217例药物不良反应报告分析

目的:了解我院药物不良反应(ADR)发生的特点,促进临床合理用药.方法:对我院收集到的217例ADR报告,按患者年龄、性别、给药途径、ADR程度、药物类型、ADR涉及器官或系统及临床表现等进行分类统计与分析.结果:涉及ADR的药物共有217种,抗微生物类药物居首位,其次为中成药;静脉注射引发的ADR为151例(占69.59%);ADR可发生于人体各个系统,但主要为变态反应,以皮肤及其附件损害最为严重,皮肤反应的ADR为总报告例数的67.74%.结论:临床应重视ADR的报告和监测工作,以减少或避免ADR的发生.     

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions

Objective

We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions.

Methods

Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed.

Results

Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001).

Conclusions

We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization–Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.     

Predisposing Factors in Adverse Reactions to Drugs

Predisposing factors were sought in 118 patients who developed adverse drug reactions in hospital. Significantly more patients of 60 years and over, and more women than men, developed adverse drug reactions. Patients with reactions had more drugs before the development of the reaction than patients who did not develop reactions. A previous adverse drug reaction and a history of allergic disease were significant factors, while a history of jaundice or the presence of diabetes mellitus and renal disease was not.     

双膦酸盐类药物致不良反应回顾性分析

目的:分析双膦酸盐类药物所致不良反应情况。方法:检索中国期刊全文数据库(CNKI)、万方数据库(Wan Fang)、中文科技期刊数据库(VIP)2004年1月至2013年8月国内有关双膦酸盐致不良反应的个案报道,按年龄、性别、原发病、药物名称、给药途径、不良反应发生时间、临床表现症状、治疗与转归等进行分类统计分析。结果:48例不良反应包括运动系统、消化系统、感官系统、循环系统、神经系统及全身性损害,高年龄段与女性发生率较高。结论:临床上应重视双膦酸盐类药物所致不良反应,坚持合理用药。     

药物不良反应造成急性肾损害的临床分析

目的：研究药物不良反应（ADR）所致急性肾损伤的相关因素并探讨其诊疗思路。,方法：对56例ADR造成急性肾损害的病例进行归类统计和分析评价。结果：56例病例中,男性略多于女性,男女之比为1．24：1,平均年龄53．1岁;抗生素发生率居首位,其次为中成药;途径以静脉注射为主。结论：合理用药,早期干预治疗,预防药源性急性肾损害的发生。     

Bias in Spontaneous Reporting of Adverse Drug Reactions in Japan

Background

Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan’s unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.

Methods

A manufacturer’s database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.

Results

For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.

Conclusions

Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.     

Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

Background

Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model.

Methods

We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset).

Results

Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively.

Conclusions

We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.     

A Structure-Based Approach for Mapping Adverse Drug Reactions to the Perturbation of Underlying Biological Pathways

Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug''s ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature.     

Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome

Identifying genetic factors responsible for serious adverse drug reaction (SADR) is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might share a common mechanism by targeting unexpectedly the same SADR-mediating protein. Hence we propose an approach of identifying the common SADR-targets through constructing and mining an in silico chemical-protein interactome (CPI), a matrix of binding strengths among 162 drug molecules known to cause at least one type of SADR and 845 proteins. Drugs sharing the same SADR outcome were also found to possess similarities in their CPI profiles towards this 845 protein set. This methodology identified the candidate gene of sulfonamide-induced toxic epidermal necrolysis (TEN): all nine sulfonamides that cause TEN were found to bind strongly to MHC I (Cw*4), whereas none of the 17 control drugs that do not cause TEN were found to bind to it. Through an insight into the CPI, we found the Y116S substitution of MHC I (B*5703) enhances the unexpected binding of abacavir to its antigen presentation groove, which explains why B*5701, not B*5703, is the risk allele of abacavir-induced hypersensitivity. In conclusion, SADR targets and the patient-specific off-targets could be identified through a systematic investigation of the CPI, generating important hypotheses for prospective experimental validation of the candidate genes.     

A Systematic Investigation of Computation Models for Predicting Adverse Drug Reactions (ADRs)

Background

Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs.

Principal Findings

In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper.

Conclusion

Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.     

Factors Affecting Detection of Burrowing Owl Nests During Standardized Surveys

Abstract: Identifying causes of declines and evaluating effects of management practices on persistence of local populations of burrowing owls (Athene cunicularia) requires accurate estimates of abundance and population trends. Moreover, regulatory agencies in the United States and Canada typically require surveys to detect nest burrows prior to approving developments or other activities in areas that are potentially suitable for nesting burrowing owls. In general, guidelines on timing of surveys have been lacking and surveys have been conducted at different times of day and in different stages of the nesting cycle. We used logistic regression to evaluate 7 factors that could potentially affect probability of a surveyor detecting a burrowing owl nest. We conducted 1,444 detection trials at 323 burrowing owl nests within 3 study areas in Washington and Wyoming, USA, between February and August 2000–2002. Detection probability was highest during the nestling period and increased with ambient temperature. The other 5 factors that we examined (i.e., study area, time of day, timing within the breeding season, wind speed, % cloud cover) interacted with another factor to influence detection probability. Use of call-broadcast surveys increased detection probability, even during daylight hours when we detected >95% of owls visually. Optimal timing of surveys will vary due to differences in breeding phenology and differences in nesting behavior across populations. Nevertheless, we recommend ≥3 surveys per year: one that coincides with the laying and incubation period, another that coincides with the early nestling period, and a third that coincides with the late nestling period. In northern latitudes, surveys can be conducted throughout the day. (JOURNAL OF WILDLIFE MANAGEMENT 72(3):688–696; 2008)     

熵权法在药品不良反应信号筛选及综合风险评价中的应用

目的：在运用经典方法对药品不良反应信号进行检测后,对信号进行再筛选并评价药品的综合风险。方法：以江苏省药品不良反应监测网络数据库为资料来源,SQL server 为后台数据库,Matlab 为算法主要实现工具,运用熵权法结合专家评分,对BCPNN 方法检测出的信号进行再调整和评级。结果：运用综合权重进行调整后,发现不同药品不良反应信号的强弱发生了一定的变化。其中,氟喹诺酮类药品中的加替沙星导致低血糖、呼吸困难等药品不良反应的风险较信号评级之前有所增加,需要专家在评审时更为留意。结论：将熵权法运用在药品不良反应信号的监测中,可使信号更接近客观筛选和主观判断的平衡值,部分罕发但严重的药品不良反应信号得到发现和重视,并能方便地研究药物引起的多种药品不良反应的综合风险。     

Timing and Factors Affecting Cannibalism in Red Drum, Sciaenops ocellatus, Larvae in Captivity

Since 1987, when the red drum, Sciaenops ocellatus, was introduced into Taiwan, research has been concentrated on its feasibility and biological studies applied to aquaculture. As a part of these biological studies, an experiment was conducted to investigate the timing and factors affecting cannibalism in red drum larvae in captivity. Experimental larvae were graded into small and large sizes. Four treatments were then applied: (1) the control group, (2) water turbidity increased by adding green algae, (3) density of larvae increased twofold, and (4) satiation feeding with Artemia nauplii. Each treatment was triplicated, each in a 12 l test tank stocked with 20 large and 20 small test larvae except those with doubled density of larvae. In a period of three days, the size difference in test larvae was found to be the most important factor affecting cannibalism, whereas water turbidity and density of larvae showed no apparent effect. Satiation feeding significantly decreased but did not stop cannibalism. The peak stage of cannibalism for red drum larvae was likely to occur at a total body length of 1.8–1.9 cm, when the ratio of lower jaw length to total body length was at its maximum.     

Adverse Drug Reactions in Hospitalised Children in Germany Are Decreasing: Results of a Nine Year Cohort-Based Comparison

Background

In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period.

Methodology

Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis.

Results

A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001).

Conclusions

Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed.     

茶叶香气的影响因素

香气是茶叶风味和品质的主要影响因子。影响茶叶香气的因素有很多,如茶树品种、自然环境、栽培条件、加工工艺、储藏方式等,文章综述了茶树品种、自然环境和栽培条件对茶叶香气的影响,旨在为茶树品种适制性和优质茶香的研究提供参考。