| 1. |
- Björkholm, Magnus, et al.
(författare)
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Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma : A population-based study from Sweden
- 2018
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Ingår i: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 101:1, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Forty percent of Hodgkin lymphoma (HL) patients are older than 50years at diagnosis, a fact which is not commonly recognized. Older patients do significantly worse than younger patients and are rarely included in clinical trials.Methods: Using data from Swedish Cancer and Lymphoma Registries, we estimated relative survival ratios (RSRs) for 7997 HL patients (diagnosed 1973-2013; 45% 50years).Results: The 1-year RSRs (95% confidence interval; CI) for males aged 45-59, 60-69, 70-80, and 81years and over, diagnosed in 2013, were 0.95 (0.91-0.97), 0.88 (0.81-0.92), 0.74 (0.63-0.81), and 0.52 (0.35-0.67), respectively. The corresponding 1-year RSRs for females were 0.97 (0.94-0.98), 0.91 (0.85-0.95), 0.82 (0.73-0.88), and 0.66 (0.50-0.77). No improvements in 1-year of 5-year relative survival from 2000 to 2013 were observed for patients aged 45-59 or 60-69 but there were modest improvements for patients aged 70years and older. Importantly, we saw no changes in the distribution of disease or patient characteristics between 2000 and 2013.Conclusions: Elderly patients constitute a large group with clearly unmet medical needs. Our findings motivate a more active approach to including elderly patients in clinical trials. Our study provides a baseline for outcome comparison after the broader introduction of targeted drugs.
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| 2. |
- Glimelius, Ingrid, 1975-, et al.
(författare)
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Comorbidities and sex differences in causes of death among mantle cell lymphoma patients – A nationwide population-based cohort study
- 2019
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141.
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Tidskriftsartikel (refereegranskat)abstract
- The prognosis for mantle cell lymphoma (MCL) remains poor. Our aim was to assess the impact of comorbidities on survival and causes of death. For 1,385 MCL patients (1,009 males, 376 females) diagnosed in 2000–2014 (median age 71 years, range 22–96) comorbidities ≤ 10 years of diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to compare lymphoma-specific and all-cause mortality rates. Model-based predictions were used to obtain probabilities of death. Overall, 44% had any comorbidity (CCI 1+) and 28% severe comorbidity (CCI 2+). Over a median follow-up of 3·7 years (range 0–16), 633 (46%) died, the majority (76%) from lymphoma. Severe comorbidity was independently associated with higher all-cause [hazard ratio (HR) = 1·52; 95% CI: 1·24–1·85) and lymphoma-specific mortality (HR = 1·31; 95% CI: 1·04–1·65). Particularly among patients with connective tissue, renal and psychiatric diseases, and dementia. Among females with any comorbidity, non-lymphoma deaths represented a larger proportion of all deaths, compared to males with any comorbidity. In general, more efficient lymphoma treatments need to be considered also for patients with severe comorbidity. However, among females with any comorbidity, the likelihood of non-lymphoma death was still considerable, perhaps favouring a more liberal use of a “wait and watch” approach.
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| 3. |
- Quinn, Patrick D., et al.
(författare)
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Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring
- 2017
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 74:6, s. 589-596
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.OBJECTIVE: To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.DESIGN, SETTING, AND PARTICIPANTS: This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.EXPOSURES: Maternal self-reported smoking during pregnancy, obtained from antenatal visits.MAIN OUTCOMES AND MEASURES: Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.RESULTS: Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.CONCLUSIONS AND RELEVANCE: This population-and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
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| 4. |
- Weibull, Caroline E, et al.
(författare)
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Contemporarily Treated Patients With Hodgkin Lymphoma Have Childbearing Potential in Line With Matched Comparators
- 2018
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:26, s. 2718-2725
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Tidskriftsartikel (refereegranskat)abstract
- Purpose With excellent cure rates for young patients with Hodgkin lymphoma (HL), there is an increasing number of female survivors of HL interested in becoming pregnant. Here, we report childbearing among contemporarily treated HL survivors in comparison with the general population. Material and Methods Using Swedish registers, 449 women (ages 18 to 40 years) diagnosed with HL between 1992 and 2009 and in remission 9 months after diagnosis were identified. Patients were age- and calendar-year-matched to 2,210 population comparators. Rates of first postdiagnosis childbirth were calculated. Hazard ratios (HRs) with 95% CIs were estimated for different follow-up periods using Cox regression. Cumulative probabilities of first childbirth were calculated in the presence of the competing risk of death or relapse. Results Twenty-two percent of relapse-free patients with HL had a child during follow-up, and first childbirth rates increased over time, from 40.2 per 1,000 person-years (1992 to 1997) to 69.7 per 1,000 person-years (2004 to 2009). For comparators, childbirth rates remained stable (70.1 per 1,000 person-years). Patients diagnosed between 2004 and 2009 had a cumulative probability of childbirth similar to comparators. Three years or more after diagnosis, no differences in childbirth rates were observed between patients and comparators, regardless of stage or treatment. Patients who received six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone had a lower childbirth rate than comparators during the first 3 years (HR, 0.23; 95% CI, 0.06 to 0.94), as did patients who received six to eight courses of chemotherapy and radiotherapy (HR, 0.21; 95% CI, 0.07 to 0.65). Conclusion Childbearing potential among female survivors of HL has improved over time, and childbirth rates 3 years after diagnosis in contemporarily treated patients are, in the absence of relapse, similar to those in the general population, regardless of stage and treatment.
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| 5. |
- Weibull, Caroline E, et al.
(författare)
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Pregnancy and the Risk of Relapse in Patients Diagnosed With Hodgkin Lymphoma
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:4, s. 337-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Many patients and clinicians are worried that pregnancy after the diagnosis of Hodgkin lymphoma (HL) may increase the risk of relapse despite a lack of empirical evidence to support such concerns. We investigated if an association exists between pregnancy and relapse in women with a diagnosis of HL.MATERIALS AND METHODS: Using Swedish healthcare registers combined with medical records, we included 449 women who received a diagnosis of HL between 1992 and 2009 and who were age 18 to 40 years at diagnosis. Follow-up started 6 months after diagnosis, when the patients' condition was assumed to be in remission. Pregnancy-associated relapse was defined as a relapse during pregnancy or within 5 years after delivery. Hazard ratios (HRs) with 95% CIs were estimated by using the Cox proportional hazards model.RESULTS: Among the 449 women, 144 (32%) became pregnant during follow-up. Overall, 47 relapses were recorded, of which one was a pregnancy-associated relapse. The adjusted HR for the comparison of the pregnancy-associated relapse rate to the non-pregnancy-associated relapse rate was 0.29 (95% CI, 0.04 to 2.18). The expected number of relapses in women with a recent pregnancy, given that they would experience the same relapse rate as that of women without a recent pregnancy, was 3.76; the observed-to-expected ratio was 0.27 (95% exact CI, 0.01 to 1.51).CONCLUSION: We found no evidence that a pregnancy after diagnosis increases the relapse rate among women whose HL is in remission. Survivors of HL need to consider a range of factors when deciding about future reproduction. However, given the results of this study, the risk of pregnancy-associated relapse does not need to be considered.
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| 6. |
- Weibull, Caroline E., et al.
(författare)
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Temporal trends in treatment-related incidence of diseases of the circulatory system among Hodgkin lymphoma patients
- 2019
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:5, s. 1200-1208
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Tidskriftsartikel (refereegranskat)abstract
- While Hodgkin lymphoma (HL) survival has improved, treatment-related complications remain a concern. As a measure of treatment-related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18-80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model-based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow-up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009-2013 vs. 1985-1988: EIRR = 0.63, 95% CI: 0.42-0.95). The 5- and 10-year excess incidence of DCS decreased between 1985 and 1994 for 25-year-olds (5-year-EIRR1994 = 0.32, 95% CI: 0.12-0.92) and 60-year-olds (5-year-EIRR1994 = 0.45, 95% CI: 0.24-0.88), but remained stable thereafter. No improvements were observed among 75-year-olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment-related incidence of DCS has declined since the mid-1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies.
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| 7. |
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| 8. |
- Sundstrom, K., et al.
(författare)
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Incidence of herpes zoster and associated events including stroke-a population-based cohort study
- 2015
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: More detailed understanding of herpes zoster (HZ) is called for in the context of an increasing observed frequency of disease, and ongoing discussions regarding potential consequences of the disease. Thus, population-based data on incidence and complications of HZ are needed. Methods: We conducted a register-based cohort study in Vastra Gotaland County (population 1.5 million) in Sweden. We collected data on all patients diagnosed with HZ during the years 2008 to 2010 from population-based registers. Incidence rates (IR) of HZ and related complications were calculated and stratified by age and sex. Results: There were 13 269 new HZ cases during the study period. Overall, the IR of herpes zoster in both genders was 3.25 (95 % CI: 3.16-3.34) per 1000 person years in 2010. The incidence was consistently higher in women than in men and in older than in young. A history of immunosuppression was more common than in the general population. The incidence was highest in individuals over 80 years of age (IR 9.2 per 1000 person years, 95 % CI: 8.8-9.6) during 2008-2010. The most common complications to HZ were ocular engagement and postherpetic neuralgia; risks for stroke and sepsis were significantly elevated during the one year following diagnosis, especially in the youngest age group of patients 0-39 years. Conclusions: Herpes zoster is more common in women, the elderly and immunosuppressed individuals. We verify a population-based association between herpes zoster and risk for stroke and sepsis, which may merit concern.
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| 9. |
- Weibull, Caroline E
(författare)
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Survivorship in Hodgkin lymphoma : childbearing and treatment-related disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is often considered a disease with, historically, poor survival that affects middle-aged and elderly individuals. Hodgkin lymphoma (HL) is a lymphatic malignancy that affects both young and old individuals, with the age-specific incidence curve having its first peak at ages 20-30 years. As survival has improved substantially over the last decades, there is an increasing number of survivors – some still at a young age. The primary purpose of this thesis was to address issues related to childbearing and treatment-associated disease among HL survivors. As a means to investigate these issues, novel statistical methods were developed and applied. Childbearing in relation to HL Some HL survivors will be at the beginning, or in the midst, of their childbearing years. Both pregnancy and HL are associated with changes to the immune system, making it plausible that pregnancy could affect the progression of the disease. Study I in this thesis aimed to answer if pregnancy affects the risk of relapse among female patients in remission from HL. Ever since the introduction of radio- and chemotherapy with the possibility to cure HL, the negative effects of therapy on fertility have been a concern. Contemporary treatments are believed to be less gonadotoxic than those previously used, but few studies have compared childbearing potential between the main treatment regimens administered today (ABVD and BEACOPP) in a real-world setting. In Study II, temporal trends in childbearing among female HL patients (of childbearing ages) were investigated, within groups of treatments, and in comparison with the general population. Both studies utilized a cohort of women diagnosed between 1992 and 2009, at ages 18-40 years, for whom detailed information on relapse as well as patient and disease characteristics was available. For the purpose of comparing childbirth rates with the general population, HL patients were individually matched to HL-free comparators. Childbirth rates were studied separately within two time windows during follow-up: 0-3 years and 3-7 years, and cumulative probability of childbirth was calculated in the presence of the competing risks of death and relapse. No evidence to support the hypothesis of pregnancy-associated relapse was found. However, since the absolute risk of relapse is at its highest levels during the first 2-3 years after diagnosis, female HL patients could, if possible, be advised to delay childbearing to avoid co-occurence. Childbearing potential improved over calendar time, reflecting reduced toxicity and changes in counseling. Women treated during recent years had childbirth potential in line with that of matched comparators three years after diagnosis. Even women treated with BEACOPP, the most gonadotoxic chemotherapy, had an increasing cumulative probability of having children after HL. Importantly, no women had children after a relapse within the first seven years af- ter diagnosis, which motivates a need for fertility advice and counseling at time of HL diagnosis. Treatment-related disease Late effects from cancer therapy are becoming increasingly important to quantify as the number of cancer survivors grows. Chemo- and radiotherapy used to treat HL increases the risk of cardio- and cerebrovascular diseases, and secondary malignancies (SMs). In Study III, excess incidence of diseases of the circulatory system (DCS) among HL patients was investigated to describe temporal trends in DCS morbidity attributable to HL and its treatment. Data on patients diagnosed with HL between 1985 and 2013 at ages 18-80 years, for whom information on inpatient DCS records was available, was used. Relative survival methods were applied to estimate excess incidence rates indirectly from the observed and expected rates of DCS. Cumulative excess incidence of DCS was calculated in the presence of competing risks. The treatment-related incidence of DCS declined between the mid-1980s and mid-1990s, after which no substantial improvements were observed. The risk of a treatment-related DCS persists for up to 10 years among patients who completed their treatment in the new millennium. When studying late effects it is important to attempt to capture the additional disease incidence associated with cancer treatment. Additionally, to gain insight in real-life risks, it is of interest to study not only time to first event, but continue to follow patients as they experience different types of late effects before reaching an absorbing state. Doing both of these simultaneously requires estimating excess transition rates to transient states in a multi-state model framework, for which no methods have existed. Study IV suggested a way to achieve this, using a recently developed simulation strategy to predict transition probabilities. As an illustrative example, data from Study III on HL patients and DCS incidence was used. Combining methods from relative survival with the multi-state framework enables investigation of complex patient pathways and can be useful for several applications related to survivorship among cancer patients.
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