Augmented renal clearance--an evolving risk factor to consider during the treatment with vancomycin.

WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance (ARC) is a new phenomenon in patients' pathophysiology without universally accepted aetiology and with various incidence rates most often described in critically ill patients in the Intensive Care Unit (ICU). The objective of this retrospective observational comparative study was to estimate the incidence rate of ARC in patients with different medical conditions employing steady state trough vancomycin serum concentrations (VSCss) for analysis. METHODS: All patients tested for VCSss during two years (2010-2011) in a tertiary level hospital were analysed and 77 VSCs were eligible for analysis: 38 (50%) and 39 cases were assigned to the ARC (eCrClCG (creatinine clearance, estimated by Cockcroft-Gault) > 130 mL/min) and the control groups (eCrClCG in the range 90-130 mL/min) respectively. RESULTS AND DISCUSSION: Patients' age, mechanical ventilation and haemodynamically unstable status had significant association with ARC occurrence (P < 0.05). Majority of ARC patients (11 patients (61 %)) were managed in non-ICU settings. ARC event showed statistically significant higher risk for under dosage (RR (relative risk for subtherapeutic VSCss), 1.84; 95% CI, 1.23\x962.74; P = 0.011), and the correlation between different thresholds (eCrClCG >130 mL/min, ≥140 mL/min and ≥150 mL/min) for ARC and VSCss allows to predict decrease of VSCss in case of eCrClCG ≥150 mL/min: every increase of eCrClCG by 40 mL/min predicts clinically relevant decrease of VSCss by 1 mmol/L (1.49 mg/mL). WHAT IS NEW AND CONCLUSION: ARC cases lead to the doubled risk of subtherapeutic VSC, and this phenomenon is a significant event in patients in any hospital department. Investigation of medical patients' status relevant to this phenomenon needs to be continued.

Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review.

Ibogaine is an indole alkaloid derived from the bark of the root of the African shrub Tabernanthe iboga. Psychoactive properties of ibogaine have been known for decades. More recently, based on experimental data from animals and anectodal reports in human, it has been found that this drug has anti-addictive effects. Several patents were published between 1969 and 1995. The pharmacology of ibogaine is quite complex, affecting many different neurotransmitter systems simultaneously. However, the pharmacological targets underlying the physiological and psychological actions of ibogaine are not completely understood. Ibogaine is rapidly metabolized in the body in noribogaine. The purpose of this article was to review data from the literature concerning physicochemical properties, bio-analytical methods, and pharmacology of ibogaine; this article will be focused on the use of this drug as anti-addictive agent.

Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross-sectional Survey Among 185 Medical Schools in 27 Countries.

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real-life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU.

Topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid: randomized controlled trial with six months follow-up.

BACKGROUND: Topical 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) with some transient adverse events. OBJECTIVE: The purpose of the study was to evaluate the efficacy and side effects of two different light doses when treating AKs with ALA-PDT on the face/scalp. METHODS: Thirty-eight patients with two histologically confirmed AKs were enrolled in the within-patient comparison study. ALA-PDT was performed twice with two weeks interval for each AK. Patients were randomized to receive a light dose of 70 or 100 J/cm2 as their first split face/scalp treatment. Follow-up examinations were carried out at months 3 and 6. Efficacy end point included clinical/histological AK clearance rate. RESULTS: No significant difference in therapeutic efficacy and adverse events of ALA-PDT was found between the two light doses at both follow-up visits. At months 3 and 6 after PDT the RATE of complete remission were respectively 100% and 92.1% for 70 J/cm2, 92.1% and 84.2% for 100 J/cm2. The adverse events of the treatment were rosacea 5/76 (6.58%), hyperpigmentation 4/76 (5.26%), hypopigmentation 4/76 (5.26%), transient milia 3/76 (3.95%). CONCLUSIONS: The topical ALA-PDT with the red light dose of 70 J/cm2 is an effective treatment for mild and moderate AKs on the face/scalp with expected adverse events of pigmentation changes, rosacea and transient milia.