1,802 research outputs found

    Longitudinal associations between stroke and psychosis: a population-based study

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    BACKGROUND: The co-occurrence of stroke and psychosis is a serious neuropsychiatric condition but little is known about the course of this comorbidity. We aimed to estimate longitudinal associations between stroke and psychosis over 10 years. METHODS: A 10-year population-based study using data from the English Longitudinal Study of Ageing. A structured health assessment recorded (i) first-occurrence stroke and (ii) psychosis, at each wave. Each were considered exposures and outcomes in separate analyses. Logistic and Cox proportional hazards regression and Kaplan-Meier methods were used. Models were adjusted for demographic and health behaviour covariates, with missing covariates imputed using random forest multiple imputation. RESULTS: Of 19 808 participants, 24 reported both stroke and psychosis (median Wave 1 age 63, 71% female, 50% lowest quintile of net financial wealth) at any point during follow-up. By 10 years, the probability of an incident first stroke in participants with psychosis was 21.4% [95% confidence interval (CI) 12.1-29.6] compared to 8.3% (95% CI 7.8-8.8) in those without psychosis (absolute difference: 13.1%; 95% CI 20.8-4.3, log rank p < 0.001; fully-adjusted hazard ratio (HR): 3.57; 95% CI 2.18-5.84). The probability of reporting incident psychosis in participants with stroke was 2.3% (95% CI 1.4-3.2) compared to 0.9% (95% CI 0.7-1.1) in those without (absolute difference: 1.4%; 95% CI 0.7-2.1, log rank p < 0.001; fully-adjusted HR: 4.98; 95% CI 2.55-9.72). CONCLUSIONS: Stroke is an independent predictor of psychosis (and vice versa), after adjustment for potential confounders

    Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles

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    HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C. A minority of positions have an incidence >1% for the 'second' most frequent nucleotide, comprising 70 positions in HLA-A, 85 in HLA-B and 54 in HLA-C. The majority of these positions have three or four alternative nucleotides. These positions were subject to positive selection and correspond to binding sites for peptides and receptors. Most alleles of HLA class I (>80%) are very rare, often identified in one person or family, and they differ by point mutation from older, more common alleles. These alleles with single nucleotide polymorphisms reflect the germ-line mutation rate. Their frequency predicts the human population harbors 8-9 million HLA class I variants. The common alleles of human populations comprise 42 core alleles, which represent all selected polymorphism, and recombinants that have assorted this polymorphism

    Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

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    Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome
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