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- Brodin, N, et al.
(författare)
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Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:2, s. e064278-
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Tidskriftsartikel (refereegranskat)abstract
- Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week.SettingCross-sectional survey, performed in 2015–2016.ParticipantsPeople with IJDs in Belgium, Denmark, Ireland and Sweden.Primary and secondary outcome measuresUse of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations.ResultsOf the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%–58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA.ConclusionsAlmost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.
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| 8. |
- Brodin, N, et al.
(författare)
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Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:2, s. e064278-
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Tidskriftsartikel (refereegranskat)abstract
- Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week.SettingCross-sectional survey, performed in 2015–2016.ParticipantsPeople with IJDs in Belgium, Denmark, Ireland and Sweden.Primary and secondary outcome measuresUse of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations.ResultsOf the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%–58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA.ConclusionsAlmost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.
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- Drosos, GC, et al.
(författare)
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EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome
- 2022
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:6, s. 768-779
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Tidskriftsartikel (refereegranskat)abstract
- To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).MethodsFollowing European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion.ResultsFour overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering.ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.
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- Fraser, AG, et al.
(författare)
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Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography
- 2003
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Ingår i: European Journal of Echocardiography. - 1525-2167 .- 1532-2114. ; 4:1, s. 43-53
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Off-line post-processing of colour tissue Doppler from digital loops may allow objective quantification of dobutamine stress echocardiography. We assessed the reproducibility of off-line measurements of regional myocardial velocities. Methods and Results: Nine observers analysed 10 studies, each making 2400 observations. Coefficients of variation in basal segments from apical windows, at rest and maximal stress, were 9-14% and 11-18% for peak systolic velocity, 16-18% and 17-19% for time-to-peak systolic velocity, 9-17% and 18-24% for systolic velocity time integral, and 18-23% and 21-27% for systolic acceleration. Coefficients of variation for diastolic velocities in basal segments at rest were 11-40%. Coefficients of variation for peak systolic velocity were 10-24% at rest and 14-28% at peak in mid segments, and 19-53% and 29-69% in apical segments. From parasternal windows coefficients of variation for peak systolic velocity were 14-16% in basal posterior, and 19-29% in mid-anterior segments. High variability makes measurement unreliable in apical and basal anterior septal segments. The feasibility of obtaining traces was tested in 92 subjects, and >90% in all basal and mid segments apart from the anterior septum. Conclusion: Quantification of myocardial functional reserve by off-line analysis of colour tissue Doppler acquired during dobutamine stress is feasible and reproducible in 11 segments of the left ventricle. The most reliable measurements are systolic velocities of longitudinal motion in basal segments.
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| 15. |
- Joseph, C, et al.
(författare)
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Cost-effectiveness of the HiBalance training program for elderly with Parkinson's disease: analysis of data from a randomized controlled trial
- 2019
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Ingår i: Clinical rehabilitation. - : SAGE Publications. - 1477-0873 .- 0269-2155. ; 33:2, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- To determine the cost-effectiveness of the HiBalance training program for managing Parkinson’s disease (PD)-related balance and gait disorders. Design: Cost comparison design following the randomized controlled trial comparing a novel balance training intervention with care as usual. Subjects: A total of 100 participants with mild–moderate PD were randomized to either the intervention ( n = 51) or the control group ( n = 49). Intervention: A 10-week (three times per week), group-based, progressive balance training program, led by two physical therapists. Main outcomes: All program costs were collected for both groups. Cost-utility was evaluated using quality-adjusted life years (QALYs) and cost-effectiveness measures were the Mini Balance Evaluation Systems Test (Mini-BESTest; assessing balance performance) and gait velocity. Incremental cost-effectiveness ratios were calculated and a probabilistic sensitivity analysis was conducted. Results: The between-group difference in QALYs was 0.043 (95% confidence interval (CI): 0.011–0.075), favoring the intervention group. Between-group differences in balance performance and gait velocity were 2.16 points (95% CI: 1.19–3.13) and 8.2 cm/second (95% CI: 2.9–13.6), respectively, favoring the intervention group. The mean cost per participant in the intervention group was 16,222 SEK (€1649) compared to 2696 SEK (€274) for controls. The estimated incremental cost-effectiveness ratios were 314,558 SEK (€31,969) for an additional QALY, 6262 SEK (€631) for one point improvement in balance performance, and 1650 SEK (€166) for 1 cm/second increase in gait velocity. Sensitivity analyses indicated a high probability (85%) of program success. Conclusion: In terms of QALYs, the HiBalance program demonstrated a high probability of cost-effectiveness in the short-term perspective when considering the willingness-to-pay thresholds used in Europe.
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- Osthoff, AKR, et al.
(författare)
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2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis
- 2018
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 77:9, s. 1251-1260
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Tidskriftsartikel (refereegranskat)abstract
- Regular physical activity (PA) is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. We evaluated if the public health recommendations for PA are applicable for people with inflammatory arthritis (iA; Rheumatoid Arthritis and Spondyloarthritis) and osteoarthritis (hip/knee OA) in order to develop evidence-based recommendations for advice and guidance on PA in clinical practice. The EULAR standardised operating procedures for the development of recommendations were followed. A task force (TF) (including rheumatologists, other medical specialists and physicians, health professionals, patient-representatives, methodologists) from 16 countries met twice. In the first TF meeting, 13 research questions to support a systematic literature review (SLR) were identified and defined. In the second meeting, the SLR evidence was presented and discussed before the recommendations, research agenda and education agenda were formulated. The TF developed and agreed on four overarching principles and 10 recommendations for PA in people with iA and OA. The mean level of agreement between the TF members ranged between 9.8 and 8.8. Given the evidence for its effectiveness, feasibility and safety, PA is advocated as integral part of standard care throughout the course of these diseases. Finally, the TF agreed on related research and education agendas. Evidence and expert opinion inform these recommendations to provide guidance in the development, conduct and evaluation of PA-interventions and promotion in people with iA and OA. It is advised that these recommendations should be implemented considering individual needs and national health systems.
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| 22. |
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| 23. |
- Venero, J. L., et al.
(författare)
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ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
- 2023
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Ingår i: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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| 24. |
- Abel, Edvard, 1970, et al.
(författare)
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Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum
- 2022
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.
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| 28. |
- Bjurehed, Linda, et al.
(författare)
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Improved Hand Function, Self-Rated Health, and Decreased Activity Limitations: Results After a Two-Month Hand Osteoarthritis Group Intervention
- 2018
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 70:7, s. 1039-1045
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate the effects on hand function, activity limitations, and self-rated health of a primary care hand osteoarthritis (OA) group intervention. Hand OA causes pain, impaired mobility, and reduced grip force, which cause activity limitations. OA group interventions in primary care settings are sparsely reported. MethodsSixty-four individuals with hand OA agreed to participate; 15 were excluded due to not fulfilling the inclusion criteria. The 49 remaining (90% female) participated in an OA group intervention at a primary care unit with education, paraffin wax bath, and hand exercise over a 6-week period. Data were collected at baseline, end of intervention, and after 1 year. Instruments used were the Grip Ability Test (GAT), the Signals of Functional Impairment (SOFI), dynamometry (grip force), hand pain at rest using a visual analog scale (VAS), the Patient-Specific Functional Scale (PSFS), the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH), and the EuroQol VAS (EQ VAS). Data were analyzed using nonparametric statistics. ResultsHand function, activity limitation, and self-rated health significantly improved from baseline to end of intervention, grip force (right hand: P < 0.001; left hand: P = 0.008), SOFI (P = 0.011), GAT (P < 0.001), hand pain at rest (P < 0.001), PSFS (1: P = 0.008, 2: P < 0.001, and 3: P = 0.004), Quick-DASH (P = 0.001), and EQ VAS (P = 0.039), and the effects were sustained after 1 year. ConclusionThe hand OA group intervention in primary care improves hand function, activity limitation, and self-rated health. The benefits are sustained 1 year after completion of the intervention.
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| 29. |
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| 30. |
- Blomstrand, Malin, et al.
(författare)
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Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma.
- 2012
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 14:7, s. 882-889
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Tidskriftsartikel (refereegranskat)abstract
- We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%), 44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial.
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| 31. |
- Bloom, O, et al.
(författare)
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Colocalization of synapsin and actin during synaptic vesicle recycling
- 2003
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 161:4, s. 737-747
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.
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| 32. |
- Brodin, Bertha A., et al.
(författare)
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Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas
- 2019
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 120:4, s. 435-443
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.
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| 33. |
- Brodin, N., et al.
(författare)
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Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
- 2008
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
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| 35. |
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| 36. |
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| 37. |
- Brodin, N, et al.
(författare)
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Effects of glossopharyngeal insufflation in ankylosing spondylitis: a pilot study
- 2014
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Ingår i: International journal of rheumatology. - : Hindawi Limited. - 1687-9260 .- 1687-9279. ; 2014, s. 594708-
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Tidskriftsartikel (refereegranskat)abstract
- In Ankylosing Spondylitis (AS), thoracic range of motion is often greatly limited. The objective of the study was to describe the effects of 12 weeks of Glossopharyngeal Insufflation (GI) training in patients with AS. Dynamic spirometry included vital capacity, forced expiratory volume, and peak expiratory flow. Thoracic and lumbar range of motion was assessed by tragus-to-wall distance, modified Schober test, and tape measure. Disease activity, activity limitation, and health perception were assessed using the BAS-Indices, and tension in the thoracic region during GI was assessed using the Borg CR-10 scale. Adherence to training was recorded in an activity log, along with any remarks on the training. Ten patients were recruited and six male patients fulfilled the study protocol. Three patients were able to learn GI by exceeding their maximal vital capacity with 5% using GI. A significant increase in thoracic range of motion both on costae IV(P=0.04)and at the level of the xiphoid process(P=0.04)was seen. Thus, patients with AS can practice GI, it is safe if maximal exertion is avoided, and patients with some mobility in the chest can increase their lung function substantially by performing GI during 12 weeks.
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| 38. |
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| 39. |
- Brodin, N Patrik, et al.
(författare)
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Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.
- 2014
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Ingår i: Neuro-oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 16:4, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy.MethodsWe included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques.ResultsMean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique.ConclusionsWe estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.
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| 40. |
- Brodin, N. Patrik, et al.
(författare)
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Life years lost-comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale
- 2012
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 118:21, s. 5432-5440
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty. Cancer 2012. (c) 2012 American Cancer Society.
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| 41. |
- Brodin, N. Patrik, et al.
(författare)
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Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure
- 2013
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 87:2, s. 422-429
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Tidskriftsartikel (refereegranskat)abstract
- Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.
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| 42. |
- Brodin, N Patrik, et al.
(författare)
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Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50:6, s. 806-16
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc(®) (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WR(neutron)). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.
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| 49. |
- Castillo, N. A., et al.
(författare)
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Understanding pharmaceutical exposure and the potential for effects in marine biota : A survey of bonefish (Albula vulpes) across the Caribbean Basin
- 2024
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 349
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Tidskriftsartikel (refereegranskat)abstract
- Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HTPC), comparing measured concentrations to a threshold of 1/3 the HTPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HTPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HTPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HTPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.
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| 50. |
- Cerveny, D., et al.
(författare)
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Water temperature affects the biotransformation and accumulation of a psychoactive pharmaceutical and its metabolite in aquatic organisms
- 2021
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental factor in nature, affects uptake, biotransformation, and the subsequent accumulation of PhACs in aquatic organisms is limited. In this study, we tested to what extent bioconcentration of an anxiolytic drugs (temazepam and oxazepam) is affected by two temperature regimes (10 and 20 °C) and how the temperature affects the temazepam biotransformation and subsequent accumulation of its metabolite (oxazepam) in aquatic organisms. We used European perch (Perca fluviatilis) and dragonfly larvae (Sympetrum sp.), which represent predator and prey species of high ecological relevance in food chains of boreal and temperate aquatic ecosystems. Experimental organisms were exposed to target pharmaceuticals at a range of concentrations (0.2–6 µg L−1) to study concentration dependent differences in bioconcentration and biotransformation. We found that the bioconcentration of temazepam in perch was significantly reduced at higher temperatures. Also, temperature had a strong effect on temazepam biotransformation in the fish, with the production and subsequent accumulation of its metabolite (oxazepam) being two-fold higher at 20 °C compared to 10 °C. In contrast, we found no temperature dependency for temazepam bioconcentration in dragonfly larvae and no detectable biotransformation of the parent compound that would result in measurable concentrations of oxazepam in this organism. Our results highlight that while organisms may share the same aquatic ecosystem, their exposure to PhACs may change differently across temperature gradients in the environment.
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