Prohormones in the early diagnosis of cardiac syncope

Background--The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregionalproadrenomedullin. Methods and Results--We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P < 0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of < 77 pmol/L and an ED probability of < 20% had a sensitivity and a negative predictive value of 99%. Conclusions--The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope

Comparing the utility of clinical risk scores and integrated clinical judgement in patients with suspected acute coronary syndrome

Aims The utility of clinical risk scores regarding the prediction of major adverse cardiac events (MACE) is uncertain. We aimed to directly compare the prognostic performance of five established clinical risk scores as well as an unstructured integrated clinical judgement (ICJ) of the treating emergency department (ED) physician. Methods and results Thirty-day MACE including all-cause death, life-threatening arrhythmia, cardiogenic shock, acute myocardial infarction (including the index event), and unstable angina requiring urgent coronary revascularization were centrally adjudicated by two independent cardiologists in patients presenting to the ED with acute chest discomfort in an international multicentre study. We compared the prognostic performance of the HEART score, GRACE score, T-MACS, TIMI score, and EDACS, as well as the unstructured ICJ of the treating ED physician (visual analogue scale to estimate the probability of acute coronary syndrome, ranging from 0 to 100). Among 4551 eligible patients, 1110/4551 patients (24.4%) had at least one MACE within 30 days. Prognostic accuracy was high and comparable for the HEART score, GRACE score, T-MACS, and ICJ [area under the receiver operating characteristic curve (AUC) 0.85–0.87] but significantly lower and only moderate for the TIMI score (AUC 0.79, P &lt; 0.001) and EDACS (AUC 0.74, P &lt; 0.001), resulting in sensitivities for the rule-out of 30-day MACE of 93–96, 87 (P &lt; 0.001), and 72% (P &lt; 0.001), respectively. Conclusion The HEART score, GRACE score, T-MACS, and unstructured ICJ of the treating physician, not the TIMI score or EDACS, performed well for the prediction of 30-day MACE and may be considered for routine clinical use. Trial registration ClinicalTrials.gov number NCT0047058

Predicting Major Adverse Events in Patients With Acute Myocardial Infarction

Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need.; The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE.; Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization.; Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI.; The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587)

First events from the CNGS neutrino beam detected in the OPERA experiment

The OPERA neutrino detector at the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in appearance mode, through the study of nu_mu to nu_tau oscillations. The apparatus consists of a lead/emulsion-film target complemented by electronic detectors. It is placed in the high-energy, long-baseline CERN to LNGS beam (CNGS) 730 km away from the neutrino source. In August 2006 a first run with CNGS neutrinos was successfully conducted. A first sample of neutrino events was collected, statistically consistent with the integrated beam intensity. After a brief description of the beam and of the various sub-detectors, we report on the achievement of this milestone, presenting the first data and some analysis results.Comment: Submitted to the New Journal of Physic

Heavy Flavour Hadro-Production from Fixed-Target to Collider Energies

We review the hadro-production data presently available on open charm and beauty absolute production cross-sections, collected by experiments at CERN, DESY and Fermilab. The published charm production cross-section values are updated, in particular for the "time evolution" of the branching ratios. These measurements are compared to LO pQCD calculations, as a function of the collision energy, using recent parametrisations of the parton distribution functions. We then estimate, including nuclear effects of the parton densities, the charm and beauty production cross-sections relevant for measurements at SPS and RHIC energies, in proton-proton, proton-nucleus and nucleus-nucleus collisions. The calculations are also compared with measurements of single D and B kinematical distributions, and DDbar pair correlations. We finish with two brief comments, concerning the importance of beauty production as a feed-down source of J/psi production, and open charm measurements performed using leptonic decays

Effect of Acute Coronary Syndrome Probability on Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin

There is concern that high-sensitivity cardiac troponin (hs-cTn) may have low diagnostic accuracy in patients with low acute coronary syndrome (ACS) probability.; We prospectively stratified patients presenting with acute chest discomfort to the emergency department (ED) into 3 groups according to their probability for ACS as assessed by the treating ED physician using a visual analog scale: ≤10%, 11% to 79%, and ≥80%, reviewing all information available at 90 min. hs-cTnT and hs-cTnI concentrations were determined in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis.; Among 3828 patients eligible for analysis, 1189 patients had low (≤10%) probability for ACS. The incidence of non-ST-segment elevation myocardial infarction (NSTEMI) increased from 1.3% to 12.2% and 54.8% in patients with low, intermediate, and high ACS probability, respectively. The positive predictive value of hs-cTnT and hs-cTnI was low in patients with low ACS probability and increased with the incidence of NSTEMI, whereas the diagnostic accuracy of hs-cTnT and hs-cTnI for NSTEMI as quantified by the area under the curve (AUC) was very high and comparable among all 3 strata, e.g., AUC hs-cTnI, 0.96 (95% CI, 0.94-0.97); 0.87 (95% CI, 0.85-0.89); and 0.89 (95% CI, 0.87-0.92), respectively. Findings were validated using bootstrap analysis as an alternative methodology to define ACS probability. Similarly, higher hs-cTnT/I concentrations independently predicted all-cause mortality within 2 years (e.g., hs-cTnT hazard ratio, 1.39; 95% CI, 1.27-1.52), irrespective of ACS probability.; Diagnostic and prognostic accuracy and utility of hs-cTnT and hs-cTnI remain high in patients with acute chest discomfort and low ACS probability. ClinicalTrials.gov Identifier: NCT00470587

Swiss students and young physicians want a flexible goal-oriented GP training curriculum.

A growing shortage of general practitioners (GPs), in Switzerland and around the world, has forced countries to find new ways to attract young physicians to the specialty. In 2017, Switzerland began to fund hundreds of new study places for medical students. This wave of young physicians will soon finish University and be ready for postgraduate training. We hypothesized that an attractive postgraduate training program would encourage interested young physicians to pursue a GP career. This is a cross-sectional survey of young physicians from the Swiss Young General Practitioners Association (JHaS), members of Cursus Romand de médecine de famille (CRMF), and all current medical students (5 &lt;sup&gt;th&lt;/sup&gt; or 6 &lt;sup&gt;th&lt;/sup&gt; years) (n = 554) in Switzerland, excluding students indicating definitely not to become GPs. We asked all if they were likely to become a GP (Likert: 1-10), and then asked them to score general features of a GP training curriculum, and likely effects of the curriculum on their career choice (Likert scale). They then rated our model curriculum (GO-GP) for attractiveness and effect (Likert Scales, open questions). Most participants thought they would become GPs (Likert: 8 of 10). Over 90% identified the same features as an important part of a curriculum ("yes" or "likely yes"): Our respondents thought the GO-GP curriculum was attractive (7.3 of 10). It was most attractive to those highly motivated to become GPs. After reviewing the curriculum, most respondents (58%) felt GO-GP would make them more likely to become a GP. Almost 80% of respondents thought an attractive postgraduate training program like GO-GP could motivate more young physicians to become GPs. Overall, medical students and young physicians found similar features attractive in the general and GO-GP curriculum, regardless of region or gender, and thought an attractive curriculum would attract more young doctors to the GP specialty. Key points An attractive postgraduate training program in general practice can attract more young physicians to become GPs. In this study cross-sectional survey including medical students (n = 242) and young physicians (n = 312) we presented general features for a curriculum and a model curriculum for general practice training, for evaluation of attractiveness to our study population. General practice training curriculum provides flexibility in choice of rotations, access to short rotations in a wide variety of medical specialties, training in specialty practices as well, mentoring and career guidance by GPs and guidance in choosing courses/certificate programs necessary for general practice. These findings help building attractive postgraduate training programs in general practice and fight GP shortage