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 ≥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 ≥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 ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Reliability of new pulse CO-oximeter in victims of carbon monoxide poisoning

Study objective: The purpose of this study was to evaluate the reliability of noninvasive real-time measurement of carboxyhemoglobin (COHb) using a pulse CO-oximeter in victims of carbon monoxide poisoning (COP). Methods: During the 7-month study period, pulse CO-oximetry was measured on patients admitted to the emergency department (ED) for suspected COP. Each patient included in the study underwent concomitant assessment of COHb by blood sampling and noninvasive pulse CO-oximetry (SpCO). Results: Twelve non-smoker patients were included. Mean age was 40 ± 17 years. No difference was found between the two COHb assessment techniques (p>0.05). Analysis using the Bland and Altman procedure suggested good alignment of the two techniques with a slight bias (i.e. -1.5%) indicating slight overestimation by the pulse CO-oximeter. Analysis using the Passing and Bablok statistical protocol further documented the reliability of the two methods. Conclusion: This study documents the precision of the correlation between readings obtained with the noninvasive pulse CO-oximeter and COHb measurements from blood samples. This preliminary result demonstrates that this simple rapid noninvasive technology could be useful before and after arrival at the ED

Spectres Raman de prerésonance de la tyrosine et de la iodotyrosine aux PH 1 et 11,5

Des mesures d’intensité de plusieurs modes de vibrations de la tyrosine et d’un dérivé iodé en solution aqueuse à pH 1 (tyrosine ψ OH) et PH 11,5 (tyrosine ψ O–) ont été effectuées à différentes longueurs d’onde comprises entre 5145 Å et 2572 Å, Les profils de prérésonance expérimentaux ont été comparés aux profils calculés pour ces modes en utilisant ce formalisme d’Albrecht. Pour les deux composés l’exaltation d’intensité implique les transitions ultraviolettes 1Bab, et 1La. Pour l’iodotyrosine, la transition 1Lb, peut aussi intervenir. Les résultats expérimentaux montrent que l’ionisation du groupement phénolique engendre une très forte exaltation des modes ν8a et ν9a de ces composés. Dans le cas où des tyrosines seraient intégrées dans une protéine, des mesures d’intensité de ces modes de vibration Raman devraient permettre de déceler un résidu ionisé parmi de nombreux autres non ionisés

Complications and failure of uterine artery embolisation for intractable postpartum haemorrhage.

International audienc

Adaptative mechanism of the equilibrative nucleoside transporter 1 (ENT-1) and blood adenosine levels in elite freedivers

International audienc