Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

Documentation of pharmaceutical care: development of an intervention oriented classification system

Background A standardised classification system of pharmaceutical interventions (PI) is in use in several Swiss hospitals, whereas none exists for community pharmacies to date. To promote information exchange between both settings, a compatible structure of the classification system is needed. Objective To develop an intervention oriented classification system for community pharmacies named PharmDISC based on the hospital system; to test it on interrater reliability, appropriateness, interpretability, and face and content validity; to assess pharmacists' opinions. Setting Seventy-seven Swiss community pharmacies. Method Based on previous studies, a modified classification system was developed. Fifth-year pharmacy students (n = 77) received a two-hour training and classified three model PIs with which Fleiss-Kappa coefficients K were calculated to determine interrater reliability. In the community pharmacies, each student consecutively collected ten prescriptions that required a PI. A focus group interview was conducted with pharmacists (n = 9). The anonymised transcript was analysed using thematic analysis. Main outcome measure Number of classified PIs, interrater reliability, pharmacists' opinion/suggestions. Results The classification system includes 5 categories and 52 subcategories. Most of the 725 PIs (94.6%) were completely classified. The PharmDISC system reached an overall substantial user agreement (K = 0.61). Despite some points for optimisation, the pharmacists were satisfied with the PharmDISC system. They recognised the importance of PI documentation and believed that this may allow traceability, facilitate communication within the team and other healthcare professionals, and increase quality of care. Conclusion The PharmDISC system was valid and reached substantial interrater reliability. Refinement based on the pharmacists' suggestions resulted in a final version to be tested in an observational study with community pharmacists

The pharmacists' potential to provide targets for interventions to optimize pharmacotherapy in patients with asthma

<p>Background Despite of pharmacists' specialized knowledge of medication and his/her regular contact with patients, the expertise of the pharmacist may not be used enough yet. Furthermore, the potential of pharmacy dispensing data is underestimated. Objective To provide targets for tailored interventions in asthma patients and to illustrate the potential value of pharmacists in the identification of these targets using individual pharmacy dispensing data. Setting We performed a cross sectional retrospective analysis assessing the quality of asthma patients' pharmacotherapeutic treatment. Method Drug dispensing data from 2008 to 2009 were retrieved from a Dutch pharmacy database. All asthma patients were screened for potential suboptimal pharmacotherapy in 2009. Results were projected to a single community pharmacy to provide an estimate of the number of patients eligible for potential interventions. Main outcome measures (1) frequent use of short-acting beta-agonists without preventive medication, (2) concomitant use of beta-blockers, (3) multiple short courses of oral corticosteroids without using inhaled corticosteroids and 4) use of long-acting beta-agonist without inhaled corticosteroids. Results A total of 8,504 patients were eligible for analysis of the quality of their asthma treatment. 20.9 % of all asthma patients used > 100 DDD short-acting beta-agonists per year, whereas between 21.2 % (a parts per thousand yen400 DDD) and 31.4 % (100-199 DDD) of these patients did not receive preventive medication. Approximately 5.2 % of the asthma patients are using beta-blockers concomitantly and 21.8 % of them received non-cardioselective beta-blockers. 6.3 % of the asthma patients received two or more oral courses of corticosteroids in 2008 and 17.4 % of these patients did not receive inhaled corticosteroids in 2009. 2.9 % of the patients used a long-acting beta-agonists without inhaled corticosteroids. 8.4 % of the asthma patients using both long-acting beta-agonists and inhaled corticosteroids received these drugs in two separate inhalers. We estimated that about 400 asthma patients could be identified in an average pharmacy population (8,000 patients) and 33 (95 % CI 22-44) of these patients would be eligible for interventions. Conclusion This study shows the potential for pharmacists to use their own pharmacy records to identify suboptimal therapy of asthma patients, who may be targets for tailored interventions.</p>