对β-内酰胺类和氟喹诺酮类抗生素失去敏感性，氨基糖苷类或多粘菌素类抗生素等其他治疗选择就会带来明显的不良反应，如肾毒性、神经毒性和耳毒性。新型头孢菌素 cefiderocol 缺乏对革兰氏阳性菌和厌氧菌的活性，但可广泛用于革兰氏阴性菌，包括铜绿假单胞菌。独特的儿茶酚侧链使其具有苷酸活性，从而增加细菌的吸收，减少外流。此外，头孢羟氨苄对多种β-内酰胺酶都很稳定。尽管头孢羟氨苄具有这些良好的特性，但目前文献中关于头孢羟氨苄用于治疗 MDR 铜绿葡萄球菌感染的详细数据极少。我们介绍了一例 46 岁男性的 MDR 铜绿假单胞菌腹腔内感染病例，该患者对氨基糖苷类和多粘菌素类抗生素产生了严重且危及生命的毒性反应，因此在获得同情使用批准后使用了头孢羟氨苄。分离出的菌株对头孢羟氨苄敏感，患者接受了 28 天的治疗。他的感染在临床和影像学上都得到了缓解，并已出院回家。

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引用次数: 35

Drs. Eggleston et al. Reply to Drs. Grundmann et al Drs。Eggleston等人。回复博士。Grundmann等

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2337

W. Eggleston, R. Stoppacher, Kyle Suen, J. Marraffa, Lewis S. Nelson

引用次数: 0

Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease l -谷氨酰胺预防镰状细胞病患者血管闭塞性疼痛危像的系统评价

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2329

Nicole E. Cieri‐Hutcherson, T. Hutcherson, Erin E. Conway‐Habes, Brianna N. Burns, Nathan A. White

l‐glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso‐occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l‐glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l‐glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l‐glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk‐of‐bias assessments were conducted using the Risk of Bias in Non‐Randomized Studies‐of Interventions (ROBINS‐I) tool and the revised Cochrane risk‐of‐bias tool for randomized studies. Three studies assessing the effect of exogenous l‐glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l‐glutamine, although some conflicting results were noted between studies. l‐glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l‐glutamine has limited high‐quality evidence supporting its use. Although l‐glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l‐glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.

l‐谷氨酰胺于2017年被美国食品和药物管理局(FDA)批准用于治疗镰状细胞病(SCD)。血管闭塞危象(VOC)发生在SCD患者中，并与急性疼痛发作有关。本系统综述总结了l -谷氨酰胺在SCD患者中预防VOC和相关疼痛的证据。我们检索了Medline、Embase和国际药物摘要中关于SCD患者使用l -谷氨酰胺的记录。资格标准确定了在给予l -谷氨酰胺的人群中进行的调查的主要报告，报告了与VOC或相关疼痛相关的结果，以英文出版，并可作为全文。提取并记录了所有相关的疗效、安全性、参与者人口统计数据和研究方法特征。使用非随机干预研究的偏倚风险(ROBINS - I)工具和修订后的Cochrane随机研究的偏倚风险工具进行偏倚风险评估。评估外源性l‐谷氨酰胺给药对SCD患者影响的三项研究符合入选标准:一项前瞻性非随机对照研究和两项前瞻性随机对照试验。在接受l -谷氨酰胺治疗的患者中，挥发性有机化合物的发生率和相关的住院率降低，尽管在研究中注意到一些相互矛盾的结果。L‐谷氨酰胺一般耐受良好。一个或多个符合条件的研究的局限性包括样本量小、非盲性和研究组在基线时不同。谷氨酰胺支持其使用的高质量证据有限。虽然l -谷氨酰胺被FDA批准用于预防VOC疼痛的频繁发作，但只有一项随机对照试验有强有力的证据支持这一适应症。基于系统评价的结果，l -谷氨酰胺可以被考虑用于不能接受羟脲治疗的患者，或者除了羟脲治疗外，还可以用于减少VOC和相关疼痛。

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引用次数: 23

Critique of “Kratom Use and Toxicities in the United States” 《在美国使用克拉托姆及其毒性》批判

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2336

O. Grundmann, P. Brown, E. Boyer, Marc T Swogger, Z. Walsh, W. Prozialeck, Andrew C. Kruegel, Charles A. Veltri, S. Dudley

Emergency Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; Department of Psychiatry, University of Rochester Medical Center, Rochester, New York; Department of Psychology, University of British Columbia, Kelowna, British Columbia; Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois; Department of Chemistry, Columbia University, New York, New York; College of Pharmacy-Glendale, Midwestern University, Glendale, Arizona; Arizona Poison and Drug information Center, Tucson, Arizona

哈佛医学院，布莱根妇女医院，波士顿，马萨诸塞州急诊科;罗彻斯特大学医学中心精神科，纽约州罗彻斯特;英属哥伦比亚大学心理学系，英属哥伦比亚基洛纳;伊利诺斯州唐纳斯格罗夫中西部大学研究生院药学系;哥伦比亚大学化学系，美国纽约;中西部大学格伦代尔药学院，亚利桑那州格伦代尔;亚利桑那州毒药和药物信息中心，图森，亚利桑那州

引用次数: 1

Impact of a New Consumer Form on the Quantity and Quality of Adverse Event Reports Submitted to the United States Food and Drug Administration 新的消费者表格对提交给美国食品和药物管理局的不良事件报告的数量和质量的影响

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2325

M. Muñoz, C. Delcher, G. D. Dal Pan, C. Kortepeter, E. Wu, Y. Wei, Hong Xiao, A. Winterstein

Consumers and healthcare professionals can voluntarily report adverse experiences associated with drug products to the United States Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Consumers and healthcare professionals used the same general voluntary reporting form (GVR) until mid‐2013, when a consumer voluntary reporting form (ConVR), written in plain language, was implemented. The objective of this study was to examine the effect of the ConVR on the quality and quantity of consumer reports submitted directly to FAERS.

消费者和医疗保健专业人员可以自愿向美国食品和药物管理局(FDA)不良事件报告系统(FAERS)报告与药品相关的不良经历。消费者和医疗保健专业人员使用相同的一般自愿报告表格(GVR)，直到2013年年中，消费者自愿报告表格(ConVR)以通俗易懂的语言编写，才开始实施。本研究的目的是检验ConVR对直接提交给FAERS的消费者报告的质量和数量的影响。

引用次数: 4

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations 布雷沙诺酮治疗产后抑郁症:临床证据和实践考虑

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-11-01 DOI: 10.1002/phar.2331

Lauren D Leader, M. O'connell, A. Vandenberg

Our aim was to review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD). Pertinent data and information were obtained via PubMed (1993 to August 2018). Articles published in English that evaluated the safety and efficacy of brexanolone and other off‐label PPD treatments were included. Literature regarding epidemiology and pathophysiology of PPD was also selected. Brexanolone, administered as an intravenous infusion over 60 hours, produced a statistically significant and clinically meaningful reduction in Hamilton Depression Rating Scale (HAM‐D) scores compared with placebo at both 60 and 90 μg/kg/hour in patients with moderate to severe PPD. Brexanolone groups had higher response and remission rates compared with placebo. Common adverse effects were somnolence, dizziness, and headache. A small percentage (4%) of patients required cessation of therapy due to excessive sedation or loss of consciousness. Although the evidence for brexanolone as a novel treatment for PPD looks promising, a Risk Evaluation and Mitigation Strategies (REMS) program requirement and the logistics of prolonged infusions serve as barriers to treatment. A discussion of these obstacles as well as pharmacokinetics, monitoring, and dosing is provided. Brexanolone is a novel antidepressant indicated for the treatment of PPD. Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of oversedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events.

我们的目的是回顾brexanolone (Zulresso)的疗效、安全性和药理学，brexanolone (Zulresso)是一种新的抗抑郁药，具有新的作用机制，治疗产后抑郁症(PPD)。相关数据和信息通过PubMed获得(1993年至2018年8月)。评估布雷沙诺酮和其他标签外PPD治疗的安全性和有效性的英文文章被纳入。还选择了有关PPD流行病学和病理生理学的文献。在中度至重度PPD患者中，静脉输注布雷沙诺酮超过60小时，与安慰剂相比，在60和90 μg/kg/小时时，汉密尔顿抑郁评定量表(HAM‐D)评分均有统计学意义和临床意义的降低。与安慰剂组相比，布雷沙诺酮组有更高的反应和缓解率。常见的不良反应是嗜睡、头晕和头痛。一小部分(4%)患者因过度镇静或意识丧失而需要停止治疗。尽管布雷沙诺酮作为一种治疗PPD的新方法的证据看起来很有希望，但风险评估和缓解策略(REMS)计划的要求和长期输注的后勤工作成为治疗的障碍。讨论了这些障碍以及药代动力学、监测和给药。Brexanolone是一种治疗PPD的新型抗抑郁药。临床试验表明，布雷沙诺酮可显著降低中度至重度PPD妇女的抑郁评分。由于过度镇静和意识丧失的风险，REMS程序将被放置到位，以减轻不良事件的风险。

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引用次数: 24

Pharmacokinetics and Pharmacodynamics of Extended‐Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open‐Label Study 接受持续肾脏替代治疗的危重患者长期输注头孢吡肟的药代动力学和药效学:一项前瞻性、开放标签研究

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-10-22 DOI: 10.1002/phar.2332

C. Philpott, C. Droege, M. Droege, D. Healy, Joshua D. Courter, N. Ernst, N. Harger, M. Foertsch, J. Winter, Kristen E. Carter, Suzanne Van Fleet, K. Athota, E. Mueller

To evaluate extended‐infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD).

评估延长输注(EI)头孢吡肟药代动力学(PK)和危重患者接受持续静脉静脉血液滤过(CVVH)或持续静脉静脉血液透析(CVVHD)的药效学目标实现情况。

引用次数: 11

Alternative Viewpoint on Tacrolimus Concentration‐to‐Dose Ratios in Kidney Transplant Recipients and Relationship to Clinical Outcomes 肾移植受者他克莫司浓度剂量比及其与临床结果关系的另一种观点

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Pub Date : 2019-10-01 DOI: 10.1002/phar.2321

G. Thölking, S. Reuter

Bartlett et al. reported in a large US-based single-center study that the tacrolimus metabolism rate, defined as the concentration-to-dose ratio (CDR), does not have an impact on biopsy-proven acute rejection as previously shown in kidney transplant recipients. In contrast to our results, they observed a higher mortality rate in nonrapid metabolizers (NRM) compared to rapid metabolizers (RM). Although estimated glomerular filtration rate values were lower at several time points in RMs compared to NRM, they vote against CDR-based tailoring of the tacrolimus therapy. First, Bartlett et al. defined RM and NRM differently compared to previous studies. Their CDR cut-off for RM/NRM was 2.04 (ng/ml)*1/ mg that is considerably higher compared to previous definitions [< 1.05 (ng/ml)*1/mg] 4 and < 0.67 (ng/ml)*1/mg. In accordance, they identified 74.3% RM compared to 39.1% and 25.2% RM. Hence, a substantial number of their RM would have been classified as NRM in the other studies. Notably, as kidney transplant recipients with a CDR between 1.05 and 1.54 (ng/ml)*1/ mg (intermediate group) showed comparable results to patients with a CDR ≥ 1.55 (ng/ml)*1/ mg we have even chosen to combine both groups in later analyses. Second, in contrast to European studies, Bartlett et al.’s study included 40% African Americans; ethnicity has a known impact. 7 Third, the low rejection rate (e.g., in contrast to Egeland et al.), might have masked differences as already stated by the authors. Different induction therapies and missing protocol biopsies, frequently detecting rejection in stable grafts, might be responsible. 8 Fourth, Bartlett et al. use a lower tacrolimus trough level compared with our data. 4 Lower troughs might mitigate tacrolimus adverse effects. 9 Fifth, the authors speculate that NRM have a higher exposure to tacrolimus over time, leading to increased toxicity, which is not supported by data. In fact, others showed comparable area under the receiver operating characteristic curve between RM and NRM. 11 A reanalysis of the study data using different CDR cut-offs would be interesting.

Bartlett等人在一项美国大型单中心研究中报道，他克莫司代谢率(定义为浓度剂量比(CDR))对肾移植受者活检证实的急性排斥反应没有影响。与我们的结果相反，他们观察到非快速代谢者(NRM)的死亡率高于快速代谢者(RM)。尽管与NRM相比，RMs在几个时间点的肾小球滤过率估计值更低，但他们反对基于cdr的他克莫司治疗。首先，Bartlett等人对RM和NRM的定义与以往的研究不同。他们对RM/NRM的CDR截止值为2.04 (ng/ml)*1/mg，与之前的定义[< 1.05 (ng/ml)*1/mg] 4和< 0.67 (ng/ml)*1/mg]相比，有很大的提高。因此，他们确定了74.3%的RM，而RM为39.1%和25.2%。因此，在其他研究中，他们的大量RM将被归类为NRM。值得注意的是，由于CDR在1.05至1.54 (ng/ml)*1/ mg(中间组)之间的肾移植受者与CDR≥1.55 (ng/ml)*1/ mg的患者的结果相当，我们甚至在后来的分析中选择将两组合并。其次，与欧洲研究相反，Bartlett等人的研究包括40%的非裔美国人;种族的影响是众所周知的。第三，低拒绝率(例如，与Egeland等人相比)可能掩盖了作者已经陈述的差异。不同的诱导疗法和缺少活检方案，在稳定的移植物中经常发现排斥反应，可能是原因。8第四，与我们的数据相比，Bartlett等人使用了较低的他克莫司谷水平。4较低的波谷可能减轻他克莫司的不良反应。第五，作者推测NRM随着时间的推移与他克莫司的接触增加，导致毒性增加，这没有数据支持。事实上，其他人在RM和NRM之间的接收者工作特征曲线下显示出相当的面积。使用不同的CDR截断值重新分析研究数据将是有趣的。

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引用次数: 1

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