Barbara de Graaff

Effect of filtration on morphine and particle content of injections prepared from slow-release oral morphine tablets

BackgroundInjections of mixtures prepared from crushed tablets contain insoluble particles which can cause embolisms and other complications. Although many particles can be removed by filtration, many injecting drug users do not filter due to availability, cost or performance of filters, and also due to concerns that some of the dose will be lost.MethodsInjection solutions were prepared from slow-release morphine tablets (MS Contin®) replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration.ResultsUnfiltered tablet extracts contained tens of millions of particles with a range in sizes from < 5 μm to > 400 μm. Cigarette filters removed most of the larger particles (> 50 μm) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm) produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 μm filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles.ConclusionsApart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 μm) filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter) should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe practice due to skin and environmental contamination by particles and microorganisms, and the risks of blood-borne infections from sharing injecting equipment.

Effects of Filtration on the Presence of Particulate and Oxycodone Content of Injections Prepared from Crushed OxyContin® Tablets

It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets. Injections were prepared from a sustained-release oxycodone tablet formulation. The filtration of tablet extracts was carried out following procedures used by IDU using makeshift filter and commercially available filters. Particulate contamination and oxycodone content were analysed using light microscopy and spectrophotometer. Unfiltered extracts contained hundreds of thousands of particles of sufficient size to cause harms. Cigarette filters removed large particles but failed to remove small particles. The combination of cigarette filter and syringe filter (0.45 μm or 0.22 μm) reduced the particle count by 90 - 95%. A double membrane syringe filter (0.8/0.2 μm) removed more than 99% of the particles. Recovery of oxycodone was more than 95% with the tested syringe filters. Particulate contamination in injections prepared from crushed tablets can be effectively removed using a combination process of cigarette filter and syringe filters, or a 0.8/0.2 μm syringe filter. Compared to other filters, the 0.8/0.2 μm syringe filter did not block, the filtration was quick and easy to perform, and did not retain oxycodone. The use of a 0.8/0.2 μm syringe filter can provide an important harm reduction measure for IDU.

A Systematic Review and Narrative Synthesis of Health Economic Studies Conducted for Hereditary Haemochromatosis

BackgroundHereditary haemochromatosis (HH) is a common genetic condition amongst people of northern European heritage. HH is associated with increased iron absorption leading to parenchymal organ damage and multiple arthropathies. Early diagnosis and treatment prevents complications. Population screening may increase early diagnosis, but no programmes have been introduced internationally: a paucity of health economic data is often cited as a barrier.ObjectiveTo conduct a systematic review of all health economic studies in HH.MethodsStudies were identified through electronic searching of economic/biomedical databases. Any study on HH with original economic component was included. Study quality was formally assessed. Health economic data were extracted and analysed through narrative synthesis.ResultsThirty-eight studies met the inclusion criteria. The majority of papers reported on costs or cost effectiveness of screening programmes. Whilst most concluded screening was cost effective compared with no screening, methodological flaws limit the quality of these findings. Assumptions regarding clinical penetrance, effectiveness of screening, health-state utility values (HSUVs), exclusion of early symptomatology (such as fatigue, lethargy and multiple arthropathies) and quantification of costs associated with HH were identified as key limitations. Treatment studies concluded therapeutic venepuncture was the most cost-effective intervention.ConclusionsThere is a paucity of high-quality health economic studies relating to HH. The development of a comprehensive HH cost-effectiveness model utilising HSUVs is required to determine whether screening is worthwhile.

Costs associated with hereditary haemochromatosis in Australia: a cost-of-illness study

Objective The aim of the present study was to assess health sector, other sector and time-related (productivity) costs associated with hereditary haemochromatosis from societal, government and patient perspectives for the Australian setting. Methods A national web-based survey of people with haemochromatosis was conducted between November 2013 and February 2015. Participants completed a health survey and resource use diaries. Costs were calculated using a bottom-up approach and calculated in 2015 Australian dollars. Results Cost data were available for 157 participants. From a societal perspective, the estimated annual cost of haemochromatosis was A

Quality of life utility values for hereditary haemochromatosis in Australia

274million. The mean (95% confidence interval) cost for symptomatic patients was almost threefold greater than that of asymptomatic patients (A

Cost-Effectiveness of Different Population Screening Strategies for Hereditary Haemochromatosis in Australia

10030 (7705-12670) vs A

Need, want and demand: What is really happening with low‐acuity presentations?

3701 (2423-5296) respectively). Health sector and productivity-related time loss were the main cost drivers. When extrapolating costs to the Australian population level, asymptomatic haemochromatosis accounted for higher costs than symptomatic haemochromatosis (A

Australian Drug Trends 2007: Findings from the Illicit Drug Reporting System (IDRS)

183million vs A

Population Screening for Hereditary Haemochromatosis in Australia: Construction and Validation of a State-Transition Cost-Effectiveness Model

91million), reflecting the low clinical penetrance estimate used. Total costs increased when higher clinical penetrance estimates were used. Conclusion The present cost-of-illness study, the first to be published for haemochromatosis, found that although costs were substantial, they could be decreased by reducing clinical penetrance. Development of cost-effective strategies to increase early diagnosis is likely to result in better health outcomes for patients and lower total costs. What is known about the topic? To date, no cost-of-illness study has been conducted for haemochromatosis. Previous economic work in this area has relied on cost estimates based on expert opinion. What does the paper add? This paper provides the first cost estimates for haemochromatosis for the Australian population. These estimates, calculated using a bottom-up approach, were extrapolated to the population level based on the most robust epidemiological estimates available for the Australian population. What are the implications for practitioners? Population screening programs have been widely suggested as an approach to reduce clinical penetrance; however, the lack of high-quality economic analyses has been cited as a barrier to implementation. The present study provides the most robust cost estimates to date, which may be used to populate economic models. In addition, the present study illustrates that reducing clinical penetrance of haemochromatosis is likely to result in substantial reductions in cost.

Uptake of and expenditure on direct-acting antiviral agents for Hepatitis C treatment in Australia

BackgroundHereditary hemochromatosis (HH) is a common autosomal recessive disorder amongst persons of northern European heritage. If untreated, iron accumulates in parenchymal tissues causing morbidity and mortality. As diagnosis often follows irreversible organ damage, screening programs have been suggested to increase early diagnosis. A lack of economic evidence has been cited as a barrier to establishing such a program. Previous analyses used poorly estimated utility values. This study sought to measure utilities directly from people with HH in Australia.MethodsVolunteers with HH were recruited to complete a web-based survey. Utility was assessed using the Assessment of Quality of Life 4D (AQOL-4D) instrument. Severity of HH was graded into four categories. Multivariable regression analysis was performed to identify parameters associated with HSUV.ResultsBetween November 2013 and November 2014, 221 people completed the survey. Increasing severity of HH was negatively associated with utility. Mean (standard deviation) utilities were 0.76 (0.21), 0.81 (0.18), 0.60 (0.27), and 0.50 (0.27) for categories 1–4 HH respectively. Lower mean utility was found for symptomatic participants (categories 3 and 4) compared with asymptomatic participants (0.583 v. 0.796). Self-reported HH-related symptoms were negatively associated with HSUV (r = −0.685).ConclusionsSymptomatic stages of HH and presence of multiple self-reported symptoms were associated with decreasing utility. Previous economic analyses have used higher utilities which likely resulted in underestimates of the cost effectiveness of HH interventions. The utilities reported in this paper are the most robust available, and will contribute to improving the validity of future economic models for HH.