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- Damberg, Mattias, et al.
(author)
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Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
- 2005
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In: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
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Journal article (peer-reviewed)abstract
- It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2beta in regulatory regions, suggesting an involvement of AP-2beta in these systems. The gene encoding AP-2beta is located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2beta genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2beta genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2beta genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2beta genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2beta genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.
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- Ekman, Anna-Karin, et al.
(author)
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Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1 alpha
- 2009
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 149:2, s. 154-160
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Journal article (peer-reviewed)abstract
- Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels analyzed and expression of MIP-1 alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP1 alpha release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1 alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time-and concentration-dependent release of MIP-1 alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappa B, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1 alpha. The release most likely originates from recruited neutrophils, via NF-kappa B-, PKC-and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apop tosis. MIP-1 alpha may constitute an important mediator in neutrophilic airway disease. Copyright (C) 2009 S. Karger AG, Basel
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- Ekman, Mattias, et al.
(author)
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Cost-effectiveness of the Taxus paclitaxel-eluting stent in the Swedish healthcare system
- 2006
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 40:1, s. 17-24
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyse the cost-effectiveness of Taxus compared to a bare-metal stent in patients with coronary artery disease in the Swedish healthcare setting. DESIGN: A decision-analytic model combining clinical data on revascularization rates with Swedish unit costs for medical resources and utility data from the literature. RESULTS: For patients of moderate risk, the average cost per patient at 12 months is 72,200 SEK for Taxus and 66,900 SEK for a bare-metal stent, while the average cost for high risk patients is nearly equivalent (73,000 vs. 71,700 SEK). The cost per revascularization avoided is generally favourable, while the incremental cost per QALY gained varies depending on the assumptions made; from 2,351,000 SEK for patients of moderate risk at 12-months to cost saving at 24 months for high risk patients. Budget impact scenarios at 12 months are cost-neutral. CONCLUSION: The Taxus stent is cost-effective in high risk patients, particularly at 24 months. Although it may be less cost-effective for the general population, there is still a substantial offset of initial procedure costs through lower rate of repeat revascularizations.
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5. |
- Ekman, Mattias, et al.
(author)
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Predicting the World Cup 2002 in soccer : performance and confidence of experts and non-experts
- 2005
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In: International Journal of Forecasting. - : Elsevier B.V. - 1872-8200 .- 0169-2070. ; 21:3, s. 565-576
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Journal article (peer-reviewed)abstract
- This paper investigates the forecasting performance and confidence of experts and non-experts. 251 participants with four different levels of knowledge of soccer (ranging between expertise and almost ignorance) took part in a survey and predicted the outcome of the first round of World Cup 2002. The participating experts (i.e., sport journalists, soccer fans, and soccer coaches) and the non-experts were found to be equally accurate and better than chance. A simple prediction rule that followed world rankings outperformed most participants. Experts overestimated their performance and tended to be overconfident, while the opposite tendency was observed for the participants with limited knowledge. Providing non-experts with information did not improve their performance, but increased their confidence.
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8. |
- Lundkvist, Jonas, et al.
(author)
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Cost-effectiveness of proton radiation in the treatment of childhood medulloblastoma
- 2005
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 103:4, s. 793-801
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Journal article (peer-reviewed)abstract
- BACKGROUND: Radiation therapy is an important component in the treatment of medulloblastoma; however, in many patients, it is associated with risk of late adverse events. Proton radiation therapy has potential to reduce the risk of adverse events compared with conventional radiation, but it is associated with a higher treatment cost. The objective of the current study was to assess the cost-effectiveness of proton therapy compared with conventional radiation therapy in the treatment of childhood medulloblastoma. METHODS: The consequences of radiation therapy were evaluated using a Markov simulation model. Children age 5 years with medulloblastoma were followed. The patients were at risk of several types of adverse events, including hearing loss, intelligence quotient (IQ) loss, hypothyroidism, growth hormone deficiency (GHD), osteoporosis, cardiac disease, and secondary malignancies. The patients also were at risk of death and were divided into risk groups for normal death, death due to tumor recurrence, treatment-related cardiac death, treatment-related subsequent tumor death, or treatment-related other death. A review of the literature was conducted to estimate the parameters in the model. RESULTS: The base-case results showed that proton therapy was associated with 23,600 in cost savings and 0.68 additional quality-adjusted life-years per patient. The analyses showed that reductions in IQ loss and GHD contributed to the greatest part of the cost savings and were the most important parameters for cost-effectiveness. CONCLUSIONS: The results of the current study indicated that proton radiation therapy can be cost-effective and cost-saving compared with conventional radiation therapy in the treatment of children with medulloblastoma if the appropriate patients are selected for the therapy. However, there have been few long-term follow-up studies, and more much information on the long-term consequences of radiation therapy is needed.
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9. |
- Lundkvist, Jonas, et al.
(author)
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Economic evaluation of proton radiation therapy in the treatment of breast cancer
- 2005
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 75:2, s. 179-85
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Proton beam therapy offers potential clinical advantages compared with conventional radiation therapy for many cancer patients. The benefits are mainly a result of a more favourable dose distribution. The treatment cost with proton radiation is higher than for conventional radiation, mainly due to the large investment cost of building a proton therapy facility. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to justify the higher treatment costs, compared with conventional radiation therapy. PATIENTS AND METHODS: The cost-effectiveness of proton therapy in the treatment of 55-year old women with left-sided breast cancer was assessed. A Markov cohort simulation model was used to simulate the life of patients diagnosed with breast cancers and treated with radiation. Cost and quality adjusted life years (QALYs) were the primary outcome measures. RESULTS: The study found a cost per QALY gained of 67,000 Euro for the base case analysis of an average breast cancer patient. The cost per QALY gained would, however, be considerably lower if a population with high-risk of developing cardiac disease was treated. Sensitivity analyses showed that the results were stable and that the risk of cardiac disease was the most important parameter. CONCLUSIONS: The results indicate that proton therapy for breast cancer can be cost-effective if appropriate risk groups are chosen as targets for the therapy.
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10. |
- Lundkvist, Jonas, et al.
(author)
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Proton therapy of cancer : potential clinical advantages and cost-effectiveness
- 2005
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 850-61
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Journal article (peer-reviewed)abstract
- Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about pounds 10,130. If the value of a QALY was set to pounds 55,000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about pounds 20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used.
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