1. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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2. |
- Asellus, Peter, et al.
(författare)
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Cholesterol and the "Cycle of Violence" in attempted suicide
- 2014
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 215:3, s. 646-50
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Tidskriftsartikel (refereegranskat)abstract
- An association between low levels of serum cholesterol and violent or suicidal behaviour has frequently been reported. However the role of serum cholesterol in the cycle of violence (Widom, 1989) has not been studied. The aim of this study was to investigate association between exposure to violence during childhood and used adult violence in suicide attempters with low and high serum cholesterol levels. 81 suicide attempters were assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6 and 14 years of age) and during adult life (15 years or older). We used median split to dichotomise groups below and above median serum cholesterol. In patients with serum cholesterol below median, the correlation between exposure to violence as a child and used adult violence was significant (rho=0.52, p=0.002), while in patients with serum cholesterol above median, the correlation between exposure to violence as a child and expressed violent behaviour as an adult was not significant (rho=0.25, p=0.2). Comorbid substance abuse predicted violent behaviour as an adult only in patients with serum cholesterol above median. Serum cholesterol may modify the effect of the "Cycle of Violence".
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3. |
- Asellus, Peter, et al.
(författare)
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CSF Apolipoprotein E in attempted suicide
- 2018
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 225, s. 246-249
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cholesterol and cholesterol metabolism, involved in continued neural plasticity, has been associated to suicide and suicidal behavior. Apolipoprotein E (ApoE) plays an important role in the cholesterol metabolism. The purpose of this study was to investigate whether ApoE in cerebrospinal fluid was related to severity of suicidal behavior as measured by number of earlier suicide attempts, reversibility/interruptabilty and violent method of suicide attempt. Methods: CSF ApoE and 5-hydroxyindolacetic acid (5-HIAA) were measured in 42 medication free suicide attempters. Earlier suicide attempts and the reversibility of suicide attempt method were assessed with the Suicide Intent Scale (SIS) and the Freeman Scale. Suicide attempts were classified according to violence of method. Results: CSF ApoE levels significantly negatively correlated to the scores on Freeman Reversibility and there was a trend for lower CSF ApoE levels in suicide attempters using a violent method. Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study. The correlation between CSF ApoE and 5-HIAA was not significant. Limitations: The main limitations to this study were a relatively small sample size and lack of a healthy control group. Conclusion: Irreversible suicide attempts, representing a high risk for completed suicide, may be associated with lower level of ApoE in CSF.
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4. |
- Asellus, Peter, et al.
(författare)
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Plasma apolipoprotein E and severity of suicidal behaviour
- 2016
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 190, s. 137-142
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour.
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5. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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6. |
- Kepp, Kasper P., et al.
(författare)
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Panel stacking is a threat to consensus statement validity
- 2024
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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7. |
- Paluch, Amanda E., et al.
(författare)
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Daily steps and all-cause mortality : a meta-analysis of 15 international cohorts
- 2022
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 7:3, s. e219-e228
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality.METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models.FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]).INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity.FUNDING: US Centers for Disease Control and Prevention.
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8. |
- Paluch, Amanda E., et al.
(författare)
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Prospective association of daily steps with cardiovascular disease : a harmonized meta-analysis
- 2023
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 147:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models.RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults.CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.
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9. |
- Scott, David, et al.
(författare)
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Adiposity Without Obesity : Associations with Osteoporosis, Sarcopenia, and Falls in the Healthy Ageing Initiative Cohort Study
- 2020
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Ingår i: Obesity. - : John Wiley & Sons. - 1930-7381 .- 1930-739X. ; 28:11, s. 2232-2241
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Obesity is commonly defined by BMI rather than adiposity, which may have differential effects on musculoskeletal health. Musculoskeletal outcomes were compared in older adults with normal adiposity and normal BMI (NA‐NBMI), those with high adiposity but normal BMI (HA‐NBMI), and those with high adiposity and high BMI (HA‐HBMI).Methods: In 3,411 70‐year‐olds, obesity was defined as BMI ≥ 30 kg/m2 and adiposity as body fat percentage ≥ 25% (men) or ≥ 35% (women) from dual‐energy x‐ray absorptiometry. Bone parameters were measured by dual‐energy x‐ray absorptiometry and peripheral quantitative computed tomography. Sarcopenia was defined as low handgrip strength with or without low appendicular lean mass. Falls were self‐reported 6 and 12 months later.Results: Prevalence of NA‐NBMI, HA‐NBMI, and HA‐HBMI was 14.2%, 68.1%, and 17.7%, respectively. Compared with HA‐HBMI, HA‐NBMI had increased likelihood for sarcopenia (adjusted odds ratio: 3.99; 95% CI: 1.41‐11.32) and osteoporosis (2.91; 95% CI: 2.35‐3.61) but similar likelihood of falls (P > 0.05). HA‐NBMI had lower values for bone geometry parameters, as well as grip strength, than both NA‐NBMI and HA‐HBMI (all P < 0.05).Conclusions: High adiposity without high BMI is more common than BMI‐defined obesity in older Swedish adults but does not provide similar protection from osteoporosis and sarcopenia.
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10. |
- Scott, David, et al.
(författare)
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Associations of accelerometer-determined physical activity and sedentary behavior with sarcopenia and incident falls over 12 months in community-dwelling Swedish older adults
- 2021
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Ingår i: Journal of Sport and Health Science. - Shanghai : Shanghai University of Sports. - 2095-2546 .- 2213-2961. ; 10:5, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study was aimed to determine associations of accelerometer-determined time and bouts of sedentary behavior, light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with sarcopenia and incident falls over 12 months.Methods: A total of 3334 Swedish 70-year-olds were assessed for sarcopenia, as defined by the revised definition of the European Working Group on Sarcopenia in Older People. Assessments were based on low scores for appendicular lean mass (dual-energy X-ray absorptiometry), hand grip strength, and the Timed Up and Go test. For 7 days after baseline, total time and total number of bouts (>10 min of continuous activity at a given intensity) of activity performed at sedentary, LPA, and MVPA intensities were assessed by accelerometer. Incident falls were self-reported 6 months and 12 months after baseline.Results: Only 1.8% of participants had probable or confirmed sarcopenia. After multivariable adjustment for other levels of activity, only greater MVPA time was associated with a decreased likelihood of having low appendicular lean mass, low hand grip strength, and slow Timed Up and Go time as defined by the European Working Group on Sarcopenia in Older People criteria (all p < 0.05), and only MVPA time was associated with lower likelihood of probable or confirmed sarcopenia (odds ratio = 0.80, 95% confidence interval: 0.71-0.91 h/week). Similar associations were identified for total number of bouts, with no evidence of threshold effects for longer duration of bouts of MVPA. A total of 14% of participants reported >1 fall, but neither total time nor bouts of activity was associated with incident falls (all p > 0.05).Conclusion: Higher amounts of accelerometer-determined MVPA are consistently associated with a decreased likelihood of sarcopenia and its components, regardless of the length of bouts or amounts of sedentary behavior.
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11. |
- Scott, David, et al.
(författare)
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Associations of Sarcopenia and Its Components with Bone Structure and Incident Falls in Swedish Older Adults
- 2019
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Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 105:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare bone structure parameters and likelihood of falls across European Working Group on Sarcopenia in Older People (EWGSOP2) sarcopenia categories. 3334 Swedish 70-year olds had appendicular lean mass (normalized to height; ALMHt), lumbar spine and total hip areal BMD (aBMD) estimated by dual-energy X-ray absorptiometry. Volumetric BMD (vBMD) and structure at the distal and proximal tibia and radius were estimated by peripheral quantitative computed tomography. Hand grip strength and timed up-and-go were assessed, and sarcopenia was defined according to EWGSOP2 criteria. Incident falls were self-reported 6 and 12 months after baseline. Only 0.8% and 1.0% of participants had probable and confirmed sarcopenia, respectively. Almost one-third of participants with confirmed sarcopenia reported incident falls, compared with 20% for probable sarcopenia and 14% without sarcopenia (P = 0.025). Participants with confirmed sarcopenia had poorer bone parameters (all P < 0.05) except endosteal circumference at the proximal radius and tibia, while those with probable sarcopenia had lower cortical area at the proximal radius (B = - 5.9; 95% CI - 11.7, - 0.1 mm2) and periosteal and endosteal circumferences at the proximal tibia (- 3.3; - 6.4, - 0.3 and - 3.8; - 7.5, - 0.1 mm2, respectively), compared with those without sarcopenia. Compared with probable sarcopenia, confirmed sarcopenic participants had significantly lower lumbar spine and total hip aBMD, distal radius and tibia total vBMD, and proximal radius and tibia cortical vBMD, area and thickness (all P < 0.05). Swedish 70-year olds with confirmed sarcopenia demonstrate poorer BMD and bone architecture than those with probable and no sarcopenia, and have increased likelihood of incident falls.
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12. |
- Scott, David, et al.
(författare)
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Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults : The Healthy Ageing Initiative
- 2019
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 120, s. 446-451
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lower skeletal muscle density, indicating greater infiltration of adipose tissue into muscles, is associated with higher fracture risk in older adults. We aimed to determine whether mid-calf muscle density is associated with falls risk and bone health in community-dwelling older adults.METHODS: 2214 community-dwelling men and women who participated in the Healthy Ageing Initiative (Sweden) study at age 70 were included in this analysis. Mid-calf muscle density (mg/cm3) at the proximal tibia, and volumetric bone mineral density (vBMD) and architecture at the distal and proximal tibia and radius, were assessed by peripheral quantitative computed tomography. Whole-body lean and fat mass, lumbar spine and total hip areal bone mineral density (aBMD) were assessed by dual-energy X-ray absorptiometry. Participants completed seven-day accelerometer measurements of physical activity intensity, and self-reported falls data were collected 6 and 12 months later.RESULTS: 302 (13.5%) participants reported a fall at the 6- or 12-month interview, and 29 (1.3%) reported a fall at both interviews. After adjustment for confounders, each standard deviation decrease in mid-calf muscle density was associated with a trend towards greater likelihood of experiencing a fall (OR 1.13; 95% CI 1.00, 1.29 per SD lower) and significantly greater likelihood of multiple falls (1.61; 1.16, 2.23). Higher muscle density was not associated with total hip aBMD, and was associated with lower lumbar spine aBMD (B = -0.003; 95% CI -0.005, -0.001 per mg/cm3) and higher proximal cortical vBMD (0.74; 0.20, 1.28) at the radius. At the tibia, muscle density was positively associated with distal total and trabecular vBMD, and proximal total and cortical vBMD, cortical thickness, cortical area and stress-strain index (all P < 0.05). Only moderate/vigorous (%) intensity physical activity, not sedentary time or light activity, was associated with higher mid-calf muscle density (0.086; 0.034, 0.138).CONCLUSIONS: Lower mid-calf muscle density is independently associated with higher likelihood for multiple incident falls and appears to have localised negative effects on bone structure in older adults.
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13. |
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14. |
- Ballin, Marcel, et al.
(författare)
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Association of dog ownership with accelerometer-measured physical activity and daily steps in 70-year-old individuals : a population-based cross-sectional study
- 2021
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dog ownership (DO) has been associated with higher levels of self-reported walking and physical activity. However, compared to device-based measures, self-reported measures of physical activity may suffer from bias due to recall and social desirability. They are also incapable of quantifying light-intensity physical activity (LPA) and step volume, both of which may have important health benefits, especially for older adults. In this study, we investigated the association of DO with accelerometer-measured physical activity of different intensities and daily steps in 70-year-old individuals.Methods: This was a population-based cross-sectional study including 1406 participants aged 70 years [54.1% female] who participated in a health survey in Umeå, Sweden between February 2017–November 2019. All participants self-reported DO [yes/no]. Daily averages of LPA, moderate-to-vigorous-intensity physical activity (MVPA), and steps per day [steps/d] were measured for 1 week using hip-mounted Actigraph GT3X+ accelerometers. Associations were investigated using linear- and logistic regression models, adjusted for sociodemographic and health-related factors, date of examination, and accelerometer wear time.Results: The prevalence of DO was 14.1% [N = 199]. After adjustment for all covariates, DO was associated with 19.2 more minutes/d of LPA [95% CI, 8.8–29.6], 11.4 more minutes/d of MVPA [95% CI, 8.0–14.9] and 1738 more steps/d [95% CI, 1326–2149]. DO was also associated with twice the odds of meeting the physical activity recommendations [OR, 2.07, 95% CI, 1.48–2.90]. Exploratory interaction analyses showed that the association between DO and steps/d was stronger [Pinteraction = 0.030] in female [β = 2165, 95% CI, 1585–2744] than in male [β =1255, 95% CI, 664–1845], with a similar trend for MVPA [Pinteraction = 0.082].Conclusions: In this study of community-dwelling 70-year-old individuals, DO was associated with higher levels of daily LPA, MVPA, and steps. With the limitation of the observational design of the study, these findings add knowledge regarding the beneficial role that DO may play for promoting physical activity in the older population. In turn, these findings could support the development and evaluation of targeted interventions seeking to promote dog-friendly environments and facilitate dog walking in the community.
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15. |
- Ballin, Marcel, et al.
(författare)
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Associations of light, moderate to vigorous, and total physical activity with the prevalence of metabolic syndrome in 4,652 community-dwelling 70-year-olds : A population-based cross-sectional study
- 2021
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Ingår i: Journal of Aging and Physical Activity. - : Human Kinetics. - 1063-8652 .- 1543-267X. ; 29:5, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- In this cross-sectional study, the authors investigated the associations of objectively measured physical activity (PA) with the prevalence of metabolic syndrome (MetS) in older adults. Accelerometer-derived light-intensity PA, moderate to vigorous PA, and steps per day were measured in (N = 4,652) 70-year-olds in Umeå, Sweden, during May 2012-November 2019. The MetS was assessed according to the American Heart Association/National Heart, Lung and Blood Institute criteria. The prevalence of MetS was 49.3%. Compared with the reference, the odds ratios for MetS in increasing quartiles of light-intensity PA were 0.91 (0.77-1.09), 0.75 (0.62-0.89), and 0.66 (0.54-0.80). For moderate to vigorous PA, the corresponding odds ratios were 0.79 (0.66-0.94), 0.67 (0.56-0.80), and 0.56 (0.46-0.67). For steps per day, the odds ratios were 0.65 (0.55-0.78), 0.55 (0.46-0.65), and 0.45 (0.36-0.55). In summary, this study shows that greater amounts of PA, regardless of intensity, are associated with lower odds of MetS. With the limitation of being an observational study, these findings may have implications for the prevention of MetS in older adults.
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16. |
- Ballin, Marcel, et al.
(författare)
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Associations of Objectively Measured Physical Activity and Sedentary Time with the Risk of Stroke, Myocardial Infarction or All‑Cause Mortality in 70‑Year‑Old Men and Women : A Prospective Cohort Study
- 2021
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Ingår i: Sports Medicine. - : Springer. - 0112-1642 .- 1179-2035. ; 51:2, s. 339-349
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the associations of objectively measured physical activity (PA) and sedentary time (ST) with the combined outcome of incident stroke, myocardial infarction (MI) or all-cause mortality in older adults.Methods: N = 3343 men and women aged 70 who participated in a health survey between 2012 and 2017 were included. Actigraph GT3X+ accelerometers were used to measure light-intensity PA (LPA), moderate-intensity PA (MPA) and ST for 1 week. Incident cases of cardiovascular disease (CVD) in terms of stroke or MI, and all-cause mortality were identified using national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable-adjusted Cox regressions.Results: During a mean follow-up of 2.7 years (0.1–5.6), there were 124 events of CVD or all-cause mortality. After adjusting for potential confounders and mediators, every 30-min/day increment in LPA was associated with 11% lower risk of CVD or all-cause mortality (HR 0.89, 95% CI 0.82–0.97), and every 30-min/day increment in MPA was associated with 36% lower risk (HR 0.64, 95% CI 0.48–0.84). Every 1-h/day increment in ST increased the risk of the outcomes by 33% (HR 1.33, 95% CI 1.14–1.56), although there was no significant association among participants who performed ≥ 30 min/day MPA (HR 1.11, 95% CI 0.82–1.50, P = 0.034 for interaction). None of the associations were modified by sex (P > 0.4 for all).Conclusion: Objectively measured LPA and MPA are each associated with lower risk of stroke, MI or all-cause mortality in 70-year-old individuals, while ST is associated with increased risk. The greatest risk reduction is observed for MPA, which also appears to attenuate some of the increased risks associated with ST.
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17. |
- Ballin, Marcel, et al.
(författare)
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Associations of visceral adipose tissue and skeletal muscle density with incident stroke, myocardial infarction, and all-cause mortality in community-dwelling 70-year-old individuals: A prospective cohort study
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aging leads to increased visceral adipose tissue (VAT) and reduced skeletal muscle density. To which extent these are associated with the risk of stroke, myocardial infarction (MI), and all-cause mortality in older adults is unknown.METHODS AND RESULTS: A total of 3294 70-year-old individuals (49.6% women) underwent a health examination in Umeå, Sweden, during 2012 to 2018. VAT and muscle density were measured using dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. Cases of stroke, MI, and all-cause mortality were collected through national registers. Cox regressions were used to calculate hazard ratios (HRs) and 95% CIs per SD greater VAT and per SD lower muscle density. During a mean follow-up of 3.6 years, there were 108 cases of stroke or MI, and 97 deaths. Greater VAT (adjusted HR [aHR], 1.56; 95% CI, 1.09– 2.22), but not lower muscle density (aHR, 1.14; 95% CI, 0.97–1.34), was associated with increased risk of stroke or MI. Neither VAT (aHR, 0.95; 95% CI, 0.65–1.41) nor muscle density (aHR, 1.11; 95% CI, 0.92–1.34) was associated with all-cause mortality. The association of VAT with stroke or MI was only significant in men (aHR, 1.86; 95% CI, 1.19– 2.91) but not women (aHR, 0.60; 95% CI, 0.25–1.42) (Pinteraction =0.038).CONCLUSIONS: With the limitation of being an observational study, these findings suggest that VAT is an important obesity-related predictor of cardiovascular risk in 70-year-old men, and by implication, that decreasing VAT may potentially reduce their risk of cardiovascular disease.
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18. |
- Ballin, Marcel, et al.
(författare)
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Cardiovascular Disease and All-Cause Mortality in Male Twins with Discordant Cardiorespiratory Fitness : A Nationwide Cohort Study
- 2020
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 189:10, s. 1114-1123
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Tidskriftsartikel (refereegranskat)abstract
- Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on 1,212,295, 18-year-old men that conscripted for military service in Sweden 1972-1996. The first comprised 4,260 twin pairs where twins in each pair had different CRF (≥1 Watt). The second comprised 90,331 non-sibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs 251 events; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.83, 1.20). The risks were similar in twin pairs with ≥60 Watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the non-sibling cohort, fitter men had a lower risk of the outcomes than less fit men (4444 vs 5298 events; HR = 0.87, 95% CI: 0.83, 0.92). The association was stronger in pairs with ≥60 Watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality.
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19. |
- Ballin, Marcel, et al.
(författare)
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Daily step count and incident diabetes in community-dwelling 70-year-olds : a prospective cohort study
- 2020
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older adults with diabetes take fewer steps per day than those without diabetes. The purpose of the present study was to investigate the association of daily step count with incident diabetes in community-dwelling 70-year-olds.Methods: This prospective cohort study included N = 3055 community-dwelling 70-year-olds (52% women) who participated in a health examination in Umeå, Sweden during 2012–2017, and who were free from diabetes at baseline. Daily step count was measured for 1 week using Actigraph GT3X+ accelerometers. Cases of diabetes were collected from the Swedish National Patient Register. The dose-response association was evaluated graphically using a flexible parametric model, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regressions.Results: During a mean follow-up of 2.6 years, diabetes was diagnosed in 81 participants. There was an inverse nonlinear dose-response association between daily step count and incident diabetes, with a steep decline in risk of diabetes from a higher daily step count until around 6000 steps/day. From there, the risk decreased at a slower rate until it leveled off at around 8000 steps/day. A threshold of 4500 steps/day was found to best distinguish participants with the lowest risk of diabetes, where those taking ≥ 4500 steps/day, had 59% lower risk of diabetes, compared to those taking fewer steps (HR, 0.41, 95% CI, 0.25–0.66). Adjusting for visceral adipose tissue (VAT) attenuated the association (HR, 0.64, 95% CI, 0.38–1.06), which was marginally altered after further adjusting for sedentary time, education and other cardiometabolic risk factors and diseases (HR, 0.58, 95% CI, 0.32–1.05).Conclusions: A higher daily step count is associated with lower risk of incident diabetes in community-dwelling 70-year-olds. The greatest benefits occur at the lower end of the activity range, and much earlier than 10,000 steps/day. With the limitation of being an observational study, these findings suggest that promoting even a modest increase in daily step count may help to reduce the risk of diabetes in older adults. Because VAT appears to partly mediate the association, lifestyle interventions targeting diabetes should apart from promoting physical activity also aim to prevent and reduce central obesity.
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20. |
- Ballin, Marcel, et al.
(författare)
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Digital exercise interventions for improving measures of central obesity : a systematic review
- 2020
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Ingår i: International Journal of Public Health. - : Springer Nature. - 1661-8556 .- 1661-8564. ; 65:5, s. 593-605
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Forskningsöversikt (refereegranskat)abstract
- Objectives: We aimed to systematically review the potential benefits of digital exercise interventions for improving measures of central obesity including visceral adipose tissue (VAT) and anthropometric surrogates for VAT in overweight or centrally obese adults aged 18 or over.Methods: A systematic literature search was conducted in three databases up until March 2020 (PROSPERO registration nr CRD42019126764).Results: N = 5 studies including 438 participants (age 48–80) with body mass index ≥ 25 kg/m2 met the eligibility criteria and were included. The duration of the interventions ranged from 8 to 24 weeks. No study measured the primary outcome VAT, although in N = 4 studies, waist circumference (WC) decreased by between 1.3 and 5.6 cm in the intervention groups.Conclusions: This systematic review shows that there is no evidence for the effects of digital exercise on VAT, although digital exercise may decrease WC. These findings highlight the need for additional randomized controlled trials to confirm the findings with respect to WC, and to further investigate the effects of digital exercise on VAT. Together, this may have important implications for reducing the burden of physical inactivity and obesity.
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21. |
- Ballin, Marcel, et al.
(författare)
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Effects of interval training on quality of life and cardiometabolic risk markers in older adults : a randomized controlled trial
- 2019
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Ingår i: Clinical Interventions in Aging. - : Dove Press. - 1176-9092 .- 1178-1998. ; 14, s. 1589-1599
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore the effects of 10 weeks of progressive vigorous interval training as a single intervention on health-related quality of life (HRQoL) and cardiometabolic risk markers in centrally obese 70-year-old individuals.Participants and methods: A randomized controlled trial (ClinicalTrials.gov registration no. NCT03450655) including seventy-seven community-dwelling 70-year-old men and women with central obesity defined as > 1 kg visceral adipose tissue for women and > 2 kg for men. Participants randomized to the intervention group were offered a 10-week progressive vigorous interval training program performed three times per week. Control subjects were asked to maintain their daily living and routines throughout the trial. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. Prespecified outcome measures included: changes in HRQoL using the Short Form Health Survey Questionnaire (SF-36), blood pressure; resting heart rate (HR) and blood lipids. All analyses were conducted on an intention-to-treat basis.Results: The intervention resulted in significant effects on the SF-36 mental component summary (MCS) score and the mental health (MH) subscale (P< 0.05 for both), when compared to the control group. Specifically, the intervention group increased their MCS score by 6.3 points (95% confidence interval [CI] = 0.3–12.3) and their MH score by 6.0 points (95% CI = 1.7–10.4) compared to the control group. Moreover, significant effects were seen on resting HR, total cholesterol and LDL-cholesterol (P<0.05 for all).Conclusion: It was shown that 10 weeks of vigorous interval training as a single intervention was sufficient to improve mental aspects of HRQoL in older individuals with central obesity, which is a critical aspect of healthy ageing. Positive effects were seen also on cardiometabolic risk markers.
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22. |
- Ballin, Marcel, et al.
(författare)
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Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals : A Randomized Controlled Trial
- 2019
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Ingår i: Journal of The American Geriatrics Society. - : John Wiley & Sons. - 0002-8614 .- 1532-5415. ; 67:8, s. 1625-1631
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the effects of 10 weeks of progressive vigorous-intensity interval training as a single intervention on body composition among 70-year-old individuals with central obesity.DESIGN: Randomized controlled trial (ClinicalTrials.gov registration No. NCT03450655).SETTING: Community-dwelling 70-year-old men and women living in the Umeå municipality in Sweden.PARTICIPANTS: Seventy-seven 70-year-old men and women with central obesity (greater than 1 kg visceral adipose tissue [VAT] for women and greater than 2 kg VAT for men).INTERVENTION: Participants allocated to the intervention group were offered a 10-week progressive concurrent exercise program performed three times per week. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation.MEASUREMENTS: The primary outcome was changes in VAT, and secondary outcomes included changes in total fat mass (FM), total lean body mass (LBM), and body mass index.RESULTS: Comparing the groups, there were no significant differences in decrease of VAT mass (P = .10), although the intervention group significantly decreased FM by 716 g (P = .01) and gained LBM by 508 g (P = .03), compared to the control group. Furthermore, the effects of the training were significantly greater in the male subcohort (P < .05 for interaction), with positive effects also on VAT and FM, where men in the intervention group decreased VAT by 175 g (P < .05) and FM by 1364 g (P = .004), compared to the male controls.CONCLUSIONS: The present trial demonstrates that 10 weeks of progressive vigorous interval training is sufficient to significantly decrease FM in older adults with central obesity, with positive effects also on LBM.
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23. |
- Ballin, Marcel, et al.
(författare)
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Excess Mortality After COVID-19 in Swedish Long-Term Care Facilities
- 2021
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 22:8, s. 1574-1580.e8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare 30-day mortality in long-term care facility (LTCF) residents with and without COVID-19 and to investigate the impact of 31 potential risk factors for mortality in COVID-19 cases.Design: Retrospective cohort study.Setting and Participants: All residents of LTCFs registered in Senior Alert, a Swedish national database of health examinations in older adults, during 2019-2020.Methods: We selected residents with confirmed COVID-19 until September 15, 2020, along with time-dependent propensity score–matched controls without COVID-19. Exposures were COVID-19, age, sex, comorbidities, medications, and other patient characteristics. The outcome was all-cause 30-day mortality.Results: A total of 3731 residents (median age 87 years, 64.5% female) with COVID-19 were matched to 3731 controls without COVID-19. Thirty-day mortality was 39.9% in COVID-19 cases and 5.7% in controls [relative risk 7.05, 95% confidence interval (CI) 6.10-8.14]. In COVID-19 cases, the odds ratio (OR) for 30-day mortality was 2.44 (95% CI 1.57-3.81) in cases aged 80-84 years, 2.99 (95% CI 1.93-4.65) in cases aged 85-89 years, and 3.28 (95% CI 2.11-5.10) in cases aged ≥90 years, as compared with cases aged <70 years. Other risk factors for mortality among COVID-19 cases included male sex (OR, 2.60, 95% CI 2.22-3.05), neuropsychological conditions (OR, 2.18; 95% CI 1.76-2.71), impaired walking ability (OR, 1.45, 95% CI 1.17-1.78), urinary and bowel incontinence (OR 1.51, 95% CI 1.22-1.85), diabetes (OR 1.36, 95% CI 1.14-1.62), chronic kidney disease (OR 1.37, 95% CI 1.11-1.68) and previous pneumonia (OR 1.57, 95% CI 1.32-1.85). Nutritional factors, cardiovascular diseases, and antihypertensive medications were not significantly associated with mortality.Conclusions and Implications: In Swedish LTCFs, COVID-19 was associated with a large excess in mortality after controlling for an extensive number of risk factors. Beyond older age and male sex, several prevalent clinical risk factors independently contributed to higher mortality. These findings suggest that reducing transmission of COVID-19 in LTCFs will likely prevent a considerable number of deaths.
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24. |
- Ballin, Marcel, et al.
(författare)
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Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding.Objective To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD.Design, Setting, and Participants This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022.Exposures Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence.Main Outcomes and Measures The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017.Results A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%.Conclusions and Relevance In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.
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25. |
- Ballin, Marcel, et al.
(författare)
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Time-varying risk of death after SARS-CoV-2 infection in Swedish long-term care facility residents: a matched cohort study
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate whether SARS-CoV-2 infection in residents of long-term care (LTC) facilities is associated with higher mortality after the acute phase of infection, and to estimate survival in uninfected residents.DESIGN: Extended follow-up of a previous, propensity score-matched, retrospective cohort study based on the Swedish Senior Alert register.SETTING: LTC facilities in Sweden.PARTICIPANTS: n=3604 LTC residents with documented SARS-CoV-2 until 15 September 2020 matched to 3604 uninfected controls using time-dependent propensity scores on age, sex, health status, comorbidities, prescription medications, geographical region and Senior Alert registration time. In a secondary analysis (n=3731 in each group), geographical region and Senior Alert registration time were not matched for in order to increase the follow-up time in controls and allow for an estimation of median survival.PRIMARY OUTCOME MEASURES: All-cause mortality until 24 October 2020, tracked using the National Cause of Death Register.RESULTS: Median age was 87 years and 65% were women. Excess mortality peaked at 5 days after documented SARS-CoV-2-infection (HR 21.5, 95% CI 15.9 to 29.2), after which excess mortality decreased. From the second month onwards, mortality rate became lower in infected residents than controls. The HR for death during days 61-210 of follow-up was 0.76 (95% CI 0.62 to 0.93). The median survival of uninfected controls was 1.6 years, which was much lower than the national life expectancy in Sweden at age 87 (5.05 years in men, 6.07 years in women).CONCLUSIONS: The risk of death after SARS-CoV-2 infection in LTC residents peaked after 5 days and decreased after 2 months, probably because the frailest residents died during the acute phase, leaving healthier residents remaining. The limited life expectancy in this population suggests that LTC resident status should be accounted for when estimating years of life lost due to COVID-19.
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26. |
- Ballin, Marcel, et al.
(författare)
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Web-based exercise versus supervised exercise for decreasing visceral adipose tissue in older adults with central obesity : a randomized controlled trial
- 2020
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Visceral adipose tissue (VAT) is a strong risk factor for cardiovascular disease and increases with age. While supervised exercise (SE) may be an effective approach, web-based exercise (WE) have other advantages such as being more readily accessible. Therefore, we evaluated the effects of WE on VAT, body composition and cardiometabolic risk markers in centrally obese older adults and compared the effects of WE to SE. We also explored the feasibility of WE.METHODS: In a randomized controlled trial conducted in Umeå, Sweden during January 2018 - November 2018, N = 77, 70-year-old men and women with central obesity (> 1 kg VAT for women, > 2 kg for men) were randomized to an intervention group (n = 38) and a wait-list control group (n = 39). The intervention group received 10 weeks of SE while the wait-list control group lived as usual. Following a 10-week wash-out-period, the wait-list control group received 10 weeks of WE. The primary outcome was changes in VAT. Secondary outcomes included changes in fat mass (FM), lean body mass (LBM), blood lipids, fasting blood glucose. Additionally, we explored the feasibility of WE defined as adherence and participant experiences.RESULTS: WE had no significant effect on VAT (P = 0.5), although it decreased FM by 450 g (95% confidence interval [CI], 37 to 836, P < 0.05). The adherence to WE was 85% and 87-97% of the participants rated aspects of the WE intervention > 4 on a scale of 1-5. Comparing SE to WE, there was no significant difference in decrease of VAT (Cohen's δ effect size [ES], 0.5, 95% CI, - 24 to 223, P = 0.11), although SE decreased FM by 619 g (ES, 0.5, 95% CI, 22 to 1215, P < 0.05) compared to WE.CONCLUSIONS: Ten weeks of vigorous WE is insufficient to decrease VAT in centrally obese older adults, but sufficient to decrease FM while preserving LBM. The high adherence and positive experiences of the WE intervention implies that it could serve as an alternative exercise strategy for older adults with central obesity, with increased availability for a larger population.TRIAL REGISTRATION: ClinicalTrials.gov (NCT03450655), retrospectively registered February 28, 2018.
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27. |
- Berginström, Nils, et al.
(författare)
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Attention in Older Adults : A Normative Study of the Integrated Visual and Auditory Continuous Performance Test for Persons Aged 70 Years
- 2015
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Ingår i: Clinical Neuropsychologist (Neuropsychology, Development and Cognition. - : Taylor & Francis. - 1385-4046 .- 1744-4144. ; 29:5, s. 595-610
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Our objective was to present normative data from 70-year-olds on the Integrated Visual and Auditory Continuous Performance Test (IVA), a computerized measure of attention and response control. Method: 640 participants (330 men and 310 women), all aged 70years, completed the IVA, as well as the Mini-Mental State Examination and the Geriatric Depression Scale. Results: Data were stratified by education and gender. Education differences were found in 11 of 22 IVA scales. Minor gender differences were found in six scales for the high-education group, and two scales for the low-education group. Comparisons of healthy participants and participants with stroke, myocardial infarction, or diabetes showed only minor differences. Correlations among IVA scales were strong (all r > .34, p < .001), and those with the widely used Mini-Mental State Examination were weaker (all r < .21, p < .05). Skewed distributions of normative data from primary IVA scales measuring response inhibition (Prudence) and inattention (Vigilance) represent a weakness of this test. Conclusions: This study provides IVA norms for 70-year-olds stratified by education and gender, increasing the usability of this instrument when testing persons near this age. The data presented here show some major differences from original IVA norms, and explanations for these differences are discussed. Explanations include the broad age-range used in the original IVA norms (66-99years of age) and the passage of 15years since the original norms were collected.
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28. |
- Berginström, Nils, 1984-
(författare)
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Fatigue after traumatic brain injury : exploring novel methods for diagnosis and treatment
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Traumatic brain injury (TBI) is one of the most common causes of disability and mortality. While some patients recover quickly, especially at the mild side of the injury severity continuum, many will experience symptoms for years to come. In this chronic phase, patients report a wide array of symptoms, where fatigue is one the most common. This fatigue makes huge impact in several areas of these patients’ lives. Despite the prevalence of fatigue after TBI, the underlying mechanisms are unclear. Further, there are no standardized way for assessment and diagnosis, and there are no treatments with satisfying empirical support. The aim of this thesis was to examine the effects of the novel compound OSU6162 on fatigue in patients with TBI, and to explore functional and structural brain imaging correlates of fatigue after TBI.Methods: Studies I and III were based on a placebo-controlled, double-blinded clinical trial examining the effects of the monoaminergic stabilizer OSU6162 on fatigue in patients in the chronic phase of traumatic brain injury. In study I, self-assessment scales of fatigue and neuropsychological tests were used as outcomes, while functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) signal was the primary outcome in study III. Studies II and IV used cross-sectional designs, comparing patients with TBI with age- and gender matched healthy controls. Study II examined whether fMRI BOLD signal could be used to detect and diagnose fatigue in patients with TBI, and study IV whether white matter hyperintensities (WMH) contribute to lower cognitive functioning and presence of fatigue after TBI.Results: Study I revealed no effects of OSU6162 during 28 days of treatment at maximum doses of 15 mg twice daily on measures of fatigue or any other outcome. The results from study II indicated that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and suggested that fMRI could be a promising technique to use in the diagnosis of fatigue after TBI. In study III the results revealed effects of treatment in the right occipitotemporal and orbitofrontal cortex. In these areas, the BOLD response was normalized in the OSU6162 group as compared to healthy controls, while the placebo group showed a steady low activity in these areas. The regional effects were located outside the network shown to be linked to fatigue in study II, which might explain why there were no effects on fatigue after treatment with OSU6162 in study I. Study IV showed that WMH lesions increased with increased TBI severity, but the presence and extent of lesions did not explain lower neuropsychological functioning or fatigue in subjects with previous TBI.Conclusions: In summary, although no effects on fatigue after treatment with OSU6162 were seen, the results provide support to the theory that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and on how fatigue after TBI could be assessed or diagnosed using fMRI. Structural damage within white matter was however not related to fatigue.
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29. |
- Berginström, Nils, 1984-, et al.
(författare)
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Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning
- 2017
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Ingår i: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 31:6-7, s. 755-755
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Tidskriftsartikel (refereegranskat)abstract
- Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.
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30. |
- Berginström, Nils, et al.
(författare)
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Pharmaco-fMRI in Patients With Traumatic Brain Injury : A Randomized Controlled Trial With the Monoaminergic Stabilizer (-)-OSU6162
- 2019
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Ingår i: The journal of head trauma rehabilitation. - : Wolters Kluwer. - 0885-9701 .- 1550-509X. ; 34:3, s. 189-198
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the effects of monoaminergic stabilizer (-)-OSU6162 on brain activity, as measured by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients in the chronic phase of traumatic brain injury suffering from fatigue.SETTING: Neurorehabilitation clinic.PARTICIPANTS: Patients with traumatic brain injury received either placebo (n = 24) or active treatment (n = 28). Healthy controls (n = 27) went through fMRI examination at one point and were used in sensitivity analysis on normalization of BOLD response.DESIGN: Randomized, double-blinded, placebo-controlled design.MAIN MEASURES: Effects on BOLD signal changes from before to after treatment during performance of a fatiguing attention task.RESULTS: The fMRI results revealed treatment effects within the right occipitotemporal cortex and the right orbitofrontal cortex. In these regions, the BOLD response was normalized relative to healthy controls at the postintervention fMRI session. No effects were seen in regions in which we previously observed activity differences between patients and healthy controls while performing this fMRI task, such as the striatum.CONCLUSION: (-)-OSU6162 treatment had influences on functional brain activity, although the normalized regional BOLD response was observed in regions that were not a priori hypothesized to be sensitive to this particular treatment, and was not accompanied by any effects on in-scanner test performance or on fatigue.
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31. |
- Berginström, Nils, et al.
(författare)
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The effects of (-)-OSU6162 on chronic fatigue in patients with traumatic brain injury : a randomized controlled trial
- 2017
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Ingår i: The journal of head trauma rehabilitation. - 0885-9701 .- 1550-509X. ; 32:2, s. E46-E54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the effects of the monoaminergic stabilizer (-)-OSU6162 on mental fatigue in patients with traumatic brain injury.SETTING: Single-center Neurorehabilitation Clinic.DESIGN: Randomized, double-blind, placebo-controlled trial.PARTICIPANTS: Sixty-four subjects with traumatic brain injury were randomized to treatment (n = 33) and placebo (n = 31).MAIN MEASURES: The effects of (-)-OSU6162 at a dose of 15 mg twice a day were evaluated using self-assessment scales and neuropsychological tests measuring mental fatigue.RESULTS: No difference between groups was observed on any scale at baseline. At follow-up, both groups showed significant improvement on the Fatigue Severity Scale and the Mental Fatigue Scale (both Ps < .01). Similarly, the performance of both groups increased significantly on many neuropsychological tests. However, no significant between-group difference in changes on these scales was observed before or after adjustment for confounders except for one neuropsychological test favoring the control group. Sensitivity analyses showed significantly greater changes in levels of prolactin and folic acid and heart rate (all Ps < .05) in the treatment group. The mean plasma concentration after 4 weeks of treatment was 0.14 (range, 0.01-0.32) μM, which was lower than expected.INTERPRETATION: Treatment with (-)-OSU6162 had no significant effect on mental fatigue in patients with traumatic brain injury compared with placebo.
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32. |
- Berginström, Nils, et al.
(författare)
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Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury : changes linked to altered Striato-Thalamic-Cortical Functioning
- 2018
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Ingår i: The journal of head trauma rehabilitation. - : Wolters Kluwer. - 0885-9701 .- 1550-509X. ; 33:4, s. 266-274
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).Setting: Neurorehabilitation clinic.Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.
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33. |
- Berginström, Nils, 1984-, et al.
(författare)
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White matter hyperintensities increases with traumatic brain injury severity : associations to neuropsychological performance and fatigue
- 2020
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Ingår i: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 34:3, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.Methods: A total of 59 patients with TBI and 27 age- and gender-matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.Results: WMH lesions were more common in patients with TBI than in healthy controls (p = .032), and increased with higher TBI severity (p = .025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > .05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = - 0.33, p = .026).Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. These lesions could not explain decreased cognitive functioning in patients with TBI but did relate to decreased self-assessment of fatigue after TBI.
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34. |
- Berginström, Nils, et al.
(författare)
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White matter hyperintensities increases with traumatic brain injuryseverity : associations to neuropsychological performance and fatigue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.Methods: A total of 59 patients with TBI and 27 age- and gender- matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.Results: WMH lesions were more common in patients with TBI than in healthy controls (p = 0.032), and increased with higher TBI severity (p = 0.025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > 0.05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = –0.33, p = 0.026).Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. However, these lesions do not seem to explain the decreased cognitive functioning or the increased fatigue in patients with TBI.
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35. |
- Bergman, Jonathan, et al.
(författare)
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Alendronate use and the risk of nonvertebral fracture during glucocorticoid therapy : a retrospective cohort study
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Cary : Oxford University Press. - 0021-972X .- 1945-7197. ; 103:1, s. 306-313
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Tidskriftsartikel (refereegranskat)abstract
- Context: Glucocorticoids increase the risk of nonvertebral fracture, but no clinical trial has shown that nonvertebral fractures can be prevented by co-administration of an anti-osteoporotic drug.Objective: To estimate the effect of alendronate on the risk of nonvertebral fracture in older adults taking oral glucocorticoids.Design: Retrospective cohort study using national Swedish registers.Setting: Hospitalized care and ambulatory specialist care.Patients: Among adults aged 50 years or older (N=3,347,959), we identified those who initiated oral glucocorticoid therapy from 2006 through 2011 (≥2.5 mg/day of prednisone or equivalent for ≥91 days). The final analysis included 16,890 alendronate users and 16,890 nonusers, who were matched using time-dependent propensity scores.Main Outcome Measure: Nonvertebral fracture. This was not pre-specified.Results: Over a median follow-up of 14.5 months, the incidence rate of nonvertebral fracture was 2.0 cases per 100 person-years in alendronate users and 2.4 cases in nonusers. This difference corresponded to a 16% lower rate in users (hazard ratio 0.84, 95% confidence interval 0.75 to 0.94). For hip fractures specifically, the rate was 34% lower in alendronate users relative to nonusers (hazard ratio 0.66, 95% confidence interval 0.55 to 0.78). The association of alendronate use with a lower risk of nonvertebral fracture was strongest in patients who received high doses of glucocorticoid.Conclusion: Alendronate use was associated with a lower risk of nonvertebral fracture, including hip fracture. Similar, but not statistically significant, associations have been reported in meta-analyses of clinical trials.
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36. |
- Bergman, Jonathan, et al.
(författare)
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Bisphosphonate use after clinical fracture and risk of new fracture
- 2018
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 29:4, s. 937-945
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Among older adults with a previous fracture, treatment for osteoporosis was initially associated with a higher risk of new fracture. However, the relative risk of new fracture decreased over time, a trend that is consistent with a beneficial effect, as treatment for osteoporosis is prescribed to reduce high fracture risks.Introduction: The purpose of this study was to examine whether bisphosphonate use is associated with a lower risk of new fracture after a clinical fracture in older adults.Methods: Data were available for 3,329,400 adults in Sweden who were aged ae 50 years between 2006 and 2011. During this period, 260,353 sustained a clinical fracture and were naïve to bisphosphonates at the time. Those who subsequently received a bisphosphonate were matched to up to three others on sex, year of birth, and type and year of initial fracture. The final cohort comprised 83,104 adults (26.3% bisphosphonate users).Results: During the period from initial fracture to initiation of bisphosphonate treatment, the incidence rate of any new clinical fracture was higher in those who later became bisphosphonate users than in those who remained nonusers (175.1 vs. 75.9 per 1000 person-years; hazard ratio 2.30, 95% confidence interval 2.19 to 2.41). Similarly, during the first 6 months of treatment, the incidence rate was higher in bisphosphonate users than in nonusers (128.8 vs. 90.2 per 1000 person-years; hazard ratio 1.41, 95% confidence interval 1.32 to 1.51). However, this difference decreased over time: by months 12 to 18, the incidence rate was similar in users and nonusers (59.3 vs. 55.3 per 1000 person-years; hazard ratio 1.03, 95% confidence interval 0.91 to 1.16).Conclusions: There was a decrease in the relative risk of new fracture during bisphosphonate treatment, a trend that is consistent with a beneficial treatment effect, as bisphosphonates are prescribed to reduce high fracture risks.
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37. |
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38. |
- Bergman, Jonathan, et al.
(författare)
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Bisphosphonates and mortality : confounding in observational studies?
- 2019
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 30:10, s. 1973-1982
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Numerous observational studies suggest that bisphosphonates reduce mortality. This study showed that bisphosphonate use is associated with lower mortality within days of treatment, although the association was not significant until the second week. Such an early association is consistent with confounding, although an early treatment effect cannot be ruled out.Introduction: The purpose of this study was to examine whether confounding explains why numerous observational studies show that bisphosphonate use is associated with lower mortality. To this end, we examined how soon after treatment initiation a lower mortality rate can be observed. We hypothesized that, due to confounding, the association would be observed immediately.Methods: This was a retrospective cohort study of hip fracture patients discharged from Swedish hospitals between 1 July 2006 and 31 December 2015. The data covered 260,574 hip fracture patients and were obtained from the Swedish Hip Fracture Register and national registers. Of the 260,574 patients, 49,765 met all eligibility criteria and 10,178 were pair matched (bisphosphonate users to controls) using time-dependent propensity scores. The matching variables were age, sex, diagnoses, prescription medications, type of hip fracture, type of surgical procedure, known or suspected dementia, and physical functioning status.Results: Over a median follow-up of 2.8 years, 2922 of the 10,178 matched patients died. The mortality rate was 7.9 deaths per 100 person-years in bisphosphonate users and 9.4 deaths in controls, which corresponded to a 15% lower mortality rate in bisphosphonate users (hazard ratio 0.85, 95% confidence interval 0.79–0.91). The risk of death was lower in bisphosphonate users from day 6 of treatment, although the association was not significant until the second week.Conclusion: Bisphosphonate use was associated with lower mortality within days of treatment initiation. This finding is consistent with confounding, although an early treatment effect cannot be ruled out.
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39. |
- Bergman, Jonathan, et al.
(författare)
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Epidemiology of osteonecrosis among older adults in Sweden
- 2019
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 30:5, s. 965-973
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Tidskriftsartikel (refereegranskat)abstract
- Summary: This study estimated the incidence of osteonecrosis in a Swedish, nationwide cohort of older adults. Osteonecrosis was approximately 10 times more common than in previous studies. The strongest risk factors were dialysis, hip fracture, osteomyelitis, and organ transplantation, but only hip fractures could have contributed substantially to the disease burden.Introduction: The aim of this study was to estimate the incidence of osteonecrosis in a Swedish, nationwide cohort of older adults and in a large number of risk groups in that cohort.Methods: In this retrospective cohort study, we included everyone who was aged 50 years or older and who was living in Sweden on 31 December 2005. We used Swedish national databases to collect data about prescription medication use, diagnosed medical conditions, and performed medical and surgical procedures. The study outcome was diagnosis of primary or secondary osteonecrosis at any skeletal site. The strength of risk factors was assessed using age- and sex-standardized incidence ratios (SIRs).Results: The study cohort comprised 3,338,463 adults. The 10-year risk of osteonecrosis was 0.4% (n = 13,425), and the incidence rate was 4.7 cases/10000 person-years (95% confidence interval [CI], 4.6 to 4.7 cases). The strongest risk factors for osteonecrosis were hip fracture (SIR, 7.98; 95% CI, 7.69–8.27), solid organ transplantation (SIR, 7.14; 95% CI, 5.59–8.99), dialysis (SIR, 6.65; 95% CI, 5.62–7.81), and osteomyelitis (SIR, 6.43; 95% CI, 5.70–7.23). A history of hip fracture was present in 21.7% of cases of osteonecrosis, but osteomyelitis, dialysis, and solid organ transplantation were present in only 0.5 to 2% of cases.Conclusions: Osteonecrosis was approximately 10 times more common than a small number of previous population-based studies have suggested. The strongest risk factors for osteonecrosis were dialysis, hip fracture, osteomyelitis, and solid organ transplantation, but only hip fractures could have contributed substantially to the disease burden.
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40. |
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41. |
- Bergman, Jonathan, et al.
(författare)
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Risk factors for COVID-19 diagnosis, hospitalization, and subsequent all-cause mortality in Sweden : a nationwide study
- 2021
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Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 36:3, s. 287-298
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a nationwide, registry-based study to investigate the importance of 34 potential risk factors for coronavirus disease 2019 (COVID-19) diagnosis, hospitalization (with or without intensive care unit [ICU] admission), and subsequent all-cause mortality. The study population comprised all COVID-19 cases confirmed in Sweden by mid-September 2020 (68,575 non-hospitalized, 2494 ICU hospitalized, and 13,589 non-ICU hospitalized) and 434,081 randomly sampled general-population controls. Older age was the strongest risk factor for hospitalization, although the odds of ICU hospitalization decreased after 60–69 years and, after controlling for other risk factors, the odds of non-ICU hospitalization showed no trend after 40–49 years. Residence in a long-term care facility was associated with non-ICU hospitalization. Male sex and the presence of at least one investigated comorbidity or prescription medication were associated with both ICU and non-ICU hospitalization. Three comorbidities associated with both ICU and non-ICU hospitalization were asthma, hypertension, and Down syndrome. History of cancer was not associated with COVID-19 hospitalization, but cancer in the past year was associated with non-ICU hospitalization, after controlling for other risk factors. Cardiovascular disease was weakly associated with non-ICU hospitalization for COVID-19, but not with ICU hospitalization, after adjustment for other risk factors. Excess mortality was observed in both hospitalized and non-hospitalized COVID-19 cases. These results confirm that severe COVID-19 is related to age, sex, and comorbidity in general. The study provides new evidence that hypertension, asthma, Down syndrome, and residence in a long-term care facility are associated with severe COVID-19.
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42. |
- Carlborg, Andreas, et al.
(författare)
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Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis
- 2010
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 68-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor.AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide.METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records.RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters.CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.
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43. |
- Carlborg, Andreas, et al.
(författare)
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Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis
- 2011
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:2, s. 101-5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers.AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA.METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register.RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age.CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.
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44. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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45. |
- Denver, Sigrid, et al.
(författare)
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Samspil mellem økologisk forbrug og sundhed
- 2018
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Ingår i: Øget efterspørgsel efter danske økologiske fødevarer: : Tre studier af motiver og ønsker hos forbrugerne med fokus på sundhed, lokale fødevarer og øget eksport. - Tre studier af motiver og ønsker hos forbrugerne med fokus på sundhed, lokale fødevarer og øget eksport.. - : Frederiksberg: Institut for Fødevare- og Ressourceøkonomi, Københavns Universitet. - 9788792591883 ; , s. 11-33
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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46. |
- Eklund, Fredrik, et al.
(författare)
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Bone mass, size and previous fractures as predictors of prospective fractures in an osteoporotic referral population.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 45:4, s. 808-813
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Tidskriftsartikel (refereegranskat)abstract
- The influence of bone mass, bone size and previous low energy fractures upon prospective fractures has not been investigated in a referral osteoporotic population. We investigated the association between bone mass, bone size, previous fractures, body constitution, and prospective validated fractures in 5701 women and 1376 men, aged 30 years and older. Bone mass measurements of the femoral neck were collected at a single study center in Sweden. Most of the subjects were measured on suspicion of osteoporosis. Data on validated low energy retrospective and prospective fractures in the cohort were collected from the corresponding health care district. Bone mineral density (BMD, g/cm(2)) and estimated volumetric BMD (vBMD, g/cm(3)) were shown to be good independent predictors for fracture in both women and men (Hazard ratio per standard deviation decrease (HR)=1.27-1.52, p<0.05). Bone size did not predict prospective fractures in either sex (HR=0.91-0.99, p>0.05), and bone size completely explained the higher BMD in men than in women. In women, retrospective low energy fractures (HR=1.78, p<0.001) and height (HR=1.02, p=0.006) were additional independent predictors of osteoporotic fractures after adjusting for age and BMD. In conclusion, we show that in a large osteoporotic referral population, age, BMD and previous fractures are independent predictors of prospective low energy fractures. These results add additional strength to the recent change in focus towards a multivariate analysis when assessing the future risk of fracture.
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47. |
- Eklund, Fredrik, et al.
(författare)
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Variation in fracture rates by country may not be explained by differences in bone mass
- 2009
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 85:1, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether the high fracture incidence in Sweden compared with other countries is related to low bone mass. We present and compare bone mineral density (BMD, g/cm(2)) at the femoral neck in a mainly osteoporotic referral population consisting of 2,031 men and 6,932 women with that of previous population-based cohorts. BMD measurements were collected at a single study center in Sweden, and data on validated hip fractures were collected from the corresponding health-care district and the cohort investigated. The BMD values of our cohort were similar to those of population-based cohorts from other countries. In contrast, the total incidence of hip fractures in 80-year-old women and men in the health-care district where our BMD measurements were performed was high (1.8% and 0.9%, respectively). The correlation between age and BMD was more negative in men aged 20-49 years than in women of the same age group (-0.011 vs. -0.006 g/cm(2) yearly, P < 0.001). In contrast, at 50-80 years of age, more negative regression coefficients were seen in women (-0.007 vs. -0.004 g/cm(2) yearly, P < 0.001 for comparison). In conclusion, a low BMD may not be the key factor explaining Sweden's comparatively high fracture incidence. In our cross-sectional data, age trends in BMD at the femoral neck differ between men and women. It would be highly interesting to further study the underlying causes of the global variations in fracture incidence rates.
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48. |
- Eriksson, Maija, et al.
(författare)
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Sedentary behavior as a potential risk factor for depression among 70-year-olds
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 263, s. 605-608
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sedentary behavior has previously been associated with the risk of depression. In addition, older adults have been proven to be more sedentary and more depressed than other age groups. However, studies using objective measures of sedentary behavior and taking physical activity into account are lacking. Thus, the purpose of this population-based study was to examine how total sedentary time and length of sedentary bouts were associated with the risk of depression among 70-year-olds.Methods: The present study used data from the Healthy Ageing Initiative (n = 3,633), an ongoing cross-sectional research project in Umeå, Sweden. Sedentary behavior was measured objectively with the ActiGraph GT3X+ accelerometer, and depression was measured with the Geriatric Depression Scale. Several covariates, including physical activity, were included in logistic regression analyses.Results: Results from two hierarchical logistic regression models showed that a greater percentage of the day spent sedentary [odds ratio (OR) = 1.031, p = 0.010] and longer average length of sedentary bouts (OR = 1.116, p = 0.045) increased the risk of depression.Limitations: Limitations include of possible underrepresentation of severely depressed participants, and possible observer effects.Conclusions: The present study verified the relationship between sedentary behavior and depression and provides new information about the risks associated with increased length of sedentary bouts. These findings may be important to consider in the development of future recommendations for the prevention of depression among older adults.
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49. |
- Freischmidt, Axel, et al.
(författare)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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50. |
- Gentile, Ambra, et al.
(författare)
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Use of alcohol, drugs, inhalants, and smoking tobacco and the long-term risk of depression in men : A nationwide Swedish cohort study from 1969–2017
- 2021
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Ingår i: Drug And Alcohol Dependence. - : Elsevier. - 0376-8716 .- 1879-0046. ; 221
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of alcohol, drugs, inhalants, and smoking tobacco may lead to mood disorders such as depression. However, knowledge on the independent contributions of the use of these substances to the risk of depression is lacking.Methods: The study cohort consisted of 24,564 men included in the Swedish national military conscription register who were conscripted in 1969–1970 and followed until 2017. Cox proportional hazard ratios were used to estimate the risk of depression according to alcohol, drug, inhalant, and cigarette consumption, and adjusted for body mass index, verbal comprehension test scores, handgrip strength, and the other main exposures investigated.Results: During an average follow-up period of 44 years, 4500 men were diagnosed with or treated for depression at a mean age of 54 years. A dose-dependent association was found in men who smoked cigarettes, with the highest risk for smoking >20 cigarettes per day, at time of conscription (aHR 1.86, 95 % CI 1.61–2.16, p < 0.001). Independent associations with an increased risk of depression were found for the use of drugs at least once (aHR 1.21, 95 % CI 1.10–1.32, p < 0.001) and >50 times (aHR 1.48, 95 % CI 1.23–1.77, p < 0.001) and the use of inhalants (aHR 1.16, 95 % CI 1.05–1.29). Excessive alcohol intake was not associated with the risk of depression.Conclusion: The results suggest that people who reported to have used cigarettes, alcohol, or drugs at 18 years of age have a moderately increased risk of depression later in life.
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