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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Entrop, Joshua P., et al.
(författare)
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Reproduction patterns among classical Hodgkin lymphoma survivors treated with BEACOPP and ABVD in Sweden, Denmark and Norway-A population-based matched cohort study
- 2023
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 153:4, s. 723-731
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Tidskriftsartikel (refereegranskat)abstract
- Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18-40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995-2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2-4 BEACOPP, 6-8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2-4 BEACOPP and 11.2% with 6-8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6-8 BEACOPP, and 2-4 BEACOPP to ABVD were 0.53 (CI: 0.36-0.77) and 0.33 (CI: 0.12-0.91) for males, and 0.91 (CI: 0.61-1.34) and 0.38 (CI: 0.12-1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%-27.0%) for males and 34.3% (CI: 25.8%-45.6%) for females treated with 6-8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2-88.6%) for males following 6-8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%-17.3%) and 10.6% (CI: 7.4%-14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.
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| 6. |
- Entrop, Joshua P., et al.
(författare)
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Reproduction patterns among non-Hodgkin lymphoma survivors by subtype in Sweden, Denmark and Norway : A population-based matched cohort study
- 2023
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 202:4, s. 785-795
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies concerning reproductive patterns among non-Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18-40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital (n = 2090). Population comparators were matched on sex, birth year and country (n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HRfemale: 0.43, 95% CI: 0.31-0.59, HRmale: 0.61, 95% CI: 0.47-0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HRfemale: 0.71, 95% CI: 0.48-1.04, HRmale: 0.94, 95% CI: 0.70-1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10-year follow-up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL.
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| 7. |
- 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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| 8. |
- Glimelius, Ingrid, 1975-, et al.
(författare)
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Unmarried or less-educated patients with mantle cell lymphoma are less likely to undergo a transplant, leading to lower survival
- 2021
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:6, s. 1638-1647
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown how many mantle cell lymphoma (MCL) patients undergo consolidation with autologous hematopoietic cell transplantation (AHCT), and the reasons governing the decision, are also unknown. The prognostic impact of omitting AHCT is also understudied. We identified all MCL patients diagnosed from 2000 to 2014, aged 18 to 65 years, in the Swedish Lymphoma Register. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models were used to compare the likelihood of AHCT within 18 months of diagnosis. All-cause mortality was compared between patients treated with/without AHCT using hazard ratios (HRs) and 95% CIs estimated from Cox regression models. Probabilities of being in each of the following states: alive without AHCT, alive with AHCT, dead before AHCT, and dead after AHCT, were estimated over time from an illness-death model. Among 369 patients, 148 (40%) were not treated with AHCT within 18 months. Compared with married patients, never married and divorced patients had lower likelihood of undergoing AHCT, as had patients with lower educational level, and comorbid patients. Receiving AHCT was associated with reduced all-cause mortality (HR 5 0.58, 95% CI: 0.40-0.85). Transplantation-related mortality was low (2%). MCL patients not receiving an AHCT had an increased mortality rate, and furthermore, an undue concern about performing an AHCT in certain societal groups was seen. Improvements in supportive functions potentially increasing the likelihood of tolerating an AHCT and introduction of more tolerable treatments for these groups are needed.
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| 10. |
- Ovlisen, Andreas K., et al.
(författare)
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Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors : A Danish Population-Based Study
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:31, s. 3463-3472
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care.MATERIALS AND METHODS All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use.RESULTS A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators.CONCLUSION The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.
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| 11. |
- 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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| 12. |
- 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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| 13. |
- Weibull, Caroline E., et al.
(författare)
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CRCBaSe : a Swedish register-based resource for colorectal adenocarcinoma research
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:4, s. 342-349
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To facilitate high-quality register-based research on colorectal cancer (CRC) in Sweden by constructing a database consisting of CRC patients, matched comparators, and relatives.MATERIAL AND METHODS: Patients with adenocarcinoma in the colon and/or rectum were identified in the Swedish Colorectal Cancer Register, a nationwide quality-of-care register. For each patient, six comparators from the general population were matched on birth year, sex, year of CRC diagnosis, and county. Comparators were free from CRC at the time of matching, but could later become cases. For both patients and comparators, first-degree relatives (parents, siblings, and children) were identified. Information from nationwide population-based registers was retrieved and linked to each individual in the database using the personal identification number unique to all Swedish residents.RESULTS: A total of 76,831 CRC patients diagnosed between 1995 and 2016 were identified (51% colon, 49% rectal; before 2007 only rectal cancer patients were included). Among all patients, 37% were stage I-II, 22% stage III, and 22% stage IV. The median follow-up time was 11.9 years (inter-quartile range, IQR: 8.6-15.3). Together with comparators and relatives, the database contains 2,413,139 individuals with information on demographics, dates and causes of death, in- and outpatient healthcare records, cancer diagnoses, prescribed and dispensed drugs, childbirths (among women), and social security information (such as sick leave and early retirement).CONCLUSION: The Colorectal Cancer Database Sweden (CRCBaSe) is a large and unique register-based data research platform, which opens up for clinically important, large epidemiological studies with innovative design in the field of colorectal adenocarcinoma.
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| 14. |
- 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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| 15. |
- Weibull, Caroline E., et al.
(författare)
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Survival by First-line Treatment Type and Timing of Progression Among Follicular Lymphoma Patients : A National Population-based Study in Sweden
- 2023
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Ingår i: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- In follicular lymphoma (FL), progression of disease <= 24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing of progression and treatment in a national population-based setting. We identified 948 stage II-IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007-2014 who received first-line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow-up using Cox regression. OS was predicted by POD using an illness-death model. During a median follow-up of 6.1 years (IQR: 3.5-8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred <= 24 months. POD was represented by a transformation in 15% of cases. Compared to progression-free patients, POD increased all-cause mortality across treatments, but less so among patients treated with rituximab(R)-single (HR = 4.54, 95% CI: 2.76-7.47) than R-chemotherapy (HR = 8.17, 95% CI: 6.09-10.94). The effect of POD was similar following R-CHOP (HR = 8.97, 95% CI: 6.14-13.10) and BR (HR = 10.29, 95% CI: 5.60-18.91). The negative impact of POD on survival remained for progressions up to 5 years after R-chemotherapy, but was restricted to 2 years after R-single. After R-chemotherapy, the 5-year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression-free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.
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| 16. |
- 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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| 17. |
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| 18. |
- Joneborg, Ulrika, et al.
(författare)
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Hydatidiform mole and subsequent pregnancy outcome : a population-based cohort study
- 2014
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 24:9, s. 1084-1084
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of the study was to investigate whether a history of hydatidiform mole (HM) is associated with an increased risk of adverse outcomes in subsequent pregnancies. STUDY DESIGN: This was a nationwide cohort study with data from population-based registers. The study population consisted of all children registered in the Swedish Medical Birth Register 1973-2009 (n = 3,730,825). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for adverse maternal and offspring pregnancy outcomes by maternal history of HM prior to the delivery, with children to women with no maternal history of HM as the reference. Risk estimates were adjusted for maternal age at delivery and maternal country of birth. RESULTS: A history of HM was not associated with an increased risk of adverse maternal outcomes in subsequent pregnancies (n = 5186). Women exposed to a molar pregnancy prior to the index birth were at an almost 25% increased risk of preterm birth (OR, 1.23; 95% CI, 1.06-1.43), whereas women with at least 1 birth between the HM and the index birth were at an increased risk of a large-for-gestational-age birth and stillbirth (OR, 1.35; 95% CI, 1.10-1.67 and OR, 1.81; 95% CI, 1.11-2.96, respectively). The risk of repeat mole was 0.4%. CONCLUSION: Women with a history of HM are at no increased risk of adverse maternal outcomes in subsequent pregnancies but have an increased risk of large-for-gestational-age birth, stillbirth, and preterm birth. However, in absolute terms, the risk of subsequent adverse offspring outcomes is very low.
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| 19. |
- Lambe, Mats, et al.
(författare)
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Reproductive patterns and maternal and pregnancy outcomes in women with psoriasis-A population-based study
- 2020
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Ingår i: The Journal of American Academy of Dermatology. - : MOSBY-ELSEVIER. - 0190-9622 .- 1097-6787. ; 82:5, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on pregnancy outcomes in women with psoriasis are conflicting.Objective: We examined whether maternal psoriasis affects the risk of adverse maternal and pregnancy outcomes.Methods: We used population-based data to compare reproductive patterns in women with and without psoriasis. Odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes were estimated with adjustments for maternal age, period of childbirth, smoking, and prepregnancy body mass index.Results: Compared with women without psoriasis, women with psoriasis were younger at first birth and had longer interpregnancy intervals but did not differ in final parity. Risk estimates in women with psoriasis were elevated for pregnancy hypertension (OR, 1.37; 95% CI, 1.19-1.58), premature rupture of membranes (OR, 1.15; 95% CI, 1.04-1.27), large for gestational age (OR, 1.11; 95% CI, 1.01-1.21), cleft palate (OR, 1.69; 95% CI, 1.07-2.66), and unspecified malformations (OR, 1.08; 95% CI, 1.01-1.16).Limitations: No information was available on lifestyle, disease severity, or type and duration of treatment. Small numbers hampered the assessment of rare outcomes.Conclusion: Although there was no evidence that fertility is negatively affected, women with psoriasis were at an increased risk of several adverse maternal and pregnancy outcomes. Our findings add to a growing body of evidence that pregnancies in women with psoriasis need special monitoring.
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| 20. |
- Ljunggren, Malin, et al.
(författare)
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Hospital factors and metastatic surgery in colorectal cancer patients, a population-based cohort study
- 2022
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Ingår i: BMC Cancer. - : Springer Nature. - 1471-2407. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Only a limited proportion of patients with metastatic colorectal cancer (mCRC) receives metastatic surgery (including local ablative therapy). The aim was to investigate whether hospital volume and hospital level were associated with the chance of metastatic surgery.Methods: This national cohort retrieved from the CRCBaSe linkage included all Swedish adult patients diagnosed with synchronous mCRC in 2009-2016. The association between annual hospital volume of incident mCRC patients and the chance of metastatic surgery, and survival, were assessed using logistic regression and Cox regression models, respectively. Hospital level (university/non-university) was evaluated as a secondary exposure in a similar manner. Both uni- and multivariable (adjusted for sex, age, Charlson comorbidity index, year of diagnosis, cancer characteristics and socioeconomic factors) models were fitted.Results: A total of 1,674 (17%) out of 9,968 mCRC patients had metastatic surgery. High hospital volume was not associated with increased odds of metastatic surgery after including hospital level in the model, whereas hospital level was (odds ratio (OR) (95% confidence interval (CI)): 1.94 (1.68-2.24)). All-cause mortality was lower in university versus non-university hospitals (hazard ratio (95% CI): 0.83 (0.78-0.88)).Conclusions: Patients with mCRC initially cared for by a university hospital experienced a greater chance to receive metastatic surgery and had superior overall survival. High hospital volume in itself was not associated with a greater chance to receive metastatic surgery nor a greater survival probability. Additional efforts should be imposed to provide more equal care for mCRC patients across Swedish hospitals.
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| 21. |
- Ljunggren, Malin, et al.
(författare)
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Sex differences in metastatic surgery following diagnosis of synchronous metastatic colorectal cancer
- 2023
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:3, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate gender differences in the likelihood to receive metastatic surgery, and to compare overall survival between men and women, among patients with synchronous metastatic colorectal cancer (mCRC) in a population-based setting. All Swedish adult patients diagnosed with synchronous mCRC in 2007-2016 were identified using the nationwide colorectal cancer database (CRCBaSe). Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression, comparing the odds of receiving treatment. The Kaplan-Meier method was used to calculate survival proportions and Cox regression models to estimate hazard ratios (HRs) and 95% CIs of all-cause mortality rates. All multivariable models were adjusted for age, ASA score, Charlson comorbidity index, year of diagnosis, location of primary tumor and single or multiple metastatic locations. A total of 12 201 patients met the study criteria. Women received 23% less metastatic surgery for mCRC (adjusted OR = 0.77, CI:0.69-0.86) and experienced a slightly higher mortality following diagnosis (adjusted HR = 1.09, CI:1.05-1.14). In analyses restricted to patients who received metastatic surgery, no significant differences in mortality were found. In conclusion, this population-based study showed that women less often received metastatic surgery of mCRC and experienced slightly higher all-cause mortality compared with men. The differences persisted despite adjustments of patient and cancer characteristics. Gender differences in receiving treatment are unacceptable if the underlying explanation cannot be motivated. Further studies are needed to understand if the differences are based on sex (i.e., biology) or gender (including clinically unmotivated differences in treatment approach).
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| 22. |
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| 23. |
- Lundqvist, Erik, et al.
(författare)
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Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Early onset of colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. We investigated preexisting autoimmune and metabolic diagnoses of 2626 EOCRC patients in Sweden, diagnosed in 2007-2016, together with 15,756 controls matched for birth year, sex, and county. Comorbid diagnoses were collected from the National Patient Register. A history of metabolic disease nearly doubled the incidence of EOCRC, and presence of inflammatory bowel disease (IBD) was associated with a sixfold increased incidence of EOCRC. Patients with both IBD and metabolic disease had a lower incidence of EOCRC compared with IBD patients without metabolic condition. Non-IBD autoimmune disease was not associated with an increased incidence of EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines. Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.
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| 24. |
- Malki, Ninoa, et al.
(författare)
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Temporal trends in incidence of myocardial infarction and ischemic stroke by socioeconomic position in Sweden 1987-2010
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e105279-
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Tidskriftsartikel (refereegranskat)abstract
- Background We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time.Materials and Methods We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country.Results The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2-1.4) in 1997 to 1.5 (1.4-1.7) in 2010 among men, and from 1.4 (1.3-1.6) in 1997 to 2.1 (1.8-2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women.Conclusion There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.
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| 25. |
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| 26. |
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| 27. |
- Nikkarinen, Anna, et al.
(författare)
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Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma
- 2023
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:18, s. 5304-5313
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Tidskriftsartikel (refereegranskat)abstract
- The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed toward the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). We aimed to investigate the prognostic value of sCD163 in 131 patients with MCL. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) in 81 patients who were newly diagnosed and subsequently treated with chemoimmunotherapy. The same was seen in a cohort of 50 patients with relapsed MCL that were mainly treated within the phase 2 Philemon-trial with rituximab, ibrutinib, and lenalidomide. In patients who were newly diagnosed and had low levels of sCD163, 5-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163. The association with a poor prognosis was independent of MCL international prognostic index, Ki67, p53 status, and blastoid morphology, as assessed in a multivariable Cox proportional hazards model. In this study, high sCD163 was associated with both shorter PFS and shorter OS, showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify patients with MCL with a very good prognosis.
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| 28. |
- Rodrigues, Joana M., et al.
(författare)
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Infiltration of CD163-, PD-L1-and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors
- 2021
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 193:3, s. 520-531
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Tidskriftsartikel (refereegranskat)abstract
- We characterised patients with mantle cell lymphoma (MCL) with poor prognosis based on differences in immune infiltration. Different expressions of the tumour cell markers Cyclin D1 and sex-determining region Y-box transcription factor 11 (SOX11), and the immune markers cluster of differentiation 3 (CD3), CD4, CD8, CD25, forkhead box protein P3 (FoxP3), T-box transcription factor TBX21 (T-bet), programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1) and CD163 were investigated for all-cause mortality in 282 patients with MCL and time-to-progression (TTP) in 106 clinical trial patients. With increasing age, a significantly lower infiltration of CD3(+) T lymphocytes was seen. T-cell infiltration was independent of cellular tumour antigen p53 (p53) expression, Ki-67, morphology and frequency of tumour cells. The all-cause mortality was higher in patients with PD-L1-expression above cut-off [hazard ratio (HR) 1 center dot 97, 95% confidence interval (CI) 1 center dot 18-3 center dot 25, adjusted for sex and MCL International Prognostic Index (MIPI)] and a higher frequency of CD163(+) cells (continuously, HR 1 center dot 51, 95% CI 1 center dot 03-2 center dot 23, adjusting for age, sex, morphology, Ki-67 and p53). In patients treated within the Nordic Lymphoma Group MCL2/3 trials, TTP was shorter in patients with a higher frequency of FoxP3(+) cells (HR 3 center dot 22, 95% CI 1 center dot 40-7 center dot 43) and CD163(+) cells (HR 6 center dot 09, 95% CI 1 center dot 84-20 center dot 21), independent of sex and MIPI. When combined a higher frequency of CD163(+) macrophages and PD-L1(+) cells or high CD163(+) macrophages and FoxP3(+) regulatory T cells indicated worse outcome independent of established risk factors. The T-cell infiltrate was in turn independent of molecular characteristics of the malignant cells and decreased with age.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Rutegård, Martin, 1982-, et al.
(författare)
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Exposure to oestrogen and risk of anastomotic leakage after colorectal cancer surgery - A clue to the different leak rates in men and women.
- 2023
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Ingår i: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 25:1, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy.METHODS: This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted.RESULTS: Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59-0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36-0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38-1.02).CONCLUSIONS: Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.
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| 33. |
- Shahrivar, Mehrnoosh, et al.
(författare)
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Low-dose aspirin use and colorectal cancer survival in 32,195 patients : A national cohort study
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:1, s. 315-324
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Results from previous studies indicate that use of aspirin may improve colorectal cancer (CRC) survival. The aim of this study was to assess whether use of aspirin influences overall survival or CRC-specific survival in an unselected cohort of patients diagnosed with CRC.METHODS: The study was performed using the Colorectal Cancer Data Base Sweden (CRCBaSe), a mega-linkage originating from the Swedish Colorectal Cancer Register, with additional linkages to other national health care registers. All patients diagnosed with primary CRC stage I-III treated with curative surgery, aged 18-85 years at diagnosis, from 2007 through 2016 were identified. Information on low-dose aspirin use was extracted from the Swedish Prescribed Drug Register. Exposure was defined as dispensed prescription for at least 6 months. Aspirin exposure was analyzed at the time of surgery (yes/no) and as a time-varying exposure during follow-up. Follow-up was restricted to a maximum 6 years, to model 5-year survival. Cox regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Adjustments were performed for sex, age, year of diagnosis, Charlson comorbidity index, hypertension, and ASA score as potential confounders.RESULTS: A total of 32,195 patients diagnosed with CRC were included. 6764 (21%) were exposed to aspirin at the time of CRC surgery. The median time of follow-up was 4.2 years. Aspirin use at the time of surgery was not associated with all-cause (adjusted HR = 1.03, 95% CI: 0.97-1.08) nor CRC-specific mortality (adjusted HR = 0.99, 95% CI: 0.91-1.07). Aspirin use during follow-up was associated with increased all-cause (adjusted HR = 1.09, 95% CI: 1.04-1.15) but not CRC-specific mortality (adjusted HR = 0.98, 95% CI: 0.91-1.06). A CRC-specific effect associated with aspirin was noted from approximately 3 years following surgery.CONCLUSIONS: In this large nation-wide cohort study there was no convincing association between aspirin use after CRC and OS or CRC-specific survival.
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| 34. |
- 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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| 35. |
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| 36. |
- 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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