159 results on '"Kristinsson SY"'
Search Results
2. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
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Went, M, Sud, A, Försti, A, Halvarsson, BM, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Jöckel, KH, Johnsson, E, Kristinsson, SY, Mellqvist, UH, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, ZS, Muir, K, Pashayan, N, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, AK, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Olama, AAA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, The PRACTICAL Consortium, and Claessens, Frank
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Male ,Quality Control ,Risk ,Chromatin Immunoprecipitation ,Genotype ,European Continental Ancestry Group ,Quantitative Trait Loci ,Bayes Theorem ,Polymorphism, Single Nucleotide ,Chromatin ,Gene Expression Regulation ,Humans ,Female ,Genetic Predisposition to Disease ,Multiple Myeloma ,Promoter Regions, Genetic ,Genome-Wide Association Study - Abstract
© 2018, The Author(s). Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM. ispartof: Nature Communications vol:9 issue:1 ispartof: location:England status: published
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- 2018
3. A109 Improved Survival in Younger Patients with Multiple Myeloma: A Population-Based Study from Malmö, Sweden
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Turesson, I, primary, Velez, R, additional, Kristinsson, SY, additional, and Landgren, O, additional
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- 2009
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4. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008.
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Björkholm M, Ohm L, Eloranta S, Derolf A, Hultcrantz M, Sjöberg J, Andersson T, Höglund M, Richter J, Landgren O, Kristinsson SY, Dickman PW, Björkholm, Magnus, Ohm, Lotta, Eloranta, Sandra, Derolf, Asa, Hultcrantz, Malin, Sjöberg, Jan, Andersson, Therese, and Höglund, Martin
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- 2011
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5. Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia.
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Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O, Kristinsson, Sigurdur Y, Koshiol, Jill, Björkholm, Magnus, Goldin, Lynn R, McMaster, Mary L, Turesson, Ingemar, and Landgren, Ola
- Abstract
Background: Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM.Methods: We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression.Results: An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjögren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjögren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain-Barré syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1).Conclusions: Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjögren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions. [ABSTRACT FROM AUTHOR]- Published
- 2010
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6. Novel therapies in multiple myeloma for newly diagnosed nontransplant candidates.
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Kristinsson SY, Landgren O, Rajkumar VS, Kristinsson, Sigurdur Yngvi, Landgren, Ola, and Rajkumar, Vincent S
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In the twenty-first century, melphalan-prednisone can no longer be regarded as the standard treatment of multiple myeloma patients not eligible for high-dose melphalan followed by autologous stem cell transplantation. The introduction of thalidomide, lenalidomide, and bortezomib has improved the arsenal of therapeutic options in multiple myeloma. Indeed, randomized studies have shown that melphalan-prednisone-thalidomide and melphalan-prednisone-bortezomib are superior to melphalan-prednisone alone. In addition, other combinations, including lenalidomide, are under study. In this review, we discuss the role of novel therapies in multiple myeloma in elderly multiple myeloma patients. Important aspects, such as toxicity and the role of prognostic factors, are also addressed. [ABSTRACT FROM AUTHOR]
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- 2009
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7. Socioeconomic differences in patient survival are increasing for acute myeloid leukemia and multiple myeloma in sweden.
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Kristinsson SY, Derolf AR, Edgren G, Dickman PW, and Björkholm M
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- 2009
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8. Genetics- and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/ Waldenström's macroglobulinemia.
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Kristinsson SY, Koshiol J, Goldin LR, Björkholm M, Turesson I, Gridley G, McMaster ML, and Landgren O
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- 2009
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9. Novel aspects pertaining to the relationship of Waldenström's macroglobulinemia, IgM monoclonal gammopathy of undetermined significance, polyclonal gammopathy, and hypoglobulinemia.
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McMaster ML, Kristinsson SY, Turesson I, Björkholm M, and Landgren O
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- 2009
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10. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003.
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Kristinsson SY, Landgren O, Dickman PW, Derolf AR, and Björkholm M
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- 2007
11. Population-based screening cohort study reveals no association between monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), multiple myeloma (MM), and alopecia.
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Sharma D, Ungar B, Adalsteinsson JA, Sigurdsson JK, Sharp K, Thorsteinsdóttir S, Rögnvaldsson S, Þórðardóttir ÁR, Viðarsson B, Önundarson PT, Agnarssond BA, Sigurðardóttird M, Þorsteinsdóttir I, Ólafsson Í, Eyþórsson E, Jónsson Á, Ólafsson A, Gíslason GK, Landgren O, Hulcrantz M, Durie BG, Harding S, Love TJ, and Kristinsson SY
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- Humans, Female, Male, Middle Aged, Aged, Cohort Studies, Adult, Mass Screening methods, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Alopecia epidemiology, Alopecia diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma diagnosis, Multiple Myeloma complications, Smoldering Multiple Myeloma diagnosis, Smoldering Multiple Myeloma epidemiology
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- 2024
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12. Deciphering the genetics and mechanisms of predisposition to multiple myeloma.
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Went M, Duran-Lozano L, Halldorsson GH, Gunnell A, Ugidos-Damboriena N, Law P, Ekdahl L, Sud A, Thorleifsson G, Thodberg M, Olafsdottir T, Lamarca-Arrizabalaga A, Cafaro C, Niroula A, Ajore R, Lopez de Lapuente Portilla A, Ali Z, Pertesi M, Goldschmidt H, Stefansdottir L, Kristinsson SY, Stacey SN, Love TJ, Rognvaldsson S, Hajek R, Vodicka P, Pettersson-Kymmer U, Späth F, Schinke C, Van Rhee F, Sulem P, Ferkingstad E, Hjorleifsson Eldjarn G, Mellqvist UH, Jonsdottir I, Morgan G, Sonneveld P, Waage A, Weinhold N, Thomsen H, Försti A, Hansson M, Juul-Vangsted A, Thorsteinsdottir U, Hemminki K, Kaiser M, Rafnar T, Stefansson K, Houlston R, and Nilsson B
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- Humans, Mendelian Randomization Analysis, B-Lymphocytes immunology, B-Lymphocytes metabolism, Case-Control Studies, Transmembrane Activator and CAML Interactor Protein genetics, Male, Telomere genetics, Multiple Myeloma genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, B-Cell Maturation Antigen genetics, Polymorphism, Single Nucleotide
- Abstract
Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development., (© 2024. The Author(s).)
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- 2024
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13. Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden.
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Rögnvaldsson S, Thorsteinsdóttir S, Syriopoulou E, Sverrisdottir I, Turesson I, Eythorsson E, Oskarsson JT, Long TE, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Olafsson I, Thorsteinsdottir I, Aspelund T, Gislason GK, Olafsson A, Sigurdsson JK, Hultcrantz M, Durie BGM, Harding S, Bjorkholm M, Landgren O, Love TJ, and Kristinsson SY
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- Humans, Iceland epidemiology, Sweden epidemiology, Male, Female, Middle Aged, Aged, Risk Factors, Multiple Myeloma epidemiology, Multiple Myeloma diagnosis, Multiple Myeloma etiology, Neoplasms epidemiology, Neoplasms etiology, Neoplasms diagnosis, Disease Progression, Adult, Population Surveillance, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance diagnosis
- Abstract
There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.
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- 2024
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14. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.
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Sverrisdottir I, Thorsteinsdottir S, Rognvaldsson S, Aspelund T, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdóttir I, Sveinsdottir SV, Palmason R, Olafsson I, Sigurdsson F, Thordardóttir AR, Eythorsson E, Jonsson A, Palsson R, Indridason OS, Gislason GK, Olafsson A, Sigurdsson J, Steingrímsdóttir H, Einarsson Long T, Hultcrantz M, Durie BGM, Harding S, Landgren O, Kristinsson SY, and Love TJ
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- Humans, Male, Female, Iceland epidemiology, Middle Aged, Cross-Sectional Studies, Aged, Adult, Prevalence, Prospective Studies, Autoimmune Diseases epidemiology, Autoimmune Diseases complications, Autoimmune Diseases diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Mass Screening methods
- Abstract
Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias., Objective: To examine whether MGUS is associated with autoimmune diseases., Design: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS., Setting: Icelandic population of adults aged 40 years or older., Patients: 75 422 persons screened for MGUS., Measurements: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex., Results: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70])., Limitation: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results., Conclusion: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted., Primary Funding Source: The International Myeloma Foundation and the European Research Council., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2867.
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- 2024
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15. Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma.
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Ghobrial IM, Gormley N, Kumar SK, Mateos MV, Bergsagel PL, Chesi M, Dhodapkar MV, Dispenzieri A, Fonseca R, Getz G, Kastritis E, Kristinsson SY, Martinez-Climent JA, Manier S, Marinac CR, Maura F, Morgan GJ, Davies FE, Nadeem O, Nuvolone M, Paiva B, O'Donnell E, Prosper F, Shah UA, Sklavenitis-Pistofidis R, Sperling AS, Vassiliou GS, Munshi NC, Castle PE, Anderson KC, and San Miguel JF
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- Humans, Research Design, Quality of Life, Multiple Myeloma therapy, Multiple Myeloma drug therapy, Clinical Trials as Topic methods
- Abstract
Summary: While the current approach to precursor hematologic conditions is to "watch and wait," this may change with the development of therapies that are safe and extend survival or delay the onset of symptomatic disease. The goal of future therapies in precursor hematologic conditions is to improve survival and prevent or delay the development of symptomatic disease while maximizing safety. Clinical trial considerations in this field include identifying an appropriate at-risk population, safety assessments, dose selection, primary and secondary trial endpoints including surrogate endpoints, control arms, and quality-of-life metrics, all of which may enable more precise benefit-risk assessment., (©2024 American Association for Cancer Research.)
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- 2024
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16. Trends of perceived disruption in healthcare services during the pandemic: findings from the COVID-19 National Resilience Cohort in Iceland.
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Wang Y, Unnarsdóttir AB, Magnúsdóttir I, Fang F, Thordardottir EB, Rúnarsdóttir H, Love TJ, Kristinsson SY, Pálsson R, Jakobsdóttir J, Zoega H, Ásbjörnsdóttir KH, Song H, Hauksdóttir A, Aspelund T, and Valdimarsdóttir UA
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- Humans, Iceland epidemiology, Pandemics, Anxiety epidemiology, Depression epidemiology, COVID-19 epidemiology, Resilience, Psychological
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Background: Coronavirus disease 2019 (COVID-19) caused major disruptions in healthcare services worldwide. Yet, little is known about the association between perceived disruption in healthcare services and socio-demographic factors, pre-existing health conditions as well as concurrent physical and psychological symptoms., Methods: Leveraging data from the Icelandic COVID-19 National Resilience Cohort, we performed a repeated measure analysis among 15 754 participants who responded to the question on perceived disruption in healthcare services from December 2020 to July 2021, to explore its association with socio-demographic factors, health indicators and conditions. Furthermore, we performed a longitudinal analysis among 7848 participants with two repeated measures to explore the association between timing and duration of perceived disruption in healthcare services and changes in depression, anxiety, sleep quality and somatic symptoms., Results: The prevalence of perceived disruption in healthcare services slightly decreased over time (P < 0.01). Perceived disruption in healthcare services was more prevalent among individuals with pre-existing health conditions, i.e. history of psychiatric disorders (prevalence ratio = 1.59, 95% confidence interval 1.48-1.72) and chronic somatic conditions [1.40 (1.30-1.52)]. However, no increase in the prevalence of perceived disruption in healthcare services was observed among individuals diagnosed with COVID-19 [0.99 (0.84-1.18)]. Moreover, we found that emerging perceived disruption in healthcare services was associated with an increase in symptoms of mental illness during the pandemic (βs 0.06-0.68)., Conclusions: A disruption in healthcare services during the COVID-19 pandemic was reported by vulnerable groups, while the Icelandic healthcare system managed to maintain accessible services to individuals with COVID-19., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)
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- 2024
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17. Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.
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Eythorsson E, Rognvaldsson S, Thorsteinsdottir S, Einarsson Long T, Reed ER, Sigurdardottir GA, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Olafsson I, Thorsteinsdottir I, Sveinsdottir SV, Sigurdsson F, Thordardottir AR, Palsson R, Indridason OS, Jonsson A, Gislason GK, Olafsson A, Sigurdsson J, Steingrimsdottir H, Hultcrantz M, Durie BGM, Harding S, Landgren O, Aspelund T, Love TJ, and Kristinsson SY
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- Adult, Humans, Bone Marrow, Cohort Studies, Prospective Studies, Immunoglobulin A, Immunoglobulin G, Disease Progression, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma therapy, Smoldering Multiple Myeloma, Paraproteinemias
- Abstract
Background: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management., Objective: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model., Design: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597)., Setting: Icelandic population of adults aged 40 years or older., Patients: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample., Measurements: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater., Results: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds., Limitation: The prediction model will require external validation., Conclusion: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology., Primary Funding Source: International Myeloma Foundation and the European Research Council., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2540.
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- 2024
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18. Screening in Multiple Myeloma and Its Precursors: Are We There Yet?
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Rögnvaldsson S, Thorsteinsdóttir S, and Kristinsson SY
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- Humans, Immunoglobulin Light Chains, Multiple Myeloma diagnosis
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Background: Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM. Screening is a hallmark of care in many malignancies, and there are accepted criteria for when screening is appropriate., Content: Here we review the available relevant evidence for the introduction of screening and discuss whether screening for MM and its precursors fulfills these criteria. We also highlight gaps in our current knowledge, most notably a lack of data on the benefits and harms of screening and the lack of a defined target population. There are ongoing studies that may fill these critical gaps in the literature, but their results are still pending., Summary: Screening could lead to a paradigm shift in the care of patients with MM, but critical scientific questions need to be answered before screening of healthy individuals can be recommended. In short, we should not screen for MM and its precursors-yet., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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19. Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.
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Pérez-Escurza O, Flores-Montero J, Óskarsson JÞ, Sanoja-Flores L, Del Pozo J, Lecrevisse Q, Martín S, Reed ER, Hákonardóttir GK, Harding S, Þorsteinsdóttir S, Rögnvaldsson S, Love TJ, Durie B, Kristinsson SY, and Orfao A
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- Humans, Plasma Cells, Bone Marrow, B-Lymphocytes, Paraproteinemias diagnosis, Multiple Myeloma diagnosis, Monoclonal Gammopathy of Undetermined Significance, Waldenstrom Macroglobulinemia, Smoldering Multiple Myeloma complications
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG., (© 2023. The Author(s).)
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- 2023
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20. Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study.
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Sigurbergsdóttir AÝ, Rögnvaldsson S, Thorsteinsdóttir S, Sverrisdóttir I, Sigurðardóttir GÁ, Viðarsson B, Önundarson PT, Agnarsson BA, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Þórðardóttir ÁR, Gíslason GK, Ólafsson A, Hultcrantz M, Durie BGM, Harding S, Landgren O, Löve TJ, and Kristinsson SY
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- Humans, Iceland, Comorbidity, Disease Progression, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Paraproteinemias diagnosis, Paraproteinemias epidemiology
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
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- 2023
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21. Author Correction: Prevalence of smoldering multiple myeloma based on nationwide screening.
- Author
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Thorsteinsdóttir S, Gíslason GK, Aspelund T, Rögnvaldsson S, Óskarsson JÞ, Sigurðardóttir GÁ, Þórðardóttir ÁR, Viðarsson B, Önundarson PT, Agnarsson BA, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Eyþórsson E, Jónsson Á, Berlanga O, Hultcrantz M, Durie BGM, Löve TJ, Harding S, Landgren O, and Kristinsson SY
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- 2023
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22. Determining hemodilution in diagnostic bone marrow aspirated samples in plasma cell disorders by next-generation flow cytometry: Proposal for a bone marrow quality index.
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Óskarsson JÞ, Rögnvaldsson S, Thorsteinsdottir S, Aspelund T, Gunnarsson SB, Hákonardóttir GK, Sigurðardóttir GÁ, Þórðardóttir ÁR, Gíslason GK, Ólafsson A, Sigurðsson JK, Eyþórsson E, Jónsson Á, Viðarsson B, Önundarson PT, Agnarsson BA, Pálmason R, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Harding S, Flores-Montero J, Orfao A, Durie BGM, Love TJ, and Kristinsson SY
- Subjects
- Humans, Flow Cytometry methods, Plasma Cells, Hemodilution, Bone Marrow Cells, Bone Marrow, Paraproteinemias
- Abstract
Hemodilution of bone marrow (BM) aspirates is a limitation of multiparameter flow cytometry (MFC) in plasma cell disorders. There is a need for a validated approach for assessing sample quality and the distribution of non-plasma cell BM populations by MFC could provide a solution. We evaluated BM-associated cell populations, assessed by next-generation flow cytometry (NGF) and white blood cell (WBC) count in 351 BM aspirated samples from 219 participants with plasma cell disorders in the Iceland Screens, Treats, or Prevents MM study (iStopMM), as markers of hemodilution by their discriminatory ability between first and (generally more hemodiluted) second pull BM aspirated samples. The most discriminating markers were used to derive a novel BM quality index (BMQI). Nucleated red blood cells and myeloid precursors provided the greatest discriminatory ability between first vs second pull samples (area under the curve (AUC): 0.87 and 0.85, respectively), significantly better than B cell precursors (AUC = 0.64; p < 0.001), mast cells (AUC = 0.65; p < 0.001), and the BM WBC count (AUC = 0.77; p < 0.05). We generated a novel BMQI that is intrinsic to current NGF protocols, for evaluating quality of diagnostic BM samples and suggest the use of a BMQI scoring system for interpreting results and guiding appropriate actions., (© 2023. The Author(s).)
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- 2023
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23. The force awakens, but questions remain: The future of MGUS.
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Rögnvaldsson S and Kristinsson SY
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- Humans, Multiple Myeloma, Monoclonal Gammopathy of Undetermined Significance diagnosis
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- 2023
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24. Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.
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Holm H, Ivarsdottir EV, Olafsdottir T, Thorolfsdottir R, Eythorsson E, Norland K, Gisladottir R, Jonsdottir G, Unnsteinsdottir U, Sveinsdottir KE, Jonsson BA, Andresdottir M, Arnar DO, Arnthorsson AO, Birgisdottir K, Bjarnadottir K, Bjarnadottir S, Bjornsdottir G, Einarsson G, Eiriksdottir B, Gardarsdottir EE, Gislason T, Gottfredsson M, Gudmundsdottir S, Gudmundsson J, Gunnarsdottir K, Helgadottir A, Helgason D, Hinriksdottir I, Ingvarsson RF, Jonasdottir SS, Jonsdottir I, Karlsdottir TH, Kristinsdottir AM, Kristinsson SY, Kristjansdottir S, Love TJ, Ludviksdottir D, Masson G, Norddahl G, Olafsdottir T, Olafsson I, Rafnar T, Runolfsdottir HL, Saemundsdottir J, Sigurbjornsson S, Sigurdardottir K, Sigurdsson E, Sigurdsson MI, Sigurdsson EL, Steinthorsdottir V, Sveinbjornsson G, Thorarensen EA, Thorbjornsson B, Thorsteinsdottir B, Tragante V, Ulfarsson MO, Stefansson H, Gislason T, Kristjansson M, Palsson R, Sulem P, Thorsteinsdottir U, Thorgeirsson G, Gudbjartsson DF, and Stefansson K
- Abstract
Background: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear., Methods: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection., Results: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection., Conclusions: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection., (© 2023. The Author(s).)
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- 2023
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25. Comment on: Strong site-specific association of pharyngeal cultures with the onset of psoriatic arthritis and psoriasis, regardless of pathogen: reply.
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Thrastardottir T, Meer E, Hauksdottir A, Gudbjornsson B, Kristinsson SY, Ogdie A, and Love TJ
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- Humans, Arthritis, Psoriatic complications, Psoriasis complications
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- 2023
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26. Correction: Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.
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Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, Sigurðardóttir GÁ, Viðarsson B, Önundarson PT, Agnarsson BA, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Þórðardóttir ÁR, Eyþórsson E, Jónsson Á, Björnsson AS, Gunnarsson GÞ, Pálsson R, Indriðason ÓS, Gíslason GK, Ólafsson A, Hákonardóttir GK, Brinkhuis M, Halldórsdóttir SL, Ásgeirsdóttir TL, Steingrímsdóttir H, Danielsen R, Dröfn Wessman I, Kampanis P, Hultcrantz M, Durie BGM, Harding S, Landgren O, and Kristinsson SY
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- 2023
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27. Validity of chronic disease diagnoses in Icelandic healthcare registries.
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Rögnvaldsson S, Long TE, Thorsteinsdottir S, Love TJ, and Kristinsson SY
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- Humans, Iceland, Predictive Value of Tests, Registries, International Classification of Diseases, Health Facilities
- Abstract
Aims: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries., Methods: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria., Results: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94-97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89-96%) and the overall negative predictive value (NPV) was 99% (95% CI 96-100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases., Conclusions: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries.
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- 2023
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28. Prevalence of smoldering multiple myeloma based on nationwide screening.
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Thorsteinsdóttir S, Gíslason GK, Aspelund T, Rögnvaldsson S, Óskarsson JÞ, Sigurðardóttir GÁ, Þórðardóttir ÁR, Viðarsson B, Önundarson PT, Agnarsson BA, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Eyþórsson E, Jónsson Á, Berlanga O, Hultcrantz M, Durie BGM, Löve TJ, Harding S, Landgren O, and Kristinsson SY
- Subjects
- Humans, Female, Adult, Middle Aged, Aged, Aged, 80 and over, Prevalence, Risk Factors, Disease Progression, Smoldering Multiple Myeloma, Multiple Myeloma therapy
- Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor to multiple myeloma. Here we define the epidemiological characteristics of SMM in the general population in Iceland. The iStopMM study (ClinicalTrials.gov ID: NCT03327597 ) is a nationwide screening study for multiple myeloma precursors where all residents in Iceland 40 years or older were invited to participate. SMM was defined as 10-60% bone marrow plasma cells and/or monoclonal (M) protein concentration ≥3 g dl
-1 , in the absence of myeloma-defining events. Of the 80,759 who gave informed consent to participate, 75,422 (93%) were screened. The prevalence of SMM in the total population was 0.53% (95% confidence interval (CI) = 0.49-0.57%) in individuals 40 years or older. In men and women, the prevalence of SMM was 0.67% (95% CI = 0.62-0.73%) and 0.39% (95% CI = 0.35-0.43%), respectively; it increased with age in both sexes. For the 193 individuals with SMM, median age was 70 years (range 44-92 years) and 60% were males. The mean M protein concentration of individuals with SMM was 0.62 g dl-1 (range 0.01-3.5 g dl-1 ) and 73% had 11-20% bone marrow plasma cell infiltration. The high prevalence of SMM has implications for future treatment policies in multiple myeloma as the evidence supporting treatment initiation at the SMM stage is emerging., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2023
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29. Strong site-specific association of pharyngeal cultures with the onset of psoriatic arthritis and psoriasis, regardless of pathogen.
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Thrastardottir T, Meer E, Hauksdottir A, Gudbjornsson B, Kristinsson SY, Ogdie A, and Love TJ
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- Humans, Risk Factors, Proportional Hazards Models, International Classification of Diseases, Arthritis, Psoriatic epidemiology, Arthritis, Psoriatic complications, Psoriasis epidemiology, Psoriasis complications
- Abstract
Objectives: The objective of this study was to evaluate any association between culture site / culture result / pathogen and incident PsA or psoriasis., Methods: Records of all samples sent for culture from a large population during a 3-year period were linked with nationwide registry data on diagnoses and death over a 15-year period. The main outcomes of interest were incident diagnoses of PsA and psoriasis, defined by International Classification of Diseases (ICD) codes. The effect of culture site, culture result (positive vs negative), and pathogen (Streptococcus vs negative culture) on the risk of developing PsA and psoriasis was calculated using Cox proportional hazards models adjusted for age and gender., Results: A total of 313 235 bacterial cultures from 128 982 individuals were analysed. Comparing individuals with pharyngeal cultures to those with urine cultures, the hazard ratio for incident PsA was 8.78 [95% confidence interval (CI) 3.23, 23.91] and for incident psoriasis it was 8.00 (95% CI 5.28, 12.12). Most of the risk was concentrated in the first 50 days after the culture date. Increased risk was also found when comparing individuals with cultures from the pharynx with those with cultures from the nasopharynx and blood. An association with streptococci was not found, neither in the pharynx nor at any other site. A positive bacterial culture from any site was associated with reduced risk for both PsA and psoriasis., Conclusion: There is a strong site-specific association between pharyngeal culture samples and an increased risk of PsA and psoriasis, regardless of the pathogen. This may indicate that the site of infection, rather than the pathogen, is associated with increased risk., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
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30. The consultant's guide to smoldering multiple myeloma.
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Thorsteinsdottir S and Kristinsson SY
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- Humans, Female, Adult, Risk Factors, Disease Progression, Smoldering Multiple Myeloma diagnosis, Smoldering Multiple Myeloma therapy, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM). The prevalence of SMM is 0.5% in persons over 40 years old; it is higher in men than women and increases with age. When SMM is diagnosed, a thorough diagnostic workup is necessary to exclude myeloma-defining events and stratify patients according to risk of progression to MM. While close monitoring for progression remains the best management for most patients with SMM, in this article, we discuss if treatment initiation before myeloma-defining events occur might be relevant in selected high-risk cases. Two randomized clinical trials have shown a clinical benefit of initiating treatment at the SMM stage, whereof 1 showed an overall survival benefit for those receiving treatment. We discuss various risk stratification models in SMM, important treatment trials, and ongoing trials. Finally, we present how to approach the clinical management of patients with SMM., (Copyright © 2022 by The American Society of Hematology.)
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- 2022
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31. The half-painted picture: Reviewing the mental health impacts of cancer screening.
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Wadsworth LP, Wessman I, Björnsson AS, Jonsdottir G, and Kristinsson SY
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- Anxiety diagnosis, Early Detection of Cancer, Humans, Mental Health, Quality of Life, Neoplasms diagnosis, Stress Disorders, Post-Traumatic psychology
- Abstract
Cancer screening is recommended for select cancers worldwide. Cancer screening has become increasingly effective and accessible and often increases overall survival. However, the mental health effects of cancer screening, such as its impact on depression, anxiety, and post-traumatic stress disorder, are largely unknown. Conflicting available literature indicates the negative, neutral, and positive mental health effects of cancer screening across cancer types. There are a limited number of randomized controlled trials measuring the mental health effects of cancer screening. Overall, the more negative and life-threatening the screening results, the greater the mental health effects. Screening for cancer without a known precursor, for example, due to family history, can have positive impacts such as decreased worry and increased quality of life. However, receiving a cancer diagnosis often has negative mental effects that increase with the life-threatening potential of malignancy. In this study, we review the existing literature and provide recommendations for future research to determine if and when cancer screening is the best practice., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2022
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32. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study.
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Long TE, Indridason OS, Palsson R, Rognvaldsson S, Love TJ, Thorsteinsdottir S, Sverrisdottir IS, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdottir I, Olafsson I, Thordardottir AR, Eythorsson E, Jonsson A, Gislason G, Olafsson A, Steingrimsdottir H, Hultcrantz M, Durie BGM, Harding S, Landgren O, and Kristinsson SY
- Subjects
- Humans, Immunoglobulin lambda-Chains, Prospective Studies, Reference Values, Immunoglobulin Light Chains, Renal Insufficiency, Chronic diagnosis
- Abstract
Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR < 60 mL/min/1.73 m
2 , not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26-1.65) in 9% of participants and outside current kidney reference interval (0.37-3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46-2.62, 0.48-3.38, and 0.54-3.30 for eGFR 45-59, 30-44, and < 30 mL/min/1.73 m2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented., (© 2022. The Author(s).)- Published
- 2022
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33. The first wave of COVID-19 and concurrent social restrictions were not associated with a negative impact on mental health and psychiatric well-being.
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Love TJ, Wessman I, Gislason GK, Rognvaldsson S, Thorsteinsdottir S, Sigurdardottir GA, Thordardottir AR, Eythorsson E, Asgeirsdottir TL, Aspelund T, Bjornsson AS, and Kristinsson SY
- Subjects
- Adult, Anxiety epidemiology, Cohort Studies, Cross-Sectional Studies, Depression epidemiology, Female, Humans, Male, Mental Health, Middle Aged, Prospective Studies, COVID-19 epidemiology
- Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic and efforts to contain it have substantially affected the daily lives of most of the world's population., Objective: We describe the impact of the first COVID-19 wave and associated social restrictions on the mental health of a large adult population., Methods: We performed a cohort study nested in a prospective randomized clinical trial, comparing responses during the first COVID-19 wave to previous responses. We calculated the odds ratio (OR) of the population moving up one severity category on validated instruments used to measure stress (PSS-10), anxiety (GAD-7), depression (PHQ-9), and Satisfaction With Life Scale (SWLS). Responses were linked to inpatient and outpatient ICD-10 codes from registries. Models were adjusted for age, sex, comorbidities, and pre-existing diagnoses of mental illness., Results: Of 63,848 invited participants, 42,253 (66%) responded. The median age was 60 (inter-quartile range 53-68) and 19,032 (45%) were male. Responses during the first wave of COVID-19 did not suggest increased stress (OR 0.97; 95% confidence interval [CI], 0.93-1.01; p = 0.28) or anxiety (OR 1.01; 95% CI, 0.96 to 1.05; p = 0.61), but were associated with decreased depression (OR 0.89; 95% CI, 0.85-0.93, p < 0.0001) and increased satisfaction with life (OR 1.12; 95% CI, 1.08-1.16, p < 0.0001). A secondary analysis of repeated measures data showed similar results., Conclusions: Social restrictions were sufficient to contain the pandemic but did not negatively impact validated measures of mental illness or psychiatric well-being. However, responses to individual questions showed signs of fear and stress. This may represent a normal, rather than pathological, population response to a stressful situation., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)
- Published
- 2022
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34. Autoimmunity, Infections, and the Risk of Monoclonal Gammopathy of Undetermined Significance.
- Author
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Sigurbergsdóttir AÝ, Love TJ, and Kristinsson SY
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- Autoimmunity, Humans, Autoimmune Diseases, Immune System Diseases complications, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance etiology, Multiple Myeloma, Paraproteinemias
- Abstract
Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in individuals with a prior history of immune-related conditions. This is believed to support the role of chronic antigen stimulation in the pathogenesis of these conditions. In this short review, we summarize some of the largest population-based studies researching autoimmune diseases, infections, and the subsequent risk of MGUS, and discuss our understanding on its etiology and pathogenesis. Furthermore, we highlight important methodological limitations of previous studies in the field, but almost all studies on MGUS have been based on clinical, possibly biased, cohorts. Finally, we discuss future directions in researching the associations of MGUS and other disorders, including immune-related conditions, where screening studies play an important role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sigurbergsdóttir, Love and Kristinsson.)
- Published
- 2022
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35. Survival, causes of death, and the prognostic role of comorbidities in chronic lymphocytic leukemia in the pre-ibrutinib era: A population-based study.
- Author
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Steingrímsson V, Lund SH, Dickman PW, Weibull CE, Björkholm M, Landgren O, and Kristinsson SY
- Subjects
- Adenine administration & dosage, Adenine adverse effects, Adenine analogs & derivatives, Adenine therapeutic use, Adult, Aged, Aged, 80 and over, Cause of Death, Comorbidity, Disease Management, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Male, Middle Aged, Mortality, Piperidines administration & dosage, Piperidines adverse effects, Piperidines therapeutic use, Population Surveillance, Prognosis, Registries, Sweden epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology
- Abstract
Objective: To evaluate temporal trends in survival and causes of death in patients with chronic lymphocytic leukemia (CLL) in a nationwide study., Methods: The cohort consisted of 13,009 Swedish CLL patients diagnosed 1982-2013. Relative survival (RS) and excess mortality rate ratios (EMRR) with 95% confidence intervals (95% CIs) were estimated using flexible parametric survival models. Cause-specific hazard ratios (HRs) were estimated for the linear effect of 10-year increase in year of diagnosis., Results: The excess mortality decreased comparing 2003-2013 to 1982-1992 (EMRR = 0.53, 95% CI 0.48-0.58). The 5-year RS increased between 1982 and 2012 for patients >51 years at diagnosis and improved for patients ≤51 years after 2002. The rate of CLL-specific deaths decreased over time (HR = 0.78, 95% CI 0.75-0.81). Compared to patients with no comorbidity, patients with 1 and 2+ Charlson Comorbidity Index points had HR = 1.35 (95% CI 1.25-1.45) and HR = 1.47 (95% CI 1.37-1.57) for CLL-related mortality, respectively., Conclusion: Survival in CLL patients improved in the era of chemoimmunotherapy, and this was largely explained by reduced CLL-related mortality. The increased rate of CLL-related mortality in patients with comorbidities emphasizes the importance of the newer and better tolerated targeted therapy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2022
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36. Diabetes mellitus and risk of plasma cell and lymphoproliferative disorders in 94,579 cases and 368,348 matched controls.
- Author
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Shah UA, Rögnvaldsson S, Derkach A, Björkholm M, Turesson I, David Y, Hultcrantz M, Tan C, Hassoun H, Korde N, Lesokhin A, Mailankody S, Kristinsson SY, and Landgren CO
- Subjects
- Humans, Plasma Cells, Diabetes Mellitus, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders etiology
- Published
- 2022
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37. Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study.
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Rognvaldsson S, Eythorsson E, Thorsteinsdottir S, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdóttir I, Olafsson I, Runolfsdottir HL, Helgason D, Emilsdottir AR, Agustsson AS, Bjornsson AH, Kristjansdottir G, Thordardottir AR, Indridason OS, Jonsson A, Gislason GK, Olafsson A, Steingrimsdottir H, Kampanis P, Hultcrantz M, Durie BGM, Harding S, Landgren O, Palsson R, Love TJ, and Kristinsson SY
- Subjects
- Adult, Aged, Cohort Studies, Female, Humans, Iceland epidemiology, Male, Middle Aged, Risk Factors, SARS-CoV-2, COVID-19 epidemiology, Monoclonal Gammopathy of Undetermined Significance epidemiology
- Abstract
Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81-1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52-1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19., (© 2021. The Author(s).)
- Published
- 2021
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38. Genetic variants associated with platelet count are predictive of human disease and physiological markers.
- Author
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Mikaelsdottir E, Thorleifsson G, Stefansdottir L, Halldorsson G, Sigurdsson JK, Lund SH, Tragante V, Melsted P, Rognvaldsson S, Norland K, Helgadottir A, Magnusson MK, Ragnarsson GB, Kristinsson SY, Reykdal S, Vidarsson B, Gudmundsdottir IJ, Olafsson I, Onundarson PT, Sigurdardottir O, Sigurdsson EL, Grondal G, Geirsson AJ, Geirsson G, Gudmundsson J, Holm H, Saevarsdottir S, Jonsdottir I, Thorgeirsson G, Gudbjartsson DF, Thorsteinsdottir U, Rafnar T, and Stefansson K
- Subjects
- Female, Humans, Male, Biomarkers analysis, Genetic Variation, Phenotype, Platelet Count, Quantitative Trait Loci
- Abstract
Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease., (© 2021. The Author(s).)
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- 2021
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39. Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma.
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Jonsdottir G, Björkholm M, Turesson I, Hultcrantz M, Diamond B, Porwit A, Landgren O, and Kristinsson SY
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- Antineoplastic Agents, Alkylating adverse effects, Disease Susceptibility, Humans, Leukemia, Myeloid, Acute diagnosis, Melphalan therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Myelodysplastic Syndromes diagnosis, Public Health Surveillance, Risk Assessment, Risk Factors, Sweden epidemiology, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute etiology, Melphalan adverse effects, Multiple Myeloma epidemiology, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes etiology, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary etiology
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Objectives: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM)., Methods: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis., Results: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P < .001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy., Conclusion: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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40. Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population.
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Saevarsdóttir KS, Hilmarsdóttir HÝ, Magnúsdóttir I, Hauksdóttir A, Thordardottir EB, Gudjónsdóttir ÁB, Tomasson G, Rúnarsdóttir H, Jónsdóttir HL, Gudmundsdóttir B, Pétursdóttir G, Petersen PH, Kristinsson SY, Love TJ, Hansdóttir S, Hardardóttir H, Gudmundsson G, Eythorsson E, Gudmundsdóttir DG, Sigbjörnsdóttir H, Haraldsdóttir S, Möller AD, Palsson R, Jakobsdóttir J, Aspelund T, and Valdimarsdottir U
- Subjects
- Anxiety epidemiology, Cross-Sectional Studies, Depression epidemiology, Humans, Iceland epidemiology, Morbidity, SARS-CoV-2, COVID-19
- Abstract
Objective: To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity., Design: Population-based cross-sectional study., Setting: Iceland., Participants: A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19., Main Outcome Measures: Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities., Results: Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44)., Conclusions: Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
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- 2021
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41. Untangling fracture risk in monoclonal gammopathy of undetermined significance: A population-based cohort study.
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Rögnvaldsson S, Aspelund T, Thorsteinsdóttir S, Turesson I, Björkholm M, Landgren O, and Kristinsson SY
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- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Fractures, Bone complications, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance complications, Peripheral Nervous System Diseases, Registries, Reproducibility of Results, Risk, Sensitivity and Specificity, Sweden epidemiology, Treatment Outcome, Young Adult, Fractures, Bone diagnosis, Monoclonal Gammopathy of Undetermined Significance diagnosis
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Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population-based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden., Methods: Data on fractures, PN, and confounders were acquired from high-quality registers in Sweden., Results: Monoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21-1.37; P < .001 and HR: 1.34; 95% CI: 1.16-1.55; P < .001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27-2.16; P < .001). Fractures were not associated with long-term risk of MGUS progression (HR: 1.08; 95% CI: 0.77-1.53; P = .64)., Discussion: Based on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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42. Comorbidities in multiple myeloma and implications on survival: A population-based study.
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Sverrisdóttir IS, Rögnvaldsson S, Thorsteinsdottir S, Gíslason GK, Aspelund T, Turesson I, Björkholm M, Gregersen H, Hveding Blimark C, Landgren O, and Kristinsson SY
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- Adult, Aged, Aged, 80 and over, Comorbidity, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prevalence, Risk Factors, Survival Rate, Sweden epidemiology, Multiple Myeloma mortality, Registries
- Abstract
High proportion of patients with multiple myeloma suffer from comorbidities which may alter clinical management. Therefore, our aims were to evaluate the prevalence of comorbidities and their impact on survival. We included patients diagnosed with multiple myeloma 1990-2013 in Sweden and all diagnoses from each patient from 1985. A total of 13 656 patients with multiple myeloma were included in the study, thereof 7404 (54%) had comorbidity at diagnosis. The risk of death was increased for those with one comorbidity at diagnosis compared to those without any comorbidity (hazard ratio = 1.19; 95% confidence interval:1.14-1.25); this risk was higher for those with two (1.38; 1.30-1.47) and three or more comorbidities (1.72; 1.62-1.83). Furthermore, the risk of death was increased in patients with prior history of cancer, arrhythmia, heart failure, diabetes mellitus, cerebrovascular disease, chronic lung disease, psychological disease, peptic ulcer, neurological disease, peripheral vascular disease, chronic kidney disease, dementia, and inflammatory bowel disease. This large study shows that over 50% of multiple myeloma patients have a comorbidity at diagnosis and survival decreased with increasing numbers of comorbidities. This emphasizes the importance of comorbidities when evaluating patients and deciding on treatment strategies for individuals with multiple myeloma., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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43. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.
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Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, Sigurðardóttir GÁ, Viðarsson B, Önundarson PT, Agnarsson BA, Sigurðardóttir M, Þorsteinsdóttir I, Ólafsson Í, Þórðardóttir ÁR, Eyþórsson E, Jónsson Á, Björnsson AS, Gunnarsson GÞ, Pálsson R, Indriðason ÓS, Gíslason GK, Ólafsson A, Hákonardóttir GK, Brinkhuis M, Halldórsdóttir SL, Ásgeirsdóttir TL, Steingrímsdóttir H, Danielsen R, Dröfn Wessman I, Kampanis P, Hultcrantz M, Durie BGM, Harding S, Landgren O, and Kristinsson SY
- Subjects
- Adult, Aged, Aged, 80 and over, Disease Progression, Female, Follow-Up Studies, Humans, Iceland epidemiology, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance epidemiology, Multiple Myeloma epidemiology, Multiple Myeloma prevention & control, Risk Factors, Monoclonal Gammopathy of Undetermined Significance diagnosis, Multiple Myeloma diagnosis
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
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- 2021
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44. Autoimmune disease is associated with a lower risk of progression in monoclonal gammopathy of undetermined significance.
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Baldursdóttir TR, Löve ÞJ, Gíslason GK, Björkholm M, Mellqvist UH, Lund SH, Blimark CH, Turesson I, Hultcrantz M, Landgren O, and Kristinsson SY
- Subjects
- Disease Progression, Disease Susceptibility, Humans, Monoclonal Gammopathy of Undetermined Significance pathology, Proportional Hazards Models, Public Health Surveillance, Registries, Risk Assessment, Risk Factors, Sweden epidemiology, Autoimmune Diseases complications, Autoimmune Diseases epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance epidemiology
- Abstract
Objectives and Methods: We conducted a population-based study including 19 303 individuals diagnosed with MGUS in Sweden from 1985 to 2013, with the aim to determine whether a prior history of autoimmune disease, a well-described risk factor for MGUS is a risk factor for progression of MGUS to multiple myeloma (MM) or lymphoproliferative diseases (LPs). Using the nationwide Swedish Patient registry, we identified MGUS cases with versus without an autoimmune disease present at the time of MGUS diagnosis and estimated their risk of progression., Results: A total of 5612 (29.1%) MGUS cases had preceding autoimmune diseases. Using Cox proportional hazards models, we found the risk of progression from MGUS to MM (HR = 0.83, 95% CI 0.73-0.94) and LPs (HR = 0.84, 95% CI 0.75-0.94) to be significantly lower in MGUS cases with prior autoimmune disease (compared to MGUS cases without)., Conclusions: In this large population-based study, a history of autoimmune disease was associated with a reduced risk of progression from MGUS to MM/other LPs. Potential underlying reason is that MGUS caused by chronic antigen stimulation is biologically less likely to undergo the genetic events that trigger progression. Our results may have implications in clinical counseling for patients with MGUS and underlying autoimmune disease., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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45. A nationwide study on inpatient opportunistic infections in patients with chronic lymphocytic leukemia in the pre-ibrutinib era.
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Steingrímsson V, Gíslason GK, Þorsteinsdóttir S, Rögnvaldsson S, Gottfreðsson M, Aspelund T, Turesson I, Björkholm M, Landgren O, and Kristinsson SY
- Subjects
- Adenine administration & dosage, Adenine adverse effects, Adenine analogs & derivatives, Adenine therapeutic use, Aged, Humans, Incidence, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Male, Piperidines administration & dosage, Piperidines adverse effects, Piperidines therapeutic use, Prognosis, Public Health Surveillance, Registries, Risk Factors, Sweden epidemiology, Cross Infection epidemiology, Cross Infection etiology, Inpatients, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology, Opportunistic Infections epidemiology, Opportunistic Infections etiology
- Abstract
Objective: Opportunistic infections in chronic lymphocytic leukemia (CLL) have been described in clinical trials, single-center studies, and case reports. We performed a nationwide study to estimate the incidence and impact of inpatient opportunistic infections., Methods: The incidence rate (IR) and incidence rate ratio (IRR) for Swedish CLL patients diagnosed 1994-2013, and matched controls were calculated, as well as the case-fatality ratio (CFR)., Results: Among 8989 CLL patients, a total of 829 opportunistic infections were registered (IR 16.6 per 1000 person-years) compared with 252 opportunistic infections in 34 283 matched controls (IR 0.99). The highest incidence in the CLL cohort was for Pneumocystis pneumonia (200 infections, IR 4.03); Herpes zoster (146 infections, IR 2.94), and Pseudomonas (83 infections, IR 1.66) infections. The highest risk relative to matched controls was observed for Pneumocystis pneumonia (IRR 114, 95% confidence interval 58.7-252). The 60-day CFR for CLL patients with opportunistic infections was 23% (188/821), highest for progressive multifocal encephalopathy (5/7, 71%) and aspergillosis (25/60, 42%)., Conclusion: We have uniquely depicted the incidence of rare and serious infections in CLL patients and found a relatively high incidence of Pneumocystis pneumonia. Of the most common opportunistic infections, CLL patients with aspergillosis had the poorest prognosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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46. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group.
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Moreau P, Kumar SK, San Miguel J, Davies F, Zamagni E, Bahlis N, Ludwig H, Mikhael J, Terpos E, Schjesvold F, Martin T, Yong K, Durie BGM, Facon T, Jurczyszyn A, Sidana S, Raje N, van de Donk N, Lonial S, Cavo M, Kristinsson SY, Lentzsch S, Hajek R, Anderson KC, João C, Einsele H, Sonneveld P, Engelhardt M, Fonseca R, Vangsted A, Weisel K, Baz R, Hungria V, Berdeja JG, Leal da Costa F, Maiolino A, Waage A, Vesole DH, Ocio EM, Quach H, Driessen C, Bladé J, Leleu X, Riva E, Bergsagel PL, Hou J, Chng WJ, Mellqvist UH, Dytfeld D, Harousseau JL, Goldschmidt H, Laubach J, Munshi NC, Gay F, Beksac M, Costa LJ, Kaiser M, Hari P, Boccadoro M, Usmani SZ, Zweegman S, Holstein S, Sezer O, Harrison S, Nahi H, Cook G, Mateos MV, Rajkumar SV, Dimopoulos MA, and Richardson PG
- Subjects
- Humans, Multiple Myeloma pathology, Neoplasm Recurrence, Local pathology, Antineoplastic Agents therapeutic use, Drug Resistance, Neoplasm drug effects, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy, Practice Guidelines as Topic standards, Salvage Therapy
- Abstract
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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47. A population-based study on serious inpatient bacterial infections in patients with chronic lymphocytic leukemia and their impact on survival.
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Steingrímsson V, Gíslason GK, Aspelund T, Turesson I, Björkholm M, Landgren O, and Kristinsson SY
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- Bacterial Infections mortality, Cross Infection mortality, Disease Susceptibility, Female, Humans, Male, Prognosis, Public Health Surveillance, Risk Assessment, Risk Factors, Sweden epidemiology, Bacterial Infections epidemiology, Bacterial Infections etiology, Cross Infection epidemiology, Inpatients, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology
- Abstract
Objective: Infections in chronic lymphocytic leukemia (CLL) have been thoroughly investigated in the setting of clinical trials and single-center studies. However, large cohort studies on real-world data and studies on temporal trends are lacking. We performed a nationwide study on serious bacterial infections in CLL., Methods: Using high-quality Swedish government-based registries, 13 009 CLL patients diagnosed in 1982-2013 and their 49 380 matched controls were included., Results: Overall, CLL patients had an increased risk of serious inpatient bacterial infections with a hazard ratio (HR) 5.32 and 95% confidence interval (95% CI) 5.11-5.53, and the highest risk was observed for septicemia (HR 6.91, 95% CI 6.46-7.39) and lung infections (5.91, 5.64-6.18). The risk of serious inpatient bacterial infections decreased overtime with HR 0.87 (0.81-0.94) and HR 0.76 (0.70-0.82) in 1993-2002 and 2003-2013, respectively, compared to 1982-1992. CLL patients had an increased risk of death following a serious inpatient bacterial infection compared to matched CLL patients, and the risk was highest in the first 12 months after the infection (HR 5.48, 95% CI 5.11-5.90)., Conclusion: We have, in this nationwide study, characterized the risk of serious bacterial infections in CLL patients and, importantly, depicted that the risk has decreased overtime., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2020
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48. Outcome and characteristics of non-measurable myeloma: A cohort study with population-based data from the Swedish Myeloma Registry.
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Wålinder G, Samuelsson J, Näsman P, Hansson M, Juliusson G, Forsberg K, Svensson R, Linder O, Carlson K, Kristinsson SY, Mellqvist UH, Hveding Blimark C, Turesson I, and Nahi H
- Subjects
- Adult, Aged, Aged, 80 and over, Asymptomatic Diseases, Biomarkers, Cohort Studies, Combined Modality Therapy, Female, Humans, Immunoglobulin Light Chains, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma metabolism, Multiple Myeloma therapy, Myeloma Proteins, Neoplasm Staging, Patient Outcome Assessment, Population Surveillance, Prognosis, Registries, Sweden epidemiology, Treatment Outcome, Young Adult, Multiple Myeloma epidemiology
- Abstract
Objective: We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM., Methods: Oligo-secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio., Results: Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7 months, non-measurable MM 40.2 months, oligo-secretory MM 38.6 months, and non-secretory MM 44.6 months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015)., Conclusion: In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2020
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49. Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden.
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Hultcrantz M, Ravn Landtblom A, Andréasson B, Samuelsson J, Dickman PW, Kristinsson SY, Björkholm M, and Andersson TM
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Incidence, Male, Middle Aged, Polycythemia Vera epidemiology, Primary Myelofibrosis epidemiology, Prospective Studies, Registries, Sweden epidemiology, Thrombocythemia, Essential epidemiology, Young Adult, Bone Marrow Neoplasms epidemiology
- Abstract
Background: The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers., Objective: We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers., Methods: Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated., Results: A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population., Conclusion: The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)
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- 2020
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50. Fractures and survival in multiple myeloma: results from a population-based study.
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Thorsteinsdottir S, Gislason G, Aspelund T, Sverrisdottir I, Landgren O, Turesson I, Björkholm M, and Kristinsson SY
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- Humans, Proportional Hazards Models, Registries, Risk Factors, Sweden epidemiology, Fractures, Bone epidemiology, Fractures, Bone etiology, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology
- Abstract
Multiple myeloma causes lytic bone lesions and fractures. The impact of fractures on multiple myeloma (MM) survival is unclear. The aim of this study was to evaluate the effect of fractures on survival in MM using data from MM patients diagnosed in Sweden in the years 1990-2013, identified from the Swedish Cancer Registry. Information on date of birth, MM diagnosis, fractures, and death was collected from central registries. A Cox regression model was used to compare survival in patients with and without a fracture at MM diagnosis and another Cox model was used with fracture as a time-dependent variable to assess the effect of fracture on survival after MM diagnosis. Results were adjusted for age, sex, year of diagnosis, and previous fractures. A total of 14,013 patients were diagnosed with MM during the study, of whom 1,213 (8.7%) were diagnosed with a fracture at MM diagnosis, and 3,235 (23.1%) after diagnosis. Patients with a fracture at diagnosis were at a significantly increased risk of death (hazard ratio=1.28; 95% confidence interval: 1.19-1.37). The risk of death was significantly increased in patients with a fracture after MM diagnosis (2.00; 1.90-2.10). The impact of fractures on survival did not change significantly between the two calendar periods 1990-1999 and 2000-2013 (0.98; 0.89-1.08). Our large study shows that MM patients with fractures are at a significantly increased risk of dying compared to those without fractures, which stresses the importance of preventing bone disease in MM., (Copyright© 2020 Ferrata Storti Foundation.)
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- 2020
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