| 1. |
- Mahr, Alfred, et al.
(författare)
-
Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis
- 2013
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:6, s. 1003-1010
-
Tidskriftsartikel (refereegranskat)abstract
- Background Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) defined historically by clinical and histological features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To identify novel subgroupings, cluster analysis was used to explore the phenotypic spectrum of AAV. Methods This study used a dataset of patients newly diagnosed as having GPA and MPA enrolled in five clinical trials. One cluster model included nine clinical baseline variables as input variables, and a second cluster model additionally included ANCA specificities. The clustering process involved multiple correspondence analyses followed by hierarchical ascendant cluster analysis. The clinical relevance of the generated clusters was analysed by their summary characteristics and outcomes. Results The analyses involved data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster models resulted in five partially redundant clusters of subjects, and the model including ANCA resulted in more pertinent separations. These clusters were named 'renal AAV with proteinase 3 (PR3)-ANCA' (40% of subjects), 'renal AAV without PR3-ANCA' (32%) and 'non-renal AAV' (12%), 'cardiovascular AAV' (9%) and 'gastrointestinal AAV' (7%). The five clusters had distinct death and relapse rates. On the basis of 4 variables, 651 subjects (97%) could be accurately allocated to 1 of the 5 classes. Conclusions This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA-MPA separation, this classification system may better reflect the phenotypic spectrum of AAV.
|
|
| 2. |
- Collin, Peter, et al.
(författare)
-
In memoriam - Bernt Johansson
- 2018
-
Ingår i: Steel Construction. - : Ernst & Sohn Verlag. - 1867-0520 .- 1867-0539. ; 11:4, s. 315-315
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Hagell, Peter, et al.
(författare)
-
Measuring fatigue in Parkinsons disease: A psychometric study of two brief generic fatigue questionnaires
- 2006
-
Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924 .- 1873-6513. ; 32:5, s. 420-432
-
Tidskriftsartikel (refereegranskat)abstract
- This study evaluated and compared the measurement properties of the 13-item Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the 9-item Fatigue Severity Scale (FSS) in 118 consecutive Parkinsons disease (PD) patients, using traditional and Rasch measurement methodologies. Both questionnaires exhibited excellent data quality and reliability (coefficient alpha greater than= 0.9), and acceptable rating scale functionality, and both discriminated between fatigued and nonfatigued patients. factor and Rasch analyses provided general support for unidimensionality of both FACIT-F and FSS, although they do not appear to measure identical aspects of fatigue. No signs of differential item functioning (DIF) were found for the FACIT-F, whereas potential age DIF, was detected for two FSS items. These results support the measurement validity of both questionnaires in PD, although the FACIT-F displayed better measurement precision and modest psychometric advantages over the FSS. Availability of psychometrically sound fatigue measures that are applicable across disorders provides a sound basis for advancing the understanding of this common and distressing complaint.
|
|
| 4. |
- Hoglund, Arja, et al.
(författare)
-
Associations Between Fluctuations in Daytime Sleepiness and Motor and Non-Motor Symptoms in Parkinson's Disease
- 2021
-
Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 8:1, s. 44-50
-
Tidskriftsartikel (refereegranskat)abstract
- Background Non-motor fluctuations are a major concern in Parkinson's disease (PD), and they have been categorized into neuropsychiatric, autonomic and sensory fluctuations. However, this categorization does not include sleep and sleep-related features, and the association between daytime sleepiness and other motor and/or non-motor fluctuations in PD remains to be elucidated. Objective To investigate the relationship between daytime sleepiness and other non-motor and motor fluctuations in people with PD. Methods A three-day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and 6 days of accelerometer (Parkinson's KinetiGraph (TM); PKG (TM)) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2 years). Participants were categorized as motor fluctuators or non-fluctuators according to the UPDRS part IV and/or the presence of motor and non-motor fluctuations. Results Fifty-two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non-fluctuators (n = 24). Stronger positive within-individual correlations were found among fluctuators in comparison to non-fluctuators. In general, PKG data did not correlate with diary data. Conclusion Episodes of daytime sleepiness, as reported by home diaries, were associated with other self-reported non-motor and motor fluctuations, but were not supported by PKG data.
|
|
| 5. |
- Hoglund, K., et al.
(författare)
-
Time-frequency and complexity analyses for differentiation of physiologic murmurs from heart murmurs caused by aortic stenosis in boxers
- 2007
-
Ingår i: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645 .- 1943-5681. ; 68:9, s. 962-969
-
Tidskriftsartikel (refereegranskat)abstract
- Objective - To investigate whether time-frequency and complexity analyses of heart murmurs can be used to differentiate physiologic murmurs from murmurs caused by aortic stenosis (AS) in Boxers. Animals - 27 Boxers with murmurs. Procedures - Dogs were evaluated via auscultation and echocardiography. Analyses of time-frequency properties (TFPs, ie, maximal murmur frequency and duration of murmur frequency > 200 Hz) and correlation dimension (T2) of murmurs were performed on phonocardiographic sound data. Time-frequency property and T2 analyses of low-intensity murmurs in 16 dogs without AS were performed at 7 weeks and 12 months of age. Additionally, TFP and T2 analyses were performed on data obtained from 11 adult AS-affected dogs with murmurs. Results - In dogs with low-intensity murmurs, TFP or T2 values at 7 weeks and 12 months did not differ significantly. For differentiation of physiologic murmurs from murmurs caused by mild AS, duration of murmur frequency > 200 Hz was useful and the combination assessment of duration of frequency > 200 Hz and T2 of the murmur had a sensitivity of 94% and a specificity of 82%. Maximal murmur frequency did not differentiate dogs with AS from those without AS. Conclusions and Clinical Relevance - Results suggested that assessment of the duration of murmur frequency > 200 Hz can be used to distinguish physiologic heart murmurs from murmurs caused by mild AS in Boxers. Combination of this analysis with T2 analysis may be a useful complementary method for diagnostic assessment of cardiovascular function in dogs.
|
|
| 6. |
- Leander, Peter, et al.
(författare)
-
CT and MR imaging of the liver. Clinical importance of nutritional status
- 2000
-
Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 41:2, s. 151-155
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: In an experimental study in rats a correlation between nutritional status and hepatic attenuation in CT and signal intensities in MR imaging was shown. Is physiological nutritional status of importance in clinical CT and MR imaging? MATERIAL AND METHODS: In a cross-over study including 12 healthy volunteers (6 women and 6 men, mean age 34 years), CT and MR imaging of the liver were performed with nutritional status at three different levels, i.e., normal, fasting and after glycogen-rich meals. CT and MR were performed on clinical imaging systems and hepatic attenuation and signal intensity, respectively, were assessed. In MR, T1-weighted, proton density-weighted and T2-weighted pulse-sequences were used. RESULTS: In CT there were significantly (p<0.01) higher liver attenuations in normal nutritional status and after glycogen rich-meals compared to the fasting condition. The difference between fasting and glycogen-rich meals were 10.5 HU for men, 7.4 for women and mean 8.8 HU for all 12 volunteers. In MR imaging the differences were small and non-significant. The results of this study are in accordance with an earlier experimental study in rats. CONCLUSION: In CT it may be of importance not to have patients in a fasting condition as it lowers the attenuation in normal liver tissue. The findings are important for planning of clinical studies where hepatic attenuation will be assessed and may be of some importance in clinical CT. In MR imaging the results indicate that the nutritional status is of less importance.
|
|
| 7. |
- Olsson, Bob, et al.
(författare)
-
Extreme Stability of Chitotriosidase in Cerebrospinal Fluid makes it a Suitable Marker for Microglial Activation in Clinical Trials
- 2012
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 32:2, s. 273-276
-
Tidskriftsartikel (refereegranskat)abstract
- Microglia is thought to be important in Alzheimer's disease. Therefore, our aim was to investigate the usefulness of the microglial marker chitotriosidase in clinical trials. Chitotriosidase was analyzed in cerebrospinal fluid from Alzheimer's disease patients on acetylcholine esterase inhibitors (AChEI) and in cerebrospinal fluid from multiple sclerosis patients before and after natalizumab treatment. Chitotriosidase activity was extremely stable during treatment with the non-inflammatory drug AChEI. However, the immunomodulatory treatment with natalizumab led to lower chitotriosidase activity. Thus, chitotriosidase may be useful in clinical trials where microglia is targeted or as a safety biomarker in other trials where the brain is a bystander organ.
|
|
| 8. |
|
|
| 9. |
- Robson, Joanna, et al.
(författare)
-
Damage in the anca-associated vasculitides: long-term data from the European Vasculitis Study group (EUVAS) therapeutic trials
- 2015
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:1, s. 177-184
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe short-term (up to 12 months) and long-term (up to 7 years) damage in patients with newly diagnosed antineutrophil-cytoplasm antibody-associated vasculitis (AAV). Methods Data were combined from six European Vasculitis Study group trials (n=735). Long-term follow-up (LTFU) data available for patients from four trials (n=535). Damage accrued was quantified by the Vasculitis Damage Index (VDI). Sixteen damage items were defined a priori as being potentially treatment-related. Results VDI data were available for 629 of 735 patients (85.6%) at baseline, at which time 217/629 (34.5%) had >= 1 item of damage and 32 (5.1%) >= 5 items, reflecting disease manifestations prior to diagnosis and trial enrolment. LTFU data were available for 467/535 (87.3%) at a mean of 7.3 years postdiagnosis. 302/535 patients (56.4%) had VDI data at LTFU, with 104/302 (34.4%) having >= 5 items and only 24 (7.9%) no items of damage. At 6 months and LTFU, the most frequent items were proteinuria, impaired glomerular filtration rate, hypertension, nasal crusting, hearing loss and peripheral neuropathy. The frequency of damage, including potentially treatment-related damage, rose over time (p<0.01). At LTFU, the most commonly reported items of treatment-related damage were hypertension (41.5%; 95% CI 35.6 to 47.4%), osteoporosis (14.1%; 9.9 to 18.2%), malignancy (12.6%; 8.6 to 16.6%), and diabetes (10.4%; 6.7 to 14.0%). Conclusions In AAV, renal, otolaryngological and treatment-related (cardiovascular, disease, diabetes, osteoporosis and malignancy) damage increases over time, with around one-third of patients having >= 5 items of damage at a mean of 7 years postdiagnosis.
|
|
| 10. |
- Senkowski, Wojciech, et al.
(författare)
-
Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer
- 2015
-
Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research. - 1535-7163 .- 1538-8514. ; 14:6, s. 1504-1516
-
Tidskriftsartikel (refereegranskat)abstract
- Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. (C) 2015 AACR.
|
|
