Evaluating a targeted multiple reaction monitoring approach to global untargeted lipidomic analyses of human plasma.

RATIONALE: The Lipidyzer platform was recently updated on a SCIEX QTRAP 6500+ mass spectrometer and offers a targeted lipidomics assay including 1150 different lipids. We evaluated this targeted approach using human plasma samples and compared the results against a global untargeted lipidomics method using a high-resolution Q Exactive HF Orbitrap mass spectrometer. METHODS: Lipids from human plasma samples (N = 5) were extracted using a modified Bligh-Dyer approach. A global untargeted analysis was performed using a Thermo Orbitrap Q Exactive HF mass spectrometer, followed by data analysis using Progenesis QI software. Multiple reaction monitoring (MRM)-based targeted analysis was performed using a QTRAP 6500+ mass spectrometer, followed by data analysis using SCIEX OS software. The samples were injected on three separate days to assess reproducibility for both approaches. RESULTS: Overall, 465 lipids were identified from 11 lipid classes in both approaches, of which 159 were similar between the methods, 168 lipids were unique to the MRM approach, and 138 lipids were unique to the untargeted approach. Phosphatidylcholine and phosphatidylethanolamine species were the most commonly identified using the untargeted approach, while triacylglycerol species were the most commonly identified using the targeted MRM approach. The targeted MRM approach had more consistent relative abundances across the three days than the untargeted approach. Overall, the coefficient of variation for inter-day comparisons across all lipid classes was ∼ 23% for the untargeted approach and ∼ 9% for the targeted MRM approach. CONCLUSIONS: The targeted MRM approach identified similar numbers of lipids to a conventional untargeted approach, but had better representation of 11 lipid classes commonly identified by both approaches. Based on the separation methods employed, the conventional untargeted approach could better detect phosphatidylcholine and sphingomyelin lipid classes. The targeted MRM approach had lower inter-day variability than the untargeted approach when tested using a small group of plasma samples. These studies highlight the advantages in using targeted MRM approaches for human plasma lipidomics analysis.

Demonstration of high value care to improve oral health of a remote Indigenous community in Australia.

BACKGROUND: The oral health of Indigenous children in remote communities is much worse than other population groups in Australia. Providing and maintaining an oral health service is challenging due to the remoteness of communities, the associated high cost, and the low retention of clinical staff. An annual preventive intervention delivered by fly-in clinicians may be a more cost-effective way to manage this problem. In this analysis we estimate the cost-effectiveness of an annual professional intervention for the prevention of dental caries in children of a remote Indigenous community in Far North Queensland. METHODS: A cost-effectiveness analysis was conducted based on an annual preventive intervention protocol. This included treating all dental decay in those with disease, applying fissure sealants, a disinfectant swab, fluoride varnish and providing oral hygiene instructions and dietary advice to all participating school children. This study included an intervention group and a natural comparison group and both groups were followed-up for 2 years after the initial preventive intervention. A Markov model was built to assess the cost-effectiveness of the intervention compared with the usual care. Costs of treatment from the Queensland Department of Health were used and effectiveness was measured as quality-adjusted life years (QALYs) with the CHU-9D. One-way and probabilistic sensitivity analyses were conducted to identify key drivers and quantify uncertainty. RESULTS: The preventive intervention was found to be highly cost-effective. The incremental cost per QALY gained was AU$3747. Probability of new caries and seeking treatment were identified as the main drivers of the model. In probabilistic sensitivity analysis intervention was cost effective in 100% of simulations. CONCLUSION: An annual preventive intervention for remote Indigenous communities in Australia is a highly cost-effective strategy to prevent dental caries and improve the quality of life of children.

Bioavailability of different brands of tetracycline in undernourished subjects.

Chemical estimation of seven different marketed brands of tetracycline/Hcl capsules for tetracycline content showed six brands were not meeting the Indian pharmacopia 1985 prescribed standards. However, their dissolution rate and disintegration time were in accordance with United States pharmacopia 1985 specifications. One standard and one substandard brand of tetracycline were selected and their bioavailability, after single dose and plasma steady-state levels after multiple dosing in well nourished and undernourished subjects were determined. The bioavailability of substandard product as determined from 48 h urinary tetracycline excretion was significantly lower as compared to standard product both in well-nourished and undernourished subjects. The plasma steady-state concentrations with the substandard product were below the generally recommended minimum inhibitory concentrations, more so in undernourished subjects. These results indicate that the use of sub-standard tetracycline products in undernourished subjects may lead to therapeutic failures and/or result in the development of resistant microorganisms.