Lack of association between PRNP 1368 polymorphism and Alzheimer's disease or vascular dementia

<p>Abstract</p> <p>Background</p> <p>Polymorphisms of the prion protein gene (<it>PRNP</it>) at codons 129 and 219 play an important role in the susceptibility to Creutzfeldt-Jakob disease (CJD), and might be associated with other neurodegenerative disorders. Several recent reports indicate that polymorphisms outside the coding region of <it>PRNP </it>modulate the expression of prion protein and are associated with sporadic CJD, although other studies failed to show an association. These reports involved the polymorphism <it>PRNP </it>1368 which is located upstream from <it>PRNP </it>exon 1. In a case-controlled protocol, we assessed the possible association between the <it>PRNP </it>1368 polymorphism and either Alzheimer's disease (AD) or vascular dementia (VaD).</p> <p>Methods</p> <p>To investigate whether the <it>PRNP </it>1368 polymorphism is associated with the occurrence of AD or VaD in the Korean population, we compared the genotype, allele, and haplotype frequencies of the <it>PRNP </it>1368 polymorphism in 152 AD patients and 192 VaD patients with frequencies in 268 healthy Koreans.</p> <p>Results and conclusion</p> <p>Significant differences in genotype, allele and haplotype frequencies of <it>PRNP </it>1368 polymorphism were not observed between AD and normal controls. There were no significant differences in the genotype and allele frequencies of the <it>PRNP </it>1368 polymorphism between Korean VaD patients and normal controls. However, in the haplotype analysis, haplotype Ht5 was significantly over-represented in Korean VaD patients. This was the first genetic association study of a polymorphism outside the coding region of <it>PRNP </it>in relation to AD and VaD.</p

Retaining women in a prenatal care randomized controlled trial in Canada: implications for program planning

<p>Abstract</p> <p>Background:</p> <p>Challenges to retention in prenatal care seem to exist under both universal systems of care, as in Canada, and non-universal systems of care, as in the United States. However, among populations being served by a system of publicly funded health care, the barriers are less well understood and universal uptake of prenatal services has not been realized. Determining the characteristics of women who dropped out of a prenatal care randomized controlled trial can help identify those who may need alternate retention and service approaches.</p> <p>Methods:</p> <p>In this study, pregnant women were randomized to: a) current standard of care; b) 'a' plus nursing support; or c) 'b' plus a paraprofessional home visitor. 16% of 2,015 women did not complete all three telephone interviews (197 dropped out and 124 became unreachable). Responders were compared to non-responders on demographics, lifestyle, psychosocial factors, and life events using chi-squared tests. Logistic regression models were constructed using stepwise logistic regression to determine the probability of not completing the prenatal program.</p> <p>Results:</p> <p>Completion rates did not differ by intervention. In comparison to responders, non-responders were more likely to be younger, less educated, have lower incomes, smoke, have low social support, have a history of depression, and have separated or divorced parents (all p < 0.05). Unreachable women were more likely to be single, use drugs, report distress and adverse life events (all p < 0.05). Non-Caucasian women were more likely to drop out (p = 0.002). Logistic regression modeling indicated that independent key risk factors for dropping out were: less than high school education, separated or divorced parents, lower social support, and being non-Caucasian. Pregnant women who were single/separated/divorced, less than 25 years old, had less than high school education, earned less than $40,000 in annual household income, and/or smoked had greater odds of becoming unreachable at some point during pregnancy and not completing the study.</p> <p>Conclusion:</p> <p>Women at risk due to lifestyle and challenging circumstances were difficult to retain in a prenatal care study, regardless of the intervention. For women with complex health, lifestyle and social issues, lack of retention may reflect incongruence between their needs and the program.</p> <p>Trial registration:</p> <p>Current Controlled Trials ISRCTN64070727</p

Brain Research to Ameliorate Impaired Neurodevelopment - Home-based Intervention Trial (BRAIN-HIT)

<p>Abstract</p> <p>Background</p> <p>This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia.</p> <p>Methods/Design</p> <p>This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors.</p> <p>Discussion</p> <p>The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00639184</p