Performance evaluation of the HPLC diode array and evaporative light scattering detection for the implementation of dose-banded gemcitabine infusion bags.

BACKGROUND: Dose banding (DB) was used to optimise the individualisation of patient treatments with gemcitabine (Gem) in order to improve workload planning at the pharmacy of the University Hospital Centre of Besançon (UHCB). A new simple and fast high-performance liquid chromatographic (HPLC) method was also developed for the quantification of Gem without dilution of the infusion bags. METHODS: Individual doses of Gem preparations were retrospectively analysed over a 1-year period to determine the frequency of prepared doses. Using a maximum gap of 7.5% around the doses chosen, the selected Gem standard doses were 1400 mg, 1600 mg, 1800 mg and 2000 mg. Following the DB scheme, the frequency of prescription of standard and individualised Gem doses was analysed over a period of 10 months. The four selected Gem standard doses were aseptically prepared in polyolefin infusion bags. Each series of 20 bags was stocked under refrigerated storage conditions (4°C) for up to 84 days. The quantification of Gem without dilution of the infusion bags was obtained by the development of a HPLC method coupled to a diode array detector (DAD) or an evaporative light scattering detector (ELSD). RESULTS: During the 10-month period following implementation of the DB, 75.6% of the 1266 prescribed doses were covered by the four standardised preparations. The number of different Gem doses was reduced from 183 to 55. Concerning the Gem quantification, both heteroscedasticity and non-linearity were observed with DAD. Using an ELSD, the trueness values were between 98.59% and 101.52% with excellent repeatability values between 0.66% and 1.42%. CONCLUSION: A new HPLC method has been developed for the quantification of Gem without dilution of the infusion bags prepared in advance as a result of a target DB scheme successfully implemented in our pharmacy department.

Interaction and toxicity of ingested nanoparticles on the intestinal barrier.

The gastrointestinal tract represents one of primary routes of entry for many nanomaterials. Their size in the nanometer range and their high surface area confer them very interesting properties as food additives. They are used as texturizing, opacifying or anticaking agents. Food packaging contains nanomaterials with antimicrobial properties. Humans are also orally exposed to nanoparticles (NPs) present in the air or drinking water. Ingested NPs can then reach the intestinal lumen and interact with the gastrointestinal fluids, microbiota, mucus layers and the epithelial barrier, allowing a potential translocation. The toxicological profile of ingested NPs is still unclear due to their variety in terms of composition and physicochemical properties as well as the limited number of investigations. Their unique properties related to their small size could however affect the intestinal ecosystem but also the physical and functional properties of the intestinal barrier. This review focuses on the fate of ingested organic and inorganic NPs in the intestinal lumen and their toxicity on the microbiota and epithelial cells.

Epidemiology and economic burden of "serious" adverse drug reactions: Real-world evidence research based on pharmacovigilance data.

AIM OF THE STUDY: Serious adverse drug reactions account for 3.6% of French hospital admissions. Of these, 48.5% are, at least potentially, preventable. The first aim of post-marketing pharmacovigilance is to detect adverse drug reactions as a safety signal to improve patients' safety. Thus, this study describes the epidemiology of "serious" adverse drug reactions reported between 2015 and 2018 to a regional pharmacovigilance centre and assesses their economic burden. METHODS: All "serious" adverse drug reactions reported to a regional pharmacovigilance centre during the four-year study period were collected and cost associated. Only congenital anomalies related to "serious" adverse drug reactions were excluded. RESULTS: All 2585 "serious" adverse drug reactions reported are related to 1242 "serious" individual case safety reports. Among 58.1% of them, patients required hospital admission or a visit to the emergency room with a median cost estimated to €3725 per "serious" individual case safety report. The most "serious" adverse drug reactions reported involved gastrointestinal disorders. Fifteen percent of the imputed drugs had a narrow therapeutic index and the most frequently drug was fluindione. Finally, high relationships with an economic burden were observed for ages over or equal to 65, and imputed drugs from "Blood and Blood-Forming Organs" and "Anti-infectives for systemic use" therapeutic groups. CONCLUSION: This study provides news data on epidemiology and cost of "serious" adverse drug reactions completing the existing literature. On a regional scale, pharmacovigilance real world data could be interesting for pharmacist clinicians in common practice to improve the good use of drugs.

A systematic review of economic evaluation in fecal microbiota transplantation.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results. OBJECTIVES: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases. DATA SOURCES: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019. STUDY ELIGIBILITY CRITERIA: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster. METHODS: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist. RESULTS: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole. CONCLUSIONS: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.