| 1. |
|
|
| 2. |
- Saevarsdottir, S., et al.
(författare)
-
Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
|
|
| 3. |
- Breznau, Nate, et al.
(författare)
-
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
|
|
| 4. |
- Peretz, A. S. R., et al.
(författare)
-
Galectin-3-binding protein is a novel predictor of venous thromboembolism in systemic lupus erythematosus
- 2021
-
Ingår i: Clinical and Experimental Rheumatology. - Pisa, Italy : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 39:6, s. 1360-1368
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Venous (VTE) and arterial (AT) thrombosis in systemic lupus erythematosus (SLE) are poorly explained and difficult to predict. Leptin and tumour necrosis factor-like weak inducer of apoptosis (TWEAK) have been linked to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment. Thus, we explore serum G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK and leptin as predictors of VTE and AT, damage accrual, and all-cause mortality during follow-up in a Swedish SLE cohort. Methods Baseline data were available from 162 SLE patients. VTE (deep vein thrombosis and/or pulmonary embolism), AT (myocardial infarction and/or stroke), damage accrual, and survival data were the main study outcomes and available at follow-up (median of five years). Baseline serum G3BP, IP-10, sCD163, TWEAK and leptin were measured and analysed by univariable and multivariable methods for association to the study outcomes. Results During the follow-up, 10 (6%) VTE and 13 (8%) AT events occurred. The SLICC/ACR Damage Index increased in 78 (48%) patients, and 19 (12%) patients died. In the univariable regression analysis G3BP levels were significantly associated with an increased risk of VTE (hazard ratio (HR) 1.11, 95% confidence interval (CI): 1.01-1.22, p=0.03). This persisted in the adjusted multivariable analyses (HR 1.18, 95% CI: 1.05-1.33, p=0.007). The other biomarkers were not associated with AT/VTE, damage accrual, or all-cause mortality. Conclusion Our study identifies serum G3BP as a novel predictor of VTE in SLE. Further studies are needed to understand the role of G3BP in VTE and translate this into clinical practice.
|
|
| 5. |
- Ekanem, Emmanuel, et al.
(författare)
-
Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study
- 2024
-
Ingår i: Nature Medicine. - : NATURE PORTFOLIO. - 1078-8956 .- 1546-170X.
-
Tidskriftsartikel (refereegranskat)abstract
- Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for similar to 1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.
|
|
| 6. |
- Enocsson, Helena, et al.
(författare)
-
Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
- 2020
-
Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 106
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
|
|
| 7. |
- Jacobsen, L., et al.
(författare)
-
Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma : 10-year follow-up on the PAT study
- 2007
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 62:8, s. 943-948
-
Tidskriftsartikel (refereegranskat)abstract
- Background: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT.Objective: We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT.Methods: One hundred and forty-seven subjects, aged 16–25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation.Results: The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1–5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5–13.7) in favor of SIT.Conclusion: A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment.Clinical implication: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
|
|
| 8. |
- Jacobsen, M.D., et al.
(författare)
-
Quantitative T-wave analysis predicts 1 year prognosis and benefit from early invasive treatment in the FRISC II study population
- 2005
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:2, s. 112-118
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the prognostic value of T-wave abnormalities in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and whether such ECG changes may predict benefit from an early coronary angiography. Although ST-segment changes are considered the most important ECG feature in NSTE-ACS, T-wave abnormalities are the most common ECG finding. We hypothesize that a new quantitative approach to T-wave analysis could improve the prognostic value of this ECG abnormality. Methods and results: Quantitative T-wave analysis was performed on the admission ECG in 1609 patients with NSTE-ACS. Nine different categories of T-wave abnormality were analysed for their prognostic value concerning clinical outcome in patients not randomized to early coronary angiography. Also, the presence of one category (i.e. T-wave abnormality in >6 leads) was analysed for its predictive value concerning benefit from early coronary angiography. The combined study endpoint was death or myocardial infarction at 1 year follow-up. Patients with >6 leads with abnormal T-waves and concomitant ST-segment depression had a higher risk when not receiving early coronary angiography (24 vs. 12%, respectively, P = 0.003), but could be brought to the same level of risk as the remaining patients with this treatment. For non-invasively treated patients five different categories of T-wave abnormality were significantly associated with an adverse outcome. Conclusion: New quantitative T-wave analysis of the admission ECG gives additional predictive information concerning clinical outcome and identifies patients who benefit from early coronary angiography.
|
|
| 9. |
- Niggemann, B., et al.
(författare)
-
Five-year follow-up on the PAT study : specific immunotherapy and long-term prevention of asthma in children
- 2006
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 61:7, s. 855-859
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up – 2 years after termination of immunotherapy.Methods: A total of 183 children, aged 6–14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation.Results: The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5-year follow-up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow-up period in the control patients. The immunotherapy-treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3–5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores (P < 0.01).Conclusion: Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long-term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.
|
|
| 10. |
- Petersen, Tom, et al.
(författare)
-
Inter-tester reliability of a new diagnostic classification system for patients with non-specific low back pain
- 2004
-
Ingår i: Australian Journal of Physiotherapy. - 0004-9514. ; 50:2, s. 85-91
-
Tidskriftsartikel (refereegranskat)abstract
- Most patients referred to physiotherapy with low back pain are without a precise medical diagnosis. Identification of subgroups of non-specific low back pain patients may improve clinical outcomes and research efficiency. A pathoanatomic classification system has been developed, classifying patients with non-specific low back pain into 12 different syndromes and three subcategories based on history and physical examination. The purpose of this study was to estimate the inter-tester reliability of clinical tests used as criteria for classifying patients. Ninety patients with chronic low back pain were each examined by two physiotherapists. A total of four physiotherapists conducted the assessments. Examination findings were recorded independently by the two examiners. Percentage of agreement and kappa coefficients were calculated for each category. The overall rate of agreement was 72% and the kappa coefficient was 0.62 for the mutually exclusive syndromes in the classification system. Agreement rates for each of the syndromes ranged from 74% to 100% and kappa coefficients ranged from 0.44 to 1.00. The findings suggest the inter-tester reliability of the system is acceptable. The relatively modest level of total agreement (39%) for the system as a whole might indicate that the utility of the system for general screening purposes is limited, compared with the utility in identification of particular syndromes. Due to low prevalence of positive findings in some of the syndromes future work should focus on testing reliability on a larger sample of patients, and testing of validity and feasibility of the system.
|
|
