Characteristics Associated with Ability to Prevent Adverse Drug Reactions in Hospitalized Patients

We conducted a retrospective analysis to identify characteristics of preventable adverse drug reactions (ADRs). We reviewed reports on 612 ADRs occurring in hospitalized patients over 4 years, identified by the hospital's spontaneous ADR reporting program, and classified the events as potentially preventable or not preventable. Characteristics related to ADR preventability in the univariate analysis were the patient's clinical service, organ system involved in the ADR, class of drug causing the ADR, relationship to dosage, type of ADR, and probability that the reaction was due to the drug. Among these, relationship to dosage (p<0.001) and type of ADR (p<0.001) appeared to be most strongly related to preventability. In a multivariate analysis, preventable ADRs were associated with dosing (OR 3.82, 95% CI 2.42-6.03) and previous allergy to the drug (OR 3.46, 95%CI 1.01–11.88). An ADR that was classified as an allergic (OR 0.50, 95% CI 0.27-0.94) or idiosyncratic reaction (OR 0.44, 95% CI 0.28-0.71) was unlikely to be considered preventable. Preventable ADRs in hospitalized patients are likely to be dosage related or to occur among patients allergic to the specific agent.     

Risk factors of adverse drug reaction caused by nimesulide in Shanghai patients with osteoarthropathy

The aim of this study was to investigate the risk factors for adverse drug reactions (ADRs) to nimesulide in patients from Shanghai with osteoarthropathy. A retrospective epidemiological study was performed to obtain information (observational variables) on demographics, primary disease, family history of disease, quality of life, dietary habits, lifestyle, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and ADR history of NSAIDs. Univariate and multivariate analyses were performed to establish the relationship between these observational variables and the occurrence of ADRs caused by nimesulide. Among the 726 variables, five risk factors for ADRs to nimesulide were identified. The study showed an increased risk for ADR occurrence with increased scoring of the following four factors: (i) "Concomitant drug therapy" (odds ratio [OR]: 4.66, 95% confidence intervals [CI]: 1.26-17.26, p < 0.05); (ii) "Compared with six months ago, how would you rate your health in general now?" (OR: 1.38, 95% CI: 1.03-1.84, p < 0.05); (iii) "General feeling of health status" (OR: 1.27, 95% CI: 1.03-1.56, p < 0.05) and (iv) "1 expect my health to get worse" (OR: 2.05, 95% CI: 1.22-3.44, p < 0.01). There was a decreased risk for ADR occurrence with increased scoring of the factor "Have you ever suffered from depression that impacted on your life?" (OR: 0.15, 95% CI: 0.03-0.66, p < 0.05). The predictive model for the overall incidence rate of ADRs caused by nimesulide was then established. In conclusion, the predictive model helps to indicate the risk of ADRs to nimesulide and provides clinicians with an alternative method for decision making when prescribing this drug.     

Risk factors associated with adverse drug reactions following hospital admission : a prospective analysis of 907 patients in two german university hospitals

BACKGROUND: Since the 1970s, studies have examined potential risk factors associated with adverse drug reactions (ADRs) in a variety of settings. However, no pharmacoepidemiological study exists that incorporates clinical and laboratory parameters in a multiple regression model in order to consider predictors for ADRs. OBJECTIVES: To characterize risk factors associated with ADRs in patients admitted to university hospital departments of internal medicine. DESIGN AND SETTING: Intensive pharmacovigilance was carried out in departments of internal medicine of two university hospitals. All admissions were followed prospectively for the occurrence of ADRs by members of a pharmacoepidemiological team consisting of physicians, pharmacologists and pharmacists. To identify patients at high risk for experiencing ADRs, patient histories and several clinical and laboratory data, determined at the time of admission, were taken into consideration. In addition to the drug prescribed, 40 parameters defined vital status at admission. These included temperature, heart rate, blood pressure (systolic-diastolic), body mass index, nicotine and alcohol use, and first laboratory test results after admission on nutrition status, inflammation, liver, kidney, pancreas or thyroid status, electrolytes, blood count and coagulation. RESULTS: 907 patients were observed during the study period. The mean age of the study population was 60 +/- 16 years. The median number of different drugs administered per patient during hospitalization was 9.6 +/- 7.7. In 345 patients, 592 ADRs were evaluated: 33.4% possible, 61.5% probable and 4.7% highly probable. Two ADR-related deaths were observed during the study period. Analysing ADR predictors, 17 of 40 parameters reached significance in univariate analysis, but only five in a multivariate binary regression model: raised temperature (odds ratio [OR] 1.609; 95% CI 1.133, 2.285), low erythrocyte levels (OR 0.386; 95% CI 0.194, 0.768), low thrombocyte levels (OR 0.788, 95% CI 0.627, 0.989), high number of drugs (OR 1.117; 95% CI 1.076, 1.159) and female sex (OR 1.562; 95% CI 0.785, 2.013) were independent predictors for ADRs. CONCLUSION: For the patients investigated, of the large number of clinical data available only five independent factors predict ADR occurrence. Taking these results into account, physicians will be able to focus early on patients at risk for ADRs. To minimize ADR occurrence, ADR predictors should be integrated into the clinical pathway.     

抗结核药物所致不良反应发生情况及相关危险因素分析

目的观察抗结核药物所致的不良反应发生情况并分析与其发生相关的危险因素。方法以2005—2010年该市使用标准化疗方案的确诊肺结核患者1 368例为研究对象,对治疗相关不良反应及其危险因素进行统计分析。结果抗结核药所致的不良反应发生率为12.97%,主要的不良反应事件为肝功能损害及胃肠道反应;单因素统计结果发现年龄、BMI、月收入、诊断分型及肝炎病史为抗结核治疗相关可疑危险因素,多因素统计分析发现年龄≥60岁（OR=3.27,95%CI=2.073～5.439,P=0.002）、BMI〈18.5（OR=1.377,95%CI=1.021～3.548,P=0.037）及肝病史（OR=1.82,95%CI=1.003～6.248,P=0.046）为治疗相关危险因素。结论抗结核药所致不良反应发生率较高,当患者存在高龄、营养状态差及肝炎病史可一定程度增加不良反应发生率。     

抗结核药致中国人群药物性肝损伤危险因素的Meta分析

摘要：目的 系统评价中国人群使用抗结核药致药物性肝损伤的危险因素。方法 检索PubMed、Embase、Cochrane Library、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库以及维普数据库(VIP)中建库至2019年10 月发表的有关中国人群使用抗结核药致药物性肝损伤的研究文献,2名研究员独立按照纳入与排除标准筛选文献、提取资料及 质量评价后,采用RevMan 5.3软件进行Meta分析。结果 共纳入12篇文献,均为中文文献,纳入8216例患者,共筛选出13种 暴露因素。Meta分析结果显示,嗜酒(OR=2.54,95%CI：1.97~3.27)、肝病史(OR=2.60,95%CI：2.19~3.08)、乙肝表面抗原携 带者(OR=3.15,95%CI：2.66~3.73)、糖尿病(OR=1.41,95%CI：1.18~1.70)、心功能不全(OR=1.72,95%CI：1.28~2.30)、贫血 (OR=4.61,95%CI：2.43~7.90)、营养不良(OR=2.48,95%CI：1.63~3.77)和结核病复治(OR=1.93,95%CI：1.43~2.60)是抗结核 药物致肝损伤的危险因素(P<0.05)。预防性予以保肝药能显著减少抗结核药致肝损伤的发生率(OR=0.36,95%CI：0.25~0.50, P<0.001)。结论 贫血、乙肝表面抗原携带者、合并其他肝病史、嗜酒、营养不良、结核病复治、心功能不全、糖尿病是我国 人群使用抗结核药致肝损伤的危险因素。对于有高危因素的患者予以保肝药能显著降低抗结核药致肝损伤的发生率。     

1857名非对乙酰氨基酚肝损患者应用乙酰半胱氨酸注射液的不良反应监测结果及分析

目的:监测乙酰半胱氨酸注射液的不良反应,寻找影响乙酰半胱氨酸注射液发生无法耐受治疗的严重不良反应的危险因素.方法:针对接受乙酰半胱氨酸注射液治疗的非对乙酰氨基酚肝损伤患者进行了回顾性分析.共收集1857名患者的乙酰半胱氨酸注射液的药物治疗方案,结合相关临床数据进行多因素分析.结果:纳入研究的1857名患者中,共有537...     

Non-puerperal lactation associated with antidepressant drug use

Aims The aim of the present study was to estimate the relative risk of non-puerperal lactation in patients using antidepressants in general, and specifically for serotonergic (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) and non-serotonergic antidepressants.
Methods All suspected adverse drug reactions in women and reported from January 1986 until August 1996 to the Netherlands Pharmacovigilance Foundation, a spontaneous adverse drug reaction reporting programme, were analysed. Adverse drug reaction (ADR) reporting odds ratios, defined as the ratio of the exposure odds among reported cases of non-puerperal lactation to the exposure odds of reported other ADRs, were calculated adjusted for age and year of reporting.
Results Thirty-eight cases of non-puerperal lactation were reported, of which 15 were associated with the use of antidepressant drugs. In general, antidepressants were associated with a higher risk of non-puerperal lactation in comparison with other drugs (ADR reporting odds ratio 8.3 [ 95%CI: 4.3–16.1]). Serotonergic antidepressants (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) were associated with a higher risk (OR 12.7 [95%CI: 6.4–25.4]), whereas other antidepressants were not (OR 1.6 [95%CI: 0.2–11.6]), compared with all other drugs.
Conclusions Our results indicate that serotonergic antidepressants are associated with an approximately eight times higher risk of non-puerperal lactation compared with other antidepressants. This effect is probably mediated by an indirect inhibition effect of serotonin on the dopaminergic transmission. This finding is in line with the occurrence of other antidopaminergic effects, such as extrapyramidal symptoms, in patients using serotonergic antidepressants.     

Adverse effect of drug-induced emotional problems on work and daily activities. A principal component as an independent predictor of ADRs in Shanghai patients with osteo-arthropathy taking nabumetone

OBJECTIVE: To discover principal components among assessed items from the WHO-SF36 survey by principal component analysis (PCA) and then to establish the relationship between the candidate principal component and the incidence of ADRs induced by nabumetone in Shanghai osteoarthropathy patients. METHOD: A total of 145 patients were interviewed using the WHO-SF36 questionnaire for quality of life (QOL) assessment before the administration of nabumetone. The sub-items of the questionnaire were analyzed using PCA and several comprehensive variables were established. Relationships between these newly formed variables and the overall incidence of adverse drug reactions (ADRs) caused by nabumetone were evaluated using univariate and multivariate analyses. RESULTS: Several principal components were identified and their linear parameters were estimated using PCA. Through univariate analysis, only 1 principal component--"adverse effect on work and daily activities as a result of emotional problems"--was found related to the incidence of ADRs. The odds ratio (OR) was 1.28 with 95% confidence intervals (CI) of 1.11 and 1.48, p = 0.0384. This result was validated using a multivariate logistic analysis performed on all the alternative candidate covariates, including family income, a history of ADRs on NSAIDs, the course of the disease, level of education, control of stress, coffee consumption and consumption of salty food. The covariate information was taken from other parts of the clinical report form (CRF) used in this research. The analysis proved that the principal component, adverse effect on work and daily activities as a result of emotional problems, was an independent factor related to the overall incidence of ADRs. The odds ratio (OR) from the logistic analysis was 1.34, with 95% confidence intervals (CI) of 1.16 and 1.55, p = 0.0309. CONCLUSIONS: The principal component identified can be applied to overcome some limitations in the WHO-SF36 questionnaire such as high correlation between variables, information overlaps and weak representation of variables and the statistical data analysis of QOL can therefore be made more effective. The study shows that the principal component "adverse effect on work and daily activities as a result of emotional problems" is an independent predictor of the overall incidence of ADRs induced by nabumetone.     

基于FAERS的头孢他啶／阿维巴坦致神经系统异常的不良反应信号挖掘与分析

目的：通过对头孢他啶/阿维巴坦（ceftazidime/avibactam, CAZ/AVI）导致神经系统异常相关药物不良反应（adverse drug reactions, ADRs）信号的挖掘分析,为临床安全合理用药提供依据。方法：基于2015年1月至2021年6月美国食品药品监督管理局的不良事件报告系统（FAERS）,采用报告比值比法（reporting odds ratio, ROR）和贝叶斯法判别可信区间产比神经网络法（bayesian confidence propagation neural network, BCPNN）进行数据挖掘,筛选CAZ/AVI给药后导致神经系统异常的相关ADRs,并将其与美罗培南、亚胺培南/西司他丁和头孢他啶进行比较。结果：该研究共收集到CAZ/AVI相关ADRs共694例,其中88例与神经系统异常相关。女性患者比例稍高于男性（54.55% vs.34.09%）,65岁以上患者所占比例较高（15.91%）,用药后中位发病时间为6.5 d。CAZ/AVI与美罗培南和头孢他啶相比,致神经系统异常的风险增加[ROR=1.66（95%CI：1.28~2.13）,IC025=0.46;ROR=1.36（95%CI：1.02~1.81）,IC025=0.21]。CAZ/AVI与美罗培南、亚胺培南/西司他丁和头孢他啶相比,CAZ/AVI发生脑病[ROR=2.73（95%CI：1.85~4.04）,IC025=0.81;ROR=2.26（95%CI：1.46~3.51）,IC025=0.52;ROR=1.81（95%CI：1.15~2.84）,IC025=0.34]、肌阵挛[ROR=4.74（95%CI：2.56~8.81）,IC025=0.97;ROR=4.31（95%CI：2.04~9.10）,IC025=0.63]、昏迷[ROR=2.77（95%CI：1.26~6.08）,IC025=0.57;ROR=2.69（95%CI：1.08~6.71）,IC025=0.39]和癫痫[ROR=1.67（95%CI：1.05~2.67）,IC025=0.30]的风险增加。结论：该研究表明CAZ/AVI具有增加神经系统异常风险的倾向,这些不良反应应引起临床注意,特别是用于有中枢神经系统病史的患者,从而为临床安全用药提供参考,或避免用于高风险人群。     

Clinical pharmacy services, pharmacy staffing, and adverse drug reactions in United States hospitals

Adverse drug reactions (ADRs) were examined in 1,960,059 hospitalized Medicare patients in 584 United States hospitals in 1998. A database was constructed from the MedPAR database and the National Clinical Pharmacy Services survey. The 584 hospitals were selected because they provided specific information on 14 clinical pharmacy services and on pharmacy staffing; they also had functional ADR reporting systems. The study population consisted of 35,193 Medicare patients who experienced an ADR (rate of 1.8%). Of the 14 clinical pharmacy services, 12 were associated with reduced ADR rates. The most significant reductions occurred in hospitals offering pharmacist-provided admission drug histories (odds ratio [OR] 1.864, 95% confidence interval [CI] 1.765-1.968), drug protocol management (OR 1.365, 95% CI 1.335-1.395), and ADR management (OR 1.360, 95% CI 1.328-1.392). Multivariate analysis, performed to further evaluate these findings, showed that nine variables were associated with ADR rate: pharmacist-provided in-service education (slope -0.469, p=0.018), drug information (slope -0.488, p=0.005), ADR management (slope -0.424, p=0.021), drug protocol management (slope -0.732, p=0.002), participation on the total parenteral nutrition team (slope 0.384, p=0.04), participation on the cardiopulmonary resuscitation team (slope -0.506, p=0.008), medical round participation (slope -0.422, p=0.037), admission drug histories (slope -0.712, p=0.008), and increased clinical pharmacist staffing (slope -4.345, p=0.009). As clinical pharmacist staffing increased from the 20th to the 100th percentile (from 0.93+/-0.77/100 to 5.16+/-4.11/100 occupied beds), ADRs decreased by 47.88%. In hospitals without pharmacist-provided ADR management, the following increases were noted: mean number of ADRs/100 admissions by 34.90% (OR 1.360, 95% CI 1.328-1.392), length of stay 13.64% (Mann-Whitney U test [U]=11047367, p=0.017), death rate 53.64% (OR 1.574, 95% CI 1.423-1.731), total Medicare charges 6.88% (U=111298871, p=0.018), and drug charges 8.16% (U=108979074, p<0.001). Patients in hospitals without pharmacist-provided ADR management had an excess of 4266 ADRs, 443 deaths, 85,554 patient-days, $11,745,342 in total Medicare charges, and $1,857,744 in drug charges. The implications of these findings are significant for our health care system, especially considering that the study population represented 15.55% of 12,261,737 Medicare patients and 5.71% of the 34,345,436 patients admitted to all U.S. hospitals.     

Anti-infectives-induced adverse drug reactions in hospitalized patients

OBJECTIVES: To assess the rate and seriousness of adverse drug reactions (ADRs) attributable to anti-infective agents in hospitalized patients; to estimate the likelihood of experiencing anti-infectives-induced ADRs at different length of drug usage in the hospital; to compare different classes of anti-infectives in inducing ADRs; to determine the impact of age and sex on anti-infectives-induced ADRs. DESIGN: Prospective cohort study. PARTICIPANTS: Patients admitted to the infectious diseases department at a university teaching hospital, on Sunday to Wednesday, over a 9 months period, who received at least one anti-infective agent were eligible to enter the study. MAIN OUTCOME MEASURES: Any suspected noxious and untoward medical events, including laboratory tests abnormalities following anti-infective therapy. METHODS: All patients admitted have received at least one anti-infective drug. Anti-infective agents induced ADRs were detected by interviewing patients and daily chart review. The seriousness, causality, and type of reactions were classified based on World Health Organization (WHO) definitions. Chi-square analysis was performed to assess the influence of sex and age on occurring ADRs. Both Kaplan-Meier and life table method were used to estimate the time to occur the ADR in anti-infective users. To compare the estimated risk of ADRs induced by different classes of anti-infectives, odds ratios were estimated. In all classes of anti-infectives, the odds ratio of each class was estimated with regard to anti-tuberculosis agents, which had the highest prevalence of ADRs. RESULTS: During the study period, 460 patients were entered the study. During the same period, 38 ADRs were recognized of which 20 (42%) were serious. The most recognized ADRs were suspected to be induced by anti-tuberculosis agents (29.8%). However in comparing with anti-tuberculosis agents, anti-fungal agents were associated with the highest ADR rate (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.41-1.256) whereas cephalosporines were associated with the lowest rate, (OR, 0.1; 95%CI, 0.04-0.26). The survival analysis shows that the likelihood of experiencing an ADR was increased at first 14 days of drug therapy. Also Chi-square analysis shows that greater risk of anti-infectives-induced ADRs was observed in women. CONCLUSION: The rate of ADRs induced by anti-infective agents in this study was 8.2%. This is higher than a standard (5%) which has been reported in other studies. This study also shows that some of the classes of anti-infective agents like anti-fungals need more attention.     

7种静脉注射碘对比剂的合理应用及其不良反应分析

目的:探讨7种碘对比剂静脉注射的临床诊疗中的合理应用,总结不良反应相关因素及最佳处理方法。方法:依据对比剂含碘浓度、渗透压、剂量、价格、患者性别、年龄、体重指数(BMI)、血压、内生肌酐清除率(Ccr,μmol·L^-1)、基础病史、CT增强扫描部位及对比剂不良反应(ADR)发生情况,初步制定碘对比剂合理应用方案;总结7种碘对比剂所致急性、晚发性及超晚发性不良反应发生率、发生特点及相应临床处理方法。结果:(1)7种类型碘对比剂临床应用情况不同;(2)碘对比剂ADR共128例,其中急性94例、晚发不良反应31例、超晚发不良反应3例,发生率在正常范围内;皮肤过敏最常见,共83例(64.8%),胃肠道反应19例(14.8%),呼吸系统17例(13.2%),心血管系统4例(3.1%),中枢神经系统3例(2.3%),泌尿系统1例(0.7%),多系统症状至死亡1例(0.7%);(3)多因素Logistic回归分析显示,年龄(OR=0.96,P=0.021),使用前加热(OR=1.74,P=0.028),注射流速(OR=1.28,P=0.001),扫描部位(OR=0.73,P=0.041)是不良反应的独立危险因素。结论:年龄、使用前加热、注射流速、扫描部位是非离子型碘对比剂不良反应的独立危险因素;正确合理使用碘对比剂能够为患者疾病诊断提供最佳的检查手段并有效降低不良反应发生率,提高医务工作者对碘对比剂不良反应处理的意识。     

A prospective study of adverse drug reactions in hospitalized children

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.     

OPCAB 患者合并颈动脉狭窄临床危险因素与预后的相关性研究

摘要： 目的 研究行非体外循环冠状动脉旁路移植术 （OPCAB） 患者合并颈动脉狭窄 （CAS） 的危险因素及对预后的影响。方法 回顾性分析 2013 年 6 月—2015 年 6 月择期行 OPCAB 治疗的 342 例患者的临床资料, 依据术前颈动脉超声结果分为 CAS 组 71 例（单侧或双侧狭窄≥50%）及对照组 271 例（狭窄＜50%或无狭窄）, 比较 2 组基本资料, 行多因素 Logistic 回归分析 CAS 的危险因素。比较 2 组术中及术后情况, 对术后死亡患者进行危险因素分析。结果 2 组患者年龄、 吸烟史、 高血压病、 慢性阻塞性肺疾病（COPD）差异有统计学意义（P＜0.05）。Logistic 回归显示, 高龄（OR=1.050, 95%CI 1.014~1.086, P＜0.01）、 高血压病（OR=2.566, 95%CI 1.299~5.071, P＜0.01）、 COPD（OR= 7.573, 95%CI 1.106~51.834, P＜0.05） 是 OPCAB 合并 CAS 的危险因素。有 CAS （OR=4.530, 95%CI 1.361~15.078, P＜ 0.05）及经皮冠状动脉介入治疗史（OR=7.685, 95%CI 2.289~25.800, P＜0.01）是 OPCAB 术后患者死亡的危险因素。结论 高龄、 高血压病、 COPD 是 OPCAB 术患者合并 CAS 的危险因素, CAS 患者行 OPCAB 术后死亡风险较高。     

万古霉素儿童临床应用安全性评价

目的 为儿童临床安全使用万古霉素提供参考.方法 采用计算机检索中国期刊全文数据库、维普期刊全文数据库、万方数据库、中国生物医学文献服务系统,以及PubMed,Springer,Wiley等数据库,儿童使用万古霉素导致药品不良反应(ADR)的相关文献,检索时限为建库起至2021年5月28日,分析ADR发生特点及严重ADR...     

老年肺部感染住院患者合并多重耐药菌感染的危险因素探讨及风险Nomogram模型的建立

摘要：目的 探讨老年肺部感染住院患者合并多重耐药菌感染的危险因素及风险Nomogram模型的建立。方法 回顾 性分析2018年9月—2019年9月我院274例老年肺部感染住院患者的临床资料,分别使用单因素和Logistic回归多因素分析老年 肺部感染住院患者合并多重耐药菌感染的独立危险因素。然后纳入筛选出的独立危险因素建立Nomogram预测模型,并对模 型的预测性及准确度进行验证。结果 通过对两组患者临床资料做Logistic回归分析可知,年龄≥80岁(OR=2.387,95%CI: 1.272~4.480)、意识昏迷(OR=2.319,95%CI: 1.143~4.703)、心脑血管疾病(OR=2.078,95%CI: 1.104~3.911)、住院天数≥2 周(OR=2.481,95%CI: 1.284~4.796)、抗菌药物使用种类≥2种(OR=2.886,95%CI: 1.477~5.641)、抗菌药物使用时间≥2周 (OR=2.386,95%CI: 1.114~5.108)及机械通气(OR=3.090,95%CI: 1.432~6.667)是老年肺部感染住院患者合并多重耐药菌感染的 独立危险因素。基于回归分析结果中的7项独立危险因素,建立预测老年肺部感染住院患者合并多重耐药菌感染的Nomogram 模型,并对该模型进行验证,预测值同实测值基本一致,说明本研究的Nomogram预测模型具有较好的预测能力,同时使用 Bootstrap内部验证法对该模型进行验证,C-index指数为0.762 (95%CI: 0.729~0.795),说明该Nomogram模型具有良好的精准度和 区分度。结论 年龄≥80岁、意识昏迷、心脑血管疾病、住院天数≥2周、抗菌药物使用种类≥2种、抗菌药物使用时间≥2周 及机械通气是老年肺部感染住院患者合并多重耐药菌感染的独立危险因素,相关Nomogram预测模型的建立有利于医护人员筛 查相关危险因素和采取相应防治措施,从而最大限度地降低多重耐药菌感染的发生率。     

Hepatic adverse drug reactions: a case/non-case study in Italy

OBJECTIVE: Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database. METHODS: Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with "certain", "probable" or "possible" causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. RESULTS: On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4-3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6-4.6), NSAIDs (ROR = 2.9; 95% CI 2.1-3.9) and macrolides (ROR = 1.7; 95% CI 1.2-2.3). CONCLUSION: Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.     

Non-sedating antihistamine drugs and cardiac arrhythmias -- biased risk estimates from spontaneous reporting systems?

AIMS: This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some of these drugs. METHODS: All suspected adverse drug reactions (ADRs) reported until July 1999 to the Netherlands Pharmacovigilance Foundation Lareb were used to calculate the ADR reporting odds ratio, defined as the ratio of exposure odds among reported arrhythmia cases, to the exposure odds of other ADRs (non-cases), adjusted for gender, age, reporter, year of reporting and comedication, stratified for the periods before and after the governmental decision in the Netherlands. RESULTS: Seven-hundred and thirty-seven cases of arrhythmia were reported, out of which there were 43 instances where the patients were using non-sedating antihistamines. In general non-sedating antihistamines are associated with cardiac arrhythmia to a higher extent in comparison with other drugs (ADR reporting odds ratio 2.05 [95% CI: 1.45, 2.89]). The association between arrhythmias and non-sedating antihistamine drugs calculated before 1998 was not significantly higher than 1 (OR 1.37 [95% CI: 0.85, 2.23]), whereas the risk estimate calculated after the governmental decision did significantly differ from 1 (OR 4.19 [95% CI: 2.49, 7.05]). CONCLUSIONS: Our data suggest that non-sedating antihistamines might have an increased risk for inducing arrhythmias. Our findings, however, strongly suggest that the increased risk identified can at least partly be explained by reporting bias as a result of publications about and mass media attention for antihistamine induced arrhythmias.     

慢性阻塞性肺疾病患者合并侵袭性肺曲霉菌感染危险因素的Meta分析

目的 系统评价慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者并发侵袭性肺曲霉菌(invasive pulmonary aspergillosis,IPA)感染的危险因素。方法 检索PubMed、Embase、Cochrane Library、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库从建库至2019年12月发表的有关COPD患者并发IPA感染危险因素的病例对照研究,2名研究员独立按照纳入与排除标准筛选文献、提取资料及质量评价后,采用RevMan 5.3软件进行Meta分析。结果 共纳入16篇文献,4篇为外文,12篇为中文。Meta分析结果显示,吸烟史(OR=1.89,95%CI：1.44~2.47)、COPD分级≥3级(OR=2.56,95%CI：2.02~3.24)、入住ICU(OR=3.29,95%CI：2.44~4.44)、低蛋白血症(OR=2.66,95%CI：1.93~3.66)、糖尿病(OR=3.10,95%CI：2.49~3.86)、肾功能不全(OR=2.59,95%CI：1.49~4.49)、呼吸衰竭(OR=4.32,95%CI：3.24~5.75)、有创机械通气(OR=4.59,95%CI：3.76~5.61)、侵袭性操作(OR=4.59,95%CI：3.60~5.84)、糖皮质激素全身给药(OR=2.17,95%CI：1.28~3.70)、糖皮质激素日剂量≥20mg(OR=3.92,95%CI：2.38~6.45)、糖皮质激素累积剂量≥700mg(OR=9.61,95%CI：5.80~15.94)、糖皮质激素用药≥14d(OR=4.64,95%CI：3.63~5.94)、广谱抗生素用药≥14d(OR=4.29,95%CI：2.43~7.58)、抗生素联用(OR=6.61,95%CI：3.03~11.58)和碳青霉烯类(OR=9.83,95%CI：4.02~24.06)是COPD患者并发IPA的危险因素(P<0.05)。患者年龄、性别、COPD病程、肝功能不全、心功能不全、糖皮质激素雾化吸入与IPA 感染未见明显关联(P>0.05)。敏感度分析提示Meta分析结果稳定。结论 COPD患者并发IPA感染危险因素较多,临床应采取针对性预防措施,以降低其感染风险。