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KRAS and BRAF: drug targets and predictive biomarkers.

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KRAS and BRAF: drug targets and predictive biomarkers.

J Pathol. 2011 Jan;223(2):220-30

Authors: Vakiani E, Solit DB

Three decades have passed since RAS was first identified as the transformative factor in the Harvey and Kirsten strains of the mouse sarcoma virus. RAS and several of its downstream effectors, including BRAF, have since been shown to be commonly mutated in broad range of human cancers and biological studies have confirmed that RAS pathway activation promotes tumour initiation, progression and metastatic spread in many contexts. With the identification of RAS mutation as a strong predictor of clinical resistance to EGFR-targeted therapies, RAS mutational testing has been incorporated into the routine clinical care of patients with colorectal and lung cancers. This article reviews the current understanding of RAS signalling as it relates to cancer biology, current efforts to develop inhibitors of RAS and its key downstream effectors and the technical challenges of RAS mutational testing in the clinical setting. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID: 21125676 [PubMed - in process]

True adherence with the Turbuhaler in young children with asthma.

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True adherence with the Turbuhaler in young children with asthma.

Arch Dis Child. 2010 Nov 19;

Authors: Nikander K, Turpeinen M, Pelkonen AS, Bengtsson T, Selroos O, Haahtela T

Objective To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence, that is correct use of the inhaler. Patients and design In an 18-month study, children aged 5-10 years with asthma received twice daily budesonide via a TBH. Parents and children were trained in the correct use of the inhaler before the study started. For each inhalation, peak inspiratory flow through the TBH (PIF(TBH)) was recorded with an electronic pneumotachograph. The PIF(TBH) recordings were used to calculate true adherence for the first and last 45-day periods in the study by multiplying adherence in using the device (percentage of days with PIF(TBH) recordings) with inhaler competence (correct use of inhaler defined as PIF(TBH) values >40 l/min). Main outcome measures True adherence, adherence, inhaler competence and PIF(TBH). Results 115 children were treated. The mean (morning and evening) true adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true adherence was due to the decline in adherence. The largest decline in true adherence occurred in older children. Conclusions True adherence with budesonide TBH treatment decreased significantly during the 18-month study due to a decrease in adherence. Inhaler competence with the correct use of the budesonide TBH was high and unchanged over the study period.

PMID: 21097795 [PubMed - as supplied by publisher]

Endpoints in respiratory diseases. free fulltext

A wide range of outcome measures or endpoints has been used in clinical trials to assess the effects of treatments in paediatric respiratory diseases. This can make it difficult to compare treatment outcomes from different trials and also to understand whether new treatments offer a real clinical benefit for patients.

Clinical trials in respiratory diseases evaluate three types of endpoints: subjective, objective and health-related outcomes. The ideal endpoint in a clinical trial needs to be accurate, precise and reliable. Ideally, the endpoint would also be measured with minimal risk and across all ages, easy to perform, and be inexpensive. As for any other disease, endpoints for respiratory diseases must be viewed in the context of the important distinction between clinical endpoints and surrogate endpoints.

The association between surrogate endpoints and clinical endpoints must be clearly defined for any disease in order for them to be meaningful as outcome measures. The most common endpoints which are used in paediatric trials in respiratory diseases are discussed. For practical purposes, diseases have been separated into acute (bronchiolitis, acute viral-wheeze, acute asthma and croup) and chronic (asthma and cystic fibrosis).

Further development of endpoints will enable clinical trials in children with respiratory diseases with the main objective of improving prognosis and safety.

Racial Disparities in Pediatric Asthma: A Review of the Literature.

The burden of asthma disproportionately affects children living in economically disadvantaged urban communities. The relationships between ethnicity, genetic differences, lower socioeconomic status, poor medication adherence, greater exposure to environmental triggers, and absence of regular asthma care all contribute to this disparity. This review aims to identify and discuss recent studies on additional factors that may also impact to pediatric asthma disparity.

The body of work examined in this review suggests that these disparities are the result of gene-environment interactions, vitamin D metabolism, socioeconomic status, urban environment, healthcare setting, and associated health beliefs.

[Recommendations of the French Language Society of Pneumology on the management of COPD (update 2009)].

Recommandations de la Société de Pneumologie de Langue Française sur la prise en charge de la BPCO (mise à jour 2009).
Presse Med. 2010 Sep;39(9):895-8
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