儿童罕见病多学科诊疗的药学服务模式探索

目的 探索儿童罕见病多学科诊疗（MDT）的药学服务模式。方法 四川大学华西第二医院（以下简称“我院”）临床药师参与儿童罕见病MDT过程，通过基于循证实践制定药物治疗方案，提高治疗药物可及性，药学监护，药物治疗管理，全程参与患儿诊疗过程，构建儿童罕见病MDT的药学服务模式。结果 2021年1月-2022年4月，我院临床药师共累计参与39例罕见病患儿的MDT，包括罕见病住院患儿21例，罕见病门诊患儿18例，共涉及23种罕见病；完成罕见病住院患儿药学查房45例次、药学会诊26例次，罕见病门诊患儿MDT讨论25例次、药学门诊5例次，院内外罕见病患儿用药教育38例次，院外患儿随访25例次。有24例（61.54%）患儿涉及超说明书用药，涉及13种罕见病和16种治疗药品，其中11种药品已完成或正在进行超说明书用药备案；3种药品完成临时采购药品审核评估；完成医保药品和高值药品处方审核268例次。结论 我院初步建立了儿童罕见病MDT“院内+院外、线上+线下”的闭环药学服务模式，该模式提高了我院儿童罕见病治疗药物的院内可及性、临床应用的规范性及儿童罕见病的诊疗水平。     

传染病医院开展临床药学工作的实践与体会

目的:建立健全传染病医院临床药学服务体系。方法:介绍我院临床药学工作模式。结果与结论:我院通过对门诊患者和住院患者分别进行药学服务,包括构建信息化系统、设立门诊咨询室、建立门诊患者药历,以及药师深入临床查漏补缺、收集药物资料为医师和患者举办药物知识讲座、深入开展药品不良反应监测、制定个体化用药方案等,使我院合理用药水平得到了进一步提升。     

我院开展用药咨询的实践与体会

收集我院2005年10月-2009年10月用药咨询资料,分析用药咨询开展情况,探索提高药学服务的方式。发现我院主要咨询对象为患者及家属,咨询的药物类型主要为抗感染药、循环系统药和消化系统药,主要咨询内容为药品的用法用量和药品供应及价格。应加强临床药师用药咨询的建设,切实提供专业的药学服务。     

医院合理用药信息化建设创新实践

目的 提高医院药事管理效能,促进临床合理用药。方法 医院药学部以原有合理用药信息化系统知识库为基础,建立了以问题为导向的双联合工作机制,主要表现为信息药师针对临床药师事后点评发现的用药问题建立管控方案,编写管控规则,不断完善知识库,通过信息化在处方和医嘱前置审核环节进行管控。在此基础上,对重点项目（如门诊适应证、围术期抗菌药物、抗肿瘤药物管理等）建立系统管控方案。结果 2020年至2022年,共改进、优化基础知识库规则5 266项,建立了具备564项自定义规则的自定义知识库;实现合理用药信息化系统版本升级4次,系统创新与改进32项;门诊/住院次均药品费用增幅、门诊处方合理率、住院医嘱合理率、抗菌药物使用强度等药事管理指标改善明显。结论 构建全面的合理用药监管体系,能有效提升医院药事管理水平与药学服务能力,促进临床合理用药水平的提升。     

药师在药学信息服务中面临的若干问题与对策

2002年卫生部出台的《医疗机构药事管理暂行规定》对药学服务提出了新的要求：药学部门要建立以病人为中心的药学管理模式，开展以合理用药为核心的临床药学工作。药学服务已开始从以药品供应保障为中心转向“以病人为中心”的服务模式，开展药学信息服务是推动药学服务模式转变的必需手段，是全程化药学服务的需要。药学信息(pharmaceutical information)包含了药学领域所有的知识和数据包括与药物直接相关药物信息如药物作用机制、代谢动力学、不良反应、     

北京协和医院互联网药学服务创新模式探索实践

目的：探索建立北京协和医院互联网药学服务模式，助力公立医院高质量发展，以期为“互联网+ 药学”发展提供参考。方法：查阅国内外文献、开展调查研究，结合医院实践经验，归纳总结北京协和医院互联网药学服务管理制度、操作规程、服务内容和质控体系。结果：初步搭建北京协和医院互联网药学服务模式，服务内容包括互联网药学咨询、互联网处方审核、互联网用药指导、药品配送到家和互联网药学门诊。截至2022年11月30日，已完成互联网用药咨询5515例，互联网处方审核152113例，互联网电子用药指导单覆盖药品959种，药品配送33583人次，配送区域覆盖全国31个省市自治区。已取得较好的社会和经济效益。结论：互联网药学服务可以更好地满足患者的医疗需求，实现以患者为中心的药学服务转型，体现创新服务模式的理念。     

疫情期间临床药师基于“互联网+”模式开展药学服务的实践与探索

目的：探索疫情期间临床药师基于“互联网+”模式开展药学服务的实践与探索,为药学服务模式的转型提供思路。方法：配合疫情防控管理,疫情期间医院临床药师开展的“互联网+”模式下的药学服务包括“云药房”药品配送、医联体“云药房”处方审方、慢病科普宣教、方舱药学咨询与人文关怀和线上药学门诊等。结果：疫情期间“云药房”累计审核与配送处方4 644张,拦截不合理处方506张;拍摄并发布科普短视频近30部,总点击量近120万;开展方舱药学咨询105条。结论：“互联网+”模式下的智慧药学拓展了医院药学服务业务,也促进了药学服务的转型,可成为药学发展的新切入点。     

开展老年患者药学服务体会

目的：对我院干部药房开展的老年患者药学服务进行总结分析，探讨如何为老年人提供更好的药学服务，促进老年人合理用药提高老年患者用药安全，提高用药的疗效，以减少药物不良反应的发生。方法我院干部药房针对老年人生理心理特点在发药交代，用药咨询，用药教育以及药物知识宣传等几方面展开药学服务。结果增加患者对药物治疗的信心，提高患者用药依从性。结论开展针对老年人的药学服务，有助于建立良好的药、患关系。     

信息化促进医院药学服务转型与学科发展

目的：响应国家卫生健康委号召,利用信息化建设促进医院药学服务转型及医院药学学科发展。方法：介绍分析近年来我院医院药学信息化建设与实践过程,总结经验,为今后的工作提供借鉴参考。结果：我院建立了涵盖药品保障与药事管理、临床药学服务、科研与教学、科务管理以及科室文化建设各方面的医院药学信息体系HPIS,信息化促进药学服务转型及学科发展作用凸显。结论：应继续探索创新医院药学信息化建设,在促进临床合理用药、临床大数据研究以及临床药学专科医联体建设方面,充分发挥我院"国家队"作用。     

基于1 例首乌藤致药物性肝损伤病例报告的临床药学服务模式研究

目的以1例首乌藤致药物性肝损伤(drug-induced liver injury，DILI)的病人为例，探讨临床药师为药源性疾病病人提供药学服务的切入点和服务模式。方法临床药师通过药学问诊，采用RUCAM因果关系评分法分析可疑药物首乌藤和肝损伤的相关性；病人住院期间，临床药师参与保肝治疗方案的优化与制定，监护用药疗效与不良反应，开展用药教育，保障病人治疗效果与用药安全性，开展分别针对医生与社会大众的药物科普宣教，避免和减少首乌类药源性疾病的发生。结果病人经过保肝治疗后，肝功能明显好转并出院，出院两周后门诊随访肝功能基本恢复正常。结论临床药师利用自己的专业特长，以药物重整、医嘱审核、合理用药指导、用药监护、用药教育以及科普宣传六项临床药学服务为切入点，全程参与1例首乌藤致DILI病人的药物治疗，探索了真正以“病人为中心”的临床药学服务模式，期望为今后临床药师在药源性疾病上的药学服务工作方向和重点提供依据。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.