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Biomedical subjects

M B Delatycki

Publications and source records attributed to M B Delatycki.

At least 19 recordsLinked to original sources
PubMed2006

How is disease progress in Friedreich's ataxia best measured? A study of four rating scales.

BACKGROUND: Friedreich's ataxia (FRDA), the most common genetic cause of ataxia, is characterised by progressive neurodegeneration and cardiomyopathy. Initial treatments are likely to slow progression rather than reverse morbidity. An appropriate and sensitive scale to measure disease progress is critical to detect the benefit of treatments. OBJECTIVE: To compare the Friedreich Ataxia Rating Scale (FARS) with other scales proposed as outcome measures for FRDA. METHODS: 76 participants were assessed with the FARS and the International Cooperative Ataxia Rating Scale (ICARS) and 72 of these participants were also assessed with the Functional Independence Measure and the Modified Barthel Index. 43 participants had repeat measures at an interval of 12 months. Sensitivity and responsiveness were assessed using the effect size for each measure and the sample size required for a placebo-controlled clinical trial. RESULTS: The FARS showed a high correlation with the other three measures. A significant change in the score over 12 months was detected by the FARS, the International Cooperative Ataxia Rating Scale and the Functional Independence Measure. The FARS had the greatest effect size and requires fewer patients for an equivalently powered study. CONCLUSIONS: Of the scales assessed, the FARS is the best to use in clinical trials of FRDA. This is based on effect size, and power calculations that show that fewer participants are required to demonstrate the same effect of an intervention. Further work is required to develop more sensitive and responsive instruments.

Activities of Daily Living↗
PubMed2006

Predictive genetic testing in young people for adult-onset conditions: where is the empirical evidence?

Predictive genetic testing in young people for severe, adult-onset conditions is advised against in current guidelines. Despite this, there has been considerable debate regarding the issue. Some perceive such testing as too potentially harmful to allow. Others perceive it as an opportunity for the promotion of benefit, an opportunity even for the prevention of harm. The only way to resolve this theoretical debate is to collect empirical data related to the effects of such testing when it occurs. However, more than 15 years after the debate began, there is virtually no such empirical evidence available. The reasons for this lack of evidence appear to relate to the rarity of such testing, which when it occurs is not studied systematically. Additionally, clinicians performing such tests may feel vulnerable in sharing the outcomes, given that such testing is contrary to current recommendations. We propose a way forward that entails the provision of tests to mature minors, where clinicians deem this appropriate. These tests should be performed as part of an international research collaboration, facilitated by one leading group.

Adolescent↗
PubMed2006

Educational outcomes of a workplace screening program for genetic susceptibility to hemochromatosis.

Education is an essential component of a genetic screening program. Knowledge outcomes were measured after large-scale workplace education and screening for genetic susceptibility to hereditary hemochromatosis. The aim was to assess knowledge of concepts presented, impact of mode of delivery, and knowledge retention. Education in a group setting was delivered via oral or video presentation and knowledge assessed using self-administered questionnaires at baseline, 1 month, and 12 months. Over 60% of 11 679 participants correctly answered all questions at baseline, scoring higher with clinical concepts (disease etiology and treatment) than genetic concepts (penetrance and genetic heterogeneity). Revising the education program significantly increased correct responses for etiology (p < 0.002), whilst modifying the knowledge assessment tool significantly increased correct responses for etiology (p < 0.001) and gene penetrance (p < 0.001). For three of the four concepts assessed, use of video was as effective as oral presentation for knowledge outcomes. A significantly higher proportion of those at increased risk of disease (n = 44) responded correctly at 12 months than did controls (n = 82; p = 0.011 for etiology, p = 0.002 for treatment and p = 0.003 for penetrance). Hence, genetic screening can be successfully offered in a group workplace setting, with participants remembering clinical concepts better than genetic concepts up to 1 year later.

Female↗
PubMed2005

Genetic susceptibility screening in schools: attitudes of the school community towards hereditary haemochromatosis.

Carrier screening to provide reproductive options has been offered to students in the school setting for a number of years; however, genetic susceptibility screening for disease predisposition has not been introduced to the school community. Experience has shown that the success of a population-based programme relies on the community's acceptance. Therefore, we sought to establish the Australian secondary school community's attitudes towards genetic susceptibility screening in schools, with hereditary haemochromatosis as the model condition with an available prevention. School students, aged 15-18 (n = 748), completed a questionnaire immediately before and following an oral educational presentation. Their parents (n = 179) and staff (n = 89) received written information and returned a questionnaire by post. Semi-structured interviews were with Government representatives. Attitudes towards genetic screening in schools and knowledge of genetic and clinical features of haemochromatosis, as well as the likelihood of accepting a genetic susceptibility test for haemochromatosis, were all measured. Participants were positive about genetic screening for disease susceptibility in schools. Their knowledge was high following education with no significant differences between participants of each group. Sixty-eight percent of students would be likely to have the test if it were offered, with parents and staff, indicating that they would like the students to be offered a test, on average. Genetic susceptibility screening in schools is a novel concept. The results of our study indicate that it could be a public health success with the support of the community.

Adolescent↗
PubMed2005

Sleep disturbance in Sanfilippo syndrome: a parental questionnaire study.

AIMS: To determine the incidence, manifestations, and best management of sleep disturbance in Sanfilippo syndrome (mucopolysaccharidosis (MPS) type III). METHODS: Families were ascertained through the MPS societies of Australasia, the UK, and the USA. Questionnaires were sent by mail and were answered anonymously. Identical questions regarding sleep disturbance were asked about unaffected siblings to provide control data. Sleep disturbance was quantified by a total sleep disturbance score. RESULTS: A total of 141 responses were received; 91.5% of children with Sanfilippo syndrome had sleep disturbance and this was significantly higher than for their unaffected sibs; 77.5% of parents had used medication for this problem, with melatonin and antihistamines being most commonly used. Melatonin and benzodiazepines were reported as the most efficacious. Many different environmental modifications had been employed for this problem and some parents reported success with behavioural therapies. CONCLUSIONS: Sleep disturbance is common, severe, and difficult to manage in Sanfilippo syndrome. Based on the parental responses and its safety profile, melatonin is the first line drug that should be tried. Behavioural therapy should be tried in all with Sanfilippo syndrome and sleep disturbance.

Adolescent↗
PubMed2005

Ethical considerations in presymptomatic testing for variant CJD.

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal, transmissible, neurodegenerative disorder for which there is currently no effective treatment. vCJD arose from the zoonotic spread of bovine spongiform encephalopathy. There is now compelling evidence for human to human transmission through blood transfusions from presymptomatic carriers and experts are warning that the real epidemic may be yet to come. Imperatives exist for the development of reliable, non-invasive presymptomatic diagnostic tests. Research into such tests is well advanced. In this article the ethical implications of the availability of these tests are elaborated and comparisons drawn with predictive genetic testing for Huntington's disease and screening for HIV. Paramount to considerations is the issue of whom to test, weighing up respect for personal autonomy against obligations to benefit and protect society. A paradigm is proposed similar to that used for HIV screening but with unique features: compulsory testing of all blood/organ donors and individuals undergoing surgery or invasive procedures who have a significant risk of disease transmission.

Animals↗
PubMed2004

Growth, behavior, and clinical findings in 27 patients with Kabuki (Niikawa-Kuroki) syndrome.

This study was undertaken to document the phenotype of Kabuki (Niikawa-Kuroki) syndrome in patients from Australia and New Zealand, with particular emphasis on growth patterns, behavior, and relationship between head circumference and intellectual level. Data on 27 children and adults with Kabuki (Niikawa-Kuroki) syndrome from Australia and New Zealand were collected by questionnaire and clinical assessment. The patients ranged in age from 7 months to 36 years with a mean age of 7 years and 2 months. The mean age at diagnosis was 3(5/6) years, but in most cases, the facial phenotype was evident from infancy. The minimum birth prevalence was calculated at 1 in 86,000. Three of our patients died. Parents reported a behavior phenotype characterized by an excellent long-term memory and avoidance of eye contact. No correlation was found between head circumference and severity of intellectual disability. Eight of 14 patients over the age of 5 years were overweight or obese. Six of these eight patients had failure to thrive in infancy. One patient developed insulin-dependent diabetes mellitus in adolescence. Some individuals with Kabuki (Niikawa-Kuroki) syndrome show a characteristic growth profile with failure to thrive in infancy progressing to obesity or overweight in middle childhood or adolescence. A behavior phenotype was noted which requires further investigation. Head size is not a predictor of degree of intellectual disability.

Abnormalities, Multiple↗
PubMed2004

A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis.

Juvenile hemochromatosis (JH) is an autosomal recessive condition that leads to significant morbidity due to early onset systemic iron overload. The majority of families with JH link to chromosome 1q and were recently found to have mutations in the HFE2 gene encoding hemojuvelin; however, several JH families have been reported to have mutations in the HAMP gene encoding hepcidin. Here, we report a multiply consanguineous family with a father and daughter showing iron overload consistent with JH. Sequence analysis of HAMP revealed homozygosity for amino acid substitution C78T due to a c.233G > A mutation. This mutation disrupts one of eight highly conserved cysteines that are believed to be critical for the function of the active enzyme. This finding adds support to the importance of the role of these conserved cysteines in the activity of hepcidin.

Adult↗
PubMed2004

Implementation of HaemScreen, a workplace-based genetic screening program for hemochromatosis.

There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace.

Adolescent↗
PubMed2003

Evaluation of a Tay-Sachs disease screening program.

Tay-Sachs Disease (TSD) is an autosomal recessive neurodegenerative disorder. TSD is prevalent in the Ashkenazi Jewish population, and carrier screening programs have been implemented worldwide in these communities. A screening program initiated in 1997 involving the Melbourne Jewish community (Australia) incorporated education, counselling and carrier testing of high-school students aged 15 to 18 years. This study aimed to assess the participation rates, level of knowledge obtained and predicted feelings and attitudes of the students involved. Seven hundred and ten students participated, there was a 67% uptake for testing with a carrier rate of 1 in 28 determined. The level of knowledge of the students following education was high and of relative importance in regard to decision making, as were their feelings and attitudes about genetic testing for carrier status. A significant impediment to test uptake was the need for blood sampling, resulting in a recommendation for the introduction of DNA analysis on cheek brush samples. The evaluation of this program has given a wider scope for further development as well as providing valuable information for the implementation of community screening programs.

Adolescent↗