精准医疗时代临床药师的机遇与挑战

精准医疗是根据基因组、蛋白质组学、生物标志物和社会心理学等"个人"信息实施个体化诊断、治疗,以达到最佳治疗、最小毒副作用的医疗模式.随着相关技术、理论、观念的发展和更新,医疗模式已进入精准医疗时代.临床药师走向临床,参与诊断疾病、优化药物治疗方案、实施以基因检测、药物浓度监测为依据的个体化治疗.精准医疗将改变现有诊断和传统治疗模式,给临床药师带来挑战的同时,也提供了机遇.     

Points-to-consider documents: Scientific information on the evaluation of genetic polymorphisms during non-clinical studies and phase I clinical trials in the Japanese population

Pharmacotherapy shows striking individual differences in pharmacokinetics and pharmacodynamics, involving drug efficacy and adverse reactions. Recent genetic research has revealed that genetic polymorphisms are important intrinsic factors for these inter-individual differences. This pharmacogenomic information could help develop safer and more effective precision pharmacotherapies and thus, regulatory guidance/guidelines were developed in this area, especially in the EU and US. The Project for the Promotion of Progressive Medicine, Medical Devices, and Regenerative Medicine by the Ministry of Health, Labour and Welfare, performed by Tohoku University, reported scientific information on the evaluation of genetic polymorphisms, mainly on drug metabolizing enzymes and transporters, during non-clinical studies and phase I clinical trials in Japanese subjects/patients. We anticipate that this paper will be helpful in drug development for the regulatory usage of pharmacogenomic information, most notably pharmacokinetics.     

麦考酚酸酯及其临床应用进展

目的:麦考酚酸酯(MMF)是一种新型的免疫抑制剂.在临床应用中,MMF的使用也越来越广泛,已不仅仅局限于器官移植,还涉及到系统性红斑狼疮(SLE)、自体免疫风湿性疾病的治疗,以及在糖尿病,肺部血管高压的辅助治疗等诸多方面.肠包衣麦考酚酸钠,是一种新的可抵抗胃溶作用的麦考酚酸肠包衣剂型,药物在肠内释放,可以降低胃肠道(GI)不良反应的发生.     

临床研究中的数据管理标准CDISC及其应用前景

数据管理标准临床数据交换标准协会(CDISC)已广泛应用于临床研究中,它能够优化临床研究数据采集、传递、储存,并简化申办者/研究者向管理部门递交数据的程序,从而提高临床研究的效率。CDISC包含临床数据采集标准(CDASH)、实验室数据模型(LAB)、操作数据模型(ODM)、研究数据表格模型(SDTM)、分析数据库模型(ADaM)等模块。文中从数据管理标准在医学研究中应用的意义、已经广泛应用的CDISC主要模块CDASH,SDTM,AdaM的介绍以及临床研究中数据管理标准CDISC的应用前景等方面加以阐述。     

MHPG excretion in endogenous depression: Relationship to clinical state and the effects of ECT

In a group of 70 patients with endogenous depression entering a controlled trial of real versus sham ECT, urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was significantly reduced by comparison with previously studied groups of control subjects, of acute and chronic schizophrenic patients and of anxious patients. However, urinary MHPG was unrelated to severity of depression, or to the presence of delusions, retardation or agitation. MHPG excretion did not predict clinical outcome, or the response to ECT. Urinary MHPG content at trial entry was unrelated to past tricyclic antidepressant or benzodiazepine medication, although an influence of the latter on the findings cannot be excluded, since all patients received benzodiazepine (nitrazepam) night sedation during the trial.During the 4-week trial MHPG excretion remained low and did not increase in relation to change in clinical state, although there was a small but significant increase in patients who received real ECT. The findings confirm that urinary MHPG excretion is reduced in depression, but establish that such reductions are not state dependent. Since the increase in MHPG excretion with ECT is not related to changes in clinical state, the former presumably does not reflect the mechanism of action of ECT.     

5-Hydroxymethyl-2-furfural,a clinical trials agent for sickle cell anemia,and its mono/di-glucosides from classically processed steamed Rehmanniae Radix

Rehmanniae Radix (Di Huang) is one of the most important traditional Chinese medicines (TCM), and is used for multiple therapeutic purposes. In our investigation of the chemical constituents of Rehmanniae Radix, steamed roots were prepared by the classical processing method. Reversed-phase HPLC of the 50% MeOH extract of steamed Rehmanniae Radix yielded three 5-hydroxymethylfurfural derivatives. The new furfural disaccharide 5-(α-d-glucopyranosyl-(1→6)-α-d-glucopyranosyloxymethyl)-2-furancarboxaldehyde (1) was isolated and characterized, together with its known aglycone 5-hydroxymethyl-2-furfural (3), which is currently in sickle cell anemia Phase I clinical trials, and its corresponding monosaccharide 5-(α-d-glucopyranosyloxymethyl)-2-furancarboxaldehyde (2), which was isolated as a natural product for the first time. The presence of these three compounds, particularly 3, which were not found in the unprocessed extract of Rehmanniae Radix, could substantiate the traditional medicinal use of steamed Rehmanniae Radix.     

亚胺培南/西司他丁治疗血流感染的蒙特卡洛模拟方案与其临床疗效的相关性研究

目的 根据药动学/药效学(PK/PD)理论,采用蒙特卡洛模拟亚胺培南/西司他丁对大肠埃希菌所致的血流感染给药方案,同时结合亚胺培南/西司他丁对血流感染的临床疗效,对两者进行相关性研究。方法 回顾性调查我院2013年7月-2016年6月引起血流感染的大肠埃希菌对亚胺培南/西司他丁的耐药监测报告,选择亚胺培南/西司他丁给药方案(0.5g q8h、0.5g q6h、1.0g q12h和1.0g q8h),分别计算出蒙特卡洛模拟10000例“真实患者”的累积反应分数(CFR)和临床疗效指数(CEI),用SPSS24.0版软件对CFR与CEI进行相关性分析。结果 亚胺培南/西司他丁给药方案中0.5g q6h的CFR为85.30%;各给药方案的CEI均大于80%。 结论 蒙特卡洛模拟方案CFR和CEI之间呈中等相关(r=0.633),相关性无显著线性关系(P=0.367)。     

重组人骨形态发生蛋白-2膜片的研制及其稳定性实验

目的研制重组人骨形态发生蛋白-2(rhBMP-2)膜片并对其稳定性进行研究,最终提供用于临床试验的合格样品。方法1.采用医用胶原蛋白海绵作为辅料,与rhBMP-2悬液复合,制作成膜片,钴60消毒后测活并送检各项指标。2.采用血清钙试剂盒的方法,通过检测不同条件处理后的rhBMP-2样品的活性变化来反映样品的生物稳定性。结果rhBMP-2膜片生物活性良好,经中国药品生物制品检定所检验各项指标符合要求;在4℃放置两年,活性依然保持良好;在室温放置6个月,活性略有降低;而在37℃条件下,放置1个月活性明显降低,但放置半年与放置1个月活性差别不大。结论所研制的rhBMP-2膜片,稳定性良好,符合临床试验的各项指标。     

Identifying the biologic closest to the ideal to treat chronic plaque psoriasis in different clinical scenarios: using a pilot multi-attribute decision model as a decision-support aid

Abstract

Objective:

Multi-attribute decision-making (MADM) models evaluate competing solutions for complex problems to identify the closest fit to the ideal solution. MADM models may assist dermatologists when selecting between biologics for plaque psoriasis. Here, is described the development of a pilot model to identify the preferred biologic from the dermatologist's perspective.     

Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety

ABSTRACT

Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM–5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed—some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds.     

视频博客+5G通信技术模式在胸外科临床教学中的应用与发展

随着网络技术和视频平台的日益发展和推广普及,Vlog(视频网络日志)+5G(第五代移动通信技术)模式在胸外科临床教学中的初步探索与应用,已经体现出巨大的优势和重要作用.本研究将从胸外科临床教学所面临的困境与思考为出发点,挖掘和拓展Vlog与5G技术融合在临床教学中的应用背景和发展前景,进一步阐明其给临床教学所带来的巨大...     

Retrospect and prospect of active principles from Chinese herbs in the treatment of dementia

With an ageing population, dementia has become one of the world''s primary health challenges. However, existing remedies offer limited benefits with certain side effects, which has prompted researchers to seek complementary and alternative therapies. China has long been known for abundant usage of various herbs. Some of these herbal decoctions are effective in stimulating blood circulation, supplementing vital energy and resisting aging, the lack of which are believed to underlie dementia. These herbs are regarded as new and promising sources of potential anti-dementia drugs. With the rapid evolution of life science and technology, numerous active components have been identified that are highly potent and multi-targeted with low toxicity, and therefore meet the requirements for dementia therapy. This review updates the research progress of Chinese herbs in the treatment of dementia, focusing on their effective principles.     

Fosphenytoin for the treatment of status epilepticus: an evidence-based assessment of its clinical and economic outcomes

INTRODUCTION: Status epilepticus (SE) is a life-threatening condition requiring prompt treatment in the emergency department to control seizures and limit potential neurologic damage. Fosphenytoin is a water-soluble prodrug of phenytoin (an established treatment option for SE) that has been developed to overcome the often severe venous adverse events that can occur following the intravenous administration of phenytoin. AIMS: The objective of this article is to review the evidence for the use of fosphenytoin in the treatment of SE. EVIDENCE REVIEW: Fosphenytoin can be infused more rapidly than phenytoin and there is evidence that therapeutic drug levels are achieved at least at a similar rate. Although few studies have been conducted in SE patients, there is evidence that fosphenytoin is at least as effective as phenytoin in terms of response and control of SE. There is also moderate evidence that there are fewer vascular adverse events following intravenous fosphenytoin compared with phenytoin administration when both drugs are infused at the recommended dosage and rate. Evidence from pharmacoeconomic studies indicates that a reduction in the incidence of adverse events and their subsequent management are critical factors for cost-effectiveness with fosphenytoin. CLINICAL VALUE: In conclusion, fosphenytoin is a valuable treatment option for the rapid treatment of SE; the risk of venous adverse events is lower than with phenytoin when administered at the recommended rate.     

Dutasteride: an evidence-based review of its clinical impact in the treatment of benign prostatic hyperplasia

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common condition affecting older men. Bothersome symptoms can progress to serious complications such as acute urinary retention (AUR) requiring surgical intervention. Dutasteride, a dual 5-alfa-reductase (5AR) inhibitor (5ARI), is a recently introduced therapy for the treatment of BPH. AIMS: The objective of this article is to review the evidence for the treatment of BPH with dutasteride. EVIDENCE REVIEW: Evidence from large clinical studies shows that men with an enlarged prostate achieve a measurable decrease in prostate volume by up to 26% after 4 years of treatment with dutasteride and urinary symptoms improve after 6 months of treatment. This is achieved by rapid suppression (through inhibition of 5AR) of the principal androgen (dihydrotestosterone or DHT) responsible for stimulating prostatic growth. Evidence suggests that dutasteride treatment results in a reduction in risk (rather than delay) of the most serious complications including episodes of AUR and the need for BPH-related surgery. Early symptom relief has been achieved with the combination of an alfa blocker and dutasteride. There is good evidence that dutasteride is well tolerated; side effects limited to sexual dysfunction (reduced libido, impotence, and gynecomastia) are more common compared with placebo but occur with a similar incidence to finasteride, another 5ARI. No pharmacoeconomic evidence from studies with dutasteride has so far been published. CLINICAL VALUE: In conclusion, dutasteride is a valuable treatment option in men with moderate to severe BPH. Reductions in prostate volume lead to symptom relief and serious complications appear to be reduced.     

SIRT 3 was involved in Lycium barbarum seed oil protection testis from oxidative stress: in vitro and in vivo analyses

ContextLycium barbarum L. (Solanaceae) seed oil (LBSO) exerts LBSO exerts protective effects in the testis in vivo and in vitro via upregulating SIRT3.ObjectiveThis study evaluates the effects and mechanism of LBSO in the d-galactose (d-gal)-induced ageing testis.Materials and methodsMale Sprague Dawley (SD) rats (n = 30, 8-week-old) were randomly divided into three groups: LBSO group (n = 10) where rats received subcutaneous injection of d-gal at 125 mg/kg/day for 8 weeks and intragastric administration of LBSO at 1000 mg/kg/day for 4 weeks, ageing model group (n = 10) received 8-week-sunbcutaneous injection of d-gal, and control group (n = 10) with same administration of normal saline. Lentivirus had established TM4 cells with SIRT3 overexpression or silencing before LBSO intervened in vitro.ResultsTreatment with LBSO, the levels of INHB and testosterone both increased, compared to ageing model. In vitro, we found the ED₅₀ of LBSO was 86.72 ± 1.49 and when the concentration of LBSO at 100 μg/mL to intervene TM4 cells, the number of cells increased from 8120 ± 676.2 to 15251 ± 1119, and the expression of SIRT3, HO-1, and SOD upregulated. However, HO-1 and SOD were dysregulated by silencing SIRT3. On the other hand, the expression of AMPK and PGC-1α upregulated as an effect of SIRT3 overexpression by lentivirus, meanwhile the same increasing trend of that being found in cells treated with LBSO, compared to control group.Discussion and conclusionsLBSO alleviated oxidative stress in d-gal-induced sub-acutely ageing testis and TM4 cells by suppressing the oxidative stress to mitochondria via SIRT3/AMPK/PGC-1α.     

Community pharmacist led medication reviews in the UK: A scoping review of the medicines use review and the new medicine service literatures

BackgroundMedicines Use Reviews (MURs) and the New Medicine Service (NMS) are services delivered by UK community pharmacists to improve adherence, improve patient understanding of their medicines and reduce medicines wastage.AimIn this scoping review we aim to identify, map and critically examine the nature of existing empirical evidence in peer reviewed journals relating to MUR and NMS consultations.MethodSystematic searches identified the available MUR and NMS empirical literature. We sought data on barriers and facilitators to conducting MUR or NMS consultations, the perceptions of pharmacists and patients, the conduct of consultations, and outcomes of consultations. Searches from 2005 (when MURs were introduced) to May 2018 were conducted in MEDLINE, PsycINFO, Embase and Scopus databases. Data were extracted into Excel for examination of study characteristics, participant characteristics, type of intervention/services delivered and key study quantitative and/or qualitative findings.ResultsForty-one papers from 37 studies met the inclusion criteria: 28 papers were of MURs, 10 of NMS and 3 for both services. Studies focused on the introduction and implementation of these services, with little attention to outcomes for patients; effectiveness was not evaluated beyond in a single NMS RCT. Observational data indicated that pharmacists and patients view MURs and the NMS positively, despite challenges implementing these services and apparent lack of communication between pharmacists and GPs. Consultations were reported to be short, typically 10–12 min, characterised by limited engagement with patients and their health problems. The extent and nature of advice on health behaviours during consultations or other content was rarely examined.ConclusionThe research literature on MURs and the NMS has developed slowly. There is much scope for further research attention to developing more patient-centred care.     

Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study

Abstract

Objectives:

The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung.