Pharmaceutical care for patients with ischemic stroke: improving the patients quality of life

Objectives To improve patients health-related quality of life (HQL) after transient ischemic attack (TIA) or ischemic stroke; to guarantee an effective secondary prevention; to increase the patient’s satisfaction with recommendations regarding their medication by pharmacists. Setting Stroke Unit, neurological ward at the Klinikum Fulda, rehabilitation hospitals and community-based pharmacies in the region of Fulda, Germany. Method Patients with TIA or ischemic stroke were included. The patients were assigned to an intervention group (IG) or a control group (CG). The individual assignment of patients to IG or CG was based on the type of the local pharmacy to which patients belong. Community-based pharmacies either delivered standard care (CG) or provided additional intensified pharmaceutical care (PC; IG). Pharmacies delivering PC belong to a pre-existing “Quality Assurance Working Group” (QAWG). To evaluate the patient’s HQL, the Short Form-36 (SF-36) was used at study entry in hospital and at 12 months. The secondary prevention was documented at study entry in hospital and at 12 months. The patients’ satisfaction was measured by a questionnaire at the end of the study. Main outcome measures Patients’ HQL; secondary prevention; patients’ satisfaction with recommendations of the pharmacists with regards to their medication. Results Out of 1316 patients screened for participation in this study, 255 were recruited with 90/255 patients assigned to the IG and 165/255 patients assigned to the CG. During the study, the HQL of the patients in the IG did not change significantly. A significant decrease in the HQL was observed for the CG in 7/8 subscales and in both summary measures of the SF-36. After 12 months, 85.3% of the patients in the IG and 86.3% of the patients in the CG were treated with antiplatelet drugs or oral anticoagulants in accordance to treatment guidelines. Patients in the IG were significantly more satisfied with the individualized recommendations of the pharmacists than patients in the CG. Conclusion Our findings indicate that an intensified PC of patients after ischemic stroke by dedicated pharmacists may have a positive impact on HQL and patients’ satisfaction. PC in this study had no impact on adherence to secondary prevention medication.     

What is the best approach for screen-detected low volume cancers?--The case for observation

The case for active surveillance as the optimal therapy for screen detected, low volume, low grade prostate cancer is presented. This is based on data from recent long term studies of conservative management, the prostate cancer prevention trial (PCPT), the Swedish trial of radical prostatectomy vs. observation, and several large Phase 2 trials of active surveillance. These studies indicate convincingly that (1) widespread screening results in a diagnosis of prostate cancer in many patients with clinical insignificant disease, (2) that these patients can be identified with reasonable accuracy, (3) that delayed intervention does not appear to put those patients who reclassify as higher risk over time at significant risk, and (4) that the psychological burden of surveillance is acceptable.     

The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications

Several different factors, including pharmacogenetics, contribute to interindividual variability in drug response. Like most other agents, many antiepileptic drugs (AEDs) are metabolised by a variety of enzymatic reactions, and the cytochrome P450 (CYP) superfamily has attracted considerable attention. Some of those CYPs exist in the form of genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure (area under the plasma concentration-time curve [AUC]) of AEDs. With regard to the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of interest. This review summarises the evidence as to whether such polymorphisms affect the clinical action of AEDs. In the case of mephenytoin, defects in its metabolism may be attributable to >10 mutated alleles (designated as *2, *3 and others) of the gene expressing CYP2C19. Consequently, poor metabolisers (PMs) and extensive metabolisers (EMs) could be differentiated, whose frequencies vary among ethnic populations. CYP2C19 contributes to the metabolism of diazepam and phenytoin, the latter drug also representing a substrate of CYP2C9, with its predominant variants being defined as *2 and *3. For both AEDs, there is maximally a 2-fold difference in the hepatic elimination rate (e.g. clearance) or the AUC between the extremes of EMs and PMs which, in the case of phenytoin (an AED with a narrow 'therapeutic window'), would suggest a dosage reduction only for patients who are carriers of mutated alleles of both CYP2C19 and CYP2C9, a subgroup that is very rare among Caucasians (about 1% of the population) but more frequent in Asians (about 10%). The minor contribution of CYP2C19 to the metabolism of phenobarbital (phenobarbitone) can be overlooked. In rare cases, valproic acid can be metabolised to the reactive (hepatotoxic) metabolite, 4-ene-valproic acid. It is not yet clear whether genetic variants of the involved enzyme (CYP2C9) are responsible for this problem. Likewise, the active metabolite of carbamazepine, carbamazepine-10,11-epoxide, is transformed by the microsomal epoxide hydrolase, an enzyme that is also highly polymorphic, but the pharmacokinetic and clinical consequences still need to be evaluated.Pharmacogenetic investigations have increased our general knowledge of drug disposition and action. As for old and especially new AEDs the pharmacogenetic influence on their metabolism is not very striking, it is not surprising that there are no treatment guidelines taking pharmacogenetic data into account. Therefore, the traditional and validated therapeutic drug monitoring approach, representing a direct 'phenotype' assessment, still remains the method of choice when an individualised dosing regimen is anticipated. Nevertheless, pharmacogenetics and pharmacogenomics can offer some novel contributions when attempts are made to maximise drug efficacy and enhance drug safety.     

Active surveillance for favorable risk prostate cancer: rationale, risks, and results

Active surveillance for favorable risk prostate cancer has become increasingly popular in populations where prostate cancer screening is widespread, due to evidence that prostate cancer screening results in the detection of disease that is not clinically significant in many patients (i.e., untreated, would not pose a threat to health). This approach is supported by data demonstrating that patients who fall into the category of clinically insignificant disease can be identified with reasonable accuracy, and that patients who are initially classified as low risk who reclassify over time as higher risk and are then treated more aggressively are in most cases still cured. An active surveillance approach means (1) identifying patients who have a low likelihood of disease progression during their lifetime, based on clinical and pathologic features of the disease and patient age and comorbidity; (2) monitoring closely over time, (3) establishing reasonable criteria for intervention, which will both identify more aggressive disease in a timely fashion, and not result in excessive treatment, and (4) meeting the communication challenge to reduce the psychological burden of living with untreated cancer. The results of active surveillance, the criteria for patient selection, and the appropriate triggers for intervention are reviewed.     

Cell specific ultrasound effects are dose and frequency dependent

Ultrasound is widely used in clinical practice, mostly in diagnostic studies, but increasingly in therapeutic applications as well. This may be the case in acceleration of wound healing or treatment of cancer. Still, little is known about the direct effect of frequency or energy density of the ultrasound upon the cells themselves. We therefore investigated the impact of three different protocols using high, medium and low energy densities at three different frequencies on normal endothelial and epithelial as well as carcinoma cell lines (neuroblastoma and adenocarcinoma cell lines).Proliferation of endothelial and epithelial cell lines was significantly increased depending on the frequency and energy density applied. No influence on actin cytoskeleton formation was seen in these cells after treatment, while a significant decrease in the density of microvilli and the length of filopodia in the epithelial cell line could be noted. The proliferation rate of the carcinoma cell lines was reduced and cells destroyed. Apoptosis was induced in the adenocarcinoma cells after ultrasound exposure. Additionally, the expression of neurofilament was increased in neuroblastoma cells as evidence of beginning differentiation.So, different settings of frequency and energy density in an ultrasonic treatment protocol lead to different impacts on proliferation, morphology and differentiation and might be used to stimulate or inhibit the growth of individual cell types.