19 research outputs found
WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren: WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren
Der Reaktordynamikcode DYN3D wird fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren (SFR) erweitert. In diesem Bericht werden neu implementierte thermomechanische Modelle fĂŒr die adĂ€quate Simulation von SFR-Transienten beschrieben, die die Simulation der axialen WĂ€rmeausdehnung von BrennstĂ€ben und die radiale Ausdehnung des Reaktorkerns umfassen. DarĂŒber hinaus wurde das Verfahren zur Erstellung von Querschnittsbibliotheken fĂŒr DYN3D fĂŒr SFR-Analysen erweitert. Die Verifizierung der neuen Modelle und der Querschnittserstellung erfolgte auf Vollkern-Ebene mit stationĂ€ren Experimenten von der BFS-Testanlage des IPPE Obninsk und Daten des groĂen oxidischen Kerns des OECD/NEA-Benchmark und den Experimenten zum Zyklusende des Phenix-Kerns. Die DYN3D-Ergebnisse wurden mit der Monte-Carlo-Referenzlösung verglichen, die durch den SERPENT-Code berechnet wurde. Die Testergebnisse zeigen, dass die neu entwickelten Modelle die WĂ€rmeausdeh-nungseffekte der Kernstruktur genau berĂŒcksichtigen können. Das neu entwickelte Verfahren zur Erstellung von Querschnittsbibliotheken wurde ebenfalls auf der Basis von SERPENT-Ergebnissen erfolgreich verifiziert. Zur Validierung wurden mehrere Tests, die sowohl stationĂ€re als auch transiente FĂ€lle aus den Phenix-Experimenten enthalten, mit DYN3D berechnet. Die DYN3D-Lösungen weisen eine gute Ăbereinstimmung mit den experimentellen Daten auf, was die Anwendbarkeit der Codes fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren bestĂ€tigt
Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for â„3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C â„100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for â„3 years, if baseline LDL-C is â„100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren: WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren
Der Reaktordynamikcode DYN3D wird fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren (SFR) erweitert. In diesem Bericht werden neu implementierte thermomechanische Modelle fĂŒr die adĂ€quate Simulation von SFR-Transienten beschrieben, die die Simulation der axialen WĂ€rmeausdehnung von BrennstĂ€ben und die radiale Ausdehnung des Reaktorkerns umfassen. DarĂŒber hinaus wurde das Verfahren zur Erstellung von Querschnittsbibliotheken fĂŒr DYN3D fĂŒr SFR-Analysen erweitert. Die Verifizierung der neuen Modelle und der Querschnittserstellung erfolgte auf Vollkern-Ebene mit stationĂ€ren Experimenten von der BFS-Testanlage des IPPE Obninsk und Daten des groĂen oxidischen Kerns des OECD/NEA-Benchmark und den Experimenten zum Zyklusende des Phenix-Kerns. Die DYN3D-Ergebnisse wurden mit der Monte-Carlo-Referenzlösung verglichen, die durch den SERPENT-Code berechnet wurde. Die Testergebnisse zeigen, dass die neu entwickelten Modelle die WĂ€rmeausdeh-nungseffekte der Kernstruktur genau berĂŒcksichtigen können. Das neu entwickelte Verfahren zur Erstellung von Querschnittsbibliotheken wurde ebenfalls auf der Basis von SERPENT-Ergebnissen erfolgreich verifiziert. Zur Validierung wurden mehrere Tests, die sowohl stationĂ€re als auch transiente FĂ€lle aus den Phenix-Experimenten enthalten, mit DYN3D berechnet. Die DYN3D-Lösungen weisen eine gute Ăbereinstimmung mit den experimentellen Daten auf, was die Anwendbarkeit der Codes fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren bestĂ€tigt
WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren: WTZ Russland - Transientenanalysen fĂŒr schnelle Reaktoren
Der Reaktordynamikcode DYN3D wird fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren (SFR) erweitert. In diesem Bericht werden neu implementierte thermomechanische Modelle fĂŒr die adĂ€quate Simulation von SFR-Transienten beschrieben, die die Simulation der axialen WĂ€rmeausdehnung von BrennstĂ€ben und die radiale Ausdehnung des Reaktorkerns umfassen. DarĂŒber hinaus wurde das Verfahren zur Erstellung von Querschnittsbibliotheken fĂŒr DYN3D fĂŒr SFR-Analysen erweitert. Die Verifizierung der neuen Modelle und der Querschnittserstellung erfolgte auf Vollkern-Ebene mit stationĂ€ren Experimenten von der BFS-Testanlage des IPPE Obninsk und Daten des groĂen oxidischen Kerns des OECD/NEA-Benchmark und den Experimenten zum Zyklusende des Phenix-Kerns. Die DYN3D-Ergebnisse wurden mit der Monte-Carlo-Referenzlösung verglichen, die durch den SERPENT-Code berechnet wurde. Die Testergebnisse zeigen, dass die neu entwickelten Modelle die WĂ€rmeausdeh-nungseffekte der Kernstruktur genau berĂŒcksichtigen können. Das neu entwickelte Verfahren zur Erstellung von Querschnittsbibliotheken wurde ebenfalls auf der Basis von SERPENT-Ergebnissen erfolgreich verifiziert. Zur Validierung wurden mehrere Tests, die sowohl stationĂ€re als auch transiente FĂ€lle aus den Phenix-Experimenten enthalten, mit DYN3D berechnet. Die DYN3D-Lösungen weisen eine gute Ăbereinstimmung mit den experimentellen Daten auf, was die Anwendbarkeit der Codes fĂŒr Kernanalysen von Natrium-gekĂŒhlten schnellen Reaktoren bestĂ€tigt
Comparison between conventional and computerised methods in the assessment of an occlusal scheme
The dica endoscopic classification for diverticular disease of the colon shows a significant interobserver agreement among community endoscopists: An international study
Background & Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (Îș) coefficient were reported as statistical measures of interrater agreement. Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal Îș was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD
Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol
Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains â„70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or â€13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402
Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial
Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4â1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1â12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65â1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)âdefined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucoseâand risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20â2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25â2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78â2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65â2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, â0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89â1·11). HRs were 0·97 (95% CI 0·87â1·09) for patients with prediabetes and 1·30 (95% CI 0·93â1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65â1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding: Sanofi and Regeneron Pharmaceuticals
Risk categorization using New American College of Cardiology/American Heart Association guidelines for cholesterol management and its relation to alirocumab treatment following acute coronary syndromes
Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol â„70 mg/dL or nonâhigh-density lipoprotein cholesterol â„100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18â924 participants followed for a median of 2.8 years, 11â935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402