| 1. |
- Ollila, Hanna M., et al.
(författare)
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Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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| 2. |
- Christensen, Jakob, et al.
(författare)
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Estimates of epilepsy prevalence, psychiatric co-morbidity and cost
- 2023
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Ingår i: Seizure. - : Elsevier. - 1059-1311 .- 1532-2688. ; 107, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study estimated epilepsy prevalence, psychiatric co-morbidity and annual costs associated with epilepsy.Methods: We used Danish national health registers to identify persons diagnosed with epilepsy and psychiatric disorders, and persons using antiseizure medication and persons using drugs for psychiatric disorders. We calculated the prevalence of epilepsy and co-morbid psychiatric disorders in Denmark on December 31, 2016, using information on epilepsy and psychiatric disorders based on combinations of hospital contacts and use of antiseizure and psychoactive medication. Further, direct and indirect annual costs associated with epilepsy were calculated using individual-level data from a range of socioeconomic registers.Results: There were 5,044,367 persons alive and living in Denmark on December 31, 2016, including 33,628 persons with at least one hospital contact with epilepsy in the previous five years (epilepsy prevalence 0.67% (0.69% males; 0.65% females)). Among these persons with epilepsy, we identified 12,562 (37.4%) persons with a psychiatric disorder or use of drugs used for psychiatric disorders as compared with 801,052 (15.9%) persons in the general population. The estimated total annual individual net costs associated with epilepsy was €30,683. Compared with prevalence estimates on December 31, 2006, the prevalence of epilepsy on December 31, 2016, was slightly higher in the older population and slightly lower in childrenConclusions: Population estimates from national registers provide epilepsy prevalence estimates of approximately 0.6–0.7% - similar to previous reviews of epilepsy prevalence. In addition, the national sample allowed idenitfication of high prevalence of psychiatric disorders and high societal costs associated with epielspy.
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| 3. |
- Clark, Alice, et al.
(författare)
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Sleep Impairment and Prognosis of Acute Myocardial Infarction : A Prospective Cohort Study
- 2014
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 37:5, s. 851-U215
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI). Design: Prospective cohort study. Setting: The Stockholm Heart Epidemiology Program, Sweden. Participants: There were 2,246 first-time AMI cases. Measurements and Results: Sleep impairment was assessed by the Karolina Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95-3.00), stroke (HR = 2.61; 95% CI: 1.19-5.76), and heart failure (HR = 2.43; 95% CI: 1.18-4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76-6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis. Conclusion: Results suggest sex-specific effects of impaired sleep that differ by short-and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention.
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| 4. |
- Gustavsson, Anders, et al.
(författare)
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Cost of disorders of the brain in Europe 2010.
- 2011
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Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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| 5. |
- Klingenberg, Lars, et al.
(författare)
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Acute Sleep Restriction Reduces Insulin Sensitivity in Adolescent Boys
- 2013
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 36:7, s. 1085-1090
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction. Objective: We aimed to investigate the effects of partial sleep deprivation on markers of glucose metabolism. Additionally, we aimed to investigate if short sleep duration induces a state of endocrine stress. Design: A randomized crossover design, with 2 experimental conditions: 3 consecutive nights of short sleep (SS, 4 h/night) and long sleep (LS, 9 h/night) duration. Subjects and Measurements: In 21 healthy, normal-weight male adolescents (mean +/- SD age: 16.8 +/- 1.3 y) we measured pre- and post-prandial glucose, insulin, C-peptide, and glucagon concentrations. Furthermore, we measured fasting cortisol, 24-h catecholamines, and sympathovagal balance. Results: Fasting insulin was 59% higher (P = 0.001) in the SS than the LS condition as was both fasting (24%, P < 0.001) and post-prandial (11%, P = 0.018) C-peptide. Pre- and post-prandial glucose and glucagon were unchanged between conditions. The homeostasis model assessment of insulin resistance (HOMA-IR) index was 65% higher (P = 0.002) and the Matsuda index was 28% lower (P = 0.007) in the SS condition compared to the LS condition. The awakening cortisol response and 24-h norepinephrine were not affected by sleep duration, whereas 24-h epinephrine was 24% lower (P = 0.013) in the SS condition. Neither daytime nor 24-h sympathovagal balance differed between sleep conditions. Short wave sleep was preserved in the SS condition. Conclusion: Short-term sleep restriction is associated with decreased insulin sensitivity in healthy normal-weight adolescent boys. There were no indications of endocrine stress beyond this.
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| 6. |
- Klingenberg, Lars, et al.
(författare)
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Sleep restriction is not associated with a positive energy balance in adolescent boys
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:2, s. 240-248
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Tidskriftsartikel (refereegranskat)abstract
- Background: A short sleep (SS) duration has been linked to obesity in observational studies. However, experimental evidence of the potential mechanisms of sleep restriction on energy balance is conflicting and, to our knowledge, nonexistent in adolescents.Objective: We investigated the effects of 3 consecutive nights of partial sleep deprivation on components of energy balance.Design: In a randomized, crossover design, 21 healthy, normal-weight male adolescents (mean +/- SD age: 16.8 +/- 1.3 y) completed the following 2 experimental conditions, each for 3 consecutive nights: an SS (4 h/night) and a long sleep (LS; 9 h/night) duration. Endpoints were 24-h energy expenditure (EE), spontaneous physical activity (SPA), postintervention diet-induced thermogenesis (DIT), appetite sensations, ad libitum energy intake (EI), and profiles of plasma ghrelin and leptin.Results: The 24-h EE on day 3 was 370 +/- 496 kJ higher in the SS condition than in the LS condition (P = 0.003). This difference in EE was explained by prolonged wakefulness in the SS condition and a 19% higher SPA (P = 0.003). In a postintervention breakfast-meal challenge, there was a 0.19-kJ/min smaller incremental AUC in DIT over 4 h in the SS condition than in the LS condition (P = 0.012) with no time X condition effect (P = 0.29). Subjects consumed 13% less energy in the ad libitum meal in the SS condition (P = 0.031), with a concomitant decreased motivation to eat. Concentrations of ghrelin and leptin remained unchanged with sleep restriction.Conclusion: Short-term sleep restriction in male adolescents is associated with a small negative energy balance driven by increased EE from prolonged wakefulness and a concomitant decreased El and motivation to eat. This trial was registered at clinicaltrials.gov as NCT01198431.
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| 7. |
- RODENSTEIN, DANIEL, et al.
(författare)
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Driving in Europe: the need of a common policy for drivers with obstructive sleep apnoea syndrome
- 2008
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Ingår i: Journal of sleep research. - : Wiley. - 1365-2869 .- 0962-1105. ; 17:3, s. 281-284
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Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnoea syndrome (OSA) increases the risk of motor vehicle crashes, and of all medical disorders, has greatest risk in this respect. There is no consistency in the way OSA is considered by the national 'Physical Fitness to Drive' legislations within the 27 member countries of the European Union (EU), and most ignore OSA. This is further reflected by the absence of any reference to OSA in Annex III of the Directive 91/439/EEC, harmonizing Driving License regulations in the EU. A recent meeting brought together experts from several European and other countries, together with a representative of the European Commission. They discussed the best way to design and implement a uniform policy within Europe, for OSA and driving. It was agreed that: (i) other forms of pathological sleepiness be included, (ii) it covers both private and professional drivers, (iii) police accident report forms should explicitly consider sleepiness as a potential cause, (iv) sleep-wake education should be incorporated into the mandatory program of continuous education for professional drivers, ideally from 2010, (v) driver screening methods should contain questions on sleepiness at the wheel, habitual snoring and witnessed apneas during sleep, as well as the Epworth Sleepiness Score and Body Mass Index and (vi) following effective and efficient treatment, patients should be permitted to drive. In the light of medical, scientific and technical progress, EU procedures exist to enable the rapid modification of existing legislation. If such a procedure could be enacted for these aspects of driver sleepiness, then roads would be safer for 400 million people.
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| 8. |
- Savvidou, Andri, et al.
(författare)
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Hypocretin Deficiency Develops During Onset of Human Narcolepsy with Cataplexy
- 2013
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 36:1, s. 147-148
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans. Setting: Paediatric Department, Blekinge Hospital, Sweden, and Danish Center for Sleep Medicine, Glostrup Hospital, Denmark. Patient and Results: Two weeks after his second Pandemrix-vaccination, a 10 year old HLA-DQB1*0602-positive boy developed NC. The CSF hypocretin-1 level was 10 pg/ml. However, CSF saved from a pre-narcolepsy episode of Lyme disease revealed a normal hypocretin-1 level (318 pg/ml). Conclusions: We confirm that hypocretin deficiency develops in parallel to the onset of human narcolepsy with cataplexy.
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