| 1. |
- Ekberg, Sara, et al.
(författare)
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Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission
- 2022
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 127:9, s. 1642-1649
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achieving lasting remission for at least 2 years is a good indicator for favourable prognosis long term after Diffuse large B-cell lymphoma (DLBCL). The aim of this study was to provide real-world probabilities, useful in risk communication and clinical decision-making, of the chance for lasting remissions by clinical characteristics. Methods: DLBCL patients in remission after primary treatment recorded in the Swedish Lymphoma register 2007–2014 (n = 2941) were followed for relapse and death using multistate models to study patient trajectories. Flexible parametric models were used to estimate transition rates. Results: At 2 years, 80.7% (95% CI: 79.0–82.2) of the patients were predicted to remain in remission and 13.2% (95% CI: 11.9–14.6) to have relapsed. The relapse risk peaked at 7 months, and the annual decline of patients in remission stabilised after 2 years. The majority of patients in the second remission transitioned into a new relapse. The probability of a lasting remission was reduced by 20.4% units for patients with IPI 4–5 compared to patients with IPI 0–1, and time in remission was shortened by 3.5 months. Conclusion: The long-term prognosis was overall favourable with 80% achieving durable first remissions. However, prognosis varied by clinical subgroups and relapsing patients seldom achieved durable second remissions.
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| 2. |
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| 3. |
- Abalo, Kossi, et al.
(författare)
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Secondary malignancies among mantle cell lymphoma patients
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 195
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:With modern treatments, mantle cell lymphoma (MCL) patients more frequently experience long-lasting remission resulting in a growing population of long-term survivors. Follow-up care includes identification and management of treatment-related late-effects, such as secondary malignancies (SM). We conducted a populationbased study to describe the burden of SM in MCL patients.Methods:All patients with a primary diagnosis of MCL, aged >= 18 years and diagnosed between 2000 and 2017 in Sweden were included along with up to 10 individually matched population comparators. Follow-up was from twelve months after diagnosis/matching until death, emigration, or December 2019, whichever occurred first. Rates of SM among patients and comparators were estimated using the Anderson-Gill method (accounting for repeated events) and presented as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age at diagnosis, calendar year, sex, and the number of previous events.Results:Overall, 1 452 patients and 13 992 comparators were followed for 6.6 years on average. Among patients, 230 (16%) developed at least one SM, and 264 SM were observed. Relative to comparators, patients had a higher rate of SM, HRadj= 1.6 (95%CI:1.4-1.8), and higher rates were observed across all primary treatment groups: the Nordic-MCL2 protocol, R-CHOP, R-bendamustine, ibrutinib, lenalidomide, and R-CHOP/Cytarabine. Compared to Nordic-MCL2, treatment with R-bendamustine was independently associated with an increased risk of SM, HRadj= 2.0 (95%CI:1.3-3.2). Risk groups among patients were those with a higher age at diagnosis (p < 0.001), males (p = 0.006), and having a family history of lymphoma (p = 0.009). Patients had preferably higher risk of melanoma, other neoplasms of the skin and other hematopoietic and lymphoid malignancies.Conclusions:MCL survivors have an increased risk of SM, particularly if treated with R-bendamustine. The intensive treatments needed for long-term remissions are a concern, and transition to treatment protocols with sustained efficacy but with a lower risk of SM is needed.
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| 4. |
- Almqvist, Catarina, et al.
(författare)
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Season of birth, childhood asthma and allergy in a nationwide cohort : Mediation through lower respiratory infections
- 2020
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley. - 0954-7894 .- 1365-2222. ; 50:2, s. 222-230
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.ObjectiveWe aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or allergic rhinoconjunctivitis in a population‐based setting, and the mediating effect of lower respiratory infections.MethodsTwo population‐based cohorts were identified from the nationwide Swedish Medical Birth, Patient and Prescribed Drug Registers. The association between birth month/season and asthma/wheeze incidence was analysed using Cox proportional regression in the younger cohort born 2005‐2010 (n = 582 494) and asthma/allergic rhinoconjunctivitis prevalence during the 7th year of life using log‐binomial models in the older cohort born 2001‐2004 (n = 367 583). Interactions were formally tested. Mediation analyses to address the effect of lower respiratory infections were performed in the older cohort using the R package “medflex.”ResultsChildren born during fall and winter had an increased risk of asthma/wheeze after 2 years of age in the younger cohort: hazard ratio 1.24 (95% confidence interval, CI 1.17, 1.33) for winter and risk of prevalent asthma during their 7th year of life in the older cohort; prevalence ratio (PR) 1.12 (95% CI 1.08, 1.16) for winter. These estimates were partly mediated by lower respiratory infections; the indirect effect for winter compared with summer was PR 1.03 (95% CI 1.03, 1.04). The association was similar for allergic rhinoconjunctivitis in the 7th year of life, but not mediated by respiratory infections.ConclusionWe found that the association between season of birth and risk of childhood asthma/wheeze, but not allergic rhinoconjunctivitis, is partly mediated through lower respiratory infections.Clinical relevanceThis has important implications for patient care, such as asthma management programmes to notify timing of seasonality for viral respiratory tract infections.
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| 5. |
- Bäckström, Torbjörn, et al.
(författare)
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Isoallopregnanolone inhibits estrus cycle-dependent aggressive behavior
- 2023
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident–intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1β2γ2L and α4β3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior.
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| 6. |
- Ekberg, Sara
(författare)
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Are opportunities and threats enough? A development of the labels of strategic issues
- 2020
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Ingår i: Journal of Media Business Studies. - : Taylor & Francis. - 1652-2354 .- 2376-2977. ; 17:1, s. 13-32
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Tidskriftsartikel (refereegranskat)abstract
- This study joins the scholarly discussion that uses strategy in media management and provides a developed framework of strategic issues. This paper assists organisations in overcoming uncertainty by helping them construct issues and not impose the opportunity or threat labels on ill-defined issues. Based on a qualitative case study of two newspapers that represent an industry in disruption, this paper extends the existing conceptual framework on strategic issues by providing an additional strategic issue label, amorphous issues, that captures the uncertainties organisation members face during periods of disruption. Moreover, this paper also illustrates how the construction of issues can change over time. This emphasises the dynamic nature of strategic issues construction, which more closely aligns with the disruptive environment in which many contemporary organisations operate.
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| 7. |
- Ekberg, Sara, et al.
(författare)
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Impact of the COVID-19 pandemic on lymphoma incidence and short-term survival - a Swedish Lymphoma Register Study
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Background & purpose: The COVID-19 pandemic posed a large challenge for healthcare systems across the world. Comprehensive data on the impact of the COVID-19 pandemic on incidence and mortality in lymphoma are lacking.Patients/methods: Using data from the Swedish lymphoma register, we compare incidence and 1-year survival of lymphoma patients in Sweden before (2017-2019) and during the pandemic (2020 and 2021).Results: Fewer patients were diagnosed with lymphomas during March-June 2020, but the annual incidence rates for 2020 and 2021 were similar to those of 2017-2019. A larger proportion of patients presented with stage IV disease during 2021. There were no differences in other base-line characteristics nor application of active treatment in pre-pandemic and pandemic years. One-year overall survival was not inferior among lymphoma patients during the pandemic years compared to pre-pandemic years i.e., 2017-2019.Interpretation: The COVID-19 pandemic had limited impact on the incidence and mortality of lymphoma in Sweden.
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| 8. |
- Ekberg, Sara, et al.
(författare)
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Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation
- 2023
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Ingår i: Blood Advances. - : Elsevier. - 2473-9529 .- 2473-9537. ; 7:5, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Studies on late effects in patients with mantle cell lymphoma (MCL) are becoming increasingly important as survival is improving, and novel targeted drugs are being introduced. However, knowledge about late effects is limited. The aim of this population-based study was to describe the magnitude and panorama of late effects among patients treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT). The study cohort included all patients with MCL, recorded in the Swedish Lymphoma Register, aged 18 to 69 years, diagnosed between 2000 and 2014 (N = 620; treated with HD-ASCT, n = 247) and 1:10 matched healthy comparators. Patients and comparators were followed up via the National Patient Register and Cause of Death Register, from 12 months after diagnosis or matching to December 2017. Incidence rate ratios of the numbers of outpatient visits, hospitalizations, and bed days were estimated using negative binomial regression models. In relation to the matched comparators, the rate of specialist and hospital visits was significantly higher among patients with MCL. Patients with MCL had especially high relative risks of infectious, respiratory, and blood disorders. Within this observation period, no difference in the rate of these complications, including secondary neoplasms, was observed between patients treated with and without HD-ASCT. Most of the patients died from their lymphoma and not from another cause or treatment complication. Taken together, our results imply that most of the posttreatment health care needs are related to the lymphoma disease itself, thus, indicating the need for more efficient treatment options.
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| 9. |
- Ekberg, Sara
(författare)
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Long-term survival and survivorship in non-Hodgkin lymphoma patients in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-Hodgkin lymphoma (NHL) is one of the top ten most common cancer types in Sweden. Although sometimes referred to as one disease, NHL is truly an umbrella term representing a heterogeneous group of diseases with varying clinical course and prognosis. The main data source for all four studies included in this thesis is the Swedish lymphoma register (SLR). This national quality register provides population-based data, detailed clinical information and the possibility to distinguish between different morphological subtypes of NHL. In Study I we provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Poisson regression was used to test for temporal trends. We found that an increasing incidence and improved survival have led to an increase in the prevalence of NHL overall and for almost all investigated subtypes between 2000 and 2016. This increase was most notable for diffuse large B-cell lymphomas (DLBCL) among aggressive subtypes and marginal zone lymphomas among indolent subtypes. The prevalence provides a measure of burden of disease, useful for health care planning and to optimize resource allocation. The prevalence also represents the number of survivors in the population, at risk for relapses and psychological and physiological side effects of their lymphoma or treatment. The increase in number of prevalent NHL patients underscores the need to develop and evaluate alternative follow-up schemes of lymphoma survivors since especially patients diagnosed with indolent lymphoma subtypes are followed in the clinic for many years. The most common subtype of NHL, DLBCL is the focus in study II-IV. In recent years, the addition of rituximab to the standard combination chemotherapy has improved outcomes in patients with DLBCL. Nevertheless, every fourth patient treated curatively is expected to experience progressive disease or relapse. Study II aimed to quantify trends and remaining loss in life expectancy due to DLBCL in a population-based cohort. Loss in life expectancy was predicted using flexible parametric models from diagnosis and among two-year survivors, by age, sex and age-adjusted international prognostic index (aaIPI). The number of life-years lost decreased over the study period 2000-2013 in all patient groups. However, especially younger patients (≤60 years) with aaIPI≥2 were still estimated to lose many life years in 2013. Among two-year survivors, the loss in life-expectancy was reduced to two years or less by the end of the study period, regardless of age, sex and aaIPI. By using novel measures, we illustrated the improvement of DLBCL survival in a population-based context and over the entire life-span. The standard chemotherapy for curative treatment of DLBCL contains the cardiotoxic anthracycline doxorubicin. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, e.g. myocardial infarction, are less well studied. In Study III we assessed the incidence, characteristics and outcome of acute myocardial infarctions (AMI) in curatively treated patients with DLBCL. Patients were matched to lymphoma-free comparators and the rate of AMI was estimated using flexible parametric survival models incorporating repeated events. Overall, DLBCL patients had a 33% excess rate of AMI compared to the general population. However, the excess rate was most pronounced during the first year after diagnosis and diminished after 2 years. The strongest risk factors for AMI were advanced age, male sex and pre-existing comorbidity. There was no difference in AMI characteristics, extent of treatment or 30-day survival following hospitalization for AMI between DLBCL patients and comparators. The increased risk of AMI especially during the first 2 years and among elderly patients calls for improved cardiac monitoring. In Study IV we estimated real-world probabilities for lasting remission by clinical disease characteristics using a multi-state model approach. DLBCL patients who achieved remission after primary treatment were followed for repeated relapses and death. Flexible parametric models were used to model transition rates between disease stages accounting for competing events at each transition. At 2 years after end of primary treatment, 81% of the patients remained in remission, 13% had relapsed and 6 % of patients had died in first remission. The probability of remaining in remission for at least 2 years was reduced by 24 percentage units for patients with international prognostic index, IPI 4-5 compared to patients with IPI 0-1. On average, these patients lost 4.4 months of being in remission the first 2 years. Only 43% of relapsing patients achieved a second remission and half of them (51%) relapsed again - reflecting the difficulties in treating relapsing patients.
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| 10. |
- Ekberg, Sara, et al.
(författare)
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Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century - a Swedish lymphoma register study
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:6, s. 1083-1092
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors.
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