| 1. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 2. |
- Dahlén, Torsten, et al.
(författare)
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A population-based, retrospective cohort study of the association between ABO blood group and risk of COVID-19.
- 2023
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 293:3, s. 398-402
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have investigated associations between ABO blood group and risk of COVID-19, with inconsistent results.To study associations between ABO blood group and risk of different stages of COVID-19.The study was based on nationwide registers encompassing all blood-grouped persons in Sweden, and all of their COVID-19-related outcomes. Associations between ABO blood group and COVID-19 outcomes were estimated using Poisson regression models. Analyses were conducted overall and stratified by vaccination status.A total of 4,986,878 individuals were included. The incidence rate ratios of testing positive for COVID-19 were 1.08 (95% confidence interval [CI], 1.07-1.08), 1.06 (95% CI, 1.05-1.07), and 1.01 (95% CI, 1.00-1.01) for blood groups A, AB, and B, respectively, as compared to O. Similar associations were seen for risk of hospital admissions, intensive care unit admissions, and risk of death. For most outcomes, associations with ABO blood group were much attenuated or even reversed in vaccinated individuals.Individuals with blood groups A, AB, and B are at increased risk of contracting COVID-19 as well as developing more severe forms of the disease.
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| 3. |
- Dahlén, Torsten, et al.
(författare)
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Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors : Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study
- 2022
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 97:4, s. 421-430
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Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.
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| 4. |
- Dahlén, Torsten
(författare)
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Agnostic studies in epidemiology
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In epidemiology there has been an consistent effort to construct refined methods aiming towards the ability to draw casual inference between an exposure and an outcome. This thesis, partly inspired by the genome-wide association studies, has on the contrary strived towards exploration of data. The fundamental idea has been to decipher associations between one or many exposures with one or many outcomes. Using population-based register data from Sweden, this thesis explored the association between ABO blood group and RhD status in 1,217 disease categories, the occurrence of transfusion-transmitted disease examining 1,155 disease categories, the spectrum of adverse events in tyrosine kinase-inhibitor treated patients with chronic phase chronic myeloid leukemia in 670 disease categories, and lastly the occurrence of familial aggregation of 60 cancerous disease. To account for multiple testing we use previously employed methods of adjustment. In Paper I, using the large-scale donation-transfusion database, SCANDAT-3S with 8 million individuals, we identified 49 associations with ABO blood group and disease. Many associations were previously known but we identified a novel association of a protective role for blood group B, as compared to O, in suffering kidney stones. For RhD status, we identified only one disease after adjustment for multiple testing, namely pregnancy-induced hypertension. In Paper II, which used the same database and the unique connection between blood donor, the blood product and the recipients of blood, we identified 15 disease categories that seemed to be transfusion-transmitted. Among them there were strong signals suggesting transmission in hepatitis virus and HIV. For most other findings, the effect sizes were small. A general conclusion was that the current practice in Sweden, regarding transfusion safety, seems acceptable in terms of the risk of transfusion-transmission of disease. In Paper III, we used a database covering the full Swedish chronic myeloid leukemia-population diagnosed since 2002. In this study, also consisting of a matched control cohort, we identified 142 disease categories with increased incidence as compared to the control cohort. We also found 41 associations between tyrosine kinase inhibitors, used for the treatment of chronic myeloid leukemia, and a disease category. No unknown severe adverse events were found. In Paper IV, we created 3.5 million pedigrees using the Multi-generation Register and explored cancerous disease clustering within pedigrees. We identified multiple cancer syndromes, e.g. BRCA1/2 and hereditary colon cancer. The approach, agnostic in that we strive towards testing all possible hypotheses without prejudice, has the advantage of removing or at least reducing the researcher bias – where the research hypothesis is constrained by the environment of the individual researcher. The approach is mainly limited by the problems of misclassification of exposures and outcomes, the inability to optimally construct modelling for a large set of hypotheses, and by false discoveries. We have proposed some solutions to overcome these issues. A main aspect is that the method should not be used to draw inference but rather to generate hypothesis for future refined studies in a world with increasing amounts of high-resolution data.
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| 5. |
- Dahlén, Torsten, et al.
(författare)
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An agnostic study of associations between abo and rhd blood group and phenome-wide disease risk
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted. Methods: Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modelled outcomes for 1,217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals. Results: We discovered 49 and 1 associations between a disease and ABO and RhD blood group, respectively, after adjustment for multiple testing. We identified new associations such as kidney stones and blood group B as compared to O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood group A and AB as compared to O and RhD positive as compared to negative. Conclusion: Our findings generate strong further support for previously known associations, but also indicate new interesting relations.
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| 6. |
- Dahlen, Torsten, et al.
(författare)
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Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia : A Population-Based Cohort Study
- 2016
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Ingår i: Annals of Internal Medicine. - Karolinska Univ Hosp, Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. Reg Canc Ctr, Uppsala, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. Umea Univ, Umea, Sweden. Skane Univ Hosp, Lund, Sweden. [Dahlen, Torsten; Bjorkholm, Magnus; Ohm, Lotta; Stenke, Leif] Karolinska Univ Hosp Solna, Div matol, Dept Med, SE-17176 Stockholm, Sweden. [Edgren, Gustaf; Lambe, Mats] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, eden. [Hoglund, Martin; Olsson-Stromberg, Ulla] Univ Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. [Hoglund, Martin; Olsson-Stromberg, Ulla] Univ Hosp, Div Hematol, SE-75185 Uppsala, Sweden. [Sandin, Fredrik] Uppsala Univ Hosp, Reg Canc Ctr, SE-75185 Uppsala, Sweden. [Sjalander, Anders] Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden. [Richter, Johan] Skane Univ Hosp, Dept Hematol & Vasc Disorders, SE-22241 Lund, Sweden. [Back, Magnus] Karolinska Univ Hosp, Dept Cardiol, SE-17176 Stockholm, Sweden.. - 0003-4819 .- 1539-3704. ; 165:3, s. 161-166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity.Objective: To investigate the incidence of vascular events in patients with CML treated with first-and second-generation TKIs.Design: Retrospective cohort study using nationwide population-based registries.Setting: Sweden.Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient.Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons.Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred.Limitations: Patients may have been exposed to multiple TKIs. Data on second-and third-generation TKIs were limited.Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs.
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| 10. |
- Flygt, Hjalmar, et al.
(författare)
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Successful tyrosine kinase inhibitor discontinuation outside clinical trials - data from the population-based Swedish chronic myeloid leukaemia registry
- 2021
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 193:5, s. 915-921
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trials show that tyrosine kinase inhibitor (TKI) treatment can be discontinued in selected patients with chronic myeloid leukaemia (CML). Although updated CML guidelines support such procedure in clinical routine, data on TKI stopping outside clinical trials are limited. In this retrospective study utilising the Swedish CML registry, we examined TKI discontinuation in a population-based setting. Out of 584 patients diagnosed with chronic-phase CML (CML-CP) in 2007-2012, 548 had evaluable information on TKI discontinuation. With a median follow-up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (>= 1 month) due to achieving a DMR (deep molecular response) and 107 (20%) due to other causes (adverse events, allogeneic stem cell transplant, pregnancy, etc). Among those stopping in DMR, 49% re-initiated TKI treatment (median time to restart 4 center dot 8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41 center dot 1% of patients discontinuing outside a study had re-initiated TKI treatment. TKI treatment duration pre-stop was longer and proportion treated with second-generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. In summary we show that TKI discontinuation in CML in clinical practice is common and feasible and may be just as successful as when performed within a clinical trial.
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