Karen Whitfield

Utilisation trends of rosiglitazone and pioglitazone in Australia before and after safety warnings

BackgroundA see on cardiovascular diseases and bladder cancer. The changes to the patterns of rosiglitazone and pioglitazone utilisation in Australia following the timing of these various health authority warnings such as the Australian Therapeutic Good Administration (TGA), European Medicines Agency (EMA) press releases or U.S. Food and Drug Administration (FDA) is unknown. This study investigated the utilisation patterns of rosiglitazone and pioglitazone in Australia before and after warnings of major drug authorities.MethodsWe evaluated rosiglitazone and pioglitazone dispensing using the Pharmaceutical Benefit Scheme (PBS) subsidised drug dispensing data for the Australian population from February 2004 to July 2012. The World Health Organisation Anatomic Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) system was used to compare the drug utilisation patterns following the announcements of EMA, FDA, and TGA safety warnings, which first occurred in May 2007. The DDD/1000population/day were examined in a series of time-series regression analysis with the drug safety warnings specified as interventions.ResultsRosiglitazone utilisation increased steadily from 2004 until reaching a peak at 1.96/1000population/day in January 2007. Then rosiglitazone use decreased significantly after the initial EMA press release and FDA warning on cardiovascular risk in May 2007 (with a 15.04% average monthly decline, p-value <0.001), however use did not significantly decrease after the TGA warning or subsequent EMA and FDA warnings. Pioglitazone utilisation proceeded rosiglitazone in September 2008 and remained above 1.5/1000/day during 2009–2010. However, pioglitazone utilisation has slightly declined after the FDA, EMA, and TGA warnings related to bladder cancer.ConclusionsDrug safety warnings were associated with a decrease in rosiglitazone and pioglitazone utilisation in Australia. Rosiglitazone began to decline prior to TGA warnings in December 2007, which suggests that Australian prescribers may have acted in response to scientific evidence or international safety warnings (EMA, FDA), prior to the response of the TGA. Minor effects were observed after bladder cancer warnings on pioglitazone utilisation.

Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography–tandem mass spectrometry

Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D2 and D3 (D2 and D3), 25-hydroxy D2 and D3, 24,25-dihydroxy D2 and D3, and 1,25-dihydroxyD2 and D3. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD3 (25(OH)D3) and its epimer (3-epi-25(OH)D3) were chromatographically resolved, to prevent over-estimation of 25(OH)D3. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30-13.5%, and 88.2-105%, respectively.

Recent trends in the determination of vitamin D

The occurrence of vitamin D deficiency has become an issue of serious concern in the worldwide population. As a result numerous analytical methods have been developed, for a variety of matrices, during the last few years to measure vitamin D analogs and metabolites. This review employs a comprehensive search of all vitamin D methods developed during the last 5 years for all applications, using ISI Web of Science(®), Scifinder(®), Science Direct, Scopus and PubMed. Particular emphasis is given to sample-preparation methods and the different forms of vitamin D measured across different fields of applications such as biological fluids, food and pharmaceutical preparations. This review compares and critically evaluates a wide range of approaches and methods, and hence it will enable readers to access developments across a number of applications and to select or develop the optimal analytical method for vitamin D for their particular application.

EFFECT OF PASTEURISATION ON THE CONCENTRATIONS OF VITAMIN D COMPOUNDS IN DONOR BREAST MILK.

Aim Breastmilk is considered the most important nutrient and source of supplementation for both term and preterm infants.1 It is composed of many important nutrients, including vitamin D.2 The content of this vitamin in breast milk is usually low, even for lactating mothers with adequate vitamin D status.2 3 Preterm infants are at the great risk of vitamin D deficiency due to decreased transplacental transfer.4 Premature infants are the main recipients of pasteurised donor human milk (PDHM), when their mothers are unable to provide their own. This study aims to evaluate the effect of pasteurisation on the concentrations of vitamin D compounds in donor breast milk. Method A total of 16 participants, who donated breast milk to the RBWH milk bank, were recruited in this study. Milk samples were obtained pre- and post-Holder pasteurisation. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyse the samples for vitamins D2 and D3 and 25-hydroxyvitamins D2 and D3 (25(OH)D2 and 25(OH)D3). The significance of differences in vitamin D concentrations between the two groups of milk samples was assessed using the Wilcoxon matched-pairs signed rank test, in which P<0.05 was considered significant. Results Pasteurisation resulted in a significant reduction (P<0.05) in the content of D2, D3, 25(OH)D2 and 25(OH)D3, with P values of 0.0001 for all targeted analytes. The concentrations of the vitamin D analogues in non-pasteurised milk ranged from 3.6 to 5.0 pM (D2), 1.0 to 9.8 pM (D3), 1.4 to 2.1 pM (25(OH)D2) and 1.2 to 9.3 pM (25(OH)D3). The concentrations of the vitamin D analogues in post-pasteurised milk ranged from 3.0 to 4.0 pM (D2), 0.6 to 9.5 pM (D3), 1.2 to 1.7 pM (25(OH)D2) and 1.1 to 9.1 pM (25(OH)D3). Losses of vitamin D compounds resulting from the pasteurisation process ranged from 10% to 20%. Conclusion Pasteurisation significantly affected the concentration of vitamin D compounds in pasteurised donor breast milk.

Effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk

Abstract Premature infants are the main recipients of pasteurised donor human milk (PDHM), when their mothers are unable to provide their own. In this study, we evaluated the effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk. Milk samples were obtained pre- and post-Holder pasteurisation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse the samples for vitamins D2 and D3 (D2 and D3) and 25-hydroxyvitamins D2 and D3 (25(OH)D2 and 25(OH)D3). The significance of differences in vitamin D concentrations between the two groups of milk samples was assessed using the Wilcoxon matched-pairs signed rank test, in which p < 0.05 was considered significant. Pasteurisation resulted in a significant reduction (p < 0.05) in the content of D2, D3, 25(OH)D2 and 25(OH)D3. The losses ranged from 10% to 20% following pasteurisation.

TO INVESTIGATE THE EFFECT OF THE PASTEURISATION PROCESS ON TRACE ELEMENTS IN DONOR BREAST MILK

Aim To investigate the effect of the pasteurisation process on trace elements in donor breast milk. Method Premature infants often receive donor breast milk when the mother is unable to produce sufficient breast milk. It is widely accepted that donor milk has considerable advantages over formula milk.1 The Royal Brisbane and Womens Hospital (RBWH) has a milk bank that receives milk donated by women which undergoes a pasteurisation process.2 This study investigated the effect of pasteurisation on a range of trace elements in donor milk. A total of 14 participants who donated to the milk bank were recruited in this study. A 2 ml sample was collected pre- and post- pasteurisation, and frozen at −80 °C. Post-natal age of the milk was documented. Inductively-coupled plasma mass-spectrometry was used to analyse the following trace elements – zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iodine (I), iron (Fe), molybdenum (Mo) and bromine (Br). The study received ethical approval from RBWH and The University of Queensland Ethics Committee. Results No significant difference was found between the levels of any of the trace elements tested pre- and post-pasteurisation. The following p-values were calculated – Zn (0.82), Cu (0.80), Se (0.97), Mn (0.63), I (0.99), Fe (0.05), Mo (0.41), Br (0.59). The following ranges in mcg/L of trace elements were calculated – Zn (365.4–5460.0), Cu (157.6–820.5), Se (10.6–23.7), Mn (0.55–3.24), I (66.4–215.3), Fe (101.5–473.1), Mo (0.20–5.45), Br (704.9–3379.0). Spearmans rank correlation analysis showed significant correlations between post-natal age of milk and trace elements – Zn (ρ=−0.578), Se (ρ=−0.627). Fe (ρ=−0.704), and Mo (ρ=−0.534). No significant correlation was found for Cu, Mn, I, and Br. Conclusion This study found that the pasteurisation process had minimal effect on trace element levels in donor breast milk. However, it was noted that there was a correlation between post-natal age of donor milk and Zn, Se, Fe and Mo. Further work is needed to establish factors that may influence levels of trace elements in donor milk such as post-natal age.

Characteristics of adverse medication events in a children's hospital.

To compare adverse medication events (AMEs) reported in children, via the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD‐10) coding with events reported via other data sources.

Psychotropic medication use during pregnancy

Globally, mental health‐related issues are a growing concern. Pregnant women with mental health‐related illnesses present a unique challenge to health professionals. During pregnancy, the decision to withhold, modify or continue psychotropic medication requires consideration of both maternal and infant outcomes. Health professionals must be aware withdrawal of these medications during pregnancy can often lead to symptom relapse. Decisions around medication management during pregnancy can be challenging due to the lack of data and occasionally conflicting data regarding safety. It is essential that women do not receive conflicting information from health professionals because this can lead to confusion and both intentional and unintentional non‐adherence. Recently, it has been suggested that pharmacists may help optimise medication management and patient outcomes in perinatal care. This review outlines the use of psychotropic medications in pregnancy and discusses key considerations for those involved in providing clinical care to pregnant women with mental illness.

The effect of pasteurization on trace elements in donor breast milk

Objective:Premature infants often receive pasteurized donor human milk when mothers are unable to provide their own milk. This study aims to establish the effect of the pasteurization process on a range of trace elements in donor milk.Study Design:Breast milk was collected from 16 mothers donating to the milk bank at the Royal Brisbane and Women’s Hospital. Samples were divided into pre- and post-pasteurization aliquots and were Holder pasteurized. Inductively coupled plasma mass spectrometry was used to analyze the trace elements zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iodine (I), iron (Fe), molybdenum (Mo) and bromine (Br). Differences in trace elements pre- and post-pasteurization were analyzed.Results:No significant differences were found between the trace elements tested pre- and post-pasteurization, except for Fe (P<0.05). The median (interquartile range, 25 to 75%; μg l−1) of trace elements for pre- and post- pasteurization aliquots were—Zn: 1639 (888–4508), 1743 (878–4143), Cu: 360 (258–571), 367 (253–531), Se: 12.34 (11.73–17.60), 12.62 (11.94–16.64), Mn: (1.48 (1.01–1.75), 1.49 (1.11–1.75), I (153 (94–189), 158 (93–183), Fe (211 (171–277), 194 (153–253), Mo (1.46 (0.37–2.99), 1.42 (0.29–3.73) and Br (1066 (834–1443), 989 (902–1396).Conclusions:Pasteurization had minimal effect on several trace elements in donor breast milk but high levels of inter-donor variability of trace elements were observed. The observed decrease in the iron content of pasteurized donor milk is, however, unlikely to be clinically relevant.

CHANGING PRESCRIBING CULTURE - A FOCUS ON CODEINE POSTPARTUM.

Aim To eliminate the prescribing of codeine and codeine combination products postpartum to improve safety in breast fed infants. Concerns have been raised over the use of codeine and codeine combination products during breast feeding after the death of a neonate whose mother had been prescribed codeine postpartum. High concentrations of morphine were found in the infants blood and this was attributed to the mother being a CYP2D6 ultrafast metaboliser.1 Methods The evidence surrounding the safety of codeine and codeine combination products in children, during the postpartum period and specifically for breast fed infants was collated. The evidence was presented to key stakeholders including obstetricians, midwives, safety and quality representatives, nurse unit managers and acute pain team representatives. Postpartum analgesia was discussed and an agreed protocol developed. Training and education sessions were undertaken to obstetric medical and nursing staff. Results The evidence that was presented to key stakeholders included: ▸ Reports over the safety concerns surrounding the use of codeine and codeine combination products during breast feeding ▸ Guidelines and contraindications about the use of codeine in children that had been issued by international regulatory bodies (US Food and Drug Administration and European Medicines Agency). ▸ Recommendations from the Australian Medicines Handbook to avoid in breast feeding2 ▸ Recommendations from Hales Medications and Mothers Milk that reported limited data and had made a recent re-classification from L3 (limited data–probably compatible) to L4 (limited data–possibly hazardous).3 Before presenting the evidence to key stakeholders and undertaking training to nursing and medical staff, more than 90% of postpartum women were prescribed a codeine containing product as part of their ‘as required’ analgesic regimen. Since the intervention, codeine combination products have now been almost completely eliminated on medication charts for postpartum women (less than 5%). Those that are prescribed are ceased once highlighted to medical staff. The obstetric pharmacist now presents a session on postpartum analgesia at every new resident medical officer orientation outlining suitable medications to prescribe. In addition all new pharmacists to the womens and new borns team receive training about postpartum analgesia. Conclusion This study highlights the impact that can be achieved when health care professionals work together to change the culture and prescribing habits in a hospital setting, to enhance patient safety. Evaluating the evidence and presenting to stakeholders as well as providing ongoing training and education to medical, nursing and pharmacy staff are all essential to a successful outcome.