Biological background of pediatric medulloblastoma and ependymoma: A review from a translational research perspective

Survival rates of pediatric brain tumor patients have significantly improved over the years due to developments in diagnostic techniques, neurosurgery, chemotherapy, radiotherapy, and supportive care. However, brain tumors are still an important cause of cancer-related deaths in children. Prognosis is still highly dependent on clinical characteristics, such as the age of the patient, tumor type, stage, and localization, but increased knowledge about the genetic and biological features of these tumors is being obtained and might be useful to further improve outcome for these patients. It has become clear that the deregulation of signaling pathways essential in brain development, for example, sonic hedgehog (SHH), Wnt, and Notch pathways, plays an important role in pathogenesis and biological behavior, especially for medulloblastomas. More recently, data have become available about the cells of origin of brain tumors and the possible existence of brain tumor stem cells. Newly developed array-based techniques for studying gene expression, protein expression, copy number aberrations, and epigenetic events have led to the identification of other potentially important biological abnormalities in pediatric medulloblastomas and ependymomas. Copyright 2008 by the Society for Neuro-Oncology

Non-dispensing pharmacist integrated in the primary care team:Effect on the quality of physician's prescribing, a non-randomised comparative study

BackgroundEspecially in elderly with polypharmacy, medication can do harm. Clinical pharmacists integrated in primary care teams might improve quality of pharmaceutical care.ObjectiveTo assess the effect of non-dispensing clinical pharmacists integrated in primary care teams on general practitioners' prescribing quality.SettingThis study was conducted in 25 primary care practices in the Netherlands.MethodsNon-randomised, controlled, multi-centre, complex intervention study with pre-post comparison. First, we identified potential prescribing quality indicators from the literature and assessed their feasibility, validity, acceptability, reliability and sensitivity to change. Also, an expert panel assessed the indicators' health impact. Next, using the final set of indicators, we measured the quality of prescribing in practices where non-dispensing pharmacists were integrated in the team (intervention group) compared to usual care (two control groups). Data were extracted anonymously from the healthcare records. Comparisons were made using mixed models correcting for potential confounders.Main outcome measureQuality of prescribing, measured with prescribing quality indicators.ResultsOf 388 eligible indicators reported in the literature we selected 8. In addition, two more indicators relevant for Dutch general practice were formulated by an expert panel. Scores on all 10 indicators improved in the intervention group after introduction of the non-dispensing pharmacist. However, when compared to control groups, prescribing quality improved solely on the indicator measuring monitoring of the renal function in patients using antihypertensive medication: relative risk of a monitored renal function in the intervention group compared to usual care: 1.03 (95% CI 1.01-1.05, p-value 0.010) and compared to usual care plus: 1.04 (1.01-1.06, p-value 0.004).ConclusionThis study did not demonstrate a consistent effect of the introduction of non-dispensing clinical pharmacists in the primary care team on the quality of physician's prescribing. This study is part of the POINT-study, which was registered at The Netherlands National Trial Register with trial registration number NTR-4389

What motivates general practitioners to change practice behaviour? A qualitative study of audit and feedback group sessions in Dutch general practice

Objectives Adopting an attributional perspective, the current article investigates how audit and feedback group sessions contribute to general practitioners’ (GPs) motivation to change their practice behaviour to improve care. We focus on the contributions of the audit and feedback itself (content) and the group discussion (process). Methods Four focus groups, comprising a total of 39 participating Dutch GPs, discussed and compared audit and feedback of their practices. The focus groups were analysed thematically. Results Audit and feedback contributed to GPs’ motivation to change in two ways: by raising awareness about aspects of their current care practice and by providing indications of the possible impact of change. For these contributions to play out, the audit and feedback should be reliable and valid, specific, recent and recurrent and concern GPs’ own practices or practices within their own influence sphere. Care behaviour attributed to external, uncontrollable or unstable causes would not induce change. The added value of the group is twofold as well: group discussion contributed to GPs’ motivation to change by providing a frame of reference and by affording insights that participants would not have been able to achieve on their own. Conclusions In audit and feedback group sessions, both audit and feedback information and group discussion can valuably contribute to GPs’ motivation to change care practice behaviour. Peer interaction can positively contribute to explore alternative practices and avenues for improvement. Local or regional peer meetings would be beneficial in facilitating reflection and discussion. An important avenue for future studies is to explore the contribution of audit and feedback and small-group discussion to actual practice change

Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors

Purpose Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor (KDR; VEGFR-2) and fms-related tyrosine kinase 4 (FLT4; VEGFR-3). This study aims at the identification of relationships between single nucleotide polymorphisms (SNPs) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure. In addition, the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored. Methods Blood samples from 33 patients enrolled in a phase I dose-escalation study of telatinib were analyzed. For correlation with dose normalized AUC(0–12), ATP-binding cassette (ABC) B1 (ABCB1), ABCC1, and ABCG2 were the genes selected. For correlation with telatinib toxicity, selected genes were the drug target genes KDR and FLT4. Results No association between dose normalized AUC(0–12) and drug transporter protein polymorphisms was observed. In addition, no association between toxicity and KDR or FLT4 genotype or haplotype was seen. Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib

Reducing pain in children with cancer: Methodology for the development of a clinical practice guideline

Abstract Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand

Non-dispensing pharmacists' actions and solutions of drug therapy problems among elderly polypharmacy patients in primary care

Objective To evaluate the process of clinical medication review for elderly patients with polypharmacy performed by non-dispensing pharmacists embedded in general practice. The aim was to identify the number and type of drug therapy problems and to assess how and to what extent drug therapy problems were actually solved. Method An observational cross-sectional study, conducted in nine general practices in the Netherlands between June 2014 and June 2015. On three pre-set dates, the non-dispensing pharmacists completed an online data form about the last 10 patients who completed all stages of clinical medication review. Outcomes were the type and number of drug therapy problems, the extent to which recommendations were implemented and the percentage of drug therapy problems that were eventually solved. Interventions were divided as either preventive (aimed at following prophylactic guidelines) or corrective (aimed at active patient problems). Results In total, 1292 drug therapy problems were identified among 270 patients, with a median of 5 (interquartile range 3) drug therapy problems per patient, mainly related to overtreatment (24%) and undertreatment (21%). The non-dispensing pharmacists most frequently recommended to stop medication (32%). Overall, 83% of the proposed recommendations were implemented; 57% were preventive, and 35% were corrective interventions (8% could not be assessed). Almost two-third (64%) of the corrective interventions actually solved the drug therapy problem. Conclusion Non-dispensing pharmacists integrated in general practice identified a large number of drug therapy problems and successfully implemented a proportionally high number of recommendations that solved the majority of drug therapy problems

Non-dispensing pharmacists' actions and solutions of drug therapy problems among elderly polypharmacy patients in primary care

Objective: To evaluate the process of clinical medication review for elderly patients with polypharmacy performed by non-dispensing pharmacists embedded in general practice. The aim was to identify the number and type of drug therapy problems and to assess how and to what extent drug therapy problems were actually solved. Method: An observational cross-sectional study, conducted in nine general practices in the Netherlands between June 2014 and June 2015. On three pre-set dates, the non-dispensing pharmacists completed an online data form about the last 10 patients who completed all stages of clinical medication review. Outcomes were the type and number of drug therapy problems, the extent to which recommendations were implemented and the percentage of drug therapy problems that were eventually solved. Interventions were divided as either preventive (aimed at following prophylactic guidelines) or corrective (aimed at active patient problems). Results: In total, 1292 drug therapy problems were identified among 270 patients, with a median of 5 (interquartile range 3) drug therapy problems per patient, mainly related to overtreatment (24%) and undertreatment (21%). The non-dispensing pharmacists most frequently recommended to stop medication (32%). Overall, 83% of the proposed recommendations were implemented; 57% were preventive, and 35% were corrective interventions (8% could not be assessed). Almost two-third (64%) of the corrective interventions actually solved the drug therapy problem. Conclusion: Non-dispensing pharmacists integrated in general practice identified a large number of drug therapy problems and successfully implemented a proportionally high number of recommendations that solved the majority of drug therapy problems