Haemochromatosis is defined as systemic iron overload of genetic origin, caused by a reduction in the concentration of the iron regulatory hormone hepcidin, or a reduction in hepcidin-ferroportin binding. Hepcidin regulates the activity of ferroportin, which is the only identified cellular iron exporter. The most common form of haemochromatosis is due to homozygous mutations (specifically, the C282Y mutation) in HFE, which encodes hereditary haemochromatosis protein. Non-HFE forms of haemochromatosis due to mutations in HAMP, HJV or TFR2 are much rarer. Mutations in SLC40A1 (also known as FPN1; encoding ferroportin) that prevent hepcidin-ferroportin binding also cause haemochromatosis. Cellular iron excess in HFE and non-HFE forms of haemochromatosis is caused by increased concentrations of plasma iron, which can lead to the accumulation of iron in parenchymal cells, particularly hepatocytes, pancreatic cells and cardiomyocytes. Diagnosis is noninvasive and includes clinical examination, assessment of plasma iron parameters, imaging and genetic testing. The mainstay therapy is phlebotomy, although iron chelation can be used in some patients. Hepcidin supplementation might be an innovative future approach.

Demand for bariatric surgery to treat severe and resistant obesity far outstrips supply. We aimed to comprehensively synthesise health economic evidence regarding bariatric surgery from 1995 to 2018 (PROSPERO registration number: CRD42018094189). Meta-analyses were conducted to calculate the annual cost changes "before" and "after" surgery, and cumulative cost differences between surgical and nonsurgical groups. An updated narrative review also summarized the full and partial health economic evaluations of surgery from September 2015. N = 101 studies were eligible for the qualitative analyses since 1995, with n = 24 studies after September 2015. Quality of reporting has increased, and the inclusion of complications/reoperations was predominantly contained in the full economic evaluations after September 2015. Technical improvements in surgery were also reflected across the studies. Sixty-one studies were eligible for the quantitative meta-analyses. Compared with no/conventional treatment, surgery was cost saving over a lifetime scenario. Additionally, consideration of indirect costs through sensitivity analyses increased cost savings. Medication cost savings were dominant in the before versus after meta-analysis. Overall, bariatric surgery is cost saving over the life course even without considering indirect costs. Health economists are hearing the call to present higher quality studies and include the costs of complications/reoperations; however, indirect costs and body contouring surgery are still not appropriately considered.

This study aimed to statistically combine multiple health state utility values (HSUVs) reported in the literature for patients with osteoporosis and osteoporotic fractures. Fracture events were associated with decrements in HSUVs which differed between fracture sites. We have provided summary values for use in future health economics analyses in osteoporosis. Osteoporotic fractures have high financial and health burden. Economic evaluations on osteoporotic fracture prevention have been frequently performed in past decades. One of the challenges in the economic evaluations was to identify consistent health state utility values (HSUVs) to use for osteoporotic fracture-related conditions. The objective of this study was to determine summary measures of multiple HSUVs reported in the literature for patients with osteoporosis and osteoporotic fractures. We performed a systematic review, meta-analysis and meta-regression of published literature that reported HSUVs for osteoporotic fracture-related conditions. There were 62 studies representing 142,477 patients included. In total, 362 HSUVs were identified: 106 for pre-fracture; 89 for post-hip fracture; 130 for post-vertebral fracture and 37 for post-wrist fracture. The pooled HSUVs, using a random-effects model were 0.76 (95% CI 0.75, 0.77, I (2) = 0.99) for pre-fracture; 0.57 (95% CI 0.52, 0.63, I (2) =1) for post-hip fracture; 0.59 (95% CI 0.55, 0.62, I (2) = 0.99) for post-vertebral facture and 0.72 (95% CI 0.67, 0.78, I (2) = 1) for post-wrist fracture. Heterogeneities were addressed through meta-regression. HSUVs immediately following hip, vertebral and wrist fractures were 0.31, 0.44 and 0.61, respectively. Patients' HSUVs improved over time following fracture events: HSUVs for the first year after hip, vertebral and wrist fractures were 0.59, 0.55 and 0.78, respectively; and 0.66, 0.66 and 0.81 for subsequent years. Fractures were associated with significant decrements in HSUVs. This study provides a standard set of HSUVs that can be used in health economic assessments in osteoporosis.

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.

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