ObjectiveTo implement a mentored laboratory quality stepwise implementation (LQSI) programme to strengthen the quality and capacity of Cambodian hospital laboratories.MethodsWe recruited four laboratory technicians to be mentors and trained them in mentoring skills, laboratory quality management practices and international standard organization (ISO) 15189 requirements for medical laboratories. Separately, we trained staff from 12 referral hospital laboratories in laboratory quality management systems followed by tri-weekly in-person mentoring on quality management systems implementation using the LQSI tool, which is aligned with the ISO 15189 standard. The tool was adapted from a web-based resource into a software-based spreadsheet checklist, which includes a detailed action plan and can be used to qualitatively monitor each laboratory’s progress. The tool – translated into Khmer – included a set of quality improvement activities grouped into four phases for implementation with increasing complexity. Project staff reviewed the laboratories’ progress and challenges in weekly conference calls and bi-monthly meetings with focal points of the health ministry, participating laboratories and local partners. We present the achievements in implementation from September 2014 to March 2016.FindingsAs of March 2016, the 12 laboratories have completed 74–90% of the 104 activities in phase 1, 53–78% of the 178 activities in phase 2, and 18–26% of the 129 activities in phase 3.ConclusionRegular on-site mentoring of laboratories using a detailed action plan in the local language allows staff to learn concepts of quality management system and learn on the job without disruption to laboratory service provision.

When a new holding chamber for administrating inhaled medication is to be marketed, it needs to be compared with existing chambers with two questions in mind: is this chamber well accepted by patients and is there an in vitro equivalence? We compared the new small volume non-electrostatic valved holding chamber, usable with all pressurized metered-dose inhalers and equipped with a funny facemask, Vortex (Pari GmbH, Germany), to the most frequently prescribed holding chamber in France, Babyhaler (GlaxoSmithKline Laboratories). Preferences were studied for 75 families with a child no more than 4 yr old, using standard questionnaires. An in vitro study assessed the delivered dose and the particle size distribution of two HFA beclomethasone dipropionate pressurized metered dose inhalers (Becotide 250 microg per dose and Nexxair 100 microg per dose) by dose uniformity sample apparatus and cascade impactor according to the European Pharmacopoeia. Vortex was preferred by 95% of the families because of its small size, its duck facemask, and its robust appearance. Among children able to give their opinion, 86% preferred Vortex to Babyhaler. In vitro, both holding chambers reduced the delivered dose of beclomethasone dipropionate and increased the quantity of particles smaller than 5 microm in diameter with both medications. A higher proportion of fine particles was obtained with Nexxair than with Becotide (p < 0.05) and with Vortex than with Babyhaler (p < 0.05). As expected, throat deposition is dramatically reduced for both drugs with both holding chambers. The in vitro difference in the particle size distribution of beclomethasone dipropionate with both holding chambers probably has no clinical influence.

Loxapine is a dibenzoxazepine neuroleptic that is metabolized by the liver in humans. In the present study, we investigated first in vitro loxapine metabolism in liver microsomes from various species including rats, mice, guinea pigs, dogs, rabbits, monkeys and humans. This enables us to choose between species to further validate drug-drug interaction studies. We observed the formation of desmethyl- and hydroxy- metabolites of loxapine after incubation of the different species liver microsomes. Hydroxylation pathway was major in all species. Wide interspecies variability of loxapine metabolism was observed. Loxapine metabolism was similar in human, guinea pig and dog microsomes. We screened in vitro effects of 67 molecules, representative of 8 therapeutic classes, on loxapine metabolism. Loxapine (100 microM) was incubated with guinea pig liver microsomes (1 mg/ml) 30 min at 37 degrees C with and without the presence of interacting drug. We found that most of psychotropics (alimemazine, cyamemazine and levomepromazine), antifungal (ketoconazole), anticancer drugs (daunorubicin, pirarubicin) and analgesic (nefopam) inhibited more than 50% of hydroxyloxapine formation in vitro. Complementary clinical and pharmacokinetic studies should be performed to confirm these results.