| 1. |
- Nyberg, Fredrik, 1961, et al.
(författare)
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Using epidemiological registry data to provide background rates as context for adverse events in a rheumatoid arthritis drug development program: a coordinated approach
- 2015
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 24:11, s. 1121-1132
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries. Methods We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data. Results Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data. Conclusions Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements. Copyright (C) 2015 John Wiley & Sons, Ltd.
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| 2. |
- Verstappen, S. M. M., et al.
(författare)
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Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries
- 2015
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 67:12, s. 1637-1645
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries. Methods. Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages >18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received >= 1 synthetic disease-modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch. Results. Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts. Conclusion. Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well-defined cohort definitions.
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| 3. |
- Askling, J., et al.
(författare)
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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
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Tidskriftsartikel (refereegranskat)abstract
- Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
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| 4. |
- Bonnesen, Trine Gade, et al.
(författare)
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Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:4, s. 702-708
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Tidskriftsartikel (refereegranskat)abstract
- Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.
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| 7. |
- Halmin, Märit, et al.
(författare)
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Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion : A Binational Cohort Study
- 2017
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Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:4, s. 248-256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists.Objective: To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects.Design: Binational cohort study.Setting: All transfusion recipients in Sweden and Denmark. Patients: 854 862 adult patients who received transfusions from 2003 to 2012.Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression.Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was -0.2% (95% CI, -0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units.Limitation: Observational study; risk of confounding by indication.Conclusion: Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed.
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| 8. |
- Holmqvist, Anders, et al.
(författare)
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Dynamic Multi-Objective Optimization of Batch Chromatographic Separation Processes
- 2015
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Ingår i: Computer Aided Chemical Engineering. - 1570-7946. - 9780444634290 ; 37, s. 815-820
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Konferensbidrag (refereegranskat)abstract
- This contribution presents a novel offline dynamic multi-objective optimization framework for high-pressure liquid chromatographic (HPLC) processes in batch elution mode. The framework allows for optimization of general elution trajectories parametrized with piecewise constant control signals. It is based on a simultaneous method where both the control and state variables are fully discretized in the temporal domain, using orthogonal collocations on finite elements, and the state variables are discretized in the spatial domain, using a finite volume weighted essentially non-oscillatory (WENO) scheme. The resulting finite dimensional nonlinear program (NLP) is solved using a primal-dual interior point method and automatic differentiation techniques. The advantages of this open-loop optimal control methodology are highlighted through the solution of a challenging ternary complex mixture separation problem for a hydrophobic interaction chromatography (HIC) system. For a bi-objective optimization of the target component productivity and yield, subject to a purity constraint, the set of Pareto solutions generated with general elution trajectories showed considerable improvement in the productivity objective when compared to the Pareto set obtained using conventional linear elution trajectories.
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| 9. |
- Holmqvist, F., et al.
(författare)
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Pacemaker programming in patients with first-degree AV-block : Programming pattern and possible consequences
- 2018
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Ingår i: Health Science Reports. - : Wiley. - 2398-8835. ; 1:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal way of pacing in patients with an indication for pacing and concomitant first-degree atrioventricular (AV)–block is not known, and consequently, firm guidelines on this topic are lacking. This study explored the current pacemaker programming pattern in patients with first-degree AV-block who have a dual chamber pacemaker without cardiac resynchronization. Methods: The study was a retrospective chart review conducted at Duke University Hospital. Patients receiving a pacemaker due to sinus node dysfunction with coexistent first-degree AV-block were studied. Baseline demographics and characteristics, as well as pacemaker programming parameters and follow-up data, were collected through chart review. Preimplantation and postimplantation electrocardiograms were analyzed. Results: A total of 74 patients were included (mean age, 75 ± 11 y; 53% men). The mean ± SD preimplant PR interval and QRS duration was 243 ± 46 and 110 ± 30 milliseconds, respectively. A history of atrial fibrillation was present in 49% of the patients, and 77% had a normal left ventricular ejection fraction. The majority of patients (65%) had their pacemakers programmed to atrial pacing (AAI/DDD +/−R), whereas 32% and 2.7% of the pacemakers were programmed to AV-sequential pacing (DDD) and ventricular pacing (VVI), respectively. There were no significant differences in baseline characteristics or electrocardiogram measures between patients programmed to the 3 pacing modes. Patients with pacemakers programmed to AAI had a lower ventricular pacing percentage at follow-up (8 vs 55, and 46% [DDD and VVI, respectively]; P <.001). Conclusions: There was no evident association between baseline characteristics and programmed pacing mode in patients with first-degree AV-block. The choice of pacing mode affects long-term pacing burden, which in turn has been shown to influence outcome.
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