17 research outputs found
Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus: a populationbased study
Background: The aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study.Methods: This was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded.Results: We identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04-3.71). Hospital mortality was 7.4% (95% CI 0-16.9%), and 1-year mortality was 25. 4% (95% CI 21.2-29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104-1.051, p = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051-1.271, p = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20-3.84, p = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537-4.243, p < 0.0001).Conclusions: Despite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality
A Comparison of Approaches to Estimate the Inbreeding Coefficient and Pairwise Relatedness Using Genomic and Pedigree Data in a Sheep Population
Genome-wide SNP data provide a powerful tool to estimate pairwise relatedness among individuals and individual inbreeding coefficient. The aim of this study was to compare methods for estimating the two parameters in a Finnsheep population based on genome-wide SNPs and genealogies, separately. This study included ninety-nine Finnsheep in Finland that differed in coat colours (white, black, brown, grey, and black/white spotted) and were from a large pedigree comprising 319 119 animals. All the individuals were genotyped with the Illumina Ovine SNP50K BeadChip by the International Sheep Genomics Consortium. We identified three genetic subpopulations that corresponded approximately with the coat colours (grey, white, and black and brown) of the sheep. We detected a significant subdivision among the colour types (FST = 5.4%, P<0.05). We applied robust algorithms for the genomic estimation of individual inbreeding (FSNP) and pairwise relatedness (ΦSNP) as implemented in the programs KING and PLINK, respectively. Estimates of the two parameters from pedigrees (FPED and ΦPED) were computed using the RelaX2 program. Values of the two parameters estimated from genomic and genealogical data were mostly consistent, in particular for the highly inbred animals (e.g. inbreeding coefficient F>0.0625) and pairs of closely related animals (e.g. the full- or half-sibs). Nevertheless, we also detected differences in the two parameters between the approaches, particularly with respect to the grey Finnsheep. This could be due to the smaller sample size and relative incompleteness of the pedigree for them
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures
Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies
The epilepsies affect around 65 million people worldwide and have a substantial missing
heritability component. We report a genome-wide mega-analysis involving 15,212 individuals
with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11
are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at
these loci, with the majority in genetic generalized epilepsies. These genes have diverse
biological functions, including coding for ion-channel subunits, transcription factors and a
vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants
associated with epilepsy play a role in epigenetic regulation of gene expression in the brain.
The results show an enrichment for monogenic epilepsy genes as well as known targets of
antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and
overlapping genetic basis to seven different epilepsy subtypes. Together, these findings
provide leads for epilepsy therapies based on underlying pathophysiology