Progression of early repolarization patterns at a four year follow-up in a female flight crew population: Implications for aviation medicine.

BACKGROUND: To assess the prevalence, the appearance, and the distribution, as well as the fluctuation over time of early repolarization patterns after four years in a female population derived from the French aviation sector. METHODS: This was a retrospective longitudinal study from 1998 to 2010 of a population of female employees who received a full clinical examination and an electrocardiogram (ECG) upon their recruitment and after a period of four years. RESULTS: A total of 306 women were included (average of 25.87 ± 3.3 years of age). The prevalence of early repolarization was 9.2%. The most common appearance was J-point slurring for 64.3% (i.e. 20/28 subjects) that occurred in the inferior leads for 28.6% (i.e. 8/28 subjects). After four years, the prevalence was 7.5%, with a regression of this aspect in five of the subjects. There were no changes in the ECG in terms of the distribution and the appearance among the 23 subjects for whom the aspect persisted. Over the course of this four year period all of the subjects remained asymptomatic. CONCLUSIONS: Early repolarization in this largely physically inactive female population was common, and it fluctuated over time. At present, no particular restrictions can be placed on asymptomatic flight crew who exhibit this feature in the absence of a prior medical history for heart disease.

Evolution of Early Repolarization Patterns after 5 Years in a Military Population at Low Cardiovascular Risk and Practical Implications in Military Medical Expertise.

BACKGROUND: The French military population is a young and athletic population with a high prevalence of early repolarization patterns (ERP) compared to the general population. Screening of military officers at risk of sudden death (SD) is a priority in military medical expertise. The aim of our study was to evaluate the prevalence of ERP and its evolution over a period of 5 years in a specific asymptomatic population, free of heart disease and cardiovascular risk factors. METHODS: From March to December 2008, we prospectively collected the electrocardiograms (ECGs) of military officers enlisted into the submarine forces of France. For 5 years (until 2012), the military officers included in the study underwent a clinical examination twice per year. A new ECG was carried out 5 years after the initial one. RESULTS: A total of 250 male subjects were included (mean age 22.87 ± 0.5 years). The prevalence of ERP was 19.2%. The most common appearance was an elevation of a slurring type J point (31/48 or 64.5%) in inferolateral leads (18/48 or 37.8%). After 5 years, the prevalence of ERP was identical to that of the previous period (19.2%) with no change in appearance, distribution, and amplitude in 47 subjects (97.9%). Repolarization changed in two patients (one occurrence of ERP and one disappearance). During the 5 years of follow-up, the subjects remained asymptomatic CONCLUSION: ERP is common in our population of young, athletic, and asymptomatic military officers and changes little in 5 years.

Prevalence of early repolarization patterns in a French military population at low cardiovascular risk: implications for preventive medicine.

BACKGROUND: Early repolarization pattern (ERP) associated with a risk of sudden death has recently been described. Very few studies have examined the prevalence of this pattern in a military population characterized by a predominance of young, active male subjects. Therefore, the main objective of this study was to evaluate the prevalence of ERP in a healthy military population free of heart disease but subjected to extreme and potentially arrhythmogenic physical activity. METHODS: This prospective, multicenter study was carried out from November 2010 to November 2011 and included 746 individuals undergoing ECG screening; 466 were men (62.4%) and 280 were women (37.5%). Each ECG was interpreted twice by trained cardiologists. RESULTS: The total prevalence of ERP was 13.8% (103/746); 16% (46/280) in women and 12% (57/466) in men (P > 0.05). It declined with age and the pattern of slurring in inferior location was the most common. Heart rate was significantly lower in military officers with ERP. CONCLUSIONS: ERP was commonly found in this healthy military population. Preventing the risk of sudden death in this population requires systematic ECG screening, medical history analysis and clinical examination to identify symptomatic patients.

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1.

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68Ga/177Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177Lu-PSMA-1.

A quality by design approach for the qualification of automating compounding device for parenteral nutrition.

Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process.

Accuracy of a new method for semi-quantitative assessment of right ventricular ejection fraction by cardiovascular magnetic resonance: right ventricular fractional diameter changes.

OBJECTIVE: Longitudinal shortening is traditionally considered the predominant part of global right ventricular (RV) systolic function. Less attention has been paid to transverse contraction. The aim of this study was to evaluate RV transverse motion by cardiovascular magnetic resonance (CMR) in a large cohort of patients and to assess its relationship with RV ejection fraction (RVEF). STUDY DESIGN: We retrospectively analyzed the CMR scans of 300 patients referred to our center in 2010. RVEF was determined from short axis sequences using the volumetric method. Transverse parameters called RV fractional diameter changes were calculated after measuring RV diastolic and systolic diameters at basal and mid-level in short axis view (respectively FBDC and FMDC). We also measured the tricuspid annular plane systolic excursion (TAPSE) as a longitudinal reference. RESULTS: Our population was divided into 2 groups according to RVEF. 250 patients had a preserved RVEF (>40%) and 50 had a RV dysfunction (RVEF ≤ 40%). Transverse and longitudinal motions were significantly reduced in the group with RV dysfunction (p<.0001). After ROC analysis, areas under the curve for FBDC, FMDC and TAPSE, were respectively 0.79, 0.82 and 0.72, with the highest specificity and sensitivity respectively of 88% and 68% for FMDC (threshold at 20%) for predicting RV dysfunction. FMDC had an excellent negative predictive value of 93%. CONCLUSION: RV fractional diameter changes, especially at the mid-level, appear to be accurate for semi-quantitative assessment of RV function by CMR. A cut-off of 20% for FMDC differentiates patients with a low (EF≤40%) or a preserved RVEF.