Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

Causality assessment of suspected drug induced liver injury(DILI) and herb induced liver injury(HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences(CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. 2014 Baishideng Publishing Group Co., Limited. All

Assessment of Drugs’ Donation Practices in Sudan

The quality requirements of drug donation are different from those of other donated items. Purpose: To describe and assess key aspects of pharmaceutical donations in Sudan, the kinds of benefits and drawbacks associated with drug donations, and the government controlling role in the donation process. Methods: Retrospective and prospective studies were conducted in the period from April 2007 to Mar 2008 in the Federal Ministry of Health (FMOH) and some working NGOs’ data bases. Some quality aspects of donated drugs were explored. Six randomly selected nongovernmental organizations (NGOs) were examined for the relevance and some aspects of quality of donated drugs such as whether the donated drugs were listed in the National Essential Drug List, or labeled in International Nonproprietary Names, their dosage forms, the language on the package and if the donated drugs were sampled or returned ones. Results: The study showed that most of the donated drugs were relevant to NEDL normative standards. The median times from the date of arrival to the date of expiration were more than 400 days. The time prior to expiration range between 44.8% and 47.5% were found less than one year in arrival. The top ten therapies were accounted for about 40 shipped items. The study was revealed that Sudan did not develop its own guidelines for drug donations and NGOs are making no effort to develop written donation policies. Conclusion: development of national guidelines for drug donations is essential to control the donated drugs in Sudan.

Drug Safety Assessment:An Urgent Task

A CAS scientist has pointed out at an international symposium that it is important for China to step up its efforts in drug safety assessment to address a hidden peril in China's pharmaceuticals industry.

Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors

Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.

Herbal hepatotoxicity:Challenges and pitfalls of causality assessment methods

The diagnosis of herbal hepatotoxicity or herb induced liver injury(HILI) represents a particular clinical and regulatory challenge with major pitfalls for the causality evaluation.At the day HILI is suspected in a patient,physicians should start assessing the quality of the used herbal product,optimizing the clinical data for completeness,and applying the Council for International Organizations of Medical Sciences(CIOMS) scale for initial causality assessment.This scale is structured,quantitative,liver specific,and validated for hepatotoxicity cases.Its items provide individual scores,which together yield causality levels of highly probable,probable,possible,unlikely,and excluded.After completion by additional information including raw data,this scale with all items should be reported to regulatory agencies and manufacturers for further evaluation.The CIOMS scale is preferred as tool for assessing causality in hepatotoxicity cases,compared to numerous other causality assessment methods,which are inferior on various grounds.Among these disputed methods are the Maria and Victorino scale,an insufficiently qualified,shortened version of the CIOMS scale,as well as various liver unspecific methods such as thead hoc causality approach,the Naranjo scale,the World Health Organization(WHO) method,and the Karch and Lasagna method.An expert panel is required for the Drug Induced Liver Injury Network method,the WHO method,and other approaches based on expert opinion,which provide retrospective analyses with a long delay and thereby prevent a timely assessment of the illness in question by the physician.In conclusion,HILI causality assessment is challenging and is best achieved by the liver specific CIOMS scale,avoiding pitfalls commonly observed with other approaches.

Can health technology assessments assist the global campaign against poverty?

Although a key tenant of the Sustainable Development Goals is to achieve universal health coverage,the global drug gap persists-cver a third of the global population lack access to essential medicines.Without access to affordable drugs,people have worse health outcomes,higher medical expenses,and productivity loss,pushing them into poverty.Health technology assessments(HTAs)offer an opportunity to decrease the global drug gap and increase access to essential medicines by overcoming barriers to medicine access.These barriers include drug procurement,drug affordability for payers and patients,a patienfs ability to obtain essential medicines,and health system capacity.Using HTAs can therefore close the global drug gap by increasing access to affordable essential medicines.In turn,people have better health outcomes,spend less money on medical care,and can have better productivity.Ultimately,use of HTAs can lift the population out of poverty and force fewer people into poverty by creating better health outcomes at affordable prices.

Comparative toxicity assessment between generic salbutamol sulphate inhaler containing hydrofluoroalkane and Ventolin Evohaler

Salbutamol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm such as asthma and chronic obstructive pulmonary disease (COPD). It is mostly taken through an inhaler device. The comparative toxicity assessment between two salbutamol sulfate preparations containing hydrofluoroalkane (HFA) metered dose inhalers with 100 μg per puff was evaluated in selected patients with asthma and COPD after prescribing. An open label, non-randomized, non-interventional observational study was designed. A large cohort of patients with asthma or related respiratory disorder of the general population from Dhaka and Chittagong of Bangladesh were recruited and treated with prescribed generic preparation Azmasol inhaler and brand preparation Ventolin Evohaler. Total 508 patients with asthma and minor obstructive airway disease were selected by the general medical practitioners in Bangladesh those who visited out patient consultation center in hospitals and physicians’ chambers and reported any adverse side effects of inhaled medications. There were no significant differences between the metered dose generic preparation Azmasol inhaler and Ventolon Evohaler among the patients treated with the medicines in asthma and related respiratory diseases in terms of adverse effects like immune system problem,dizziness,tremor,headache,nervousness,diarrhea,nausea,vomiting,heartburn,palpitation,skin rash,hypertension and taste feeling. It is concluded that Azmasol Inhaler, the generic salbutamol sulphate metered dose preparation containing HFA was as safe as the Ventolin Evohaler,a salbutamol sulfate brand preparation containing HFA when given to the patients in primary care after their physicians’ visits. Both the preparations have shown the similar safety profiles after regular use.

Assessing Drug Use Indicators in Health Insurance Facilities, Gezira State, Sudan, 2017-2018

Background: Inappropriate use of medicines is a global concern with serious consequences related to prescribing, dispensing, and use. WHO estimated that 50% of medicines are not used correctly on their journey from the facility to home. Objective: To assess medicines use using WHO drug core indicators regarding prescribing, patient, and facilities. Setting: Outpatients, Health centers in Wadmadani locality (Urban area) in Gezira State, Sudan. Method: A cross-sectional, prospective, analytical study was conducted in 30 health centers and 60 patients from each center were selected using a simple random sampling technique. WHO indicators form was used to collect data containing different variables. T-test at a level of confidence of 95% was used to test differences between indicators. Statistical Package for Social Science (SPSS) was used for data analysis. Results: The main prescribing indicators were 2.5 ± 0.6 for drugs per encounter, 44.1% ± 14.2%. Generic 54 ± 18.0 antibiotics, 12.0% ± 9.3% injectable, and 95.2% ± 11.5% of drugs were prescribed according to the NHIF-EML. The main patient’s indicators were, 2.9 ± 0.8 minutes for consultation time, 99.5 ± 36.8 seconds for dispensing time, and 72.5% ± 16.0% for medicines actually dispensed, 49.0% ± 18.0% for medicines adequately labeled, and 22.5% ± 7.3% of the patient’s knowledge about the correct dose. The Facility specific indicators were 66.7% for the availability of a copy of EML, while the percentage of key drugs in the stock was 75.3% ± 11.6%. No statistically significant differences were found between direct and indirect facilities except in generic prescribing. Main Outcome Measure: • Interventions to improve Generic and antibiotics prescribing indicators. • The patient-to-physician ratio should be revised to optimize consultation time. • The availability of key drugs should be improved to make sure effective treatment. • The pharmacy cadre should be oriented and trained to improve patients’ compliance. Conclusion: The study concluded that there was irrational use of medicines when investigated by WHO drug core indicators. So, the study recommended interventions to improve the rationale prescribing, dispensing, and use of medicines.

An in-vitro cocktail assay for assessing compound-mediated inhibition of six major cytochrome P450 enzymes

An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450 （CYP） enzymes. This method employed a cocktail of six probe substrates （i.e., phenacetin, amodiaquine, diclofenac, S-mephenytoin, dextromethorphan and midazolam for CYPIA2, 2C8, 2C9, 2C19, 2D6 and 3A4, respectively） as well as individual prototypical inhibitors of the six CYP enzymes in human liver microsomes under optimized incubation conditions. The corresponding marker metabolites （i.e., acetaminophen, N-desethylamodiaquine, 4-OH-diclofenac, 4-OH-S- mephenytoin, dextrorphan and 1-OH-midazolam） in the incubates were quantified using LC-MS/MS methods either by an internal standard （IS） calibration curve or a simpfified analyte-to-IS peak area ratio approach. The results showed that the IC5o values determined by the cocktail approach were in good agreement with those obtained by the individual substrate approach as well as those reported in the literature. Besides, no remarkable difference was observed between the two quantification approaches. In conclusion, this new cocktail assay can be used for reliable screening of compound-mediated CYP inhibition.

Ayurvedic drug induced liver injury

Drug induced liver injury is responsible for 50% of acute liver failure in developed countries. Ayurvedic and homeopathic medicine have been linked to liver injury. This case describes the first documented case of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. Drug induced liver injury may be difficult to diagnosis, but use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging, is recommended. Advanced imaging, such as magnetic resonance cholangiopancreatography, may possibly have a greater role than previously reported in literature.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.

Drug treatment

930015 Treatment of soil-transmittedhelminth infections by helminthicides in currentuse.XU Longqi(许隆祺),et al.Instit ParasitDis,Acad Chin Pre Med,Shanghai 200025.Chin J Parasitol & Parasit Dis 1992;10(2):95—98.The efficacy of broad-spectrum helminthi-cides in current use was studied in HengshanCounty,Hunan Province.The vermicides

^238U and^232Th concentrations measured in different medical drugs by using solid-state nuclear track detectors and resulting radiation doses to the skin of patients

Urban populations in Morocco receive free medical drugs as prescribed by doctors in district health centres.To explore the exposure pathway of ^(238)U and^(232)Th and their decay products on the skin of patients,these radionuclides were measured in various medical drugs by using solid-state nuclear track detectors(SSNTDs).The measured concentrations range of ^(238)U and ^(232)Th in the medical drug samples of interest vary from(4.3±0.3) to(11.1±0.7) mBq 1^(-1) and(0.49±0.03) to(1.3±0.1)mBq 1^(-1),respectively.A new dosimetric model,based on the concept of specific alpha-dose and alpha-particle residual energy,was developed for evaluating radiation doses to skin following the application of different medical drugs by patients.The maximum total equivalent effective dose to skin due to the ^(238)U and ^(232)Th series from cutaneous application of different medical drugs by patients was found to be 2.8 mSv year^(-1) cm^(-2).

Evaluation of Mass Drug Administration Impact on Transmission of Lymphatic Filariasis in 13 Sanitary Districts in Burkina Faso

Introduction: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for elimination as a public health issue in the world by 2020. To achieve this goal, one of the strategies is interruption of transmission using chemotherapy (mass drug administration). Burkina Faso in west Africa, an endemic country, has endorsed this resolution. In 2000, all Sanitary Districts (SD) in the country were endemic, and then a national elimination program has made it possible to stop mass treatment in 45 out of 70 SD over 12 years. Sixteen years later, 13 other SD were reeligible for Transmission Assessment Surveys (TAS). This study aimed to determine the current level of the Mass drugs Administration (MDA) impact indicators in these 13 targeted SD in order to decide whether we need to continue MDA. Method: It was a descriptive study that took place from June to September 2017 in 13 SD regrouped into 7 Evaluation Units (EU). The population of the study was 6 to 7 years old children. The community-based cluster survey method was used. The diagnostic test used to detect Wuchereria bancrofti’s circulating antigen (W. bancrofti) is the Filariasis Test Strip (FTS). The critical threshold of positivity was set at 18 positive subjects per EU. Results: We sampled a total of 12,060 children, 48.9% were female and 51.1% male. In the 7 EU, 13 children were positive to W. bancrofti test. The average antigenic prevalence was 0.11% (13/12,060). In all EU, the number of positive subjects was below the critical threshold. Conclusion: At the end of this evaluation of the transmission of lymphatic filariasis in 13 SD of Burkina Faso, we can tell the MDA could be stopped in these areas without risk of resurgence of the disease, according to the current recommendations of WHO. This can be possible by setting up post-TMM surveillance, considering migratory flows, and including villages where positive cases were found to search possible residual transmission zones.

重庆市部分区县鸡肉和鸡蛋兽药残留监测分析及膳食暴露风险评估

目的:了解重庆市部分地区鸡肉和鸡蛋食品中15种兽药残留情况,并评估人体摄入健康风险。方法:2021—2023年,在重庆市17个区县的商场超市、农贸市场随机抽取鸡肉、鸡蛋样品共计107份,采用液相色谱-质谱/质谱法测定鸡肉及鸡蛋中6种喹诺酮类、2种四环素族类、1种硝基咪唑类、2种酰胺醇类抗生素及4种抗球虫药含量。根据重庆市居民的饮食消费情况,采用点评估法和食品安全指数法对鸡肉和鸡蛋中兽药的暴露风险进行评估。结果:76份鸡蛋样品兽药残留检出率为25.00%(19/76),不合格率为2.63%(2/76);鸡肉样品兽药残留检出率为70.97%(22/31),不合格率为0%(0/31);鸡蛋及鸡肉中检出率较高的多西环素,食品安全指数均值分别为0.000 293和0.000 119,最大值分别为0.002 710和0.001 770,均远低于1。结论:重庆市部分区县鸡肉及鸡蛋中兽药残留有不同程度的检出,部分样品不合格,但总体风险较低,健康危害在可接受范围。

基于医院卫生技术评估的5种二肽基肽酶4抑制剂的临床应用情况

目的通过医院卫生技术评估(HB-HTA)对5种二肽基肽酶4抑制剂(DPP-4i)(西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀)进行评估,为医疗机构药品的遴选、临床的合理安全使用提供依据。方法通过HB-HTA,依照百分制评分体系,参考药品说明书、临床指南和文献,从安全性、有效性、经济型、创新性、适宜性和可及性等方面分别对5种DPP-4i进行评估。结果西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀得分分别为85.0、75.0、77.0、80.0、78.5分。评分差异主要在安全性、经济性、适宜性和可及性方面。西格列汀综合得分最高。结论HB-HTA评估DPP-4i结果比较合理,为医院药品遴选、安全合理使用提供依据。

4种治疗糖尿病周围神经病变补气活血类中成药的卫生技术评估

目的为临床选择糖尿病周围神经病变(DPN)治疗用补气活血类中成药提供参考。方法参考《医疗机构中成药遴选专家共识(第一版)》,结合临床实际,制订药物卫生技术评估细则,参考药品说明书、临床指南和文献,对4种中成药的安全性、有效性、经济性、适宜性、创新性、可及性、传承性进行评分,并计算总分。结果通心络胶囊、木丹颗粒、糖脉康颗粒、芪蛭降糖胶囊的评分分别为74.5分、72分、64.5分、57分。结论临床在选择治疗DPN的补气活血类中成药时,相对于糖脉康颗粒、芪蛭降糖胶囊,建议优先使用木丹颗粒、通心络胶囊。

医院药学绩效考核模式探索与实践

目的促进医院药学工作提质增效。方法探索医院药学绩效考核模式,经人才队伍建设、制度分层保障、药师配备网格化、以目标为导向的项目式管理,建立院内药事绩效考核体系及药剂科绩效考核体系,以信息化系统对药学工作进行监管,并于2022年1月对体系进行修订。比较医院2021年(修订前)及2022年(修订后)超常处方、合理用药指标、临床科室对临床药师药学服务满意度的相关数据,以评价院内药事绩效考核体系的应用效果;比较2021年7月至12月(381315例)及2022年7月至12月(387105例)门诊患者的取药等候时间,2021年及2022年门诊药房与住院药房的处方调配差错情况,以评价药剂科绩效考核体系的应用效果。结果院内药事绩效考核体系应用后,超常处方数、抗菌药物超常处方数、麻醉药品和精神药品超常处方数占不合理处方数的比例分别由5.83%,3.33%,0.83%降至0.55%,0.55%,0;点评处方占比、抗菌药物使用强度、住院患者基本药物使用率等合理用药指标均改善;30个临床科室(599名医护人员)对临床药师各项药学服务的总满意度均提升。药剂科绩效考核体系应用后,门诊患者的取药等候时间由(10.27±0.49)min缩短为(9.29±0.60)min(P<0.05);门诊药房、住院药房的处方调配差错率分别由0.32‱和0.04‱降至0.08‱和0.02‱,存在药品质量问题、数量错误、一品多规、厂家错误的门诊药房处方及存在数量错误、一品多规、厂家错误、剂型错误的住院药房处方调配差错占比均降低。结论该医院药学绩效考核模式科学可行,有助于提升药师的工作效率与工作质量,促进临床合理用药。

不同评估量表在药物性肝损伤中的诊断价值分析

目的采用RUCAM评估量表、Maria&Victorino评估量表、RECAM评估量表3种因果关系评估量表分别对药物性肝损伤(DILI)确诊病例进行评分,比较3种量表之间的诊断准确性差异,探讨其对于DILI诊断的临床意义。方法纳入2011年1月—2022年12月于北京大学第一医院住院、肝组织学活检病理结果支持DILI及有明确用药史的98例DILI确诊患者。采集研究对象的临床资料,并用上述因果关系评估量表评分,应用χ^(2)检验分析因果关系评估量表的诊断准确性,应用加权kappa系数(κw系数)分析因果关系评估量表的一致性。结果在纳入的所有DILI患者中,RECAM评估量表的准确性最高,与RUCAM评估量表比较差异有统计学意义(χ^(2)=5.667,P=0.017)。RUCAM评估量表和RECAM评估量表的诊断一致性中等(κw=0.469),而RECAM评估量表和Maria&Victorino评估量表的诊断一致性较差(κw=0.156)。在急性DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为3.7%、11.1%、42.6%;在肝细胞型DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为8.9%、21.4%、62.5%;在胆汁淤积型和混合型DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为10.0%、22.5%、47.5%。结论在急性DILI中使用RECAM评估量表和RUCAM评估量表能提高诊断率;在肝细胞型DILI和临床表现包含胆汁淤积的DILI(胆汁淤积型DILI和混合型DILI)中使用RECAM评估量表和RUCAM评估量表能提高诊断率;根据不同的病程及临床分型选择诊断准确性较高的因果关系评估量表有助于进一步提高临床诊断率。

新型口服小分子抗新型冠状病毒感染药物的快速遴选评价实践

目的:应用《中国医疗机构药品评价与遴选快速指南(第二版)》(以下简称“指南”)对新型口服小分子抗新型冠状病毒感染(COVID-19)药物进行快速遴选评价,为医疗机构合理引进药物提供参考。方法:基于指南制定的百分制评估体系,参照药品说明书、疾病诊治指南,并检索中国知网、万方数据库、PubMed等数据库中的文献,从药学特性、有效性、安全性、经济性、其他属性5个方面对奈玛特韦片/利托那韦片、莫诺拉韦胶囊、阿兹夫定片进行卫生技术评估,并依据评分结果推荐各种药品的引进级别。结果:经量化评分,阿兹夫定片、奈玛特韦片/利托那韦片和莫诺拉韦胶囊的最终得分分别为75.00、71.78和73.36分。上述3药均为早期治疗轻、中型COVID-19患者的一线药物。阿兹夫定片适用人群更广泛,价格便宜,但腹泻、头晕等不良反应发生率略高。奈玛特韦片/利托那韦片、莫诺拉韦胶囊仅限于有发展为重型风险因素的成人患者使用,奈玛特韦片/利托那韦片的疗效优于莫诺拉韦胶囊,但不良药物相互作用较多,且价格昂贵。莫诺拉韦胶囊用于肝肾功异常患者时无需调整剂量,无不良药物相互作用,轻中度不良反应发生率最低。上述3药的总分均>70分,属强推荐范畴,医疗机构可根据用药群体特点酌情选择1~2种引进。结论:本次卫生技术评估可为医疗机构开展药品遴选评价提供实践经验,同时为临床合理使用抗COVID-19药物提供循证依据。