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  • 2019
  • Tidskriftsartikel (refereegranskat)
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5.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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6.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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7.
  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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8.
  • Huyghe, Jeroen R., et al. (författare)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Tidskriftsartikel (refereegranskat)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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9.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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10.
  • Schmit, Stephanie L, et al. (författare)
  • Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
  • 2019
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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11.
  • Lakens, Daniel, et al. (författare)
  • Justify your alpha
  • 2018
  • Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
  • Tidskriftsartikel (refereegranskat)abstract
    • In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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12.
  • Hunter, R. M., et al. (författare)
  • The health, education, and social care costs of school-aged children with active epilepsy: A population-based study
  • 2015
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 56:7, s. 1056-1064
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo provide data on the health, social care, and education costs of active childhood epilepsy and factors associated with these costs over an 18-month period in a population-based sample. MethodsThe Children with Epilepsy in Sussex Schools (CHESS) study is a population-based study involving school-aged children (5-15years) with active epilepsy (taking one or more antiepileptic drug and/or had a seizure in the last year) in a defined geographical area in England. Clinical data were collected on 85 children (74% of eligible population) who underwent comprehensive psychological assessment. Health, education, and social care resource use was collected retrospectively over an 18-month period. Regression analysis was used to identify variables associated these with costs. ResultsThe mean (standard deviation) 18-month cost of health care for a child with active epilepsy was 3,635 (5,339) pound, with mean education and social care cost of 11,552 pound (8,937) pound and 1,742 pound (8,158) pound, respectively, resulting in total mean costs per participant of 16,931 pound (14,764) pound. Health care costs were significantly associated with seizure frequency and etiology (all p-values<0.05). Combined health care, social care, and education costs were significantly related to cognitive impairment (intelligence quotient [IQ] <85) and seizure frequency (p<0.05). The mean cost of health care, social care, and education over 18months for participants with cognitive impairment was 23,579 pound (95% confidence interval [CI] 16,489- pound 30,670) pound compared to 7,785 pound (95% CI 4,943- pound 10,627) pound for those without impairment. SignificanceActive childhood epilepsy has significant health, social care, and education costs. This is the first study to comprehensively document the economic impact on these sectors as well as factors associated with these costs. When caring for children with epilepsy in England, costs incurred by education and social care sectors are approximately four times the costs incurred by the health care sector. Increased costs were associated with cognitive impairment (IQ <85) and weekly or greater seizure frequency.
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13.
  • Martinos, M. M., et al. (författare)
  • Long-term behavioural outcomes after paediatric convulsive status epilepticus: a population-based cohort study
  • 2018
  • Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 60:4, s. 409-416
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To describe behavioural and psychiatric outcomes of children within 10 years of convulsive status epilepticus (CSE). Method: Children originally identified by the population-based North London Convulsive Status Epilepticus in Childhood Surveillance Study were followed-up between July 2009 and February 2013. They were grouped into epilepsy- and non-epilepsy-related CSE, and compared with population norms and healthy controls using the Strengths and Difficulties Questionnaire; the Autism Spectrum Screening Questionnaire; and the Swanson, Nolan, and Pelham questionnaire. Children who scored above recommended clinical cut-offs on any scale were invited for a neuropsychiatric assessment. Regression models were fitted to identify clinically relevant covariates associated with behavioural outcomes. Results: At a mean follow-up of 8.1 years post-CSE, 28% of enrolled children were found to have a psychiatric disorder. Children with epilepsy-related CSE scored higher than norms on all scales and children with non-epilepsy-related CSE scored higher than norms on the Strengths and Difficulties Questionnaire and the Autism Spectrum Screening Questionnaire. Presence of seizures at baseline and recurrence of CSE was associated with worse outcomes in the group with epilepsy. Intellectual abilities were associated with behavioural outcomes in all participants. Interpretation: A large proportion of children manifest behavioural issues 8 years after CSE. The present data highlight the need for behavioural screening in children with neurodevelopmental impairments post-CSE. What this paper adds: Eight years post convulsive status epilepticus (CSE), 37% of parents report behavioural issues. Of enrolled children, 28% were found to have a Diagnostic and Statistical Manual mental disorder. Intellectual abilities are strongly associated with behavioural outcomes in children post-CSE. © 2017 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.
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14.
  • Moshontz, Hannah, et al. (författare)
  • The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
  • 2018
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
  • Tidskriftsartikel (refereegranskat)abstract
    • Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
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15.
  • Pujar, S. S., et al. (författare)
  • Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study
  • 2018
  • Ingår i: Lancet Child & Adolescent Health. - : Elsevier BV. - 2352-4642. ; 2:2, s. 103-111
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The prognosis of convulsive status epilepticus (CSE), a common childhood medical neurological emergency, is not well characterised. We aimed to investigate the long-term outcomes in a cohort of participants who previously had CSE. Methods In this prospective study, we followed up a population-based childhood CSE cohort from north London, UK (the north London convulsive status epilepticus surveillance study cohort; NLSTEPSS). We collected data from structured clinical neurological assessment, neurocognitive assessment (Wechsler Abbreviated Scale of Intelligence), brain MRI, medical records, and structured interviews with participants and their parents to determine neurological outcomes, with adverse outcome defined as presence of one or more of epilepsy (active or in remission), motor disability, intellectual disability, or statement of special educational needs. We applied multiple imputation to address missing data and performed binary logistic regression analyses on complete-case and imputed datasets to investigate sociodemographic and CSE factors associated with adverse outcomes. Findings Of 203 survivors (90% of inception cohort), 134 (66%) were assessed at a median follow-up of 8.9 years (IQR 8.2-9.5). The cumulative incidence of epilepsy was 24.7% (95% CI 16.2-35.6), with most (89%) emerging within 18 months after CSE. The cumulative incidence of epilepsy was lower in patients with prolonged febrile seizures (14.3%, 6.3-29.4) and survivors of acute symptomatic CSE (13.3%, 3.7-37.9) than in those of remote symptomatic CSE (45.5%, 21.3-72.0) and unclassified CSE (50.0%, 25.4-74.6). One participant (2.9%, 0.5-14.5) in the prolonged febrile seizures group developed temporal lobe epilepsy with mesial temporal sclerosis. The absence of fever at CSE was the only predictor of incident epilepsy (odds ratio [OR] 7.5, 95% CI 2.25-25.1). Motor and intellectual disability was seen predominantly in participants who had idiopathic and cryptogenic CSE (seven [36.8%, 95% CI 19.1-59.0] and 16 [84.2%, 62.4-94.5] of 19, respectively) and remote symptomatic CSE (33 [62.3%, 48.8-74.1] and 40 [75.5%, 62.4-85.1] of 53), and most of these participants had pre-existing disabilities. Pre-existing epilepsy was the only predictor of intellectual disability (OR 8.0, 95% CI 1.1-59.6). 51.5% (95% CI 43.1-59.8) of those followed up had a statement of special educational needs. Interpretation Childhood CSE is associated with substantial long-term neurological morbidity, but primarily in those who have epilepsy, neurological abnormalities, or both before the episode of CSE. Survivors without neurological abnormalities before CSE have favourable outcomes. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.
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16.
  • Reilly, Colin, 1977, et al. (författare)
  • Cognition in school-aged children with "active" epilepsy: A population-based study.
  • 2015
  • Ingår i: Journal of clinical and experimental neuropsychology. - : Informa UK Limited. - 1744-411X .- 1380-3395. ; 37:4, s. 429-438
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: There is a lack of population-based data on specific cognitive profiles in childhood epilepsy. This study sought to determine the frequency of impairments in global cognition and aspects of working memory and processing speed in a population-based sample of children with "active" epilepsy (on antiepileptic Drugs (AEDs), and/or had a seizure in the last year). Factors significantly associated with global and specific difficulties in cognition were also identified. METHOD: A total of 85 (74% of eligible population) school-aged children (5-15 years) with "active" epilepsy underwent comprehensive psychological assessment including assessment of global cognition, working memory, and processing speed. Scores on cognitive subtests were compared via paired-samples t tests. The factors associated with cognitive difficulties were analyzed via linear regression. RESULTS: A total of 24% of children were functioning below IQ 50, and 40% had IQ scores below 70. Scores on the Processing Speed Index were significantly lower than scores on the Verbal or Performance indexes on Wechsler instruments. The Coding subtest was a significant weakness compared with the other Wechsler subtests. A total of 58% of children displayed "memory underachievement" (memory score 1 SD below assessed IQ) on at least one of the four administered working memory subtests. Factors significantly associated with globally impaired cognition included being on polytherapy (β = -13.0; 95% CI [-19.3, -6.6], p = .000) and having attention-deficit/hyperactivity disorder (ADHD; β = -11.1, 95% CI [-3.0, -19.3], p = .008). Being on polytherapy was also associated with lower scores on the working memory and processing speed composite scores. Having developmental coordination disorder (DCD) was associated with a lower score on the processing speed composite. CONCLUSIONS: There is a high rate of global and specific cognitive difficulties in childhood epilepsy. Difficulties are most pronounced in aspects of working memory and processing speed. Predictors of cognitive impairment in childhood epilepsy include epilepsy-related and behavioral factors, which may differ depending on the domain of cognition assessed.
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17.
  • Reilly, Colin, 1977, et al. (författare)
  • Factors associated with quality of life in active childhood epilepsy: A population-based study.
  • 2015
  • Ingår i: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - : Elsevier BV. - 1532-2130. ; 19:3, s. 308-313
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving health-related quality of life (HRQOL), rather than just reducing seizures, should be the principal goal in comprehensive management of childhood epilepsy. There is a lack of population-based data on predictors of HRQOL in childhood epilepsy. METHODS: The Children with Epilepsy in Sussex Schools (CHESS) study is a prospective, population-based study involving school-aged children (5-15 years) with active epilepsy (on one or more AED and/or had a seizure in the last year) in a defined geographical area in the UK. Eighty-five of 115 (74% of eligible population) children underwent comprehensive psychological assessment including measures of cognition, behaviour, and motor functioning. Parents of the children completed the Quality of Life in Childhood Epilepsy (QOLCE).Clinical data on eligible children was extracted using a standardised pro forma. Linear regression analysis was undertaken to identify factors significantly associated with total Quality of Life in this population. RESULTS: Factors independently significantly associated (p < .05) with total QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85), anxiety, and parent reported school attendance difficulty. These factors were also significantly associated with total QOLCE when children with IQ < 50 were excluded from analysis. CONCLUSIONS: The majority of factors associated with parent reported HRQOL in active childhood epilepsy are related to neurobehavioural and/or psychosocial aspects of the condition.
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18.
  • Reilly, Colin, 1977, et al. (författare)
  • Features of autism spectrum disorder (ASD) in childhood epilepsy: A population-based study.
  • 2015
  • Ingår i: Epilepsy & behavior : E&B. - : Elsevier BV. - 1525-5069. ; 42C, s. 86-92
  • Tidskriftsartikel (refereegranskat)abstract
    • In a defined geographical area in the south of the UK, 115 children with active epilepsy (i.e., children who had seizures in the last year and/or children who are currently taking antiepileptic drugs (AEDs)) were identified via a computerized database and liaison with local pediatricians. Eighty-five (74%) of the children (5-15years of age) underwent a comprehensive psychological assessment. Twenty-one percent of the children met the DSM-IV-TR criteria for ASD, and 61% of them had another DSM-IV-TR behavioral or motor disorder. The Autism Spectrum Screening Questionnaire (ASSQ) was completed by parents (n=69) and by teachers (n=67) of children with an IQ>34. Only 9% of children on parent ratings and 15% of children on teacher ratings had no features of ASD. Parents reported significantly (p<.05) more features of ASD on the ASSQ compared with teachers. Factors significantly associated with responses on the ASSQ included respondent (parents reported more features), school placement (more features in specialized settings), and respondent by school placement interaction. Effective screening for ASD in children with epilepsy will need a consideration of the impact of informant and school placement on ratings. In conclusion, features of ASD were common in children with epilepsy regardless of cognitive ability. The ASSQ was a useful screening instrument in this population, and combining parent and teacher forms was optimal in terms of screening properties.
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19.
  • Reilly, Colin, 1977, et al. (författare)
  • Features of developmental coordination disorder in active childhood epilepsy: a population-based study.
  • 2015
  • Ingår i: Developmental medicine and child neurology. - : Wiley. - 1469-8749 .- 0012-1622. ; 57:9, s. 829-834
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To provide data on parent-reported features of developmental coordination disorder (DCD) and describe neurobehavioural comorbidity in children with epilepsy and DCD. METHOD: Eighty-five (74% of those eligible) children (44 males, 41 females; age range 5-15y) with active childhood epilepsy (an epileptic seizure in the last year and/or currently taking antiepileptic drugs) in a population-based cohort underwent comprehensive multidisciplinary assessment. The DCD Questionnaire (DCD-Q) was completed by parents (n=69) of children with an IQ>34, of whom 56 did not have cerebral palsy (CP), and were considered for a diagnosis of DCD. RESULTS: Of those considered for a DCD diagnosis, 16 (29%) met DSM-IV-TR criteria whereas 34 (61%) scored in the at-risk range on the DCD-Q. The sensitivity of the DCD-Q was 100% (95% CI 76-100) and specificity was 55% (95% CI 39-70). Significant predictors of higher scores on the DCD-Q included the presence of autism spectrum disorder, CP, and early seizure onset. Increasing age and IQ were independently associated with higher DCD-Q scores. Intellectual disability, attention-deficit-hyperactivity disorder, academic underachievement, and specific memory problems were the most common neurobehavioural difficulties in those with both DCD and epilepsy. INTERPRETATION: Parent-reported symptoms of DCD are very common in childhood epilepsy. The DCD-Q has good sensitivity but lower specificity in this population.
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20.
  • Reilly, Colin, 1977, et al. (författare)
  • Parent- and Teacher-Reported Symptoms of ADHD in School-Aged Children With Active Epilepsy: A Population-Based Study.
  • 2017
  • Ingår i: Journal of attention disorders. - : SAGE Publications. - 1557-1246 .- 1087-0547. ; 21:11, s. 887-897
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Provide data on the distribution of parent- and teacher-reported symptoms of ADHD in childhood epilepsy and describe coexisting cognitive and behavioral disorders in children with both epilepsy and ADHD. METHOD: Eighty-five (74% of those eligible) children (5-15 years) in a population-based sample with active epilepsy underwent psychological assessment. The ADHD Rating Scale-IV (ADHD-RS-IV) scale was completed by parents (n = 69) and teachers (n = 67) of participating children with an IQ > 34. ADHD was diagnosed with respect to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). RESULTS: Parents reported significantly more symptoms of ADHD than teachers (p < .001). Symptoms of inattention were more commonly reported than symptoms of hyperactivity-impulsivity (p < .001). Neurobehavioral comorbidity was similar in those with ADHD and non-ADHD with the exception of oppositional defiant disorder (ODD) and developmental coordination disorder (DCD), which were more common in those with both epilepsy and ADHD. CONCLUSION: Symptoms of ADHD are very common in childhood epilepsy but prevalence is influenced by informant.
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21.
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