药物临床试验的质量问题分析

目的研究药物临床试验中存在的质量问题,以确保临床试验的伦理性和科学性。方法通过查阅机构临床试验资料,分析本机构2011年以来承担的Ⅱ~Ⅳ期药物临床试验项目中的质量问题。结果对157个药物临床试验进行问题分析后,获得研究者培训情况、监查频率执行情况、标准操作规程的更新3个因素对知情同意书亲笔签名情况、数据的可溯源性、纳入排除标准的遵守情况、不良事件/严重不良事件的记录处理和报告、研究病历和病例报告表数据的一致性等质量问题的影响的详细数据。结论药物临床试验实践过程中还存在问题,建立完善的质量保证体系,加强过程管理对解决这些问题具有重要意义。     

关于静脉滴注给药速度的几个问题

<正>静脉滴注抗感染药物是临床上进行药物治疗的重要用药途径,因其起效快,生物利用度高,便于血药浓度控制等优点,倍受临床医生重视,在抢救病人生命中发挥着越来越积极的作用。随着危重病人抢救水平的不断提高和抢救技术的进步,对静脉     

Changes in patterns of drug injection concurrent with a sustained reduction in the availability of heroin in Australia

Between 1996 and 2000, heroin was the drug most frequently injected in Australia, and viable heroin markets existed in six of Australia's eight jurisdictions. In 2001, there was a dramatic and sustained reduction in the availability of heroin that was accompanied by a substantial increase in its price, and a 14% decline in the average purity of seizures analysed by forensic laboratories. The shortage of heroin constitutes a unique natural experiment within which to examine the impact of supply reduction. This paper reviews one important correlate of the shortage, namely changes in patterns of illicit drug injection. A number of studies have consistently suggested that between 2000 and 2001, there was a sizeable decrease in both prevalence and frequency of heroin injection among injecting drug users. These changes were accompanied by increased prevalence and frequency of stimulant injection. Cocaine was favoured in NSW, the sole jurisdiction in which a cocaine market was established prior to the heroin shortage; whereas methamphetamine predominated in other jurisdictions. Some data suggest that, at least in the short-term, some drug injectors left the market altogether subsequent to the reduced heroin availability. However, the findings that (1) some former heroin users switched their drug preference to a stimulant; and (2) subsequently attributed this change to the reduced availability of heroin, suggests that reducing the supply of one drug may serve to increase the use of others. Given the differential harms associated with the use of stimulants and opiates, this possibility has grave implications for Australia, where the intervention and treatment system is designed primarily to accommodate opiate use and dependence.     

Botanical drug clinical trial:Common issues and future options

In order to understand this disparity between human use and drugs approved by regulatory agencies,we analyzed botanical drug clinical trials registered at Clini...     

Patient compliance with drug therapy in schizophrenia. Economic and clinical issues

The effectiveness of drug treatment in clinical practice is considerably lower than the efficacy shown in controlled studies. The lower effectiveness in practice presumably leads to lower cost effectiveness of drug treatment in real-life situations compared with that demonstrated by studies based on results from controlled trials. Improved cost effectiveness in routine clinical practice would be a significant advantage in the treatment of schizophrenia, one of the most costly diseases in society. The aetiology of schizophrenia is unknown, and there is no cure. The main aims of therapy with antipsychotic medication include the effective relief of symptoms without the introduction of adverse effects or serious adverse events, improved quality of life, cost effectiveness and a positive long term outcome. The older classical antipsychotic drugs do not always meet these requirements because of their well-known limitations, such as a lack of response in a subgroup of individuals with schizophrenia and intolerable adverse effects. There has long been a need for new antipsychotics that can ameliorate more symptoms and have no or few adverse effects. Some of the recently introduced antipsychotics have been shown to be more effective in certain clinical situations and to have a more favourable adverse effect profile than the classical antipsychotics. A major factor contributing to the lower effectiveness of drug treatment is noncompliance, which may be very high in schizophrenia. There are several factors influencing compliance, including drug type and formulation, patient, disease status, physician, health care system, community care and family. There have been very few studies of compliance improvement strategies in schizophrenia or, indeed, in medicine in general. Current methods are relatively complex and there are differing opinions on their effectiveness. There are several ways to increase compliance in schizophrenia--the evidence is strongest for psychoeducative methods, changing to a new drug or using a depot formulation. However, considerably more research is needed in the field of compliance strategies.     

卡前列素氨丁三醇注射液联合缩宫素预防产后出血的疗效观察

目的观察卡前列素氨丁三醇注射液联合缩宫素预防产后出血的临床效果。方法将50例宫缩乏力性产后出血高危因素产妇随机分为观察组和对照组各25例。观察组胎儿娩出后予缩宫素20U宫体注射,卡前列素氨丁三醇注射液0．25mg肌内注射。对照组予缩宫素20U宫体注射,缩宫素20U静脉滴注。应用称重法计算2组产后2h及24h出血量、出血率和不良反应。结果观察组产后2h及24h出血量明显少于对照组,差异均有统计学意义（P〈0．05）。观察组产后出血率为16．0％（4／25）低于对照组的56．0％（14／25）,差异均有统计学意义（P〈0．05）。结论卡前列素氨丁三醇注射液联合缩宫素治疗宫缩乏力性产后出血较单独使用缩宫素疗效显著,具有临床意义。     

新药临床试验中医学伦理学问题的探讨

目的通过对新药临床试验中存在的医学伦理学问题的探讨,阐明在新药临床试验研究过程中,如何解决好试验阶段相关的医学伦理学问题。方法以相关的法律、法规、原则、规范以及社会伦理、道德为依据,探讨新药临床试验中的医学伦理学问题。结果临床受试者是一群生理甚至于心理均处于非正常状态的病人,因此在新药临床试验研究过程中,不但涉及到大量的技术问题,更重要的是存在相关的医学伦理学问题。结论在新药临床试验研究过程中,试验者必须执行和遵守相关的法律法规,解决好试验阶段相关的医学伦理学问题。     

Methodological issues associated with preclinical drug development and increased placebo effects in schizophrenia clinical trials

Recent failures to detect efficacy in clinical trials investigating pharmacological treatments for schizophrenia raise concerns regarding the potential contribution of methodological shortcomings to this research. This review provides an examination of two key methodological issues currently suspected of playing a role in hampering schizophrenia drug development; 1) limitations on the translational utility of preclinical development models, and 2) methodological challenges posed by increased placebo effects. Recommendations for strategies to address these methodological issues are addressed.     

Using a group approach to preventing heroin overdose in North London

Aims: This study used group psycho-education methods to assist injecting heroin users in preventing, and responding to overdose. Methods: An ‘OD Prevention’ group was advertised in a London prescribing service and associated primary care unit. The intervention took place in a small group over one afternoon (3.5 hours), and trained participants in recognizing, and responding to heroin overdoses (defining overdose, discussing known risk factors and on-site instruction in cardio-pulmonary resuscitation (CPR). Participants were all injecting heroin users in service contact with the primary care unit, drug dependence unit, or hostels for the homeless in central London. Participants self-referred, or were referred by key workers. Participants completed pre- and post-group questionnaires concerning their personal experience of overdose, the witnessing of others’ overdoses and fatalities, their current response in overdose situations, and their overall confidence in helping others who have overdosed. Findings: In total 107 people attended the group. Of these, 42% had witnessed others’ overdose, and 29% had witnessed one or more deaths as a result of overdose. Following the group intervention more participants reported feeling ‘quite or very confident’ in managing an OD situation, confident in undertaking CPR with someone who had overdosed, and were less likely to pursue ‘folklore’ remedies to overdose. Conclusions: Using psycho-educational group approaches can be an effective tool in attempts to prevent and respond to heroin overdoses, and is seen as useful by users.     

氯胺酮联合利多卡因预防儿童异丙酚注射痛

目的评价和比较单独使用氯胺酮预注射、利多卡因与异丙酚混合注射、氯胺酮与利多卡因联合3种方法减轻异丙酚注射痛的效果。方法选择150例3～10岁择期行外科手术的患儿为实验对象,共分成3组,每组50例。L组接受盐水3 mL,15 s后给予混合有2%利多卡因的异丙酚（容积比1∶19）;K组给予0.4 mg/kg的氯胺酮3 mL,15 s后给予1%异丙酚;KL组给予利多卡因＋氯胺酮。实验由一名不知分组情况的麻醉师依据4分法给注射痛评分。结果 KL组注射痛发生率（8%）显著低于K组（28%,P〈0.05）、L组（32%,P〈0.05）。三组之间异丙酚诱导用量、意识消失时间及并发症（呕吐、喉痉挛、苏醒期躁动、苏醒延迟和注射部位水肿皮疹）方面比较,差异无统计学意义。结论氯胺酮与利多卡因联合可显著降低异丙酚注射痛,完全消除重度疼痛,且不良事件发生率低,诱导平稳。     

Testing drug response in the presence of genetic information: sampling issues for clinical trials

Progress towards construction of a dense map of di-allelic markers across the human genome has generated considerable enthusiasm for pharmacogenomic applications. To date, however, nearly all of the effort on single nucleotide polymorphism (SNP) projects has been focused on marker identification and screening, not on how the SNP genotype data actually can be used in clinical trials to advance medical practice. Here, we explore how different properties of SNPs impact the size, scope and design of clinical trials using a simple trial design. We evaluate the clinical trial sampling requirements under different allele frequencies, gene action, gene effect size and number of markers in a genome screen. Power and sample size calculations suggest that allele frequency and type of gene action can have a dramatic impact on trial sample sizes, in that under some conditions the required sample sizes are too large to be applicable in a costly clinical trial setting. In other situations, however, pharmacogenomic clinical trials can yield significant sampling/cost savings over traditional trials. These properties are discussed with regard to the general usage of genetic information in clinical trial settings.     

药物注射剂临床不规范使用案例分析

目的 通过临床药物注射剂使用中的实际案例,找到使用中的关注点,为更规范临床使用药物注射剂,减少药物不合理使用的医疗行为,保证药物的使用安全性和有效性.方法 收集并分析临床上不规范使用注射剂的18个具体案例,归纳总结其关注点.结果和结论 建议关注以下几方面：药品说明书、药物副作用、药物配伍禁忌、药物稳定性、给药途径、药物滴注速度、药物对注射局部的影响、头孢类药物的过敏反应、中药注射剂的使用等,全面了解、熟悉药品的使用信息,规范使用药品.     

Practical issues in the methadone management of pregnant heroin users

Methadone management of pregnant heroin-using patients has become a standard approach to this particular population of patients. This paper discusses the establishment and running of an out-patient stabilization programme and highlights areas of difficulty experienced in this exercise. Guidelines are suggested for those who wish to establish such a service in the future.     

静脉注射海洛因合并佐匹克隆片剂成瘾一例

患者,女,28 a,汉族,未婚,中专毕业,因滥用海洛因成瘾近2 a,于2007年9月6日入劳教所.