Reporting of adverse drug and biologic reactions in Mississippi hospitals.

There can be no doubt of the therapeutic need for adverse drug reaction (ADR) monitoring in hospitals. In addition, JCAHO requirements mandate the maintenance of concurrent ADR monitoring programs. In order to obtain data pertaining to ADR reporting in hospitals in Mississippi, a survey of statewide hospital-pharmacy directors was conducted. Respondents indicated the average number of ADRs reported to the pharmacy departments was 19.2 ADRs per year. An average of 2.2 ADRs were forwarded to the FDA yearly. Respondents who had recently (since 1984) undergone JCAHO inspection agreed to a greater extent than others that it was the P & T Committee's responsibility to monitor ADRs. The results indicate a need for other health professionals in hospitals to monitor and report ADRs. In addition, submission of ADRs to the FDA must occur to a greater extent than presently is occurring.     

Assessment of adverse drug reactions in psychiatric hospitals

Summary A system for monitoring adverse drug reactions (ADR) in psychiatric inpatients was introduced in psychiatric hospitals in the FRG in May 1979. It consists of intensive drug monitoring (IDM) and a so-called organized spontaneous reporting system (OSR). ADR are rated separately according to impact on therapy and probability of causal relationship. With IDM all ADR (Grades I–III) are assessed in a randomly selected sample of inpatients. With OSR only ADR leading to discontinuation of the drugs in question (=ADR Grade III) are assessed. In 406 drug-treated inpatients monitored by IDM in the psychiatric hospitals of Berlin and Munich from May 1979 to Dec. 1981, ADR were observed in 60,4%. In 15% of IDM-patients ADR led to discontinuation of the drugs in question; with OSR the relative frequency of these Grade III ADR was 9,0% in 5096 patients monitored throughout the entire period. Life-threatening events were observed in 1,2% of patients undergoing IDM as well as 1.2% of those undergoing OSR. The most frequently observed ADR by IDM were sedation, extrapyramidal signs, disturbances of the autonomic nervous system and increase in transaminases, and by OSR Parkinsonism, akathisia, sedation, toxic delirium and increased transaminases. The relative frequency of Grade III ADR was similar for neuroleptics and antidepressants (5,4% and 5,3% in OSR); a very low relative frequency of ADR Grade III was found for tranquilizers and hypnotics (0,7% and 0,2%). Methodological aspects of this drug monitoring system are discussed in the light of current literature.     

“医共体”体系下基层医院2017至2018年药物不良反应分析及建议

目的分析"医共体"体系下基层医院2017至2018年期间药物不良反应(ADR)及药师工作建议,促进合理用药。方法以"医共体"为契机,回顾性分析15家基层医院国家药品不良反应监测系统、病例系统及药师工作笔记,对不良反应的数量变化、报告类型;报告人职业构成;药品涉及类别、剂型;药品所累及系统器官、年龄进行整理,并对典型ADR提出药师建议。结果共发现ADR 648例,无季节变化规律,2018年发生数是2017年的1.4倍,一般不良反应占74%,药师上报占69%,皮肤及其附件损害发生次数占42%,抗感染药物发生占42%,注射剂发生占76%,特殊人群发生占60%。结论基层医务工作者需保障特殊人群药品使用,注意用药患者皮肤变化,避免抗感染药物、注射剂的滥用,药师做好安全合理用药建议。     

Relevance and limits of pharmacogenetics to detect patients at risk of adverse drug reactions

For more than 15 years genetic polymorphism of drug metabolism has been extensively studied. Poor Metabolizer (PM) and Extensive Metabolizer (EM) Slow Acetylators (SA) Rapid Acetylators (RA) phenotype and genotype can be defined for CYP2D6 (Debrisoquine) and N-AT (acetylation). Lists of drugs whose metabolism is CYP2D6 or N-AT dependent have been published. So it is theoretically possible to forecast an adverse drug reaction (ADR) for a specific patient who is given a drug affected by a polymorphism. However, not only PM are at risk of ADRs. When an active or reactive metabolite is produced, EM might be at risk whatever the enzyme involved. Drug interactions must also be taken into account. Competitive inhibition of the metabolism of a drug CYP2D6 dependent provokes not only a blurring effect on phenotyping, leading to a misclassification, but also increases the risk of ADRs. New drug metabolic polymorphism is under scrutiny. Determination of phenotypes and genotypes when possible, development of investigations of drug metabolic capacity at large, in patients exhibiting ADR's, might improve the efficiency of pharmacovigilance to forecast at-risk subjects.     

Genetic susceptibility to adverse drug reactions

Adverse drug reactions (ADRs) are a major clinical problem. Genetic factors can determine individual susceptibility to both dose-dependent and dose-independent ADRs. Determinants of susceptibility include kinetic factors, such as gene polymorphisms in cytochrome P450 enzymes, and dynamic factors, such as polymorphisms in drug targets. The relative importance of these factors will depend on the nature of the ADR; however, it is likely that more than one gene will be involved in most instances. In the future, whole genome single nucleotide polymorphism (SNP) profiling might allow an unbiased method of determining genetic predisposing factors for ADRs, but might be limited by the lack of adequate numbers of patient samples. The overall clinical utility of genotyping in preventing ADRs needs to be proven by the use of prospective randomized controlled clinical trials.     

The systems for monitoring adverse drug reactions in Hong Kong

Post-marketing surveillance is essential for providing additional safety information on drugs. In Hong Kong, a scheme to monitor ADRs was introduced in October 1986. It relies on voluntary reporting by hospital doctors and general practitioners of suspected ADRs. There appeared to be gross under-reporting as only 68 reports were received between 1986 to 1991. Although hospital-based studies have provided us with information on the pattern of and the risk factors for ADRs, spontaneous reporting on a national scale remains the only feasible and inexpensive method for monitoring ADRs. In order to increase reporting, we hope to convince the medical profession in Hong Kong of the importance in reporting ADRs and to make it easier for them to report.     

Methods for causality assessment of adverse drug reactions: a systematic review.

Numerous methods for causality assessment of adverse drug reactions (ADRs) have been published. The aim of this review is to provide an overview of these methods and discuss their strengths and weaknesses. We conducted electronic searches in MEDLINE (via PubMed), EMBASE and the Cochrane databases to find all assessment methods. Thirty-four different methods were found, falling into three broad categories: expert judgement/global introspection, algorithms and probabilistic methods (Bayesian approaches). Expert judgements are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality. Algorithms are sets of specific questions with associated scores for calculating the likelihood of a cause-effect relationship. Bayesian approaches use specific findings in a case to transform the prior estimate of probability into a posterior estimate of probability of drug causation. The prior probability is calculated from epidemiological information and the posterior probability combines this background information with the evidence in the individual case to come up with an estimate of causation. As a result of problems of reproducibility and validity, no single method is universally accepted. Different causality categories are adopted in each method, and the categories are assessed using different criteria. Because assessment methods are also not entirely devoid of individual judgements, inter-rater reliability can be low. In conclusion, there is still no method universally accepted for causality assessment of ADRs.     

Ocular adverse drug reactions

Drug-induced ocular side effects are described according to recent reports from the literature, the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization (WHO) and the FDA. Adverse events are categorised as certain, probable/likely, possible, unlikely, conditional/unclassified and unassessable/unclassifiable where indicated. Ocular side effects of clinical importance are highlighted with guidelines for recognition, reporting and treatment of adverse drug reactions (ADRs). The current and future status of pharmacovigilance in ocular toxicology is addressed.     

Evaluation of outpatient adverse drug reactions leading to hospitalization.

Outpatient adverse drug reaction (ADR)related hospitalization through the emergency department of a nonprofit hospital and the contributing factors are reviewed. Patients who were hospitalized because of suspected ADRs were selected from daily admissions reports and patient medication profiles from 1997 and 1998 by the pharmacy department of a nonprofit community teaching hospital. Hospital charges for individual patients were obtained from the institution's accounting system. Suspected drugs, their therapeutic class, and the organ systems involved in the ADRs were identified. A total of 191 patients who had a complete medical history and cost information were included in the study. Of those patients, 56% were female, and 45% of the patients were 75 years of older. The average hospital charge per ADR patient was $9491. Room and board accounted for more than 50% of total charges. The average length of stay for study patients was 8.0 +/- 10.3 days. Major therapeutic classes implicated in ADRs included antidiabetic agents (27.8%), anticoagulants (15.2%), anticonvulsants (10.0%), beta-blockers (7.9%), and angiotensin-converting-enzyme inhibitors (7.9%). Organ systems most commonly involved in ADR admissions were the endocrine (30.9%) and cardiovascular (24.1%) systems. The implicationed therapeutic groups and organ systems exhibited a different pattern from those of earlier ADR studies. The elderly and the poor are most affected by ADRs. The availability of new drugs and the shift in disease treatment necessitate the continuous monitoring of new ADRs. Patients and family members should be integral components of a multidisciplinary strategy for minimizing the personal and social impact of ADRs.     

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.