A new clinical approach to improve the appropriate use of peripherally inserted central catheters: a prospective study.

OBJECTIVES: Peripherally inserted central catheters (PICCs) are central venous catheters commonly used for administration of chemotherapy, prolonged antibiotic treatment, or parenteral nutrition. It is advisable to use the PICC with the fewest lumens and the smallest possible diameter to reduce major complications. A pharmaceutical analysis and validation of PICC requests was designed to improve efficiency and patient safety. The aim of this study was to evaluate the impact of pharmaceutical interventions (PIs) by the clinical pharmacist in the PICC process. METHODS: A prospective pilot study was conducted in a French university hospital. Four categories of PIs were defined according to the different stages of the PICC insertion process: before insertion to validate with the physician the relevance of the request and the choice of PICC model (PI applicant); during insertion (PI installer); during usage by nurses for analysis of drug incompatibilities (PI user); and at hospital discharge for reassessment of the device maintenance (PI reassessment). Each PI applicant was designated a potential harm from 1 to 4, with a cut-off of 2 representing harm for the patient. RESULTS: Over 6 months, 277 requests were analysed and 297 PIs were completed (109 applicants, 98 installers, 84 users, and 6 PIs for reassessment). The acceptance rate by the physicians was 93.6%. 52% of the PI applicants had a potential harm of 2 or more. 5% of PICC requests were refused by the pharmacist due to an inappropriate choice of device. A total of 207 (74.7%) of the requests analysed by the clinical pharmacist led to insertion. CONCLUSIONS: The implementation of a clinical pharmacy activity applied to PICC requests analysis and validation leads to improved patient care by securing the PICC circuit. This analysis demonstrates the beneficial role of the clinical pharmacist in PIs associated with medical devices.

Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation.

BACKGROUND: Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11) is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane x Receptor (PXR), we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. RESULTS: PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies. CONCLUSION: Our results demonstrate that tumoral metabolism of SN38 is affected by PXR and point to potential therapeutic significance of PXR quantification in the prediction of irinotecan response. Furthermore, our observations are pharmacologically relevant since many patients suffering from cancer diseases are often exposed to co-medications, food additives or herbal supplements able to activate PXR. A substantial part of the variability observed among patients might be caused by such interactions.