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- Friman, S., et al.
(författare)
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Sotrastaurin, a Novel Small Molecule Inhibiting Protein-Kinase C : Randomized Phase II Study in Renal Transplant Recipients
- 2011
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:7, s. 1444-1455
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Tidskriftsartikel (refereegranskat)abstract
- Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1: 2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (+/- standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 +/- 22.3 vs. 49.5 +/- 17.7 mL/min/1.73 m(2), p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
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- Henriksson, Martin, et al.
(författare)
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Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery
- 2010
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Ingår i: BRITISH MEDICAL JOURNAL. - : BMJ. - 0959-535X. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of 20 pound 000-30 pound 000 ((sic)22 000-(sic)33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was andlt;410 pound compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of 245 pound 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches.
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- Lee, S. H., et al.
(författare)
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Matchmaker, matchmaker, make me a match: Migration of populations via marriages in the past
- 2014
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Ingår i: Physical Review X. - : American Physical Society. - 2160-3308. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data-including banknote flows, mobile phone records, and transportation data-has led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present an analysis of long-term human migration, which is important for processes such as urbanization and the spread of ideas. We demonstrate that the data record from Korean family books (called "jokbo") can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the "ergodicity" of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration inKorea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.
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- Misko, T. P., et al.
(författare)
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Characterization of nitrotyrosine as a biomarker for arthritis and joint injury
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:1, s. 151-156
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To characterize the utility of nitrotyrosine (NT) as a biomarker for arthritis and joint injury. Design: Synovial fluid, plasma, and urine from patients diagnosed with osteoarthritis (OA), rheumatoid arthritis (RA), anterior cruciate ligament (ACL) injury, meniscus injury and pseudogout, and knee-healthy volunteers were analyzed for concentrations of NT, nitrate and nitrite (NOx), matrix metalloproteinase (MMP)-3, MMP-1, MMP-9, more than 40 chemokines and cytokines. Results: In OA, plasma and synovial fluid NT were increased versus healthy volunteers. Synovial fluid to plasma NT ratios were elevated in OA patients. Synovial fluid from patients with ACL and meniscus injury and pseudogout had increased levels of NT (P < 0.001). In these samples, NT levels significantly correlated with ARGS-aggrecan neoepitope generated by aggrecanase cleavage of aggrecan (P <= 0.001), cross-linked C-telopeptides of type II collagen (P < 0.001), MMP-1 (P = 0.008), and MMP-3 (P <= 0.001). In RA, plasma NT decreased following 6 months of anti-tumor necrosis factor (TNF) treatment. For every 1.1% change in log(10) NT, there was a 1.0% change in the log(10) disease activity scores (DAS28-3 CRP). Both predicted and observed DAS28-3 CRP showed a robust linear relationship with NT. RA plasma NT positively correlated with CRP, MMP-3 and interferon gamma-induced protein 10. Conclusions: NT may serve as a useful biomarker for arthritis and joint injury. In RA, NT is highly correlated with several biomarkers and clinical correlates of disease activity and responds to anti-TNF therapy. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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