Prevalence and incidence rates of atrial fibrillation in Norway 2004-2014

Objective: To study time trends in incidence of atrial fibrillation (AF) in the entire Norwegian population from 2004 to 2014, by age and sex, and to estimate the prevalence of AF at the end of the study period. Methods: A national cohort of patients with AF (≥18 years) was identified from inpatient admissions with AF and deaths with AF as underlying cause (1994–2014), and AF outpatient visits (2008–2014) in the Cardiovascular Disease in Norway (CVDNOR) project. AF admissions or out-of-hospital death from AF, with no AF admission the previous 10 years defined incident AF. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated. All AF cases identified through inpatient admissions and outpatient visits and alive as of 31 December 2014 defined AF prevalence. Results: We identified 175 979 incident AF cases (30% primary diagnosis, 69% secondary diagnosis, 0.6% out-of-hospital deaths). AF IRs (95% confidence intervals) per 100 000 person years were stable from 2004 (433 (426–440)) to 2014 (440 (433–447)). IRs were stable or declining across strata of sex and age with the exception of an average yearly increase of 2.4% in 18–44 year-olds: IRR 1.024 (1.014–1.034). In 2014, the prevalence of AF in the adult population was 3.4%. Conclusions: We found overall stable IRs of AF for the adult Norwegian population from 2004 to 2014. The prevalence of AF was 3.4% at the end of 2014, which is higher than reported in previous studies. Signs of an increasing incidence of early-onset AF (<45 years) are worrying and need further investigation.publishedVersio

Retts Syndrom og MECP2 Duplication Syndrome - Det kliniske bildet og betydningen av MeCP2

Abstract Objective: The aim of this review is to investigate the two syndromes Rett syndrome (RTT) and MECP2 duplication syndrome (MECP2ds), with emphasis on phenotypic traits that are shared by the two syndromes. Additional goals is to explore the role of the MeCP2 protein in an epigenetic context, and in the pathogenesis of the two syndromes. Finally I will look at the future prospects of finding treatments for the two syndromes that extend beyond conservative reliever therapy. Background: RTT and MECP2ds are both neurological disorders related to faulty X chromosome, which both provide developmental disorders. RTT targets females and is caused by a deletion of the MECP2 gene encoding the methyl-CpG-binding protein 2 (MeCP2), and thus loss of function of the protein. MECP2ds almost exclusively affects males and is caused by a duplication of the MECP2 gene, leading to gain of function of the MeCP2 protein. Nevertheless the two syndromes show a noteworthy number of similar phenotypic characteristics. Method: Literature searches including both review articles and original publications in McMaster Plus, PubMed/Medline, Ovid, Cochrane, and Google Scholar. Only articles written in english or norwegian were included. Searches were based on relevant keywords focused on the genetic and clinical aspects of RTT and MECP2ds, correlation between the two syndromes and the MeCP2 protein, the epigenetic aspect of the MeCP2 protein, as well as the more recent publications regarding treatment. Result and Conclusion: Despite a great deal of differences between RTT and MECP2ds, there are remarkably many similarities in the phenotypic expression shown by the two syndromes, such as aberrant psychomotor development and motor dysfunction, regression, reduced or absent speech and walking ability, ataxia and spasticity, autism, stereotypical movements, epilepsy and gastrointestinal dysfunction. The MeCP2 protein is a transcription factor that controls gene expression, and is a key epigenetic factor in development and maintenance of the central nervous system. Common features of neurological diseases in humans which are caused by either loss or increased MeCP2 function, suggest that even small changes in the level of MeCP2 protein results in developmental neurological problems. There is intense research in the field to find gene therapy and various drugs as potential treatments for diseases related to disorders of the MeCP2 protein. Gene therapy has shown some promising results in vitro using retroviral vectors. Medications such as IGF1 and Gentamicin may be promising as a therapy directed at early stages of development in RTT, as they may reduce the consequences of MECP2 mutations. But to restore the protein levels remains a great challenge, since an excess of MeCP2 can be just as damaging as the loss of expression. Clinical trials are not currently within reach. Considering MECP2ds it is also necessary to facilitate research on the molecular background of immunodeficiency, which is a major cause of premature death in this patient population