| 1. |
- Yang, Fei, et al.
(författare)
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Moist smokeless tobacco (Snus) use and risk of Parkinson's disease
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 872-880
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease.METHODS: Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking.RESULTS: During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83).CONCLUSIONS: Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.
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| 2. |
- Wagner, Ryan G, 1984-
(författare)
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The Burden of Epilepsy : using population-based data to define the burden and model a cost-effective intervention for the treatment of epilepsy in rural South Africa
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rationale Epilepsy is a common, chronic, neurological condition that disproportionately affects individuals living in low- and middle- income countries, including much of sub-Saharan Africa. Epilepsy is treatable, with the majority of individuals who take anti-epileptic drugs experiencing a reduction, or elimination, of seizures. Yet the number of individuals taking and adhering to medication in Africa is low and interventions aimed at improving treatment are lacking.Aims To define the epidemiology of convulsive epilepsy in rural South Africa in terms of incidence, mortality and disability-adjusted life years; to determine outpatient, out-of-pocket costs resulting from epilepsy treatment; to establish the level of adherence to anti-epileptic drugs amongst people with epilepsy; and, to determine whether the introduction of routine visits to people with epilepsy by community health workers is a cost-effective intervention for improving adherence to anti-epileptic drugs.Methods Nested within the Agincourt Health and Demographic Surveillance System, this work utilized a cohort of individuals diagnosed with convulsive epilepsy in 2008 to determine health care utilization and out-of-pocket costs due to care sought for epilepsy. Additionally, using blood samples from the cohort, anti-epileptic drug adherence was measured and, following the cohort, mortality rates were determined. Using these collected epidemiological parameters, disability-adjusted life years due to convulsive epilepsy were determined. Finally, combining the epidemiological and cost parameters, a community health worker intervention was modeled to determine its incremental cost-effectiveness ratio.Key Findings The burden of convulsive epilepsy is lower in rural South Africa than other parts of Africa, likely due to lower levels of known risk factors. Yet the burden, especially in terms of mortality, remains high, as does the treatment gap and health care utilization. Findings from the economic evaluation found the introduction of a community health worker to be highly cost-effective and would likely lower the burden of epilepsy in rural South Africa.Implications Epilepsy contributes to the burden of disease in rural South Africa, with high levels of mortality and a substantial treatment gap. The introduction of a community-health worker is likely to be one cost-effective, community based intervention that would lower the burden of epilepsy by improving adherence to anti-epileptic drugs. Implementing this intervention, based on these findings, is a justified and important next step.
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| 3. |
- Jakobson Mo, Susanna, 1968-, et al.
(författare)
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I-123-FP-Cit and I-123-IBZM SPECT uptake in a prospective normal material analysed with two different semiquantitative image evaluation tools
- 2013
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Ingår i: Nuclear Medicine Communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 34:10, s. 978-989
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Tidskriftsartikel (refereegranskat)abstract
- Objective The need for age-adjusted and/or sex-adjusted reference values in dopamine transporter (DAT) and dopamine D2 receptor (D2R) imaging with single-photon emission computed tomography (SPECT) in a longitudinal study of parkinsonian diseases was investigated. We used two different image evaluation tools with a cross-sectional and longitudinal statistical approach.Materials and methods Baseline DAT and/or D2R SPECT were performed in 51 healthy controls (HC), age-matched to patients in an ongoing prospective study on idiopathic parkinsonism. Twenty-four HC were re-examined after 3 years and 21 HC were examined again after 5 years. SPECT was performed with I-123-FP-Cit and I-123-IBZM on a two-headed hybrid gamma camera. Regions of interest and volumes of interest (VOIs) were used for image evaluation. A cross-sectional and longitudinal statistical analysis was carried out.Results Fewer sex-based differences and less age dependency were seen in DAT SPECT uptake ratios compared with D2R SPECT uptake ratios and when comparing uptake ratios obtained with regions of interest against those with VOIs. In the cross-sectional analysis, a significant age-dependent decline was seen in women in both DAT and D2R uptakes with the VOI method but not in men with either evaluation method. In the longitudinal dataset, both a slight decline and increase over time were seen in DAT uptake; however, a general pattern of decrease was seen in both men and women in D2R uptake.Conclusion The choice of the image evaluation method can influence the pattern of sex-based and age-related differences. The results speak for the use of age-stratified reference values for women, in particular when using a VOI method.
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| 4. |
- Lill, Christina M., et al.
(författare)
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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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| 5. |
- Ekman, Urban, et al.
(författare)
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Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment
- 2014
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Ingår i: Frontiers in Neuroscience. - : Frontiers. - 1662-4548 .- 1662-453X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes.
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| 6. |
- Lenfeldt, Niklas, et al.
(författare)
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Diffusion tensor imaging and correlations to Parkinson rating scales
- 2013
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Ingår i: Journal of Neurology. - : Springer Berlin/Heidelberg. - 0340-5354 .- 1432-1459. ; 260:11, s. 2823-2830
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.
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| 7. |
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| 8. |
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| 9. |
- Blomstedt, Patric, et al.
(författare)
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Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 17:8, s. 617-620
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.
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| 10. |
- Bolin, Kristian, et al.
(författare)
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Retigabine as add-on treatment of refractory epilepsy a cost-utility study in a Swedish setting
- 2013
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Ingår i: Acta Neurologica Scandinavica. - Hoboken : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 127:6, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To calculate comparative incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) and net marginal benefits for retigabine as add-on treatment for patients with uncontrolled focal seizures as compared to add-on lacosamide treatment and no add-on treatment, respectively. Materials & Methods Calculations were performed using a validated decision-tree model. The study population consisted of adult patients with focal-onset epilepsy in published randomized placebo-controlled add-on trials of retigabine or lacosamide. Healthcare utilization and QALY for each treatment alternative were calculated. Probabilistic sensitivity analysis was performed using the specification of this model as a basis for Monte Carlo simulations. 2009 prices were used for all costs. Results Results were reported for a 2-year follow-up period. Retigabine add-on treatment was both more effective and less costly than lacosamide add-on treatment, and the cost per additional QALY for the retigabine no add-on (standard) therapy comparison was estimated at 2009Euro 15,753. Using a willingness-to-pay threshold for a QALY of Euro 50,000, the net marginal values were estimated at 2009Euro 605,874 for retigabine vs lacosamide and 2009Euro 2,114,203 for retigabine vs no add-on, per 1,000 patients. The probabilistic analyses showed that the likelihood that retigabine treatment is cost-effective is at least 70%. Conclusions The estimated cost per additional QALY, for the retigabine vs no add-on treatment comparison, is well within the range of newly published estimates of willingness to pay for an additional QALY. Thus, add-on retigabine treatment for people with focal-onset epilepsy with no/limited response to standard antiepileptic treatment appears to be cost-effective.
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