Prevalence of drug-drug interactions at hospital entry and during hospital stay of patients in internal medicine

OBJECTIVE: The aim of this study was to assess potential drug-drug interactions (pDDIs) at hospital admission, during hospitalization and at discharge and to evaluate the number of pDDIs created during hospitalization. METHODS: The medication of 851 patients was screened for pDDIs (major and moderate severity) using the screening program Pharmavista. The frequency of pDDIs per patient, per number of drugs and drug pairs was estimated. RESULTS: During hospitalization, the frequency of major and moderate pDDIs per patient was 1.11, which was higher compared to hospital admission (0.59) or to hospital discharge (0.60). The frequency of major and moderate pDDIs per drug prescribed (13.7% vs. 9.1%) or per drug pairs analyzed (4.5% vs. 2.3%) was higher at hospital admission compared to hospital discharge. 47% of all major and moderate pDDIs at discharge were due to a medication change during hospitalization. CONCLUSIONS: Although the number of major and moderate pDDIs per patient did not increase from hospital admission to discharge, it is important to realize that 47% of all major and moderate DDIs at hospital discharge were created during hospitalization. Prescribing drugs with a low risk for pDDIs as well as careful monitoring for adverse drug reactions are important measures to minimize harm associated with DDIs.     

Complement anaphylatoxin receptors on neurons: new tricks for old receptors?

Activation of the complement system has been reported in a variety of inflammatory diseases and neurodegenerative processes of the CNS. Recent evidence indicates that complement proteins and receptors are synthesized on or by glial cells and, surprisingly, neurons. Among these proteins are the receptors for the chemotactic and anaphylactic peptides, C5a and C3a, which are the most-potent mediators of complement inflammatory functions. The functions of glial-cell C3a and C5a receptors (C3aR and C5aR) appear to be similar to immune-cell C3aRs and C5aRs. However, little is known about the roles these receptors might have on neurons. Indeed, when compared with glial cells, neurons display a distinct pattern of C3aR and C5aR expression, in either the normal or the inflamed CNS. These findings suggest unique functions for these receptors on neurons.     

Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells

Little is known about the expression of the receptor for complement anaphylatoxin C3a (C3aR) in the central nervous system (CNS). In this study, we provide the first evidence that neurons are the predominant cell type expressing C3aR in the normal CNS. By using in situ hybridization (ISH) and immunohistochemistry, we found that C3aR is constitutively expressed at high levels in cortical and hippocampal neurons as well as in Purkinje cells. Moreover, we showed that primary culture of human astrocytes and microglia express the C3aR mRNA as assessed by RT‐PCR. In situ hybridization performed on rat primary astrocytes confirmed the RT‐PCR result demonstrating C3aR expression by astrocytes. In experimental allergic encephalitis (EAE), C3aR expression was elevated on microglia, infiltrating monocyte‐macrophage cells and a few astrocytes, whereas neuronal expression remained unchanged during the course of the disease. These data demonstrate that the C3aR is expressed primarily by neurons in the normal CNS and that its neuronal expression is not dramatically upregulated under inflammation. This is in contrast to the increased neuronal expression of the C5aR in several inflammatory CNS conditions. The high constitutive expression of the C3aR by neurons suggests this receptor may play an important role in normal physiological conditions in the CNS. GLIA 26:201–211, 1999. © 1999 Wiley‐Liss, Inc.     

ALK translocation and crizotinib in non-small cell lung cancer: an evolving paradigm in oncology drug development

Advances in our understanding of tumour biology have encouraged reassessment of tumour classification by the site of origin in favour of molecular characteristics and/or oncogenic drivers amenable to treatment. The identification of EML4-anaplastic lymphoma kinase (ALK) as an oncogenic driver in non-small cell lung cancer (NSCLC) early in the clinical development of crizotinib and the observation of promising clinical responses in patients with NSCLC harbouring ALK translocations accelerated its clinical development in ALK-positive NSCLC. Phase I and II trials of crizotinib in patients with ALK-positive advanced NSCLC reported notably high response rates that tended to be rapid and of prolonged duration. Crizotinib was well tolerated; treatment-related adverse events were typically gastrointestinal (grade 1/2) and visual disorders (almost exclusively grade 1). Crizotinib provided NSCLC symptom relief and maintained quality of life. Based on the phase I and II trial data, the US Food and Drug Administration granted approval of crizotinib in August 2011. The consistency of the crizotinib data to date suggests accurate selection of the target population for crizotinib treatment. The ability to molecularly select patients likely to respond to an investigational agent argues that future clinical development of targeted agents should be re-evaluated. Updated trial designs incorporating molecular testing, early use of enrichment biomarkers and intermediary endpoints may accelerate and optimise clinical evaluation of targeted agents. Such trial designs should allow rapid clinical evaluation, minimise exposure of patients to therapies unlikely to be of benefit and, potentially, allow accelerated drug approval in molecularly specified populations.     

Maintenance treatment of advanced non-small-cell lung cancer: results of an international expert panel meeting of the Italian association of thoracic oncology

Several randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4-6 cycles of first-line chemotherapy, who are fit (performance status 0-1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a "treatment-free period". Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection.     

The Masterclass of the European School of Oncology: The ‘key educational event’ of the school

The European School of Oncology (ESO) Clinical Masterclass is a one-week, full-immersion course, where students and teachers intensively interact with each other. This educational event is designed for medical or clinical oncologists who are defining and orientating their professional careers. Since 2002 nine Masterclasses have been organised in different European cities in which more than 500 oncologists have participated.In this paper, we are presenting data derived from the analysis of the questionnaire distributed to all participants.