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.

[Metformin Therapy During Surgical Interventions and Iodinated Contrast Agent Use]. / Metformin-Therapie bei operativen Eingriffen und Gabe jodhaltiger Kontrastmittel.

Metformin as first-line treatment in type 2 diabetes mellitus (T2 D) shows benefits in terms of reducing cardiovascular events, but the risk of a lactic acidosis as a serious adverse event especially in patients with decreased renal function is still relevant. Since the perioperative management of Metformin or its use in diagnostic procedures with contrast agents is inconsistent in literature and different in practice, the results of various guidelines are reviewed below showing the current state of evidence. Despite many guidelines, the evidence on both issues is low, as they are mainly based on consensus recommendations. The guidelines are still based on weak data and many international recommendations have clearly different statements. A fundamental problem with drugs is that expert information does specify eGFR limits for dose reduction, but not the method to be used. Depending on the formula, this can then lead to different treatment decisions. At present, it is not possible to give reliable recommendations for practice with the aim of minimising the interruption of therapy. For this reason, only a strictly conservative approach with 48-hour breaks before and after both measures can be recommended at present. For the situations mentioned in this overview, the question of the right approach has not yet been conclusively and definitely answered, therefore further studies should be carried out.

CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System-Results From the ADRED Study.

Cytochrome P450 (CYP) 2D6 is a polymorphic enzyme expressed in the central nervous system (CNS), important in drug metabolism and with a potentially constitutive role in CNS function such as vigilance. This study aimed to analyze variability in CYP2D6 activity linked to vigilance-related adverse drug reactions (ADRs) in the CNS. A dataset of N = 2939 ADR cases of the prospective multicenter observational trial in emergency departments (EDs) (ADRED; trial registration: DRKS-ID: DRKS00008979) was analyzed. Dizziness as the most frequent reported CNS ADR symptom (12.7% of patients, n = 372) related to vigilance was chosen as the outcome. The association of dizziness with CYP2D6 activity markers was analyzed. The number of CYP2D6 substrates taken, a CYP2D6 saturation score (no, moderate, and strong saturation), a CYP2D6 saturation/inhibition score (no, weak, moderate, and strong), and composed CYP2D6 activity using a genotyped subsample (n = 740) calculating additive effects of genotype and CYP2D6 saturation by drug exposure were used as CYP2D6 activity markers. Effects were compared to other frequent nonvigilance-related CNS ADR symptoms (syncope and headache). Secondary analyses were conducted to control for other ADR symptoms frequently associated with dizziness (syncope, nausea, and falls). The majority of all patients (64.5%, n = 1895) took at least one drug metabolized by CYP2D6. Around a third took a CNS drug (32.5%, n = 955). The chance to present with drug-related dizziness to the ED increased with each CYP2D6 substrate taken by OR 1.11 [1.01-1.23]. Presenting with drug-related dizziness was more likely with CYP2D6 saturation and saturation/inhibition (both OR 1.27 [1.00-1.60]). The composed CYP2D6 activity was positively associated with dizziness (p = 0.028), while poorer activity affected patients more often with dizziness as an ADR. In contrast, nonvigilance-related ADR symptoms such as syncope and nausea were not consistently significantly associated with CYP2D6 activity markers. This study shows an association between the number of CYP2D6 substrates, the predicted CYP2D6 activity, and the occurrence of dizziness as a CNS ADR symptom. As dizziness is a vigilance-related CNS symptom, patients with low CYP2D6 activity might be more vulnerable to drug-related dizziness. This study underlines the need for understanding individual drug metabolism activity and individual risks for ADRs.

Hemocompatibility of PMEA coated oxygenators used for extracorporeal circulation procedures.

An inflammatory response to cardiopulmonary bypass (CPB) caused by bioincompatibility of extracorporeal circuits is one of the major clinical issues in cardiac surgery. Recently a new coating material, poly-2-methoxyethylacrylate (PMEA), was developed to improve the biocompatibility of blood contacting surfaces. In a simulated cardiopulmonary bypass model, using fresh human whole blood, 15 membrane oxygenators (Capiox SX18, Terumo Corp., Tokyo, Japan) were compared. Five of them had the PMEA coating, five had a heparin-coated surface, and five had no surface treatment. Blood samples were taken at several time-points during a 90 minute circulation period. Changes in coagulation, complement, and blood cell alteration factors were measured by ELISA methods, plasma bradykinin levels were measured by radioimmunoassay, and expression of genes encoding cytokines TNF-alpha, interleukin-1beta, interleukin-6, and interleukin-8 was determined by semiquantitative real time RT-PCR. Platelet adhesion was significantly reduced in both the PMEA and the heparin coated circuits. Release of platelet activation marker beta-thromboglobulin was significantly higher in the uncoated control group (p < 0.01). After 5 minutes of blood circulation bradykinin levels significantly increased in all three groups (p < 0.01); however, the group with the PMEA coated oxygenators showed the lowest values. Expression of genes encoding proinflammatory cytokines in monocytes was increased in all groups, with the lowest being in the PMEA coated group. PMEA coated CPB surfaces in an in vitro experimental model showed an improved thrombogenicity, reduced bradykinin release, less platelet activation and less proinflammatory cytokines gene expression in comparison with a noncoated group. The authors assume that PMEA coating may ameliorate some of intra- and postperfusion syndromes, particularly hypotension, unspecific inflammation, hyperfibrinolysis, and blood loss.