| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events during endovascular treatment of ruptured aneurysms : A prospective nationwide study on subarachnoid hemorrhage in Sweden
- 2023
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Ingår i: BRAIN AND SPINE. - : Elsevier. - 2772-5294. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.
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| 3. |
- Erlinge, D., et al.
(författare)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 4. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 5. |
- Marklund, Peter, et al.
(författare)
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Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultra-endurance exercise bout in experienced athletes.
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 114:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- The impact of a 24h ultra-endurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (PRE), immediately after the exercise (POST) and after 28h of recovery (POST28). Circulating blood levels of leukocytes, CK, CRP and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3(+), CD8(+), CD68(+)) and the expression of major histocompatibility complex class-I (MHC class-I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes and the number of CD3(+), CD8(+) and CD 68(+) cells were 2-3 fold higher at POST28 compared to PRE (P<0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class-I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP and CK at POST. At POST28 total leukocytes, IL-6 and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1β and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the ultra-endurance exercise bout. In conclusion, a low-intensity but very prolonged single endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultra-endurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.
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| 6. |
- Aineskog, Helena, et al.
(författare)
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Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage
- 2022
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Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:8, s. 2209-2218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation.METHODS: Eighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10.RESULTS: S100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828-0.968, p < 0.0001), with a cutoff of 0.4 μg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 μg/l vs ≤ 0.4 μg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis.CONCLUSIONS: For the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 μg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.
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| 7. |
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| 8. |
- Appelros, Peter, et al.
(författare)
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Comorbidity in Stroke-Survivors : Prevalence and Associations with Functional Outcomes and Health
- 2021
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier. - 1052-3057 .- 1532-8511. ; 30:10
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of this study was to evaluate the prevalence and impact of stroke-related comorbidity in a community-based sample of stroke survivors. We sought to find out which types of comorbidity that were most important with respect to the patients' functional outcomes and general health.MATERIALS AND METHODS: All stroke survivors (n = 330) living in a medium-sized Swedish municipality were included. Patient records were reviewed to determine the presence of comorbidities. A selection of patient reported outcomes were used to assess subjective symptoms, functional outcomes, and general health. Logistic regression models were used to investigate the association between comorbidities, residual symptoms, and subjective symptoms on the one hand, and functional outcomes and general health on the other hand.RESULTS: Hypertension (80%) was the most common cardiovascular risk factor. Ischemic heart disease was found in 18% and congestive heart failure in 10%. Of non-cardiovascular disorders, orthopaedic diseases were commonest (30%). Psychiatric disorders and cognitive impairment were present in 11% and 12% respectively. Hemiparesis is associated with both functional outcomes and general health. Additionally, orthopedic disorders, vertigo, cognitive impairment, nicotine use, chronic pulmonary disorders, and age, are associated with different functional outcomes. Psychiatric, orthopedic and neurological disorders are related to general health. The patient-reported outcome measure "feeling of tiredness" is important for many of the outcomes, while "feeling depressed" and "having pain" are associated with general health.CONCLUSIONS: Many medical conditions, several of which have received little attention so far, are associated with functional outcome and general health in stroke survivors. If the intention is to describe comorbidity relevant to function and general health in stroke patients, disorders that hitherto have received little attention, must be considered.
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| 9. |
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| 10. |
- Appelros, Peter, et al.
(författare)
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Comorbidity in stroke survivors in a medium-sized Swedish municipality
- 2023
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Ingår i: Brain Injury. - : Informa Healthcare. - 0269-9052 .- 1362-301X. ; 37:Suppl. 1, s. 135-136
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The purpose of this study was to evaluate the prevalence and impact of stroke-related comorbidity in a community-based sample of stroke survivors. With respect to the patients’ functional outcomes and general health, we wanted to find out which types of comorbidity were most important.Materials and Methods: All stroke survivors (n = 330) living in a medium-sized Swedish municipality were included. To determine the presence of comorbidities patient records were reviewed. A selection of patient reported outcomes were used to assess subjective symptoms, functional outcomes, and general health. All patients were asked to answer a questionnaire, the Swedish Stroke Register (Riksstroke). Three questions from the questionnaire were used as additional measures of comorbidity. “Do you feel tired?,” “Do you have pain?” and “Do you feel depressed?” As outcome measures the patient reported measures from the Riksstroke questionnaire were used: * Do you still have problems after your stroke? * Have you been able to return to the life and activities you had before the stroke? * How is your mobility now? * Do you get help from someone when visiting the toilet? * Do you get help with dressing and undressing? * How do you assess your general health? Logistic regression models were used to investigate the association between comorbidities, residual symptoms, and subjective symptoms on the one hand, and functional outcomes and general health on the other hand.Results: Hypertension (80%) was the most common cardiovascular risk factor. Ischemic heart disease was found in 18% and congestive heart failure in 10%. Of non-cardiovascular disorders, orthopedic diseases were commonest (30%). Psychiatric disorders and cognitive impairment were present in 11% and 12% respectively. Logistic regression analyses found that hemiparesis was associated with both poorer functional outcomes and lower general health. Additionally, orthopedic disorders, vertigo, cognitive impairment, nicotine use, chronic pulmonary disorders, and older age, were also associated with poorer functional outcomes. Psychiatric, orthopedic and neurological disorders were associated with poorer general health. The patient-reported outcome measure “feeling of tiredness” was a predictor of both outcomes, while “feeling depressed” and “having pain” were associated with poorer general health.Conclusions: Many medical conditions, several of which have received little attention so far, are associated with poorer functional outcome and lower general health among stroke survivors. Future research into comorbidities relevant to function and general health in stroke patients could further focus on these disorders that hitherto have received little attention.
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