Identification and comparison of sex-specific serious adverse drug reactions in spontaneous reports and systematically collected reports (ADRED).

AIMS: Adverse drug reactions (ADRs) are known to show sex-specific differences in occurrence and phenotype. The aim of this study was to analyse sex-specific differences in ADR-drug combinations that required hospitalization based on two different datasets. METHODS: We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR-drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR-drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis-)concordance. RESULTS: In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1-2.1] for quetiapine in spontaneous reports to 41.3 [13.1-130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR-drug combination self-injurious behaviour-quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3-11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports. CONCLUSIONS: Our results can contribute to raise awareness and further knowledge regarding sex-specific ADRs. The findings require further in-depth investigation.

Pharmacist-Led Medication Management in Acute Geriatric Medicine and Its Associations with Rehospitalizations: A Cohort Study.

INTRODUCTION: Hospitalization and discharge in older patients are critical and clinical pharmacists have shown to ameliorate risks. Our objective was to assess their benefit as part of the geriatric team regarding rehospitalizations and related outcomes after discharge focusing on general practitioners' decision to continue or change discharge medication (GPD). METHODS: Prospective implementation study with 6-month follow-up in an acute geriatric clinic. Patients ≥70 years with comorbidities, impairments, and a current drug therapy were consecutively assigned to three groups: control group (CG), implementation group (IG), and wash-out group (WG). CG only received medication reconciliation (MR) at admission; IG and their hospital physicians received a pharmaceutical counseling and medication management; during WG, pharmaceutical counseling except for MR was discontinued. We used a negative-binomial model to calculate rehospitalizations and days spent at home as well as a recurrent events survival model to investigate recurrent rehospitalizations. RESULTS: One hundred thirty-two patients (mean age 82 years, 76 women [57.6%]) finished the project. In most of the models for rehospitalizations, a positive GPD led to fewer events. We also found an effect of pharmaceutical counseling on rehospitalizations and recurrent rehospitalizations in the CG versus WG but not in the CG versus IG models. 95.3% of medication recommendations by the pharmacist in the clinic setting were accepted. While the number of positive GPDs in CG was low (38%), pharmaceutical counseling directly to the GP in IG led to a higher number of positive GPDs (60%). DISCUSSION: Although rehospitalizations were not directly reduced by our intervention in the CG versus IG, the pharmacist's acceptance rate in the hospital was very high and a positive GPD led to fewer rehospitalization in most models.

Medical education in pharmacogenomics-results from a survey on pharmacogenetic knowledge in healthcare professionals within the European pharmacogenomics clinical implementation project Ubiquitous Pharmacogenomics (U-PGx).

PURPOSE: Due to the diversity within Europe, the implementation of pharmacogenomic testing in clinical practice faces specific challenges. In the context of the European pharmacogenomics implementation project "Ubiquitous Pharmacogenomics" (U-PGx; funded by the European Commission), we studied the current educational background. METHODS: We developed a questionnaire including 29 questions. It was spread out to healthcare professionals working at the future implementation sites (in Austria, Greece, Italy, Netherlands, Slovenia, Spain and Great Britain) of the U-PGx project in preparation of an educational programme. Aim of the survey was to analyse the current educational situation at the implementation sites. RESULTS: In total, 70 healthcare professionals participated in the survey. Of participants, 84.3% found pharmacogenomics relevant to their current practice, but experience was still rare. More than two-thirds (65.7%) did not order nor recommend a pharmacogenomic test in the past year. This was mainly attributed to not having enough knowledge on pharmacogenomics (40.0%). Needs were identified in application of pharmacogenomics (identifying drugs 41.4%, interpreting test results 37.2%) as well as in underlining mechanisms (better knowledge on drug metabolism 67.1%, better knowledge on basic principles of pharmacogenomics 60.0%). CONCLUSIONS: This study analysed the specific attitudes, experience and education on pharmacogenomics of future users. There was a general positive attitude and interest towards pharmacogenomic testing. However, the grade of own experience, and knowledge about application and interpretation of pharmacogenomics caused uncertainty. Thus, education and training programmes may be helpful for implementation of pharmacogenomics at a homogenous level within Europe.

Falls: the adverse drug reaction of the elderly and the impact of pharmacogenetics.

Falls is a frequent type of adverse drug reactions causing significant morbidity and mortality in the elderly. We reviewed, with which drugs the risk of falls is relevant and might depend on genomic variation. Pharmacogenetic variability may contribute to drug-induced falls for instance mediated by impaired drug elimination due to inherited deficiency in enzymes like CYP2C9, CYP2C19 and CYP2D6. The relative role of specific genes and polymorphisms in old age may differ from younger people. Biomarkers for frailty, but also genomic biomarkers might help identifying patients at high risk for drug-induced falls. Many other factors including disease and drug-drug interactions also contribute to risk of falls. Further studies analyzing the impact of genomic variation on the medication-related fall risk in the older adult are urgently needed.