| 1. |
- Bai, Ge, et al.
(författare)
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Frailty trajectories in three longitudinal studies of aging : Is the level or the rate of change more predictive of mortality?
- 2021
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 50:6, s. 2174-2182
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: frailty shows an upward trajectory with age, and higher levels increase the risk of mortality. However, it is less known whether the shape of frailty trajectories differs by age at death or whether the rate of change in frailty is associated with mortality.OBJECTIVES: to assess population frailty trajectories by age at death and to analyse whether the current level of the frailty index (FI) i.e. the most recent measurement or the person-specific rate of change is more predictive of mortality.METHODS: 3,689 individuals from three population-based cohorts with up to 15 repeated measurements of the Rockwood frailty index were analysed. The FI trajectories were assessed by stratifying the sample into four age-at-death groups: <70, 70-80, 80-90 and >90 years. Generalised survival models were used in the survival analysis.RESULTS: the FI trajectories by age at death showed that those who died at <70 years had a steadily increasing trajectory throughout the 40 years before death, whereas those who died at the oldest ages only accrued deficits from age ~75 onwards. Higher level of FI was independently associated with increased risk of mortality (hazard ratio 1.68, 95% confidence interval 1.47-1.91), whereas the rate of change was no longer significant after accounting for the current FI level. The effect of the FI level did not weaken with time elapsed since the last measurement.CONCLUSIONS: Frailty trajectories differ as a function of age-at-death category. The current level of FI is a stronger marker for risk stratification than the rate of change.
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| 2. |
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| 3. |
- Bower, Hannah, et al.
(författare)
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Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.
- 2023
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Ingår i: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking.Through Swedish registers, we identified 13493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age.Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%).As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
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| 4. |
- Bower, Hannah
(författare)
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Flexible parametric models for cancer patient survival : loss in expectation of life and further developments
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Population-based cancer studies can contribute to a better understanding of cancer patient survival. The general aim of this thesis was to develop and apply statistical methods for population-based cancer studies to ensure understanding in this area. In any analysis setting, it is important that the statistical methods are appropriate. Since nonproportional hazards are common in population-based data where follow-up is long, Study I assessed the ability of flexible parametric models (FPMs) in capturing time-dependent effects in a simulation setting. This study also attempted to determine whether the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC) were more appropriate in selecting a good-fitting model. Results indicated that bias was small for estimated survival proportions, hazard rates and log hazard ratios when degrees of freedom were selected using guidance from the AIC or BIC. Neither the AIC nor the BIC constantly outperformed the other. We concluded that FPMs accurately capture time-dependent effects but that users should perform appropriate sensitivity analyses. There have been large changes in treatments for chronic myeloid leukaemia (CML) patients over time; most notably is the introduction of imatinib mesylate, a targeted therapy, in 2001. Studies have shown that relative survival of CML patients greatly improved after the introduction of this treatment. Since CML is a chronic disease, quantifying survival in terms of life expectancy is highly relevant. In Study II we aimed to quantify life expectancy improvements using the loss in expectation of life measure. Results indicated that patients diagnosed in 2013 would be expected to lose less than three of their remaining life years due to their CML diagnosis. We concluded that the life expectancy among CML patients is approaching that seen in the general population and improvements over time are largely due to imatinib mesylate and allogeneic stem cell transplantation. Population-based mortality rates are often used as a proxy for the mortality rate a diseased population would have experienced had they been disease-free; these are used in relative survival analysis and when calculating standardised mortality ratios. Population-based mortality rates are commonly available by age, calendar year and sex which might limit analyses to these factors. In Study III we described methodology to adjust population mortality rates by additional variables, such as socioeconomic status, that are available in a control population. We presented both Poisson and flexible parametric methods and found that both methods estimate similar mortality rates by socioeconomic status. Adjusting for the additional uncertainty associated with the methodology presented made little difference to five-year relative survival of breast cancer patients. Socioeconomic status is known to affect the survival of breast cancer patients. Stage at diagnosis of breast cancer is also known to have a strong effect on survival and the distribution of stage at diagnosis often differs by socioeconomic status. In Study IV we aimed to quantify survival differences between education groups as a proxy for socioeconomic status. We estimated that 572 life years could be saved, and 25 deaths could be postponed five years beyond diagnosis, if differences between education group in the breast cancer stage-distribution could be removed in three regions of Sweden. If differences between education groups in stage-specific breast cancer survival could be removed, we estimated that 692 life years could be saved, and 27 deaths postponed five years beyond diagnosis. In conclusion, this thesis reassures users of FPMs of their performance under non-proportional hazards. Secondly, methodology is described to further adjust expected mortality rates which could aid researchers in estimating survival measures by additional, non-standard variables. Finally, this thesis provides a greater understanding of the probable prognosis and the burden of CML and breast cancer diagnoses via the loss in expectation of life and other similar measures.
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| 5. |
- Bower, Hannah, et al.
(författare)
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Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
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| 6. |
- Bower, Hannah, et al.
(författare)
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Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:24, s. 2851-2858
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A dramatic improvement in the survival of patients with chronic myeloid leukemia (CML) occurred after the introduction of imatinib mesylate, the first tyrosine kinase inhibitor (TKI). We assessed how these changes affected the life expectancy of patients with CML and life-years lost as a result of CML between 1973 and 2013 in Sweden.MATERIALS AND METHODS: Patients recorded as having CML in the Swedish Cancer Registry from 1973 to 2013 were included in the study and followed until death, censorship, or end of follow-up. The life expectancy and loss in expectation of life were predicted from a flexible parametric relative survival model.RESULTS: A total of 2,662 patients with CML were diagnosed between 1973 and 2013. Vast improvements in the life expectancy of these patients were seen over the study period; larger improvements were seen in the youngest ages. The great improvements in life expectancy translated into great reductions in the loss in expectation of life. Patients of all ages diagnosed in 2013 will, on average, lose < 3 life-years as a result of CML.CONCLUSION: Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today. This will be an important message to convey to patients to understand the impact of a CML diagnosis on their life. In addition, the increasing prevalence of patients with CML will have a great effect on future health care costs as long as continuous TKI treatment is required.
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| 7. |
- Bower, Hannah, et al.
(författare)
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Reply to D. Pulte et al.
- 2017
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 35:6, s. 696-697
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Caffrey Osvald, Emma, et al.
(författare)
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Asthma and all-cause mortality in children and young adults : a population-based study
- 2020
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 75:12, s. 1040-1046
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES).METHODS: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model.RESULTS: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83).CONCLUSION: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.
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| 9. |
- Koltowska, Katarzyna, et al.
(författare)
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The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function
- 2021
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Ingår i: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679. ; 23:11, s. 1136-1147
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Tidskriftsartikel (refereegranskat)abstract
- Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells. The development of a functional vasculature requires the coordinated control of cell fate, lineage differentiation and network growth. Cellular proliferation is spatiotemporally regulated in developing vessels, but how this is orchestrated in different lineages is unknown. Here, using a zebrafish genetic screen for lymphatic-deficient mutants, we uncover a mutant for the RNA helicase Ddx21. Ddx21 cell-autonomously regulates lymphatic vessel development. An established regulator of ribosomal RNA synthesis and ribosome biogenesis, Ddx21 is enriched in sprouting venous endothelial cells in response to Vegfc-Flt4 signalling. Ddx21 function is essential for Vegfc-Flt4-driven endothelial cell proliferation. In the absence of Ddx21, endothelial cells show reduced ribosome biogenesis, p53 and p21 upregulation and cell cycle arrest that blocks lymphangiogenesis. Thus, Ddx21 coordinates the lymphatic endothelial cell response to Vegfc-Flt4 signalling by balancing ribosome biogenesis and p53 function. This mechanism may be targetable in diseases of excessive lymphangiogenesis such as cancer metastasis or lymphatic malformation.
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| 10. |
- Osvald, Emma Caffrey, et al.
(författare)
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Asthma and all-cause mortality in children and young adults - a Swedish population based study
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:Suppl. 63
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Little is known about the relationship between asthma in children and young adults and all-cause mortality. Studies suggest an increased rate of death among adults with asthma. Additionally among children, there is a rising prevalence of life-limiting conditions, defined as conditions with no hope of cure.Aim: To investigate the association between asthma and all-cause mortality in children and young adults aged 1-25 years and to explore if this effect is modified by life-limiting conditions.Method: This register based study includes 2,775,430 individuals born in Sweden between January 1986 and December 2012. Asthma cases, those with life-limiting conditions and other covariates were identified using Swedish national registers. The association between asthma and all-cause mortality was estimated using Cox proportional hazards model. A Cox model with an interaction term between asthma and life-limiting condition was also fitted to assess effect modification.Results: 261,322 asthma cases were identified during the follow-up. The unadjusted all-cause mortality rate for asthma cases was greater than for non-asthma cases with a hazard ratio (HR) of 1.67 (95% CI 1.54-1.83). Adjusting for covariates altered the HR to 1.46 (95% CI 1.33-1.62). Having a life-limiting condition was a significant effect modifier (p=0.002); for patients with a life-limiting condition the HR was 1.86 (95% CI 1.57-2.22) and in patients without a life-limiting condition the HR was 1.33 (95% CI 1.18-1.49).Conclusion: All-cause mortality in children and young adults is higher in those with asthma compared to those without asthma. Life-limiting conditions modify the effect of asthma on all-cause mortality.
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