| 1. |
- Abrahamsson, L, et al.
(författare)
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A statistical model of breast cancer tumour growth with estimation of screening sensitivity as a function of mammographic density
- 2016
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 25:4, s. 1620-1637
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Tidskriftsartikel (refereegranskat)abstract
- Understanding screening sensitivity and tumour progression is important for designing and evaluating screening programmes for breast cancer. Several approaches for estimating tumour growth rates have been described, some of which simultaneously estimate (mammography) screening sensitivity. None of the continuous tumour growth modelling approaches has incorporated mammographic density, although it is known to have a profound influence on mammographic screening sensitivity. We describe a new approach for estimating breast cancer tumour growth which builds on recently described continuous tumour growth models and estimates mammographic screening sensitivity as a function of tumour size and mammographic density.
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| 2. |
- Abrahamsson, L, et al.
(författare)
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Continuous tumour growth models, lead time estimation and length bias in breast cancer screening studies
- 2020
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 29:2, s. 374-395
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Tidskriftsartikel (refereegranskat)abstract
- Comparisons of survival times between screen-detected and symptomatically detected breast cancer cases are subject to lead time and length biases. Whilst the existence of these biases is well known, correction procedures for these are not always clear, as are not the interpretation of these biases. In this paper we derive, based on a recently developed continuous tumour growth model, conditional lead time distributions, using information on each individual's tumour size, screening history and percent mammographic density. We show how these distributions can be used to obtain an individual-based (conditional) procedure for correcting survival comparisons. In stratified analyses, our correction procedure works markedly better than a previously used unconditional lead time correction, based on multi-state Markov modelling. In a study of postmenopausal invasive breast cancer patients, we estimate that, in large (>12 mm) tumours, the multi-state Markov model correction over-corrects five-year survival by 2–3 percentage points. The traditional view of length bias is that tumours being present in a woman's breast for a long time, due to being slow-growing, have a greater chance of being screen-detected. This gives a survival advantage for screening cases which is not due to the earlier detection by screening. We use simulated data to share the new insight that, not only the tumour growth rate but also the symptomatic tumour size will affect the sampling procedure, and thus be a part of the length bias through any link between tumour size and survival. We explain how this has a bearing on how observable breast cancer-specific survival curves should be interpreted. We also propose an approach for correcting survival comparisons for the length bias.
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| 3. |
- Albajes-Eizagirre, A, et al.
(författare)
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Meta-analysis of non-statistically significant unreported effects
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:12, s. 3741-3754
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Tidskriftsartikel (refereegranskat)abstract
- Published studies in Medicine (and virtually any other discipline) sometimes report that a difference or correlation did not reach statistical significance but do not report its effect size or any statistic from which the latter may be derived. Unfortunately, meta-analysts should not exclude these studies because their exclusion would bias the meta-analytic outcome, but also they cannot be included as null effect sizes because this strategy is also associated to bias. To overcome this problem, we have developed MetaNSUE, a novel method based on multiple imputations of the censored information. We also provide an R package and an easy-to-use Graphical User Interface for non-R meta-analysts.
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| 4. |
- Alchi, B, et al.
(författare)
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Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry
- 2013
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 22:3, s. 245-253
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Tidskriftsartikel (refereegranskat)abstract
- Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients. Methods This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008. Results Median disease duration before ASCT was 52 (nine to 396) months, 25/28 SLE patients (89%) were female, age 29 (16–48) years. At the time of ASCT, eight (one to 11) American College of Rheumatology (ACR) diagnostic criteria for SLE were present and 17 (60%) patients had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony stimulating factor in 93% of patients, and ex vivo CD34 stem cell selection was performed in 36%. Conditioning regimens were employed with either low ( n = 10) or intermediate (18) intensities. With a median follow-up of 38 (one to 110) months after ASCT, the five-year overall survival was 81 ± 8%, disease-free survival was 29 ± 9%, relapse incidence (RI) was 56 ± 11% and non-relapse mortality was 15 ± 7%. Graft manipulation by CD34+ selection was associated with a lower RI ( p = 0.001) on univariate analysis. There were five deaths within two years after ASCT: three caused by infection, one by secondary autoimmune disease and one by progressive SLE. Conclusions Our data further support the concept of immunoablation and ASCT to re-induce long-term clinical and serologic remissions in refractory SLE patients even in the absence of maintenance therapy. This study also suggests a beneficial effect of ex vivo graft manipulation on prevention of relapses post-transplantation in SLE.
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| 5. |
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| 6. |
- Anania, C, et al.
(författare)
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Microcirculation as determined by iontophoresis in SLE-patients and controls
- 2012
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 21:8, s. 815-820
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of cardiovascular disease (CVD), microangiopathy and prevalence of atherosclerotic plaques are increased in Systemic Lupus Erythematosus (SLE). As systemic endothelial dysfunction is one of the earliest signs of these vascular outcomes in the general population we assessed skin microvascular endothelial function in SLE patients. Methods: Endothelial function in skin was tested with local application of acetylcholine (inducing endothelium-dependent vasodilatation) and any concomitant increase in skin perfusion was measured with Laser Doppler Fluxmetry (LDF) in 84 SLE-patients (83% women, mean age 47 years) and 81 age and sex matched controls. Common carotid intima-media thickness (cIMT) and plaque occurrence were also determined using B-mode ultrasound. Results: There were no significant differences in skin microvascular endothelial function between SLE-patients and controls. In the SLE group, endothelial function did not vary in relation to skin manifestations, Raynaud's phenomenon, nephritis or plaque occurrence. In SLE patients with CVD, however, endothelial function was impaired. Conclusion: Skin microvascular endothelial function is associated with CVD but not with early signs of atherosclerosis in SLE-patients. The endothelial function is not different in SLE-patients as compared to controls.
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| 7. |
- Andersson, Eva M., 1968, et al.
(författare)
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Modeling influenza incidence for the purpose of on-line monitoring
- 2008
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Ingår i: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 17:4, s. 421-438
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Tidskriftsartikel (refereegranskat)abstract
- We describe and discuss statistical models of Swedish influenza data, with special focus on aspects which are important in on-line monitoring. Earlier suggested statistical models are reviewed and the possibility of using them to describe the variation in influenza-like illness (ILI) and laboratory diagnoses (LDI) is discussed. Exponential functions were found to work better than earlier suggested models for describing the influenza incidence. However, the parameters of the estimated functions varied considerably between years. For monitoring purposes we need models which focus on stable indicators of the change at the outbreak and at the peak. For outbreak detection we focus on ILI data. Instead of a parametric estimate of the baseline (which could be very uncertain,), we suggest a model utilizing the monotonicity property of a rise in the incidence. For ILI data at the outbreak, Poisson distributions can be used as a first approximation. To confirm that the peak has occurred and the decline has started, we focus on LDI data. A Gaussian distribution is a reasonable approximation near the peak. In view of the variability of the shape of the peak, we suggest that a detection system use the monotonicity properties of a peak.
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| 8. |
- Arkema, EV, et al.
(författare)
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Perinatal risk factors for future SLE: a population-based nested case-control study
- 2015
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 24:8, s. 869-874
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association between perinatal characteristics and the offspring’s risk of lupus using population-based registers in Sweden. Methods We conducted a nested case-control study, identifying systemic lupus erythematosus (SLE) cases from the National Patient Register and controls sampled from the general population matched on birth year, sex, and residential county. We obtained data on the mother’s health and age during pregnancy and characteristics of labor and delivery from the Medical Birth Register (births from 1973 through 2008) for cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models overall and separately for males and females. Results We identified 774 cases and 3337 controls. Age at which SLE was first observed ranged from 0 to 36 years old. High birth weight was not a risk factor for SLE and did not differ by sex. Males had a 2.4-fold increased odds of SLE if born preterm (<37 weeks; OR = 2.41; 95% CI 1.09, 5.36). Birth order was significantly associated with SLE, particularly among females (first born vs. not OR = 0.77, 95% CI 0.64, 0.94; continuous birth order OR = 1.12. 95% CI 1.02, 1.24). Conclusion Being born first was associated with reduced odds of SLE and the odds of SLE increased by 12% for every additional birth. Preterm birth was associated with increased odds in males only. Unlike previous work, high birth weight was not a risk factor for SLE.
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| 9. |
- Barkauskaite, V, et al.
(författare)
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Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus
- 2007
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 16:10, s. 794-802
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Tidskriftsartikel (refereegranskat)abstract
- HMGB1 is a pro-inflammatory cytokine that together with TNF-α and IL-1β is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-α and IL-1β expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-α and IL-1β was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1β was seen predominantly in late biopsies. In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-α and IL-1β, and formation of a pro-inflammatory loop between HMGB1, TNF-α, and IL-1β may be responsible for the prolonged and sustained inflammation in CLE. Lupus (2007) 16, 794—802.
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| 10. |
- Bengtsson, Anders, et al.
(författare)
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Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
- 2000
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 9:9, s. 664-671
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.
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