Drug-induced gastrointestinal disorders in surgical patients admitted to the University Hospital, Jena, Germany

The use of drugs is always accompanied by the risk of adverse drug reactions (ADRs). Particularly important among these are serious ADRs that require hospital admission. Such cases often include patients with gastrointestinal ADRs and many reports have been published on drug-induced gastrointestinal bleeding and ulcers. The objective of the project described here was to detect gastrointestinal ADRs by systematic screening of all medical files in three university departments of surgery, i.e. visceral surgery, vascular surgery and traumatic surgery in the University Hospital of Jena, Germany. The study was retrospective involving the analysis of patients records for the period January 1, 2000 to June 30, 2001. The evaluation concerned all the medical files of individual patients in surgery and in particular those with gastrointestinal disorders due to adverse drug reactions. Side effects were classified according to their severity, duration, symptomatology and pathogenesis and assessed according to frequency, age and sex of the patient and the surgical unit in which the side effect was being treated. Out of a total of 7,715 patients evaluated in the university surgical departments, 471 (6.1%) had gastrointestinal disorders, in 144 (1.9%) of these patients 202 adverse drug reactions were diagnosed and in 70 patients (49.3%) the adverse drug reactions affecting the gastrointestinal tract were classified as serious. Gastric ulcers were present in 86 patients (42.6%) and intestinal ulcerations in 62 patients (30.7%) with intestinal bleeding occurring in 21 (10.4%). In 33 patients (16.3%) the etiology of the gastrointestinal bleeding was uncertain. The average age of patients with gastrointestinal ADRs was 66.1 years in men and 74.4 years in women. Only 1.7% of our patients were aged below 40 years. In approximately 20% of patients analgetic drugs had been withdrawn because of side effects. It is known that there is a correlation between polypharmacy, multiple morbidity and advancing age. The relationship however is complex and the extent to which age is a causative factor in ADRs is difficult to determine. In addition, it is often difficult to obtain clear documentation on the drug history prior to admission to hospital. Physicians are usually unable to devote enough time for a thorough analysis of adverse drug effects and there is a need to correct this deficiency.     

我院药品不良反应报告的特点分析

目的了解该院上报全国药品不良反应（ADR）监测网络中心的报告特点,促进ADR监测工作的全面开展,提高ADR报表质量。方法对该院的149例ADR报告分别从给药途径、涉及药品种类、临床表现及报告人职业等方面进行统计分析。结果以静脉滴注给药方式引发的ADR较多（93.9%）;抗菌药物引发的ADR比例最高（42.3%）;ADR的临床表现以皮肤损害为主（50.3%）。结论抗菌药物是不良反应监测的重点,应进一步加强药品不良反应监测,确保用药安全。     

我院2011年66例中药注射剂不良反应报告分析

目的了解中药注射剂在我院发生药品不良反应的情况,为临床用药提供参考。方法采用回顾性分析方法,对2011年该院收集到的66例中药注射剂不良反应报告进行统计分析。结果66例中药注射剂不良反应报告中女性43例（占65．15％）,男性23例（占34．85％）,且40岁以上中老年患者占绝大多数,有58例（约占87．87％）。引起不良反应的的药物中多为生脉注射液（13例）,参麦注射液（13例）,注射用双黄连（12例）,痰热清注射液（6例）等。药物引起的不良反应率最高的为全身性损害,有31例,约占38．75％,其次为心血管系统损害,有12例,约占15．00％。结论辩证看待中药注射剂不良反应,提倡合理使用中药注射剂,加强中药注射剂用药监护,减少和避免ADR的发生。     

Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients. III. Drug-induced leucopenia

OBJECTIVES: The purpose of this study was to develop, implement, and assess an estimation procedure for preventing adverse drug reaction by subjective symptoms (complaints) of patients. This time, we carried out this study focusing on drug-induced leucopenia. METHODS: We have built a database for CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) since 1987, and the total number of case reports of adverse drug reaction accumulated in the CARPIS database amounts to about 16,000. Using the date obtained from 139 cases of drug-induced leucopenia accumulated in the CARPIS database, we investigated a relationship between leucopenia and patients. The evaluation scores were created based on the subjective symptoms and backgrounds of the patients. RESULTS: We could estimate 91 cases (65.5%) in 139 cases to be drug-induced leucopenia by the use of these evaluation scores. The validity of this evaluation scores was estimated to be as follows; sensitivity = 65.5%, specificity = 80.0% and predictive value of positive test (PVP) = 82.0%. The positive likelihood (LR) ratio was 3.3 and negative likelihood ratio 0.43. CONCLUSIONS: In this study, PVP and LR values were not good, because among the symptoms of leucopenia a very few specific symptoms could be detected. But we reported previous by the evaluation scores about drug-induced liver disorders. Therefore, in order to apply these evaluation scores to the clinical practice, we prepared an evaluation form for subjective symptoms and backgrounds of the patients with adverse drug reactions. In the future, we plan to examine other adverse reactions which adds the data to this form.     

Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting.

OBJECTIVE: To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. DESIGN: A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. SETTING: This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. PATIENTS AND PARTICIPANTS: 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. METHODS: All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. RESULTS: Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year ($US59 600/year) [ 1999 values]. CONCLUSION: Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.     

96例地塞米松注射剂致恶心呕吐反应回顾性分析

目的：回顾性分析地塞米松注射剂致恶心呕吐反应发生情况。方法：通过医院电子病历系统和国家药品不良反应监测系统,收集2014年1月1日—2018年12月31日,在某口腔三级甲等医院住院治疗期间使用地塞米松磷酸钠注射液的患者资料,采用描述性分析对总体人群和不良反应发生人群的基本特点、不良反应发生与处理和药物使用情况进行分析,使用χ²检验和独立样本T检验进行样本结构差异分析。结果：5年共有28 959人次患者住院治疗,使用地塞米松注射剂后发生恶心、呕吐96人次,发生率为0.3%。总体人群和不良反应发生人群间男性比例（52.1%vs 26.0%,P<0.01）、平均年龄（35.1 vs 26.3,P<0.01）存在显著性差异。96例不良反应均为一般程度,94例发生在用药后10 min内,91例未经处理症状自行缓解,5例采取了停药或降低输液速度、给予甲氧氯普胺注射液或维生素B₆注射液后症状缓解,3例再次使用药物后出现同样反应,79例存在合并用药的情况,所有药物使用均符合说明书内容规定。结论：地塞米松注射剂与恶心呕吐反应之间是"肯定"的关联性关系,女性和较低年龄者更容易发生该反应,用药后10 min内需重点关注,一般自行缓解,症状严重者需停药,协助清洁口鼻腔,必要时给予甲氧氯普胺或维生素B₆。     

某院消化内科病房40例药物性肝损伤综合分析

目的 探讨药物性肝损伤病例发生的特点.方法 收集2011年1月-2015年12月某医院消化内科病房的药物性肝损伤病例,每例患者填写药品不良反应报告表,详细记录患者性别、年龄、可疑药品使用情况、药物性肝损伤发生及处理情况,并进行临床分型,将所有数据使用Excel软件进行统计分析.结果 共收集药物性肝损伤病例40例,其中女性18例,男性22例;＞45岁的中老年患者占所有发病人数的70％;中草药和中成药导致的药物性肝损伤共有25例,高达62.5％,其他依次为抗感染药物、免疫系统用药、消化系统用药、抗痛风药、心血管系统用药、内分泌系统用药.33例(82.50％)患者用药开始到肝损伤发生的时间在5～90 d.39例患者从停药开始到肝损伤发生的时间≤15 d,只有1例肝血管损伤型超过30 d.32例患者对症治疗后好转,8例由土三七导致的肝小静脉闭塞症无法逆转,留下后遗症.结论 临床药师应积极推动药物性肝损伤的防治工作,协助医师制定合理的药物治疗方案,避免药物滥用,以减少药物性肝损伤的发生.     

Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients. IV. Drug eruptions

OBJECTIVES: The purpose of this study is to develop, implement, and assess an estimation procedure for preventing adverse drug reaction by subjective symptoms (complaints) of patients. This time, we focused and studied on drug eruptions. METHODS: We have built a database for CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) since 1987, and the case reports of adverse drug reactions accumulated in the CARPIS database to be total about 20,000. We studied 1473 cases of drug eruptions cumulated in CARPIS database. The evaluation scores were created based on the subjective symptoms and backgrounds of the patients. We estimated 1473 cases using this evaluation scores. RESULTS: We could estimate 1455 cases (98.8%) in 1473 cases to be drug eruptions using this evaluation scores. The validity of this evaluation scores were sensitivity = 98.8%, specificity = 91.0% and predictive value of positive test = 99.4%. The positive likelihood ratio was 11.0 and negative likelihood ratio was 0.01. CONCLUSIONS: This study confirmed the validity of our evaluation scores. We reported the evaluation scores about drug-induced liver diseases, drug-induced extra-pyramidal symptoms and drug-induced leukopenia before. In order to apply these evaluation scores to the clinical practice, we prepared an evaluation form for subjective symptoms and backgrounds of the patients with adverse drug reactions.     

Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients. II. Drug-induced extrapyramidal symptoms

OBJECTIVES: The purpose of this study was to develop, implement, and assess an estimation procedure for preventing adverse drug reaction by subjective symptoms (complaints) of patients. This time, we focused and studied on drug-induced extrapyramidal symptoms. METHODS: We have built a database for CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information Systems) since 1987, and the case reports of adverse drug reaction accumulated in the CARPIS database to be total about 16,000. We studied for 180 cases of drug-induced extrapyramidal symptoms cumulated in CARPIS database. The evaluation scores were created based on the subjective symptoms and backgrounds of the patients. We estimated 180 cases using these evaluation scores. RESULTS: We could estimate 178 cases (98.9%) in 180 cases to be drug-induced extrapyramidal symptoms using these evaluation scores. The validity of these evaluation scores were sensitivity = 98.9%, specificity = 98.0% and predictive value of positive test = 98.9%. The positive likelihood ratio was 49.5 and the negative likelihood ratio was 0.01. CONCLUSIONS: This study confirmed the validity of our evaluation scores. We reported the evaluation scores about drug-induced liver diseases before. Therefore, to apply these evaluation scores onto the clinical practice, we prepared an evaluation form for subjective symptoms and backgrounds of the patients with adverse drug reactions.     

痰热清药物不良反应报告分析

目的了解痰热清不良反应发生的特点,为临床用药提供参考。方法采用回顾性调查方法对2007～2009年不良反应报表进行统计分析。结果中药制剂诱发的不良反应共41例,涉及18种中药制剂,其中痰热清注射液引起的不良反应为8例。不良反应主要表现为过敏反应、皮肤及附件损害等。结论痰热清注射液药物引起的不良反应不是很多,但在使用过程中仍需密切观察,以防止严重不良反应的发生,提高用药的安全性。     

471例药物胃肠道不良反应回顾性分析

目的对我院5年来药物引起的471例胃肠道不良反应进行回顾性分析,为临床合理用药和预防胃肠道不良反应提供参考。方法对我院2005～2008年收集的471例胃肠道不良反应报表进行分类统计和分析。结果药品引发的胃肠道不良反应涉及201个品种,抗感染药居首位（218例,占46.28%）,其次是中药制剂（88例,占18.68%）;55岁以上的患者居多（占36.94%）;口服给药引发胃肠道不良反应为257例（占54.57%）。结论临床应重视胃肠道不良反应的报告和致病原因,从而加强胃肠道不良反应的预防及监测,以减少和避免胃肠道不良反应的发生,保障患者用药合理、安全、有效。     

心理干预法对抑郁症病人的临床疗效观察

目的 观察心理干预法对抑郁症病人的临床疗效.方法 抑郁症病人60例,采用随机数字表法分为心理干预组(治疗组)和对照组各30例,其中治疗组在常规抑郁症对症药物处理基础上予以心理干预法,对照组病人仅采用常规抑郁症对症药物处理措施.心理干预在入院时进行,每天上下午各1次,每次干预时间为20 min,共7 d.两组病人均在入院时和入院后7 d分别采用汉密尔顿抑郁量表(HAMD)、焦虑自评量表(SAS)和抑郁自评量表(SDS)对其焦虑、悲观等消极不良情绪状况进行相关的综合临床疗效评分,不良反应指标评分评价其用药期间的不良反应情况. 结果 治疗组在实施心理干预后,其汉密尔顿抑郁量表评分(10.2±2.1)分、焦虑自评量表评分(30.2±2.1)分和抑郁自评量表评分(30.7±2.9)分均较对照组改善更优,均差异有统计学意义(P<0.05);治疗组不良反应中度10例(33.3%)、重度3例(10.0%)、总积分46和总不良反应率43.3%,对照组不良反应中度14例(46.7%)、重度5例(16.7%)、总积分54和总不良反应率63.3%.结论 心理干预措施有利于改善抑郁症病人的心理状态,减少其焦虑、悲观等消极不良情绪的发生发展,保障常规药物对症处理治疗抑郁症的疗效,同时能更好地辅助改善病人用药的不良反应,体现医学人文情怀.     

我院参麦注射液应用情况及不良反应分析

目的对我院参麦注射液应用情况及不良反应进行分析,为临床应用和药品监管部门决策提供参考。方法采用医院集中监测的方法,对2011年1月～10月期间我院应用参麦注射液的住院患者病历,进行回顾性调查,并进行统计。结果共收集到468份应用参麦注射液的住院患者病历,85.5%为50岁以上老年患者;适应证、用法用量和疗程均比较规范,基本符合药品说明书规定;不良反应发生率为1.7%,属常见范畴;主要表现为头晕、乏力、胸闷、不适等,临床表现多样,无明显特异性,且多为一过性,停药即可,不需特别处理。结论医院集中监测法是对自发性呈报系统良好的补充,其得出的不良反应发生率具有可参考性,但需要进行多中心的研究,使数据更具代表性。     

Developing an adverse drug reaction program in nursing homes

The study of 826 geriatric nursing home patients was undertaken by a pharmacist to determine the incidence of adverse reactions to drugs. A formalized adverse drug reaction reporting program was used as the basis for the detection of unwanted drug effects. Approximately 27% of patients experienced a moderate to severe adverse effect. Five groups of drugs accounted for three-quarters of the reactions detected. The majority of these reactions were predictable and preventable. Females over the age of 70 on large quantities of drugs were significantly more susceptible to experiencing an adverse reaction. Physicians implemented 76% of pharmacist initiated recommendations for the treatment of adverse effects and were appreciative of increased pharmacy involvement. The implementation of such recommendations was felt to have substantially reduced the incidence of drug-induced acute hospitalizations. Although the information was generated in nursing homes, it may be generalized to other geriatric specialty areas such as medical wards and extended care units. Several recommendations are provided on how other pharmacists can implement similar clinical services in their areas of professional practice.     

曲妥珠单抗致不良反应分析

目的：探讨曲妥珠单抗（trastuzumab）致不良反应的特点,为临床合理用药提供参考。方法：选择本院乳腺内科应用曲妥珠单抗所致不良反应38例,又检索到中国期刊全文数据库、万方数据库、维普资讯网和PubMed筛选出的曲妥珠单抗相关不良反应的文献10篇（39例）,合并作为研究对象,针对患者的一般情况、合并化疗方案、不良反应出现时间及临床表现、治疗及转归进行分析。结果：我院38例患者中不良反应发生在给药后0～90 min者21例（55%）,1~2 d者9例（24%）,3~7 d者8例（21%）;最常见不良反应为输液反应,严重不良反应为2例,表现为严重输液反应（过敏反应）,永久终止曲妥珠单抗的治疗。在数据库检索到的39例中,不良反应发生在给药后0～90 min者30例（77%）,大于7 d者4例（10%）,未报道发生时间5例（13%）;最常见不良反应为输液反应,严重不良反应为9例,包括非感染性肺炎和心脏毒性,未影响治疗。结论：曲妥珠单抗最常见的不良反应为输液反应,多在第一次输注时发生;用药前先给予苯海拉明、地塞米松预防,可降低其发生率;加强监测,预防心脏毒性,保证治疗的顺利进行。     

静脉输液中发生药物不良反应的防治

目的探讨发生输液不良反应及相应的防治措施。方法对笔者所在医院门诊输液室发生的输液不良反应120例患者的临床资料包括药物不良反应类型、引起不良反应的药物等进行分析,并探讨静脉药物不良反应的防治措施。结果本研究输液不良反应包括发热反应(6.7%)、静脉炎(5.8%)、空气栓塞(0.8%)、过敏反应(55.0%)、疼痛(20.8%)以及胃肠道反应(恶心、呕吐)(10.8%)等,其中中药注射剂77例,占64.2%,抗菌药物和抗病毒药物产生的不良反应共34例,约占28.3%,消化系统类药物共5例,占4.2%,血液系统类药物4例,占3.4%。结论对静脉输液患者进行预见性的观察和针对输液反应进行针对性的处理,并引入药学服务,可以明显的改善患者的输液反应症状,减轻患者痛苦。     

Drug-induced skin, nail and hair disorders.

Drug eruptions are among the most common adverse drug reactions, affecting approximately 3% of hospitalised patients. Although the rate of severe cutaneous adverse reactions to medications is low, these reactions can affect anyone who takes medication, and can result in death or disability. Two general patterns can be distinguished, depending on the type of onset of these cutaneous adverse drug reactions: acute or chronic. Acute-onset events are usually rather specific cutaneous 'syndromes' that constitute emergencies and should therefore be promptly recognised and treated, while chronic-onset events often present as dermatological diseases. The challenge is therefore to recognise the drug aetiology in front of a 'classical' dermatosis such as acne, lichen or pemphigus. Therefore, clinicians should carefully evaluate the signs or symptoms of all adverse reactions thought to be drug related, and discontinue the offending agent when feasible. Erythematous drug eruptions are the most frequent and less severe acute immune drug-induced rashes, and are sometimes difficult to differentiate from viral eruptions. On the other hand, acute urticaria and angioedema are sometimes life-threatening eruptions for which a drug aetiology must be investigated. Photosensitivity, vasculitis and skin necrosis belong to the acute onset reactions, which are not always drug-induced, in contrast to fixed drug eruptions. The early recognition of acute generalised exanthematous pustulosis, DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis are of high importance because of the specific mechanisms involved and the different prognosis of each of these diseases. Chronic onset drug-induced disorders include pigmentary changes, drug-induced autoimmune bullous diseases, lupus, pseudo lymphoma and acneiform eruptions; these are discussed, along with specific data on drug-induced hair and nail disorders. As the disorders are numerous, the mechanisms and the drugs involved in the development of these various reactions are multiple. The list of drugs discussed in relation to the different disorders are as accurate as possible at the time of preparation of this review, but will need updating as new drugs emerge onto the market. We emphasize the clinical recognition, pathophysiology and treatment of skin, hair and nail adverse drug reactions, and the role of each doctor involved in the management of these patients in the notification of the adverse drug reaction to health authorities, using the minimal requirement for notification proposed.     

Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients. V. Drug-induced gastrointestinal system disorders

OBJECTIVES: The purpose of this study was to develop, implement, and assess an estimation procedure for preventing adverse drug reaction by subjective symptoms (complaints) of patients. This time, we focused and studied on drug-induced gastrointestinal system disorders. METHODS: We have built a database for CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) since 1987. We studied 224 cases of drug-induced Gastrointestinal System Disorders (stomach or colon disorders: 148, esophagus disorders: 31, pancreas disorders: 45) cumulated in the CARPIS database. The evaluation scores were created based on the subjective symptoms and backgrounds of the patients. We estimated 224 cases using these evaluation scores. RESULTS: We could estimate 137 cases (92.6%) in 148 cases to be stomach or colon disorders by the use of these evaluation scores. The validity of this evaluation scores was estimated to be as follows: Sensitivity = 92.6%, Specificity = 95.0% and Predictive Value of Positive Test (PVP) = 96.5%. The positive likelihood ratio (LR) was 18.5 and negative likelihood ratio was 0.08. On the other hand, in the case of esophagus disorders, PVP was 84.8% and LR was 18.1. In the case of pancreas disorders, PVP was 90.7% and LR was 21.7. CONCLUSIONS: In this study, PVP and LR values were good. We thought that these evaluation scores could pick up the drug-induced gastrointestinal system disorders efficiently. We reported previously the evaluation scores about drug-induced liver disorders, extra-pyramidal symptoms, leukopenia and eruption before. In order to apply these evaluation scores onto the clinical practice, we prepared an evaluation form for subjective symptoms and backgrounds of the patients with adverse drug reactions. As a result, the adverse reactions symptoms of each one defined more.