Genetic epidemiology of amyotrophic lateral sclerosis in Norway - a 2-year population based study

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.publishedVersio

En sammenligning av økonomiske teorier for regional vekst

Formålet med denne oppgaven er å sammenligne to teorier for økonomisk vekst i regioner. På den ene siden har jeg en keynesiansk tilnærming hvor jeg har benyttet en modell utledet av Thirlwall (1980). Thirlwalls modell fokuserer på etterspørselen etter eksportvarer som kilde til økonomisk vekst, hvor tilbudet i markedet tilpasser seg etterspørselen. Jeg har supplert med teori fra blant annet Kaldor (1970) og Setterfield (1997; 2003) for å belyse ulike element ved etterspørselbasert teori. Jeg ser for eksempel på kausalkumulativ vekst som er viktig for å forklare vekst i regioner ut fra etterspørselen i markedet. Den andre tilnærmingen tar utgangspunkt i neoklassiske modeller hvor tilbudet i markedet er utgangspunktet for å forklare økonomisk vekst. Som sammenligningsgrunnlag til Thirlwalls modell har jeg benyttet Solow-modellen som representant for den neoklassiske tilnærmingen. Jeg har sett på modellenes teoretiske forskjeller, hvilke svakheter de har og hvilke politiske implikasjoner de gir. Forskjellene i de teoretiske tilnærmingene ligger i antagelsen bak hva som generer økonomisk vekst og hvilke faktorer som er avgjørende for å oppnå vekst. Modellene kritiseres blant annet for å ha et for ensidig fokus på markedssynet som antas. Den neoklassiske tilnærmingen har vært mest brukt som grunnlag for å forklare økonomisk vekst i regioner, men det jobbes for å få et større fokus på den keynesianske tilnærmingen for å oppnå full forståelse av hvorfor det oppstår forskjeller i vekstratene mellom regioner

Initiation of anti-osteoporotic drugs in high-risk female patients starting glucocorticoid treatment: a population study in Norway

Summary: Glucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively. Purpose: Use of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis. Methods: We used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010–2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses. Results: Among 105,477 women initiating GC treatment during 2010–2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016. Conclusions: Having had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated

Initiation of anti-osteoporotic drugs in high-risk female patients starting glucocorticoid treatment: a population study in Norway

Summary Glucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively. Purpose Use of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis. Methods We used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010–2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses. Results Among 105,477 women initiating GC treatment during 2010–2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016. Conclusions Having had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated

Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020.

INTRODUCTION We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020. PATIENTS AND METHODS We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively. RESULTS The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016. CONCLUSION Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised

Genetic epidemiology of amyotrophic lateral sclerosis in Norway - a 2-year population based study

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well