| 1. |
- Heikkilä, Katriina, et al.
(författare)
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Job strain and COPD exacerbations: an individual-participant meta-analysis
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 247-251
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor:Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and disability worldwide (1). The clinical course of COPD is characterised by exacerbations, which can be minor and manageable at home or in primary care, or severe, leading to hospitalisation or even death. Known causes of exacerbations include tobacco smoke, air pollution, dusts and fumes, and respiratory infections (1, 2). One less well understood risk factor is stress, which could plausibly lead to COPD exacerbations as it can trigger inflammation (3, 4) and is associated with increased smoking (5), which are both implicated in COPD pathology (2). Work is an important source of stress in the age groups in which COPD is typically diagnosed (1, 6). However, we are not aware of previous investigations of work-related stress and the risk of COPD exacerbations.In this study, we examined the associations between job strain (the most widely studied conceptualisation of work-related stress) and severe COPD exacerbations using individual-level data from 10 prospective cohort studies from the Individual Participant Data Meta-analysis in Working Populations (IPD-Work) Consortium (7). Job strain is defined as a combination of high demands (excessive amounts of work) and low control (having little influence on what tasks to.
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| 2. |
- Hodgins, S., et al.
(författare)
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Individuals developing schizophrenia are hidden among adolescent substance misusers
- 2016
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 46:14, s. 3041-3050
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Tidskriftsartikel (refereegranskat)abstract
- Background Strategies are needed to identify youth developing schizophrenia. The present study aimed to determine whether adolescents treated for substance misuse were at elevated risk to develop schizophrenia, whether this risk has changed since the late 1960s, and whether substance misuse in adolescence predicted poorer outcomes through adulthood. Method In a Swedish city, since the mid-1960s there has been only one clinic for adolescent substance misuse. Three samples from this clinic were studied: 1992 individuals treated from 1968 to 1971 followed to age 50 years; 1576 treated from 1980 to 1984 followed to age 35 years; and 180 treated in 2004 followed to age 22 years. Each clinical sample was matched on age, sex and place of birth to an equal, or larger, number of randomly selected individuals from the general population. Schizophrenia, substance use disorders, physical disorders related to substance misuse, criminal convictions, poverty and death were identified using national registers. Results Individuals treated for substance misuse in adolescence were at increased risk to subsequently develop schizophrenia: in males the increase was approximately four-fold and in females between five- and seven-fold. There was no difference in risk for those treated in 1968-1971 and from 1980 to 1984 when cannabis use increased from 37.6% to 49.8% of the clinical samples. Among males who developed schizophrenia, treatment for substance misuse was associated with increased risk of substance use disorders and criminal convictions through adulthood. Conclusions Treatment programmes for adolescents misusing substances include a disproportionate number developing schizophrenia. Early detection and treatment have the potential to improve long-term outcomes.
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| 3. |
- Moens, Lotte N. J., et al.
(författare)
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HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples
- 2015
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Ingår i: Journal of Molecular Diagnostics. - : Elsevier BV. - 1525-1578 .- 1943-7811. ; 17:6, s. 729-739
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, the advent of massively parallel next-generation sequencing technologies has enabled substantial advances in the study of human diseases. Combined with targeted DNA enrichment methods, high sequence coverage can be obtained for different genes simultaneously at a reduced cost per sample, creating unique opportunities for clinical cancer diagnostics. However, the formalin-fixed, paraffin-embedded (FFPE) process of tissue samples, routinely used in pathology departments, results in DNA fragmentation and nucleotide modifications that introduce a number of technical challenges for downstream biomotecular analyses. We evaluated the HaloPlex target enrichment system for somatic mutation detection in 80 tissue fractions derived from 20 clinical cancer cases with paired tumor and normal tissue available in both FFPE and fresh-frozen format. Several modifications to the standard method were introduced, including a reduced target fragment Length and two strand capturing. We found that FFPE material can be used for HaloPlex-based target enrichment and next-generation sequencing, even when starting from small amounts of DNA. By specifically capturing both strands for each target fragment, we were able to reduce the number of false-positive errors caused by FFPE-induced artifacts and Lower the detection limit for somatic mutations. We believe that the HaloPlex method presented here will be broadly applicable as a tool for somatic mutation detection in clinical cancer settings.
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| 4. |
- Leuzy, Antoine, et al.
(författare)
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Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:5, s. 652-663
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Cross-sectional findings using the tau tracer [F-18] THK5317 (THK5317) have shown that [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information. Methods: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change. Results: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317. Discussion: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.
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| 5. |
- Lindahl Norberg, Annika, 1960-, et al.
(författare)
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Relationship between problems related to child late effects and parent burnout after pediatric hematopoietic stem cell transplantation
- 2014
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Ingår i: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 18:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- A few studies have indicated that parents' reactions to a child's serious disease may entail long-term stress for the parents. However, further knowledge of its consequences is valuable. The aim of the study was to investigate the occurrence of burnout in a Swedish national sample of parents of children who had undergone HSCT and survived. Burnout (Shirom-Melamed Burnout Questionnaire) and estimations of the child's health status (Lansky/Karnofsky estimations and study-specific questions) were self-reported by 159 mothers and 123 fathers. In addition, physicians made estimations of the child's health status (Lansky/Karnofsky estimations). Nonparametric tests revealed that burnout symptoms occurred more often among fathers of children who had undergone transplantation within the last five yr compared to fathers of children with no history of serious disease (34.4% vs. 19.9%). Burnout among mothers and fathers was associated with the child's number and severity of health impairments up to five yr after the child underwent HSCT (Spearman's rho for mothers 0.26-0.36 and for fathers 0.36-0.61). In conclusion, chronic stress in parents after a child's HSCT seems to abate eventually. However, parents should be monitored and offered adequate support when needed. Moreover, the situation of fathers in the often mother-dominated pediatric setting should receive more attention in research as well as in the clinic.
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| 6. |
- Sjölund, Britt-Marie, et al.
(författare)
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Incidence of ADL Disability in Older Persons, Physical Activities as a Protective Factor and the Need for Informal and Formal Care : Results from the SNAC-N Project
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to examine 1) the incidence of disability in Activities of Daily Living (ADL), in persons 78 years and older 2) explore whether being physical active earlier is a significant predictor of being disability free at follow-up and 3) describe the amount of informal and formal care in relation to ADL-disability.METHODS: Data were used from a longitudinal community-based study in Nordanstig (SNAC-N), a part of the Swedish National Study on Aging and Care (SNAC). To study objectives 1) and 2) all ADL-independent participants at baseline (N = 307) were included; for objective 3) all participants 78 years and older were included (N = 316). Data were collected at baseline and at 3- and 6-year follow-ups. ADL-disability was defined as a need for assistance in one or more activities. Informal and formal care were measured using the Resource utilization in Dementia (RUD)-instrument.RESULTS: The incidence rates for men were similar in the age groups 78-81and 84 years and older, 42.3 vs. 42.5/1000 person-years. For women the incidence rate for ADL-disability increased significantly from the age group 78-81 to the age group 84 years and older, 20.8 vs.118.3/1000 person-years. In the age group 78-81 years, being physically active earlier (aOR 6.2) and during the past 12 month (aOR 2.9) were both significant preventive factors for ADL-disability. Both informal and formal care increased with ADL-disability and the amount of informal care was greater than formal care. The incidence rate for ADL-disability increases with age for women and being physically active is a protective factor for ADL-disability.CONCLUSION: The incidence rate for ADL-disability increases with age for women, and being physical active is a protective factor for ADL-disability.
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| 7. |
- Wellander, Lisa, et al.
(författare)
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Does Prevention Pay? : Costs and Potential Cost-savings of School Interventions Targeting Children with Mental Health Problems
- 2016
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Ingår i: Journal of Mental Health Policy and Economics. - 1091-4358 .- 1099-176X. ; 19:2, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, the local government is responsible for funding schools in their district. One funding initiative is for schools to provide students with mental health problems with additional support via extra teachers, personal assistants, and special education classes. There are evidence-based preventive interventions delivered in schools, which have been shown to decrease the levels of students' mental health problems. However, little is known about how much the local government currently spends on students' mental health support and if evidence-based interventions could be financially beneficial. AIMS OF THE STUDY: The aim of this study was to estimate the costs of providing additional support for students' mental health problems and the potential cost-offsets, defined as reduced school-based additional support, if two evidence-based school interventions targeting children's mental health problems were implemented in routine practice. METHODS: This study uses data on the additional support students with mental health problems received in schools. Data was collected from one school district for students aged 6 to 16 years. We modeled two Swedish school interventions, Comet for Teachers and Social and Emotional Training (SET), which both had evidence of reducing mental health problems. We used a cost-offset analysis framework, assuming both interventions were fully implemented throughout the whole school district. Based on the published studies, the expected effects and the costs of the interventions were calculated. We defined the cost-offsets as the amount of predicted averted additional support for students with ongoing mental health problems who might no longer require receiving services such as one-on-one time with an extra teacher, a personal assistant, or to be placed in a special education classroom. A cost-offset analysis, from a payer's perspective (the local government responsible for school financing), was conducted comparing the costs of both interventions with the potential cost-savings due to a reduction in the prevalence of mental health problems and averted additional support required. RESULTS: The school district was comprised of 6,256 students, with 310 students receiving additional support for their mental health problems. Of these, 143 received support in their original school due to either having ADHD (n = 111), psychosocial problems (n = 26), or anxiety/depression (n = 6). The payers' total cost of additional support was 2,637,850 Euro per school year (18,447 Euro per student). The cost of running both interventions for the school district was 953,643 Euro for one year, while the potential savings for these interventions were estimated to be 627,150 Euro. The estimated effects showed that there would be a reduction of students needing additional support (25 for ADHD, eight for psychosocial problems, and one for anxiety/depression), and the payer would receive a return on their invested resources in less than two years (1.5 years) after implementation. DISCUSSION: Preventive school interventions can both improve some children's mental health problems and be financially beneficial for the payer. However, they are still limited in their scope of reducing all students' mental health statuses to below clinical cut-offs; therefore, the preventive school interventions should be used as a supplement, but not a replacement, to current practices. IMPLICATIONS FOR HEALTH POLICIES: The findings have political and societal implications, in that payers can reallocate their funds toward preventive measures targeting students' mental health problems, while reducing the costs. IMPLICATIONS FOR FUTURE RESEARCH: When evaluating public health actions, it is necessary to consider their economic impact. The resources are scarce and the decision makers need knowledge on how to allocate their resources in an efficient way. Cost-offset analysis is seen as one way for decision makers to comprehend research findings; however, such analyses tend to not include the full benefits of the interventions, and actual impacts need to be fully evaluated in routine implementation.
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| 8. |
- Furmark, Tomas, et al.
(författare)
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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- 2016
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Ingår i: Journal of Psychopharmacology. - London, United Kingdom : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1028-1035
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Tidskriftsartikel (refereegranskat)abstract
- It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ -C-11]tryptophan, [C-11]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [C-11]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.
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| 9. |
- Kivimäki, Mika, et al.
(författare)
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Associations of job strain and lifestyle risk factors with risk of coronary artery disease : a meta-analysis of individual participant data
- 2013
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Ingår i: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel. - : CMA Joule Inc.. - 0820-3946 .- 1488-2329. ; 185:9, s. 763-769
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear whether a healthy lifestyle mitigates the adverse effects of job strain on coronary artery disease. We examined the associations of job strain and lifestyle risk factors with the risk of coronary artery disease.Methods: We pooled individual-level data from 7 cohort studies comprising 102 128 men and women who were free of existing coronary artery disease at baseline (1985–2000). Questionnaires were used to measure job strain (yes v. no) and 4 lifestyle risk factors: current smoking, physical inactivity, heavy drinking and obesity. We grouped participants into 3 lifestyle categories: healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2–4 risk factors). The primary outcome was incident coronary artery disease (defined as first nonfatal myocardial infarction or cardiac-related death).Results: There were 1086 incident events in 743 948 person-years at risk during a mean follow-up of 7.3 years. The risk of coronary artery disease among people who had an unhealthy lifestyle compared with those who had a healthy lifestyle (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.18–2.98; population attributable risk 26.4%) was higher than the risk among participants who had job strain compared with those who had no job strain (HR 1.25, 95% CI 1.06–1.47; population attributable risk 3.8%). The 10-year incidence of coronary artery disease among participants with job strain and a healthy lifestyle (14.7 per 1000) was 53% lower than the incidence among those with job strain and an unhealthy lifestyle (31.2 per 1000).Interpretation: The risk of coronary artery disease was highest among participants who reported job strain and an unhealthy lifestyle; those with job strain and a healthy lifestyle had half the rate of disease. A healthy lifestyle may substantially reduce disease risk among people with job strain.
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| 10. |
- Kivimäki, Mika, et al.
(författare)
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Long working hours as a risk factor for atrial fibrillation : a multi-cohort study
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 38:34, s. 2621-2628
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Tidskriftsartikel (refereegranskat)abstract
- Aims Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working long hours (>= 55 per week) and those working standard 35-40 h/week. Methods and results In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium, the study population was 85 494 working men and women (mean age 43.4 years) with no recorded atrial fibrillation. Working hours were assessed at study baseline (1991-2004). Mean follow-up for incident atrial fibrillation was 10 years and cases were defined using data on electrocardiograms, hospital records, drug reimbursement registers, and death certificates. We identified 1061 new cases of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared with those working standard hours (hazard ratio = 1.42, 95% CI= 1.13-1.80, P= 0.003). There was no significant heterogeneity between the cohort-specific effect estimates (I-2= 0%, P = 0.66) and the finding remained after excluding participants with coronary heart disease or stroke at baseline or during the follow-up (N= 2006, hazard ratio= 1.36, 95% CI= 1.05-1.76, P = 0.0180). Adjustment for potential confounding factors, such as obesity, risky alcohol use and high blood pressure, had little impact on this association. Conclusion Individuals who worked long hours were more likely to develop atrial fibrillation than those working standard hours.
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