Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
  • Time Trends in Atrial Fibrillation-Associated Stroke and Premorbid Anticoagulation.

    7 January 2019

    Background and Purpose- Prevalence of atrial fibrillation (AF) is increasing, but the impact on overall burden of stroke is uncertain, as is the proportion that could be attributed to under anticoagulation. We did a population-based study of AF-associated stroke and a systematic review of time trends in other stroke incidence studies and of rates of premorbid anticoagulation. Methods- The proportion of incident strokes with associated AF was determined in the OXVASC (Oxford Vascular Study; 2002-2017) and in other prospective, population-based stroke incidence studies published before December 2017. Proportions were pooled by Mantel Haenszel methods, and the pooled percentage of cases with premorbid anticoagulation was determined. Analyses were stratified by the age of study population, mid-study year, country, and ethnicity. Results- Of 1928 patients with incident ischemic stroke in OXVASC, 629 (32.6%; 95% CI, 30.5-34.7) were AF associated, consistent with the pooled estimate from 4 smaller studies over the same study period (608/1948; 31.2%, 30.0-32.4; Phet=0.80). The pooled estimate from all studies reporting premorbid AF over 25 million person-years of observation (1960 onwards; 33 reports) was lower (18.6%, 16.8-20.3) and more heterogeneous ( Phet<0.0001), but 62% of heterogeneity was explained by the age of study population, study period, country, and ethnicity. The proportion of incident strokes on premorbid anticoagulation increased over time, both for ischemic stroke in OXVASC (2002-2007: 15.1%, 2008-2012: 19.6%, and 2013-2017: 35.9%; Ptrend<0.0001), and across all studies ( P=0.002), but the pooled estimates suggested substantial undertreatment even in the most recent periods (2001-2015: 25.7%, 21.1-30.3 and ≥2010: 31.6%, 18.2-44.9). Conclusions- About 1 in 3 incident ischemic strokes are still AF associated, due partly to low rates of anticoagulation for known prior AF, which therefore represents a major public health opportunity to reduce the burden of stroke.

  • Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference

    4 December 2018

    <jats:p>White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27x10-5, which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature.</jats:p>

  • Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative clues for subtyping schizophrenia patients.

    10 December 2018

    Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene-expression, grey matter volume (GMV) and the Positive and Negative Syndrome Scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal regions. The patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for schizophrenia. Our results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease phenotypes. The method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.

  • Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial.

    10 December 2018

    BACKGROUND: Infant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain. METHODS: In this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34-42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile-Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25). FINDINGS: Between Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI -2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40-1·56) with morphine and 0·75 (0·33-1·22) with placebo (median difference 0·25, 95% CI -0·16 to 0·80; p=0·25). INTERPRETATION: Administration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants. FUNDING: Wellcome Trust and National Institute for Health Research.

  • What Is a Cognitive Map? Organizing Knowledge for Flexible Behavior.

    22 November 2018

    It is proposed that a cognitive map encoding the relationships between entities in the world supports flexible behavior, but the majority of the neural evidence for such a system comes from studies of spatial navigation. Recent work describing neuronal parallels between spatial and non-spatial behaviors has rekindled the notion of a systematic organization of knowledge across multiple domains. We review experimental evidence and theoretical frameworks that point to principles unifying these apparently disparate functions. These principles describe how to learn and use abstract, generalizable knowledge and suggest that map-like representations observed in a spatial context may be an instance of general coding mechanisms capable of organizing knowledge of all kinds. We highlight how artificial agents endowed with such principles exhibit flexible behavior and learn map-like representations observed in the brain. Finally, we speculate on how these principles may offer insight into the extreme generalizations, abstractions, and inferences that characterize human cognition.