Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

The influence of perfusion solution on renal graft viability assessment

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall’s hypertonic citrate (HOC) and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard

Wake up, wake up! It's me! It's my life! patient narratives on person-centeredness in the integrated care context: a qualitative study

Person-centered care emphasizes a holistic, humanistic approach that puts patients first, at the center of medical care. Person-centeredness is also considered a core element of integrated care. Yet typologies of integrated care mainly describe how patients fit within integrated services, rather than how services fit into the patient's world. Patient-centeredness has been commonly defined through physician's behaviors aimed at delivering patient-centered care. Yet, it is unclear how 'person-centeredness' is realized in integrated care through the patient voice. We aimed to explore patient narratives of person-centeredness in the integrated care context

The side effect profile of Clozapine in real world data of three large mental health hospitals

Objective: Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. Material and methods: We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Results: Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. Conclusion: A better understanding of how drugs work in the real world can complement clinical trials

Effect of Peierls transition in armchair carbon nanotube on dynamical behaviour of encapsulated fullerene

The changes of dynamical behaviour of a single fullerene molecule inside an armchair carbon nanotube caused by the structural Peierls transition in the nanotube are considered. The structures of the smallest C20 and Fe@C20 fullerenes are computed using the spin-polarized density functional theory. Significant changes of the barriers for motion along the nanotube axis and rotation of these fullerenes inside the (8,8) nanotube are found at the Peierls transition. It is shown that the coefficients of translational and rotational diffusions of these fullerenes inside the nanotube change by several orders of magnitude. The possibility of inverse orientational melting, i.e. with a decrease of temperature, for the systems under consideration is predicted.Comment: 9 pages, 6 figures, 1 tabl

Uterine Fibroid Embolisation for Symptomatic Uterine Fibroids: A Survey of Clinical Practice in Europe

Item does not contain fulltextPURPOSE: To assess current uterine fibroid embolisation (UFE) practice in European countries and determine the clinical environment for UFE in different hospitals. MATERIAL AND METHODS: In May 2009, an invitation for an online survey was sent by e-mail to all members of the Cardiovascular and Interventional Radiologic Society of Europe, representing a total number of 1,250 different candidate European treatment centres. The survey covered 21 questions concerning local UFE practice. RESULTS: A total of 282 respondents completed the questionnaire. Fifteen questionnaires were excluded because they were doubles from centres that had already returned a questionnaire. The response rate was 267 of 1,250 centres (21.4%). Ninety-four respondents (33%) did not perform UFE and were excluded, and six centres were excluded because demographic data were missing. The remaining 167 respondents from different UFE centres were included in the study. Twenty-six percent of the respondents were from the United Kingdom (n = 43); 16% were from Germany (n = 27); 11% were from France (n = 18); and the remaining 47% (n = 79) were from other European countries. Most centres (48%, n = 80) had 5 to 10 years experience with UFE and performed 10 to 50 procedures annually (53% [n = 88]) of respondents). Additional demographic data, as well as specific data on referral of patients, UFE techniques used, and periprocedural and postprocedural, care will be provided. CONCLUSION: Although UFE as an alternative treatment for hysterectomy or myomectomy is widespread in Europe, its impact on the management of the patient with symptomatic fibroids seems, according to the overall numbers of UFE procedures, somewhat disappointing. Multiple factors might be responsible for this observation

An Early Cambrian Rift to Post-Rift Transition in the Cordillera of Western North America

The upper Proterozoic and lower Palaeozoic wedge of miogeoclinal strata in the North American Cordillera is widely regarded as evidence for a proto-Pacific passive margin. The rifting history of this margin appears to have been protracted, possibly spanning more than 200 Myr in a tectonic setting that is not well understood. Quantitative subsidence analyses of lower Palaeozoic strata between British Columbia and Utah, however, provide indirect evidence that the transition from rifting to post-rift cooling occurred within a relatively short interval of time, although probably not synchronously, between 600 and 555 Myr. This age is significantly younger than that implied in previous studies. We describe here new field data, which, together with published geological data, provide direct evidence of a latest Proterozoic or early Cambrian age for the rift to post-rift transition. The data support recent arguments for widespread initiation of passive margins around the edge of the North American craton close to the Cambrian-Precambrian boundary