Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy

Objective: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. Methods: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. Results: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01–0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1–2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3–4 ASMs. Significance: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. Plain Language Summary: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.OBJECTIVE: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. METHODS: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. RESULTS: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. SIGNIFICANCE: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. PLAIN LANGUAGE SUMMARY: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.Peer reviewe

Complex executive functions assessed by the trail making test (TMT) part B improve more than those assessed by the TMT part A or digit span backward task during vagus nerve stimulation in patients with drug-resistant epilepsy

IntroductionThere is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years.MethodsThe study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes.ResultsOn average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1–2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively).ConclusionPerformance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects

ad-up tilt. Methods Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20–72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. Results Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. Conclusions Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.BioMed Central open acces

Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.</p

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust

Aikuisten suhtautuminen rokottamiseen influenssaa vastaan : kirjallisuuskatsaus

Opinnäytetyömme on osa Rokotuskattavuuden nostaminen rokotusosaamista vahvistamalla -projektia, jonka tarkoituksena on suunnitella ja toteuttaa tutkimusprojekti tulevina vuosina rokotuskattavuuden kohottamiseksi ja rokottajien rokotusosaamisen vahvistamiseksi. Hanke toteutetaan yhteistyönä Terveyden ja hyvinvoinnin laitoksen (THL) Rokotusten ja immuunisuojan osaston kanssa. Opinnäytetyömme tarkoituksena oli selvittää, millaista tutkimusta on tehty aikuisten suhtautumisesta rokottamiseen. Työmme analyysissa tavoitteenamme oli löytää luotettavaa ja tutkittua tietoa sovelletulla kirjallisuuskatsauksella aikuisten suhtautumisesta rokottamiseen influenssaa vastaan. Aikuisilla tarkoitamme pääasiassa yli 18-vuotiaita, mutta osassa tutkimuksia on mukana nuorimmillaan 14-vuotiaita. Kirjallisuuskatsauksemme aineisto koostui 14 tieteellisestä tutkimusartikkelista, jotka löytyivät systemaattisella hakumenetelmällä eri tietokannoista. Aineisto on analysoitu sisällönanalyysillä. Tuloksista käy ilmi, että tärkeimmät rokotteen ottoon kannustavat tekijät olivat saadut suositukset, suoja influenssaa ja sen oireita vastaan sekä tietoisuus taudista. Rokotteen ottoa estävistä tekijöistä tärkeimmiksi nousivat kokemus influenssasta vähäisenä uhkana, epäuskoisuus rokotteen vaikutuksista ja tehosta sekä pelot ja uhat rokotteen suhteen. Rokottamattomilla aikuisilla rokotteen ottoon rohkaisevista tekijöistä tärkeimmät olivat muilta saadut suositukset ja rokotteen saaminen halvalla tai ilmaiseksi. Tuloksistamme yleisistä rokottamiseen liittyvistä tekijöistä rokottamisen antama suoja ja kieltäytyminen rokotteesta olivat useimmin mainitut aihealueet. Kirjallisuuskatsauksemme tuloksia rokotteen ottoon kannustaneista ja rohkaisevista sekä rokotteen ottoa estäneistä tekijöistä voidaan hyödyntää tutkimusprojektia suunniteltaessa, alan perus- ja täydennyskoulutuksissa ja rokottajien työssä.Our final project was part of the project “Increasing vaccination coverage through boosting vaccination competence”. The purpose of the project was to plan and to implement a research project in the coming years. The Project will be realized in co-operation with the department of Vaccination and Immune Protection of the National Institute for Health and Welfare (THL). The purpose of our final project was to determine what kind of research has been con-ducted in adults’ attitudes towards vaccination. Our analysis was focused adults’ attitudes to vaccination against influenza. In our final project adult refers to people over 18 years old but part of the studies include participants from 14 years of age. Our goal was to find reliable and researched information through the method of applied literature review. Our data consists of 14 research articles, which have been found through systematic search from different electronic databases. Results indicate that the most important factors encouraging vaccine uptake were received recommendations, protection against influenza and its symptoms and the awareness of the disease. The most important factors hindering vaccine uptake were experiencing flu as a minor threat, disbelief concerning efficacy and effects of the vaccine and fears and threats in relation to flu vaccine. The most important encouraging factors for unvaccinated adults to vaccinate themselves were recommendations from other people and the price of the vaccine. The most frequently mentioned topics regarding to general vaccination-related factors were protection afforded by vaccination and refusing the vaccine. The results of our thesis can be used when designing the study project, in education and in the field work

Pyöreän puun ja sahatavaran mitta- ja laatuvaatimukset, hintatasot sekä valmistuskustannukset. Metsäntutkimuslaitos, Joensuun tutkimusasema. Moniste

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