Search

Background: The paediatric use of ophthalmic chloramphenicol in New Zealand (NZ) is relatively high; however, little more is known about its utilisation, including whether this is equitable. This study aimed to describe chloramphenicol utilisation in NZ children aged five years and under, by patient ethnicity, socioeconomic deprivation, and urban/non-urban domicile. Methods: This analysis included every publicly subsidised chloramphenicol dispensing received from birth to five years of age, for every child born in NZ in 2013. Cumulative proportion of first exposure, dispensing rate per person-year, and seasonality of dispensing were quantified. These were calculated following stratification by ethnicity, socioeconomic deprivation quintile, and urban/non-urban health district. For cumulative proportion of first exposure, odds ratios (OR) were calculated and multivariate logistic regression was performed. For dispensing rate, incidence rate ratios (IRR) were calculated and zero-inflated Poisson regression was performed. Results: Almost one-quarter of NZ children received their first dispensing within the first year of life. By five years of age, 55.2% of children had received their first dispensing. By five years of age, children of Pacific ethnicity, those in the highest deprivation quintile, and in those non-urban health districts had lower odds of receiving chloramphenicol (adjusted OR 0.90, 0.79, and 0.81, respectively, all p < 0.001). In contrast, children of Māori ethnicity had higher odds (adjusted OR 1.99, p < 0.001). Māori and Pacific ethnicity, and residence in non-urban health districts, were associated with fewer dispensings (adjusted IRR 0.88, 0.75 and 0.87, all p < 0.001). In contrast, deprivation quintile was not significantly associated with dispensing rate. Conclusion: Chloramphenicol utilisation is prevalent among NZ children, and utilisation may be lower among children of Pacific ethnicity and those in non-urban areas

Immune therapy for cancer patients is a new and promising area that in the future may complement traditional chemotherapy. The cell expansion phase is a critical part of the process chain to produce a large number of high-quality, genetically modified immune cells from an initial sample from the patient. Smart sensors augment the ability of the control and monitoring system of the process to react in real-time to key control parameter variations, adapt to different patient profiles, and optimize the process. The aim of the current work is to develop and calibrate smart sensors for their deployment in a real bioreactor platform, with adaptive control and monitoring for diverse patient/donor cell profiles. A set of contrasting smart sensors has been implemented and tested on automated cell expansion batch runs, which incorporate advanced data-driven machine learning and statistical techniques to detect variations and disturbances of the key system features. Furthermore, a ‘consensus’ approach is applied to the six smart sensor alerts as a confidence factor which helps the human operator identify significant events that require attention. Initial results show that the smart sensors can effectively model and track the data generated by the Aglaris FACER bioreactor, anticipate events within a 30 min time window, and mitigate perturbations in order to optimize the key performance indicators of cell quantity and quality. In quantitative terms for event detection, the consensus for sensors across batch runs demonstrated good stability: the AI-based smart sensors (Fuzzy and Weighted Aggregation) gave 88% and 86% consensus, respectively, whereas the statistically based (Stability Detector and Bollinger) gave 25% and 42% consensus, respectively, the average consensus for all six being 65%. The different results reflect the different theoretical approaches. Finally, the consensus of batch runs across sensors gave even higher stability, ranging from 57% to 98% with an average consensus of 80%.

Ocular antibiotics are integral to the prevention and treatment of bacterial ocular infections. This study aimed to describe their utilisation across New Zealand according to patient and healthcare factors. Every subsidy-eligible community dispensing of ocular chloramphenicol, fusidic acid and ciprofloxacin in New Zealand, between 2010 and 2019, was included in this analysis. Number of dispensings/1000 population/year was quantified, stratified by patient age and urban/non-urban health districts. Dispensing rates by ethnicity were determined and were age adjusted. The proportion of dispensings by socioeconomic deprivation quintile was also determined. Chloramphenicol was the most commonly dispensed antibiotic; however, its utilisation decreased over time. Ciprofloxacin use was higher in children, while chloramphenicol use was higher in older patients. Ciprofloxacin usage was higher among Māori and Pasifika ethnicities, while fusidic acid use was lower. Chloramphenicol usage was higher among Pasifika. Antibiotic utilisation was higher in urban health districts, and in the most deprived quintile; both were most marked with ciprofloxacin. The utilisation of publicly funded ocular antibiotics across New Zealand varied between patient subgroups. These findings will help improve the prevention, management and outcomes of bacterial ocular infections, and support wider initiatives in antibiotic stewardship and medicine access equity.

Little is known regarding the pharmacological properties of extended-release local anesthetics in the setting of diabetic peripheral neuropathy. We investigated and compared the duration of sciatic nerve block following administration of clinically relevant concentrations of liposomal bupivacaine (LB) and bupivacaine hydrochloride (BH) in diabetic mice with peripheral neuropathy. In this prospective, randomized, and double-blind study, twenty-four female C57BL/6J-OlaHsd mice were assigned to a streptozotocin-induced type 1 diabetes group and a control group without diabetes. The presence of peripheral neuropathy was established by assessing the duration of thermal latency of the plantar and tail-flick tests, following which both groups were subdivided into two subgroups in which 35 mg/kg of 1.31% LB and 7 mg/kg of 0.25% BH were respectively administered for sciatic nerve block. The average sensory block duration with BH was 106 min and 117.1 min in the control and diabetic groups, respectively. With LB, the average sensory block duration was 118 min in the control mice, while in mice with diabetic peripheral neuropathy, the average block duration was significantly longer and above the 270 min limit set in our study. Accordingly, sensory block duration was longer with LB compared to BH, and diabetic peripheral neuropathy significantly increased sciatic nerve block duration with LB.

The objective of this study was to compare the effects of >Your< Iron Syrup, a novel oral liquid iron-containing food supplement, with the commonly prescribed iron sulphate (Fe-sulphate) in a mouse model of diet-induced iron deficiency. Standard inbred BALB/cOlaHsd mice were fed low-iron diet for 11 weeks to induce significant decrease in blood haemoglobin and haematocrit and were then supplemented by gavage with either >Your< Iron Syrup or Fe-sulphate for two weeks. In >Your< Iron Syrup group, several markers of iron deficiency, such as serum iron concentration, transferrin saturation and ferritin level were significantly improved in both female and male mice. Fe-sulphate induced similar responses, except that it did not significantly increase iron serum in females and serum ferritin in both sexes. Fe-sulphate significantly increased liver-iron content which >Your< Iron Syrup did not. Transcription of Hamp and selected inflammatory genes in the liver was comparable between the two supplementation groups and with the Control diet group. Some sex-specific effects were noted, which were more pronounced and less variable in males. In conclusion, >Your< Iron Syrup was efficient, comparable and in some parameters superior to Fe-sulphate in improving iron-related parameters without inducing a response of selected liver inflammation markers in a mouse model of diet-induced iron deficiency.

Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.