Objectives: Adverse drug events (ADEs) are unintended and harmful consequences of medication use. They are associated with high health resource use and cost. Yet, high levels of inaccuracy exist in their identification in clinical practice, with over one-third remaining unidentified in the emergency department (ED). The study objective was to derive clinical decision rules (CDRs) that are sensitive for the detection of ADEs, allowing their systematic identification early in a patient's hospital course.Methods: This was a prospective observational cohort study carried out in two Canadian tertiary care hospitals. Participants were adults presenting to the ED having ingested at least one prescription or overthe-counter medication within 2 weeks. Nurses and physicians evaluated patients for standardized clinical findings. A second evaluator performed interobserver assessments of predictor variables in a subset of patients. Pharmacists, who were blinded to the predictor variables, evaluated all patients for ADEs. An independent committee reviewed and adjudicated cases where the ADE assessment was uncertain or the pharmacist's diagnosis differed from the physician's working diagnosis. The primary outcome was an ADE that required a change in medical therapy, diagnostic testing, consultation, or hospital admission. CDRs were derived using kappa coefficients, chi-square statistics, and recursive partitioning.Results: Among 1,591 patients, 131 (8.2%, 95% confidence interval [CI] = 7.0% to 9.7%) were diagnosed with the primary outcome. The following variables were associated with ADEs and were used to derive two CDRs: 1) presence of comorbid conditions, 2) antibiotic use within 7 days, 3) medication changes within 28 days, 4) age ‡80 years, 5) arrival by ambulance, 6) triage acuity, 7) recent hospital admission, 8) renal failure, and 9) use of three or more prescription medications. The more sensitive rule had a sensitivity of 96.7% (95% CI = 91.8% to 98.6%) and required 40.8% (95% CI = 37.7% to 42.9%) of patients to have medication review. The more specific rule had a sensitivity 90.8% (95% CI = 81.4% to 95.7%) and required 28.3% of patients to proceed to medication review. Conclusions:The authors derived CDRs that identified patients with ADEs with high sensitivity. These rules may improve the identification of ADEs early in a patient's hospital course while limiting the number of patients requiring a detailed medication review.

1. Generically based pharmaceutical systems exist in a few countries of the world, such as Iran. Most developed countries have free market pharmaceutical systems. Drug-related problems (DRP) have been reported mostly in the Western world but few data are available for generic systems. In this study, we tried to measure the prevalence of drug-related problems leading to hospital admissions in Isfahan, Iran. 2. One thousand consecutive hospital admissions in three major teaching hospitals were studied for a period of 6 months for the presence of DRP as a cause of hospital admissions. Two subcategories of DRP were considered: (i) drug therapy failure; and (ii) adverse drug reactions. Preventability and outcome measures were also assessed. Medications responsible for DRP were classified according to the Anatomic Therapeutic Chemical (ATC) classification of the World Health Organization. 3. Of the 1000 admissions studied, 115 (11.5%) were owing to DRP, 81% as a result of drug therapy failure and 19% as adverse drug reactions. A total of 106 out of the 115 DRP cases (92%) were either preventable or probably preventable, most of which had to do with either prescriber or patient error. An overview of DRP showed that 58.3% resulted in complete recovery, 33.9% in relative recovery and 7.8% in death. Close to 1% of hospital admissions resulted in DRP-related deaths. 4. The overall prevalence of hospital admissions caused by DRP is similar to that in free market pharmaceutical systems. The high preventability rate of these problems should alert clinicians and policy makers to design strategies to curtail this. Also, reasons for differences in subtypes of DRP between the results of this study and those of the literature from free market systems needs to be investigated further.

Agranulocytosis is a rare yet life-threatening complication of methimazole therapy for hyperthyroidism. We present the case of a 37-year-old female recently started on methimazole for hyperthyroidism who presented to our facility for evaluation of suspected thyroid storm. In addition to having abnormal thyroid indices, she was noted to have an odontogenic abscess, and was septic with profound neutropenia. Her symptoms resolved quickly following incision and drainage of her abscess and treatment with broad-spectrum antibiotics. Her neutrophil count improved significantly following cessation of methimazole and administration of granulocyte colony-stimulating factor. Diagnosis was initially confounded by the similarity between symptoms of early sepsis and those of thyroid storm. This case report discusses the factors leading to diagnostic delay and highlights the dangerous manifestations of neutropenia in patients on methimazole therapy.