Issues in the design and implementation of vaccine trials in less developed countries

There is a growing need for vaccine trials in developing countries. This need arises from the fact that some vaccines do not perform as well in developing as in industrialized country populations and because some newly developed candidates target diseases found only in less-developed countries. Here we discuss several key issues in the design and implementation of vaccine trials in less-developed countries. These include the phasing of vaccine trials on safety, immunogenicity and efficacy to achieve licensure; the recent use of trials to obtain other information crucial to the ultimate deployment of vaccines (such as immunological correlates of protection, indirect vaccine effects, and practical information on the feasibility, costs and acceptability of vaccine introduction); and several ethical issues that have arisen in connection with trials done in developing countries.     

家庭医生责任制管理的实施对社区高血压患者的影响

目的:探讨家庭医生责任制管理的实施对社区高血压患者的影响.方法:将400例高血压患者分为干预组(200例)和对照组(200例),对照组采用传统的高血压患者管理方案,干预组实施家庭医生责任制管理,分别观察干预前后的诊室血压、清晨血压、总胆固醇、(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、高血压疾病相关知识知晓率以及治疗依从性的变化.结果:经过1年的干预,两组患者的血压、血脂方面均较干预前明显降低(P<0.05),但干预组的诊室血压、清晨血压、TC、TG、LDL-C均明显低于对照组(P<0.05);.两组患者的高血压相关知识知晓率和治疗依从性好的比例均较干预前明显提高(P<0.05),但干预组高血压相关知识知晓率和治疗依从性好的比例明显高于对照组(P<0.05).结论:家庭医生责任制管理社区高血压患者能够更好的控制患者血压血脂水平,提高患者疾病知识知晓率和服药依从性,值得推广.     

Structural process and implementation programs of pharmaceutical care in different countries

Pharmaceutical care started in the nineties in the United States and has rapidly extended in many other countries. Although there are different trends, such as clinical pharmacy services, cognitive services, medication management, medication review, they all share the same philosophy and objectives, namely "the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient's quality of life". To attain these objectives, a pharmaceutical care process has to be followed point-by-point in order to detect possible medication-related problems. Furthermore, pharmacists have to work together with patients, and ultimately with physicians to establish a care plan. This methodology requires basic skills of documentation and communication and therefore, it is important to establish implementation programs aimed at community-, hospital-, and consultant pharmacists, and to consider PC as a basic element of University teaching programs and postgraduate studies. Moreover, there are still barriers that hinder the provision of this service and have to be overcome. In this article, we have revised the implementation process and the existing projects in many countries and we conclude that despite the enormous amount of work, there is still much to be done from sides of Administration and pharmacists themselves.     

The European Directive on the legal protection of biotechnological inventions

The European Biotechnology Directive, which finally came into force on 30 July 1998, will clarify a number of issues in connection with patents for biotechnological inventions and has generally been welcomed by the pharmaceutical and biotechnology industries. The Directive generally confirms that, in principle, patent protection should be available in all European Union (EU) countries for most biotechnological inventions, including human and non-human-derived gene sequences and cell-lines and transgenic plants and animals. It should bring the laws of EU member states substantially in line with the practice which has already been adopted at the European Patent Office (EPO), although some confusion remains over the patentability of transgenic plants. Certain inventions will not be patentable on moral grounds, including processes for human cloning or germ line gene therapy, certain uses of human embryos, certain transgenic animals and human/animal chimeras. In many cases, the Directive will extend the scope of protection available for biotechnology patents so that the patentee can prevent unauthorised replication of patented biological material, although farmers will have the right to propagate transgenic crops and breed transgenic animals in certain circumstances. Finally, the Directive also addresses issues arising from the interaction of patent and plant variety rights, the deposit of biological material in recognised institutions in connection with filing for a patent, and the provision of further information on the impact of the Directive and developments in biotechnology patent law by the European Commission to the European Parliament.     

家属哀伤疗护对患者生活质量的影响

目的 :探讨对恶性肿瘤家属实施哀伤疗护对患者生活质量的影响。方法 :选择2012年9月-2013年12月中心肿瘤患者及家属106对,分为研究组和对照组各53对,在对患者实施常规护理外,对研究组家属实施哀伤疗护,用健康状况调查表(SF-36)评估两组患者的生活质量。结果 :研究组患者在家属实施哀伤疗护前后的生活质量比较,除身体疼痛维度外,其余维度评分差异有统计学意义(P<0.05)。对照组患者相同时间生活质量比较,除生理功能和生理职能2个维度外,其余维度差异无统计学意义(P>0.05)。结论 :实施家属哀伤疗护可提高肿瘤患者的生活质量。     

Ecological impact of repeated applications of chlorpyrifos on zooplankton community in mesocosms under Mediterranean conditions

The effects of the insecticide chlorpyrifos were studied in plankton-dominated mesocosms under Mediterranean conditions. Chlorpyrifos was applied four times at 1 week intervals at nominal concentrations of 0.033, 0.1, 0.33, and 1 μg/l simulating repeated agricultural applications. The lowest 7 days time weighted averaged concentrations (TWAC) during the 28 days exposure period were calculated using the FOCUS equation to express the no observed effect concentration (NOEC) values. At population level the lowest NOEC calculated was 0.012 μg/l (treatment concentration 0.033 μg/l). The most affected taxon was Cladocera (Daphnia group galeata) followed by Copepoda (cyclopoids and nauplii). No effects were observed on phytoplankton (chlorophyll-a biomass) at any treatment level. The smallest NOEC_community calculated by means of multivariate techniques was 0.1 μg/l when expressed in terms of the nominal treatment level and 0.074 μg/l when based on the lowest 7 days TWA concentration during the 28 days application period. Indirect effects on zooplankton populations were observed due to shifts in competition and predation between populations. Compared with previous micro/mesocosm experiments simulating a single application exposure regime, results from our study revealed a lower threshold level for the most sensitive measurement endpoint (difference a factor of three (in terms of nominal treatment level), more severe indirect effects and longer recovery periods of the affected populations (>13 weeks in the test systems treated with 1 μg/l). These differences could be attributed to the repeated pulse exposure scenario approach designed for our studies together with the particular climatic conditions involving our Mediterranean mesocosms (i.e., temperature, cladocerans life history, and algae blooms).     

小儿慢性腹痛414例胃镜检查结果分析

目的 探讨小儿慢性腹痛胃镜检查的临床价值.方法 应用PENTAX EPM-3500电子胃镜对414例慢性腹痛患儿进行胃镜检查并行快速尿素酶试验.结果 414例患儿中浅表性胃炎224例(54.1%),十二指肠球炎136例(32.9%),消化性溃疡51例(12.3%),3例未见异常,总检出率99.3%.其中幽门螺杆菌感染259例(62.6%).结论 慢性胃炎、十二指肠球炎及消化性溃疡是小儿慢性腹痛的主要病因,且幽门螺杆菌感染率高,电子胃镜是明确病因不可替代的手段.     

Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries

ABSTRACT

Objectives: To explore the effects of generic substitution of the antiepileptic drug (AED) topiramate (Topamax in Canada; to convert observed Canadian costs into the settings of France, Germany, Italy, and the United Kingdom (UK); and to forecast the economic impact of generic topiramate entry in these four European countries.

Research design and methods: Health claims from Régie de l'assurance maladie du Québec (RAMQ) plan (1/2006–9/2008) and IMS Health data (1998–2008) were used. Patients with epilepsy and ≥2 topiramate dispensings were selected. An open-cohort design was used to classify observation into mutually-exclusive periods of branded versus generic use of topiramate. Canadian healthcare utilization and costs (2007 CAN$/person-year) were compared between periods using multivariate models. Annualized per-patient costs (2007€ or 2007£/person-year) were converted using Canadian utilization rates, European prices and service-use ratios. Non-parametric bootstrap served to assess statistical significance of cost differences. Topiramate market was forecasted following generic entry (09/2009–09/2010) using autoregressive models based on the European experience. The economic impact of generic topiramate entry was estimated for each country.

Results: A total of 1164 patients (mean age: 39.8 years, 61.7% female) were observed for 2.6 years on average. After covariates adjustment, generic-use periods were associated with increased pharmacy dispensings (other AEDs: +0.95/person-year, non-AEDs: +12.28/person-year, p?<?0.001), hospitalizations (?+?0.08/person-year, p?=?0.015), and lengths of hospital stays (+0.51 days/person-year, p?<?0.001). Adjusted costs, excluding topiramate, were CAN$1060/person-year higher during generic use (p?=?0.005). Converted per-patient costs excluding topiramate were significantly higher for generic relative to brand periods in all European countries (adjusted cost differences per person-year: €706–815, p?<?0.001 for all comparisons). System-wide costs would increase from 3.5 to 24.4% one year after generic entry.

Limitations: Study limitations include the absence of indirect costs, possible claim inaccuracies, and IMS data limitations.

Conclusions: Higher health costs were projected for G4 European countries from the Canadian experience following the generic entry of topiramate.     

Assessing the impact of substandard copy medicines in developing countries: the experience with imatinib copies

Access to safe, high-quality medicines is an important international healthcare issue. In developing countries, copy medicines may be attractive due to low acquisition price, but their potential risks due to inadequately demonstrated bioequivalence have garnered only limited attention. As a result, policy-makers, physicians and patients may have incomplete information regarding their real-world safety and efficacy. Using chronic myeloid leukemia (CML) treatment as an example, we conducted a literature review of case reports and study publications to assess whether the available literature provides evidence on the real-world safety and efficacy of imatinib copies. While several publications described clinical outcomes with imatinib copy treatment, significant gaps in interpretability and quality exist. We conclude that clear demonstration of bioequivalence is critical for copy drugs, and in the presence of uncertain bioequivalence, greater pharmacovigilance and real-world data benchmarked against originator medications are needed to assess the impact of copy medicines and protect patients in developing countries.     

树突状细胞与细胞因子诱导的杀伤细胞疗法对心脏的影响

目的探讨树突状细胞/细胞因子诱导的杀伤细胞（DC/CIK）疗法对心脏的影响。方法回顾性分析152例接受DC/CIK细胞治疗的癌症患者的心电图资料。结果 152例患者中有15例出现心电图异常,发生率为9.8%,其中窦性心动过缓3例,窦性心动过速6例,心肌缺血6例。结论 DC/CIK细胞治疗对癌症患者心脏有一定影响。但是,如果给予高度重视,早期发现,早期处理,可避免严重后果。     

Trends in Ostreopsis proliferation along the Northern Mediterranean coasts

Harmful benthic microalgae blooms represent an emergent phenomenon in temperate zones, causing health, ecological and economic concern. The main goal of this work was to compile records of Ostreopsis at large temporal and spatial scales, in order to study the relationship between cell abundances, the periodicity and intensity of the blooms and the role of sea water temperature in 14 Spanish, French, Monegasque and Italian sites located along the northern limits of the Mediterranean Sea. General trends were observed in the two considered basins: the north-western Mediterranean Sea, in which higher cell abundances were mostly recorded in mid-summer (end of July), and the northern Adriatic Sea where they occur in early fall (end of September). The sea-water temperature does not seem to be a primary driver, and the maximal abundance periods were site and year specific. Such results represent an important step in the understanding of harmful benthic microalgae blooms in temperate areas, and provide a good base for policy makers and managers in the attempt to monitor and forecast benthic harmful microalgae blooms.     

414例慢性肾脏病患者中医体质特征研究

目的探讨慢性肾脏病与中医体质特征的关系。方法按王琦中医体质类型的分类方法将慢性肾脏病分类并统计其临床表现在各类型体质中的分布。结果发现414例慢性肾脏病患者中各型体质分布差异较大,其中气虚质、阴虚质和阳虚质比例最高,分别占25．60％、22．70％和16．90％。结论气虚质与蛋白尿合并血尿密切相关;阴虚质与镜下血尿或蛋白尿有关;阳虚质与大量蛋白尿、低蛋白血症、高脂血症有关。上述各种指标的变化均会加重慢性肾脏病的病情及症状,提示上述三种体质可能对慢性肾脏病的形成和发展具有某种内在相关性。