Economic evaluation of cystic fibrosis screening: A Review of the literature, CHERE Working Paper 2006/6

Objectives: To critically examine the economic evidence on Cystic Fibrosis (CF) screening and to understand issues relating to the transferability of findings to the Australian context for policy decisions. Methods: A systematic literature search identified 25 economic studies with empirical results on CF published between 1990 and 2005. These articles were then assessed against international benchmarks on conducting and reporting of economic evaluations, focusing on the transferability of the evidence to the local setting. Results: Six studies described only costs, 12 were cost-effectiveness studies, 6 were cost-benefit studies and one had a combined design (cost utility, cost benefit and cost effectiveness). Most of the cost-effectiveness studies compared screening versus ?no-screening? but the screening programs under consideration differed markedly. Four considered neonatal screening, three prenatal screening, three pre-conception and carrier screening, and one considered all types of screening programs. The outcome measures also varied considerably between studies. One study included a quality adjusted life year measure. Cost?benefit measures mostly included economic savings ? evaded lifetime medical costs of avoiding CF child birth. Conclusion: The variability in study design, model inputs and reporting of economic evaluations of CF carrier screening raises issues on the applicability and transferability of such evidence to the Australian context.Cystic fibrosis, economic evaluation

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Offering fragile X syndrome carrier screening: a prospective mixed-methods observational study comparing carrier screening of pregnant and non-pregnant women in the general population

Article focus▪ This article is a protocol of a study that involves&nbsp;offering fragile X syndrome carrier screening to&nbsp;pregnant and non-pregnant women in the&nbsp;general population. We are undertaking a programme&nbsp;evaluation approach using mixed&nbsp;methods to collect data about informed decisionmaking&nbsp;and predictors of test uptake, with a&nbsp;focus on psychosocial measures. We are also&nbsp;undertaking an economic appraisal.Key messages▪ Carrier screening for fragile X syndrome is the&nbsp;subject of debate because of concerns around&nbsp;education and counselling for this complex conditionand the potential for psychosocial harms. ▪ This study will inform policy and practice in the&nbsp;area of population carrier screening by examining&nbsp;psychosocial aspects of screening, including&nbsp;informed decision-making; models of screening,&nbsp;through antenatal care or other access points&nbsp;and health economics of carrier screening for&nbsp;fragile X syndrome.Strengths and limitations of this study▪ This study seeks to recruit 1000 women in total.&nbsp;This large sample size will give us sufficient&nbsp;power to address the aims of the study.▪ Collecting quantitative and qualitative data will&nbsp;provide a more in-depth picture of screening for&nbsp;fragile X syndrome.▪ A limitation of the study is that the data on&nbsp;models of screening may not be applicable to&nbsp;other countries that have different healthcare&nbsp;systems.</div

Вирішення проблеми поводження з твердими побутовими відходами на території м. Павлоград

В Україні практично відсутня система переробки твердих побутових відходів (ТПВ). Більша кількість ТПВ вивозиться на сміттєві звалища, які не відповідають європейським стандартам. Звалища ТПВ є джерелом утворення значної кількості токсичних фільтратів і газів, що негативно впливає на комфортність проживання населення. Тому виникає необхідність в оцінці рівнів забруднення прилеглих територій та рівня екологічної небезпеки звалищ ТПВ для довкілля та здоров’я місцевих мешканців. Таку оцінку доцільно проводити за допомогою методів фітоіндикації

Views of reproductive genetic carrier screening participants regarding screening for genes associated with non-syndromic hearing loss.

OBJECTIVE: Reproductive genetic carrier screening (RGCS) panels often include genes associated with non-syndromic hearing loss (NSHL) despite a lack of evidence of acceptability. Although some couples take steps to avoid having a child who is deaf, there are effective interventions for children who are deaf. There is no consensus whether deafness is considered a disabling condition. METHOD: This study explored views of people who had RGCS, without genes for NSHL, about this topic. Online surveys were sent to 2186 people who had a low chance RGCS result and 655 completed the survey (participation rate 30%). RESULTS: Sixty-three percent (N = 412) think deafness is a serious health condition. The majority agreed (60%, N = 391) that with support (i.e. hearing aids/cochlear implants) deafness is a minor condition in children. Most (84%, N = 545) agreed genes for NSHL should be included in RGCS. Thirty-five percent (N = 231) indicated they would make different reproductive decisions if they had an increased chance of having a child born deaf; 31% would not change their reproductive plans and 34% were unsure what they would do. CONCLUSION: While the majority support inclusion of genes associated with NSHL in RGCS, there was uncertainty about the severity of deafness as a health condition and there was no consensus on whether it is a health condition that warrants changing reproductive decisions

Targeting lipid peroxidation and mitochondrial imbalance in Friedreich's ataxia

Friedreich's ataxia (FRDA) is an autosomal recessive disorder, caused by reduced levels of the protein frataxin. This protein is located in the mitochondria, where it functions in the biogenesis of iron-sulphur clusters (ISCs), which are important for the function of the mitochondrial respiratory chain complexes. Moreover, disruption in iron biogenesis may lead to oxidative stress. Oxidative stress can be the cause and/or the consequence of mitochondrial energy imbalance, leading to cell death. Fibroblasts from two FRDA mouse models, YG8R and KIKO, were used to analyse two different categories of protective compounds: deuterised poly-unsaturated fatty acids (dPUFAs) and Nrf2-inducers. The former have been shown to protect the cell from damage induced by lipid peroxidation and the latter trigger the well-known Nrf2 antioxidant pathway. Our results show that the sensitivity to oxidative stress of YG8R and KIKO mouse fibroblasts, resulting in cell death and lipid peroxidation, can be prevented by d4-PUFA and Nrf2-inducers (SFN and TBE-31). The mitochondrial membrane potential (ΔΨm) of YG8R and KIKO fibroblasts revealed a difference in their mitochondrial pathophysiology, which may be due to the different genetic basis of the two models. This suggests that variable levels of reduced frataxin may act differently on mitochondrial pathophysiology and that these two cell models could be useful in recapitulating the observed differences in the FRDA phenotype. This may reflect a different modulatory effect towards cell death that will need to be investigated further.RA is supported by FARA and GoFar, A&C Simeone Foundation.PG has received funding from FARA and GoFar, A&C Simeone Foundation and the European Union Seventh Framework Programme(FP7/2007-2013) under grant agreement number 242193/EFACTS.PG is supported by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre. EU and IR were supported by MSc scholarships

Genetics, Insurance and Professional Practice: Survey of the Australasian Clinical Genetics Workforce

In Australia and New Zealand, by contrast with much of the developed world, insurance companies can use genetic test results to refuse cover or increase premiums for mutually-rated insurance products, including life, income protection and disability insurance. Genetics professionals regularly discuss insurance implications with clients and report the issue as a clinical challenge, yet no studies have examined clinical practices or opinions. This study surveyed genetic counsellors and clinical geneticists from Australia and New Zealand to (i) investigate variability in professional practice across the Australasian clinical genetic workforce relating to the insurance implications of genetic testing, and (ii) ascertain views regarding current regulation of the issue. There was considerable variability in training and clinical policies, especially around the communication of insurance implications. Almost half of participants reported receiving no training on the insurance implications of genetic testing, and almost 40% were unsure whether they could adequately advise clients. A number of deficits in professional knowledge and understanding of the issue were identified. Widespread concerns regarding regulation of this area were reported, with &lt; 10% of Australian participants considering current Australian regulations as adequate to protect clients from genetic discrimination. The findings from this study highlight scope for greater education, consistency and professional training on the issue of genetics and insurance in Australasia, and strong agreement about the need for regulatory reform

Should genes for non-syndromic hearing loss be included in reproductive genetic carrier screening: Views of people with a personal or family experience of deafness.

Many commercial reproductive genetic carrier screening (RGCS) panels include genes associated with non-syndromic hearing loss (NSHL), however little is known about the general acceptability of their inclusion. Although some couples wish to avoid having a deaf child, there are effective interventions and supports available for deafness, and no consensus on whether it is appropriate to reproductively screen NSHL genes. This study explored views of people with personal experience of deafness regarding carrier screening for genes associated with NSHL. We interviewed 27 participants; 14 who identified as deaf and 13 hearing parents of a deaf child. Thematic analysis was undertaken on transcripts of interviews. The findings reveal the complexity of attitudes within these groups. Some vacillated between the wish to support prospective parents' reproductive autonomy and concerns about potential harms, especially the expression of negative messages about deafness and the potential loss of acceptance in society. While some participants felt carrier screening could help prospective parents to prepare for a deaf child, there was little support for reproductive screening and termination of pregnancy. Participants emphasized the need for accurate information about the lived experience of deafness. The majority felt deafness is not as severe as other conditions included in RGCS, and most do not consider deafness as a disability. People with personal experience of deafness have diverse attitudes towards RGCS for deafness informed by their own identify and experience, and many have concerns about how it should be discussed and implemented in a population wide RGCS program

Views of healthcare professionals on the inclusion of genes associated with non-syndromic hearing loss in reproductive genetic carrier screening.

Genes associated with non-syndromic hearing loss (NSHL) are frequently included in panels for reproductive genetic carrier screening (RGCS), despite a lack of consensus on whether NSHL is a condition appropriate for inclusion in RGCS. We conducted a national online survey using a questionnaire to explore the views of clinicians who facilitate RGCS or provide care to deaf individuals in Australia and New Zealand regarding the inclusion of such genes in RGCS. Results were analysed descriptively, and free-text responses were analysed thematically. The questionnaire was completed by 386 respondents including genetic healthcare providers, obstetricians, ear nose and throat specialists, and general practitioners. The majority of respondents agreed that genes associated with NSHL should be included in RGCS, but there were differences between the groups. 74% of clinicians working in a hearing clinic agreed these genes should be included compared to 67% of genetic healthcare providers, 54% of reproductive care healthcare providers, and 44% of general practitioners. A majority of respondents agreed that moderate to profound deafness is a serious disability, although genetic healthcare providers were less likely to agree than other groups. Overall, respondents agreed that including NSHL in RGCS upholds prospective parents' right to information. However, they also identified major challenges, including concern that screening may express a discriminatory attitude towards those living with deafness. They also identified the complexity of defining the severity of deafness