The phenotype of adverse drug effects: Do emergency visits due to adverse drug reactions look different in older people? Results from the ADRED study.

AIMS: Older patients in particular suffer from adverse drug reactions (ADR) when presenting in the emergency department. We aimed to characterise the phenotype of those ADRs, to be able to recognise an ADR in older patients. METHODS: Cases of ADRs in emergency departments collected within the multicentre prospective observational study (ADRED) were analysed (n = 2215). We analysed ADR-associated diagnoses, symptoms and their risk profiles. We present frequencies and odds ratios (OR) with 95% confidence intervals for adults (18-64 years) compared to older adults (≥65 years; young-old 65-79, old-old ≥80 years) and regression coefficients (B) for each year of age. RESULTS: Most prominent differences were seen for drug-associated confusion, dehydration, and bradycardia (OR 6.70 [1.59-28.27], B .054; OR 6.02 [2.41-15.03], B .081, and 4.82 [2.21-10.54], B .040), more likely seen in older adults. Bleedings were reported in all age groups, but gastrointestinal bleedings occurred with more than doubled chance in older adults (OR 2.46 [1.77-3.41], B .030), likewise did other bleedings such as haemorrhage from respiratory passages (OR 2.89 [1.37-6.11], B.036). Falls were more likely in older adults (OR 2.84 [1.77-4.53], B .030), while dizziness was frequent in both age groups. CONCLUSION: Our data point to differences in symptoms of ADRs between adults and older individuals, with dangerous drug-associated phenomena in the older adult such as bleedings or falls. Physicians should consider drug-associated origins of symptoms in older adults with an increased risk for serious health problems.

Personalising drug safety-results from the multi-centre prospective observational study on Adverse Drug Reactions in Emergency Departments (ADRED).

PURPOSE: Adverse drug reactions (ADR) account for 5 to 7% of emergency department (ED) consultations. We aimed to assess medication risk profiles for ADRs leading to ED visits. METHODS: We analysed medication intake and patient demographics in a prospective multi-centre observational study collecting ADR cases in four large EDs in Germany. Odds ratios (OR) were calculated to relate drug classes taken to those suspicious for an ADR after a causality assessment. RESULTS: A total of 2215 cases of ED visits due to ADRs were collected. The median age of the cohort was 73 years; in median, six co-morbidities and an intake of seven drugs were documented. Antineoplastic/immunomodulating agents had the highest OR for being suspected for an ADR (OR 20.45, 95% CI 14.54-28.77), followed by antithrombotics (OR 2.94, 95% CI 2.49-3.47), antibiotics (OR 2.65, 95% CI 1.78-3.95), systemic glucocorticoids (OR 2.43, 95% CI 1.54-3.82) and drugs affecting the central nervous system (CNS), such as antipsychotics (OR 2.36, 95% CI 1.46-3.81), antidepressants (OR 2.10, 95% CI 1.57-2.83), antiparkinsonian medication (OR 2.11, 95% CI 1.15-3.84), opioids (OR 1.79, 95% CI 1.26-2.54) and non-opioid analgesics (OR 1.32, 95% CI 1.01-1.72). CONCLUSIONS: Patients experiencing ADRs leading to ED visits are commonly old, multi-morbid and multi-medicated. CNS drugs may be more relevant than prior expected. With calculating ORs, we could replicate involvement of antineoplastic agents, antithrombotics, antibiotics, systemic glucocorticoids and non-opioid analgesics as frequently suspected for ADRs in EDs. TRIAL REGISTRATION: DRKS-ID: DRKS00008979.

Adverse Drug Reactions (ADR) and Emergencies.

BACKGROUND: Adverse drug reactions (ADR) are a common reason for emergency room visits and for hospitalization. An ADR is said to have occurred when the patient's symptoms and signs are considered to be possibly, probably, or definitely related to the intake of a drug. METHODS: In four large hospital emergency departments, one in each of four German cities ( Ulm, Fürth, Bonn, and Stuttgart), the percentage of suspected ADR cases among all patients presenting to the emergency room was determined during a 30-day period of observation. ADRs were ascertained by screening the digital records of all patients seen in the emergency room; causality was assessed as specified by the WHO-UMC (Uppsala Monitoring Center). RESULTS: ADR were sought in a total of 10 174 emergency department visits. 665 cases of suspected ADR were found, yielding a prevalence of 6.5%. The prevalence of ADR among patients with documented drug intake was 11.6%. Among the patients with documented suspected ADRs, 89% were hospitalized (in contrast to the 43.7% hospitalization rate in the entire group of 10 174 emergency department visits). A possible causal relationship between the patient's symptoms and signs and the intake of a drug was found in 74-84% of cases. Patients with ADR were found to be taking a median of 7 different drugs simultaneously. CONCLUSION: Adverse drug reactions are a relevant cause of emergency department visits, accounting for 6.5% of the total visits in this study, and often lead to hospital admission. The ADRED (Adverse Drug Reactions in Emergency Departments) study, which is now being conducted, is intended to shed further light on their causes, patient risk factors, and potential avoidability.

Data Requirements for the Correct Identification of Medication Errors and Adverse Drug Events in Patients Presenting at an Emergency Department.

BACKGROUND: Adverse drug events (ADE) involving or not involving medication errors (ME) are common, but frequently remain undetected as such. Presently, the majority of available clinical decision support systems (CDSS) relies mostly on coded medication data for the generation of drug alerts. It was the aim of our study to identify the key types of data required for the adequate detection and classification of adverse drug events (ADE) and medication errors (ME) in patients presenting at an emergency department (ED). METHODS: As part of a prospective study, ADE and ME were identified in 1510 patients presenting at the ED of an university teaching hospital by an interdisciplinary panel of specialists in emergency medicine, clinical pharmacology and pharmacy. For each ADE and ME the required different clinical data sources (i.e. information items such as acute clinical symptoms, underlying diseases, laboratory values or ECG) for the detection and correct classification were evaluated. RESULTS: Of all 739 ADE identified 387 (52.4%), 298 (40.3%), 54 (7.3%), respectively, required one, two, or three, more information items to be detected and correctly classified. Only 68 (10.2%) of the ME were simple drug-drug interactions that could be identified based on medication data alone while 381 (57.5%), 181 (27.3%) and 33 (5.0%) of the ME required one, two or three additional information items, respectively, for detection and clinical classification. CONCLUSIONS: Only 10% of all ME observed in emergency patients could be identified on the basis of medication data alone. Focusing electronic decisions support on more easily available drug data alone may lead to an under-detection of clinically relevant ADE and ME.

Adverse drug events in patients admitted to an emergency department: an analysis of direct costs.

PURPOSE: Several economic evaluations of adverse drug events (ADEs) exist, but the underlying methodology has not been standardized so far. The aim of the study was to combine prospective, intensive pharmacovigilance methods, and standardized accounting data to calculate direct costs of community-acquired ADEs (caADEs) contributing to emergency department (ED) admission and subsequent hospitalization. METHODS: A prospective observational study with three phases extending over 2 years was implemented in a 749 bed tertiary care hospital with an annual ED census of approximately 45 000 patients. The patient records of all adult non-trauma ED admissions were systematically analyzed by a team of emergency physicians, clinical pharmacologists, and pharmacists for potential ADE. Associated diagnosis related group costs were extracted from standardized accounting data. RESULTS: Of 2262 patients attending the ED during the study periods, the hospitalization of 366 patients (16.2%) was related to one or more caADEs of which 97.5% were considered predictable and 62.0% were classified as preventable. The mean caADE-related diagnosis related group costs were €2743 (95% bias-corrected and accelerated CI: €2498 to €3018). Extrapolated to a national scale, this corresponds to caADE-related costs of €2.245bn for the German health insurance funds, annually. Costs of €1.310bn could be attributed to events classified as predictable and preventable. CONCLUSIONS: In an ED, caADEs are frequent, and a significant proportion of these events and their related costs appear to be predictable and preventable. The ED as a first-line provider for ADE cases appears to be an appropriate environment to implement strategic and operative improvements for enhanced patient safety.

Application of the Pareto principle to identify and address drug-therapy safety issues.

PURPOSE: Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. METHODS: In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. RESULTS: In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. CONCLUSIONS: The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

Medication safety and knowledge-based functions: a stepwise approach against information overload.

AIMS: The aim was to improve medication safety in an emergency department (ED) by enhancing the integration and presentation of safety information for drug therapy. METHODS: Based on an evaluation of safety of drug therapy issues in the ED and a review of computer-assisted intervention technologies we redesigned an electronic case sheet and implemented computer-assisted interventions into the routine work flow. We devised a four step system of alerts, and facilitated access to different levels of drug information. System use was analyzed over a period of 6 months. In addition, physicians answered a survey based on the technology acceptance model TAM2. RESULTS: The new application was implemented in an informal manner to avoid work flow disruption. Log files demonstrated that step I, 'valid indication' was utilized for 3% of the recorded drugs and step II 'tooltip for well-known drug risks' for 48% of the drugs. In the questionnaire, the computer-assisted interventions were rated better than previous paper based measures (checklists, posters) with regard to usefulness, support of work and information quality. CONCLUSION: A stepwise assisting intervention received positive user acceptance. Some intervention steps have been seldom used, others quite often. We think that we were able to avoid over-alerting and work flow intrusion in a critical ED environment.

A new approach to identify, classify and count drug-related events.

AIMS: The incidence of clinical events related to medication errors and/or adverse drug reactions reported in the literature varies by a degree that cannot solely be explained by the clinical setting, the varying scrutiny of investigators or varying definitions of drug-related events. Our hypothesis was that the individual complexity of many clinical cases may pose relevant limitations for current definitions and algorithms used to identify, classify and count adverse drug-related events. METHODS: Based on clinical cases derived from an observational study we identified and classified common clinical problems that cannot be adequately characterized by the currently used definitions and algorithms. RESULTS: It appears that some key models currently used to describe the relation of medication errors (MEs), adverse drug reactions (ADRs) and adverse drug events (ADEs) can easily be misinterpreted or contain logical inconsistencies that limit their accurate use to all but the simplest clinical cases. A key limitation of current models is the inability to deal with complex interactions such as one drug causing two clinically distinct side effects or multiple drugs contributing to a single clinical event. Using a large set of clinical cases we developed a revised model of the interdependence between MEs, ADEs and ADRs and extended current event definitions when multiple medications cause multiple types of problems. We propose algorithms that may help to improve the identification, classification and counting of drug-related events. CONCLUSIONS: The new model may help to overcome some of the limitations that complex clinical cases pose to current paper- or software-based drug therapy safety.

Comparative evaluation of different medication safety measures for the emergency department: physicians' usage and acceptance of training, poster, checklist and computerized decision support.

BACKGROUND: Although usage and acceptance are important factors for a successful implementation of clinical decision support systems for medication, most studies only concentrate on their design and outcome. Our objective was to comparatively investigate a set of traditional medication safety measures such as medication safety training for physicians, paper-based posters and checklists concerning potential medication problems versus the additional benefit of a computer-assisted medication check. We concentrated on usage, acceptance and suitability of such interventions in a busy emergency department (ED) of a 749 bed acute tertiary care hospital. METHODS: A retrospective, qualitative evaluation study was conducted using a field observation and a questionnaire-based survey. Six physicians were observed while treating 20 patient cases; the questionnaire, based on the Technology Acceptance Model 2 (TAM2), has been answered by nine ED physicians. RESULTS: During field observations, we did not observe direct use of any of the implemented interventions for medication safety (paper-based and electronic). Questionnaire results indicated that the electronic medication safety check was the most frequently used intervention, followed by checklist and posters. However, despite their positive attitude, physicians most often stated that they use the interventions in only up to ten percent for subjectively "critical" orders. Main reasons behind the low usage were deficits in ease-of-use and fit to the workflow. The intention to use the interventions was rather high after overcoming these barriers. CONCLUSIONS: Methodologically, the study contributes to Technology Acceptance Model (TAM) research in an ED setting and confirms TAM2 as a helpful diagnostic tool in identifying barriers for a successful implementation of medication safety interventions. In our case, identified barriers explaining the low utilization of the implemented medication safety interventions - despite their positive reception - include deficits in accessibility, briefing for the physicians about the interventions, ease-of-use and compatibility to the working environment.

Adverse drug events in older patients admitted as an emergency: the role of potentially inappropriate medication in elderly people (PRISCUS).

BACKGROUND: Lists of potentially inappropriate medications (PIMs) for the elderly, such as the German PRISCUS list, have been published as expert recommendations with the aim of improving drug safety for this patient group. In this study, we tried to determine how often adverse drug events occur in the emergency department and what role PRISCUS medications might play in these events. METHODS: We prospectively reviewed the medical records of 752 patients who were treated in the emergency department (ED) of a level III hospital in Germany for adverse drug events due to medication errors (MEs) and for adverse drug reactions (ADRs). The evaluation was performed in two steps by pharmacologists, clinical pharmacologists, and board-certified internists. RESULTS: Both clinically important MEs and ADRs became more common with advancing age. Among the 351 patients who were over age 65, 307 (87.5%) were taking at least one medication at home. Of these 307 patients, 16.6% (95% confidence interval [CI]: 12.9-21.2%) were taking at least one PIM, as defined by the German PRISCUS list. In relative terms, PIMs were more commonly associated with ADRs or MEs than other drugs (27.0% [95% CI: 17.5-39.1% versus 15.7% [95% CI: 14.1-17.4%], Odds ratio 1.99 [95% CI: 1.23-3.52: p = 0.018), but in absolute terms ADRs and MEs involved non-PIM more often than PIM. CONCLUSION: Elderly patients more frequently suffer from ADR and from the clinical consequences of medication errors. Elderly patients taking PIMs are more likely to suffer from ADRs and MEs, even though most drug-related events are still attributable to non-PIM.