| 51. |
- Grodzinsky, A., et al.
(författare)
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Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy
- 2016
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 182, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI(DMvs no DM: BARC = 1: 78.0% vs 87.7%, P <.001; BARC >= 2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC = 1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83-0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.
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| 52. |
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| 53. |
- Khan, Muhammad Shahzeb, et al.
(författare)
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Leveraging electronic health records to streamline the conduct of cardiovascular clinical trials
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1890-1909
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Forskningsöversikt (refereegranskat)abstract
- Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.
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| 54. |
- Kobel, M., et al.
(författare)
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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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| 55. |
- Koven, C. D., et al.
(författare)
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A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback
- 2015
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Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 373:2054
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Tidskriftsartikel (refereegranskat)abstract
- We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (gamma sensitivity) of -14 to -19 PgC degrees C-1 on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.
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| 56. |
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| 57. |
- McGuire, D. K., et al.
(författare)
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Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes
- 2004
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Ingår i: Am Heart J. - 1097-6744. ; 147:2, s. 246-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.
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| 58. |
- McGuire, J, et al.
(författare)
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Comparative Adsorption Studies with Synthetic, Structural Stability and Charge Mutants of Bacteriophage T4 Lysozyme.
- 1995
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Ingår i: Proteins at Interfaces II. - Washington, DC : American Chemical Society. - 9780841233041 - 9780841215276 ; 602, s. 52-65
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Bokkapitel (refereegranskat)abstract
- We have purified wild type, three structural stability mutants and four charge mutants of bacteriophage T4 lysozyme from E. coli strains harboring desired expression vectors. Structural stability mutants were produced by substitution of the isoleucine at amino acid position three, yielding a set of proteins with stabilities ranging from 1.2 kcal/mol greater, to 2.8 kcal/mol less, than that of the wild type. Charge mutants were produced by replacement of positively charged lysine residues with glutamic acid, yielding a set of molecules with formal charges ranging from +5 to +9 units. Adsorption kinetic data, along with the dodecyltrimethylammonium bromide-mediated elutability of each protein, has been monitored with in situ ellipsometry at hydrophobic and hydrophilic silica surfaces. A simple mechanism that allows adsorbing protein to adopt one of two states, each associated with a different resistance to elution and a different interfacial area occupied per molecule, has been used to assist interpretation of the adsorption data. Conditions implicit in the model have been used to estimate the fraction of molecules present on the surface just prior to surfactant addition that had adopted the more resistant state, and this fraction has been observed to correlate positively with resistance to elution. For the stability mutants, these properties were clearly related to protein stability as well. Concerning the charge mutants, results have not been clearly explainable in terms of protein net charge, but rather in terms of the probable influence of the location of each substitution relative to other mobile, solvent-exposed, charged side chains of the molecule.
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| 59. |
- Olefeldt, D., et al.
(författare)
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Circumpolar distribution and carbon storage of thermokarst landscapes
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Thermokarst is the process whereby the thawing of ice- rich permafrost ground causes land subsidence, resulting in development of distinctive landforms. Accelerated thermokarst due to climate change will damage infrastructure, but also impact hydrology, ecology and biogeochemistry. Here, we present a circumpolar assessment of the distribution of thermokarst landscapes, defined as landscapes comprised of current thermokarst landforms and areas susceptible to future thermokarst development. At 3.6 x 10(6) km(2), thermokarst landscapes are estimated to cover similar to 20% of the northern permafrost region, with approximately equal contributions from three landscape types where characteristic wetland, lake and hillslope thermokarst landforms occur. We estimate that approximately half of the below-ground organic carbon within the study region is stored in thermokarst landscapes. Our results highlight the importance of explicitly considering thermokarst when assessing impacts of climate change, including future landscape greenhouse gas emissions, and provide a means for assessing such impacts at the circumpolar scale.
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| 60. |
- Post, Eric, et al.
(författare)
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Ecological Dynamics Across the Arctic Associated with Recent Climate Change
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 325:5946, s. 1355-1358
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Forskningsöversikt (refereegranskat)abstract
- At the close of the Fourth International Polar Year, we take stock of the ecological consequences of recent climate change in the Arctic, focusing on effects at population, community, and ecosystem scales. Despite the buffering effect of landscape heterogeneity, Arctic ecosystems and the trophic relationships that structure them have been severely perturbed. These rapid changes may be a bellwether of changes to come at lower latitudes and have the potential to affect ecosystem services related to natural resources, food production, climate regulation, and cultural integrity. We highlight areas of ecological research that deserve priority as the Arctic continues to warm.
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