Clinical Pharmacist Impact on Care, Length of Stay, and Cost in Pediatric Cystic Fibrosis (CF) Patients.
Clinical pharmacist impact on care, length of stay, and cost in pediatric cystic fibrosis (CF) patients.
Filed under: Drug and Alcohol Rehabilitation
Pediatr Pulmonol. 2012 Dec 31;
Cies JJ, Varlotta L
BACKGROUND: Cystic fibrosis (CF) patients are often treated with aminoglycoside (AG) antibiotics during infective pulmonary exacerbations. Achieving pharmacokinetic and pharmacodynamic (PK/PD) targets to improve outcomes and counteract resistance is paramount. PURPOSE: The primary objective was to compare the number of pediatric CF patients achieving AG PK/PD targets when a clinical pharmacist (CP) managed therapeutic drug monitoring (TDM) compared with usual care (UC). METHODS: A retrospective cohort study was conducted on the records of 40 CF patients that received AGs and ?2 serum samples between 1/2007 and 5/2009. Chi-square and Student’s t-test were used to analyze nominal and continuous variables, respectively. RESULTS: Twenty-nine patients with 52 courses of AGs were included the CP group, and 22 patients with 42 courses were included the UC group. Ninety-eight percent of patients in the CP group reached AG PK/PD targets compared with 71% in the UC group, P?HubMed – drug
Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to anti-epidermal growth factor receptor antibody.
Filed under: Drug and Alcohol Rehabilitation
Proteomics. 2012 Dec 26;
Monteleone F, Rosa R, Vitale M, D’Ambrosio C, Succoio M, Formisano L, Nappi L, Romano MF, Scaloni A, Tortora G, Bianco R, Zambrano N
Cetuximab is a chimeric antibody approved for the treatment of metastatic colorectal cancer that selectively targets epidermal growth factor receptor (EGFR) signalling. Treatment efficacy with this drug is often impaired by acquired resistance and poor information has been accumulated on the mechanisms underlying such a phenomenon. By taking advantage of a syngenic cellular system of sensitivity and acquired resistance to anti-EGFR therapy in the colorectal carcinoma GEO cell line, we profiled protein expression differences between Cetuximab-sensitive and resistant cells. Combined 2D-DIGE and MS analyses revealed a main proteomic signature resulting from selective deregulation of various metabolic enzymes, including glucose-6-phosphate dehydrogenase, transketolase, lactate dehydrogenase B and pyruvate dehydrogenase E1, which was also confirmed by western blotting experiments. Lactate dehydrogenase B down-regulation has been already related to an increased anaerobic utilization of glucose by tumor cells; accordingly, we verified that Cetuximab-resistant cells have a significantly higher production of lactate. Resistant cells also showed decreased NADPH levels. Observed protein deregulations were not related to functional alterations of the hypoxia-inducible factor 1-associated pathways. Our data demonstrate that increased anaerobic metabolism is a prominent feature observed in the GEO syngenic model of acquired resistance to anti-EGFR therapy in colorectal cancer.
HubMed – drug
Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report of the childhood, adolescent and young adult cancer survivor (CAYACS) research program.
Filed under: Drug and Alcohol Rehabilitation
Pediatr Blood Cancer. 2012 Dec 31;
Deyell RJ, Lorenzi M, Ma S, Rassekh SR, Collet JP, Spinelli JJ, McBride ML
BACKGROUND: Although survivors of childhood, adolescent, and young adult (AYA) cancer are at risk for late psychological sequelae, it is unclear if they are more likely to be prescription antidepressant users than their peers. PROCEDURE: All 5-year survivors of childhood or AYA cancer diagnosed before age 25 years in British Columbia from 1970 to 1995 were identified. Those with complete follow-up in the provincial health insurance registry from 2001 to 2004 were included (n?=?2,389). A birth-cohort and gender-matched set of population controls 10 times the size of the survivor group was randomly selected (n?=?23,890). All prescriptions filled between 2001 and 2004 were identified through linkage to the provincial prescription drug administrative database. Logistic regression analyses determined the impact of cancer survivorship on the likelihood of ever filling an antidepressant prescription. RESULTS: After adjusting for sociodemographic factors, survivors of childhood and AYA cancer were more likely to have filled an antidepressant prescription compared to controls (OR 1.21, 95% CI 1.09-1.35). Cancer survivors had an increased likelihood of using all categories of antidepressants, and of using drugs from two or more antidepressant categories, compared to peers (OR 1.31, 95% CI 1.11-1.55 [?2 antidepressant categories]). Treatment was not a significant predictor of antidepressant use. Female survivors, those in young adulthood and those more than 20 years post-treatment had increased antidepressant use. CONCLUSIONS: Survivors of childhood and AYA cancer are more likely to fill antidepressant prescriptions compared to peer controls. This may indirectly reflect an increased underlying prevalence of mental health conditions among survivors. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
HubMed – drug
Spatial heterogeneity of the relation between resting-state connectivity and blood flow: An important consideration for pharmacological studies.
Filed under: Drug and Alcohol Rehabilitation
Hum Brain Mapp. 2012 Dec 26;
Khalili-Mahani N, Osch MJ, Rooij MD, Beckmann CF, Buchem MA, Dahan A, Gerven JM, Rombouts SA
Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations-mostly in the blood oxygen level dependent (BOLD) signal-across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and CBF signals are linked to common neurovascular and hemodynamic mechanisms that necessitate increased oxygen transportation to the site of neuronal activation; however, the scale and the sources of variation in static CBF and spatiotemporal BOLD correlations are likely different. We tested this hypothesis by examining the relation between CBF and resting-state-network consistency (RSNC)-representing average intranetwork connectivity, determined from dual regression analysis with eight standard networks of interest (NOIs)-in a crossover placebo-controlled study of morphine and alcohol. Overall, we observed spatially heterogeneous relations between RSNC and CBF, and between the experimental factors (drug-by-time, time, drug and physiological rates) and each of these metrics. The drug-by-time effects on CBF were significant in all networks, but significant RSNC changes were limited to the sensorimotor, the executive/salience and the working memory networks. The post-hoc voxel-wise statistics revealed similar dissociations, perhaps suggesting differential sensitivity of RSNC and CBF to neuronal and vascular endpoints of drug actions. The spatial heterogeneity of RSNC/CBF relations encourages further investigation into the role of neuroreceptor distribution and cerebrovascular anatomy in predicting spontaneous fluctuations under drugs. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
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