Sophie Jacob

Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review

The existence of an increased risk of childhood leukaemia near nuclear installations is a recurrent issue. A review of the related epidemiological literature is presented here. Results for 198 nuclear sites throughout 10 countries were included in the review. In addition to local studies, 25 multi-site studies have been published for eight countries. A large variability was noticed in the quality of the data as well as in the definition of the study population and in the methods of analysis. Many studies present important limits that make the results difficult to interpret. The review confirms that some clusters of childhood leukaemia cases exist locally. However, results based on multi-site studies around nuclear installations do not indicate an increased risk globally. Many studies were launched to investigate possible origins of the observed clusters around specific sites, but up to now, none of the proposed hypotheses have explained them.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study

Aims The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. Methods and results A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41–94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56–2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07–2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. Conclusion When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

A correlation study of eye lens dose and personal dose equivalent for interventional cardiologists.

This paper presents the dosimetry part of the European ELDO project, funded by the DoReMi Network of Excellence, in which a method was developed to estimate cumulative eye lens doses for past practices based on personal dose equivalent values, H(p)(10), measured above the lead apron at several positions at the collar, chest and waist levels. Measurement campaigns on anthropomorphic phantoms were carried out in typical interventional settings considering different tube projections and configurations, beam energies and filtration, operator positions and access routes and using both mono-tube and biplane X-ray systems. Measurements showed that eye lens dose correlates best with H(p)(10) measured on the left side of the phantom at the level of the collar, although this correlation implicates high spreads (41 %). Nonetheless, for retrospective dose assessment, H(p)(10) records are often the only option for eye dose estimates and the typically used chest left whole-body dose measurement remains useful.

Contributions of Advanced Techniques to the Success and Safety of Transvenous Leads Extraction

Purpose: We measured the proportion of intravascular leads, which can be extracted by simple traction versus with newer techniques, and examined the overall safety and success rate of lead extractions.

Uranium carcinogenicity in humans might depend on the physical and chemical nature of uranium and its isotopic composition: results from pilot epidemiological study of French nuclear workers.

ObjectiveTo study the cancer risk related to protracted, low-dose exposure to different industrial uranium compounds, paying attention to their isotopic composition and solubility.MethodsTwo thousand and ninety-seven workers employed at the AREVA NC uranium processing plant (France) were followed up for mortality from 1960 to 2006. Historical exposure to uranium and other carcinogenic chemical and physical pollutants was assessed on the basis of the plant-specific job-exposure matrix. For each type of uranium, Cox regression models stratified on sex and calendar period, and adjusted for socioeconomic status and potentially confounding co-exposures were used to estimate hazard ratios (HRs) for mortality from lung cancer (53 deaths) and lymphatic and hematopoietic tissue malignancies (21 deaths).ResultsWe observed that exposure to reprocessed uranium entails increasing risks of mortality from lung cancer and lymphatic and hematopoietic malignancies (the most significant HR being respectively 1.14 (95% CI: 1.00–1.31) and 1.20 (95% CI: 1.01–1.43) per unit of a time-lagged log-transformed continuous exposure scores), and that the HRs tend to increase with decreasing solubility of the compounds.ConclusionOur results suggest that uranium carcinogenicity may depend on isotopic composition and solubility of uranium compounds. This study is the first to show the carcinogenic effect of slowly soluble reprocessed uranium on two uranium target organs. This finding is consistent with data from epidemiological and experimental studies on similar compounds but need to be confirmed in the more powerful dose–response analysis.

Incidence and prognostic significance of sustained ventricular tachycardias in heart failure patients implanted with biventricular pacemakers without a back-up defibrillator: results from the prospective, multicentre, Mona Lisa cohort study

AIMS The aim of this study was to investigate the 12-month incidence, predictive factors, and prognosis of sustained ventricular tachycardia (VT) in chronic heart failure patients implanted with biventricular pacemakers without a back-up defibrillator (CRT-P), assessed by continuous intracardiac ventricular electrograms. METHODS AND RESULTS The Mona Lisa study, a prospective, multicentre, cohort study, designed to determine the incidence of sustained VT and its prognostic impact in CRT-P recipients within the year after implant enrolled 198 patients with moderate or severe chronic heart failure, despite optimal pharmacological therapy. An independent committee reviewed the data from all arrhythmic episodes as well as causes of death according to predefined criteria. During a mean follow-up of 9.8 +/- 3.1 months after implantation, 8 patients experienced at least one episode of sustained VT [4.3%; 95% confidence interval (CI), 1.1-7.5] and 21 deaths occurred, giving a 12-month mortality rate of 11.7% (95% CI, 6.4-16.9). The presence of sustained VT was associated with a high risk of sudden cardiac death (SCD) and the lowest 12-month overall survival (P < 0.0001). CONCLUSION The incidence of sustained VT remains relatively low in the first year after CRT-P implantation, but when present appears closely associated with short-term adverse outcomes, especially SCD. This emphasizes the possible value of remote monitoring to detect high-risk patients for urgent upgrading.

Does uranium induce circulatory diseases? First results from a French cohort of uranium workers

Objectives Increased risk of circulatory system diseases (CSDs) was observed in nuclear workers handling uranium and plutonium in Russia and the UK. This work examines the CSD mortality after chronic intake of uranium among 2897 workers (79 892 person-years) at a uranium processing plant (1960–2006) in France. Methods Cumulative exposure to different uranium compounds, classified by their isotopic composition and solubility type, was quantified on the basis of a plant-specific job-exposure matrix and individual job histories. HRs and associated 95% CI for CSD (n=111) and specific CSD categories were estimated using Cox regression models, stratified on sex and birth cohort and adjusted for potential confounders. The effect of smoking was analysed among 260 smokers (42 CSD deaths). Results Compared to unexposed workers, CSD mortality was increased among workers exposed to slowly soluble reprocessed uranium (RPU) (HR=2.13, 95% CI=0.96 to 4.70) and natural uranium (HR=1.73, 95% CI=1.11 to 2.69). The risk increased with cumulative exposure and exposure duration. In the subgroup of smokers, the risk estimates were higher but with larger CIs: HR=1.91 (95% CI=0.92 to 3.98) for natural uranium and HR=4.78 (95% CI=1.38 to 16.50) for RPU. Conclusions The authors observed that exposure to slowly soluble uranium, namely RPU, may increase the risk of CSD mortality. However, these results are preliminary since the study is lacking statistical power and many other biological and lifestyle-related factors may cause CSD. More detailed investigations are necessary to confirm these findings and analyse in depth the effects of internal radiation exposure on the circulatory system.

Predicting favourable outcomes in the setting of radiofrequency catheter ablation of long-standing persistent atrial fibrillation: a pilot study assessing the value of left atrial appendage peak flow velocity.

BACKGROUND Catheter ablation is an effective and potentially curative treatment in patients with atrial fibrillation (AF). AIM To test the hypothesis that left atrial appendage peak flow velocity (LAV) assessed by echocardiography can accurately predict successful catheter ablation as well as favourable outcome in the setting of long-standing persistent AF. METHODS This prospective pilot study enrolled 40 patients with long-standing persistent AF (age 60 ± 11 years; persistence of AF 4.2 ± 2 years) who underwent a first catheter ablation procedure using a standardized sequential stepwise protocol. LAV was assessed before the catheter ablation procedure along with classical factors (age, sex, left atrial area, AF cycle length, AF duration and left ventricular ejection fraction), all of which were tested using logistic regression for ability to predict restoration of sinus rhythm during catheter ablation as well as absence of recurrence during a 1-year follow-up. RESULTS Eighteen patients (45%) experienced AF termination during the procedure and 18 patients (45%) did not develop any recurrence during the first 12 months. Multivariable analysis demonstrated that high LAV (>0.3 m/s) was the only independent predictor of AF termination (odds ratio 5.91, 95% confidence interval 1.06-32.88; P=0.04) and absence of recurrence at 1 year (odds ratio 4.33, 95% confidence interval 1.05-17.81; P=0.04). CONCLUSIONS This pilot study demonstrated the feasibility and importance of LAV measurement in the setting of long-standing persistent AF to predict successful catheter ablation and favourable mid-term outcome.

Frequency of Atrial Tachyarrhythmias in Patients Treated by Cardiac Resynchronization (from the Prospective, Multicenter Mona Lisa Study)

The continuous measurement of sustained atrial tachyarrhythmia (AT) is now possible with some permanently implanted devices. Data on this subject remain controversial. The aim of this study was to evaluate the incidence of sustained AT in patients treated with cardiac resynchronization therapy using pacemakers without backup defibrillators (CRT-P), within the first year after implantation, using strict definition criteria for sustained AT and a systematic review of all high-quality electrographically recorded episodes. The Mona Lisa study was a prospective, multicenter, cohort study carried out from February 2004 to February 2006, with a 12-month follow-up period. Sustained AT was defined as an episode lasting > or =5 minutes; episodes were confirmed by a systematic review of electrograms in the whole study population. Of the 198 patients who underwent CRT-P device implantation and were enrolled in the study, 173 were in stable sinus rhythm at baseline and were included in the analysis (mean age 70 +/- 9 years, 66% men, 91% in New York Heart Association class III, mean QRS duration 164 +/- 26 ms, mean left ventricular ejection fraction 25 +/- 7%). During a mean follow-up period of 9.9 +/- 3.6 months, 34 patients experienced > or =1 episode of sustained AT, for an incidence rate of 27.5% (95% confidence interval 18.2 to 36.7). Only a history of AT was independently associated with the occurrence of sustained AT within the 12 months after CRT-P device implantation (hazard ratio 2.3, 95% confidence interval 1.2 to 4.4, p = 0.02). In conclusion, this first prospective electrogram-based evaluation of AT incidence demonstrated that 27% of patients developed > or =1 episode of sustained AT lasting > or =5 minutes in the 12 months after CRT-P device implantation.

REPROCESSED URANIUM EXPOSURE AND LUNG CANCER RISK

This study investigated the risk of lung cancer in regards to protracted occupational exposure to reprocessed uranium compounds. Two thousand seven hundred and nine male workers employed at the AREVA NC uranium processing plant between 1960 and 2005 in France were included in the cohort. Historical exposure to reprocessed uranium compounds classified by their solubility type was assessed on the basis of the plants specific job-exposure matrix. Cox proportional hazard models adjusted for attained age, calendar period, and socioeconomic status were used to estimate relative risks in regards of each type of uranium compound. The relative risk of lung cancer tended to increase with decreasing solubility of reprocessed uranium compounds. The highest—though not statistically significant—relative risk was observed among workers exposed to slowly soluble reprocessed uranium dioxide. This study is the first suggesting an increasing risk of lung cancer associated with exposure to reprocessed uranium. Our results are consistent with data from experimental studies of biokinetics and the action mechanism of slowly soluble uranium compounds, but need to be confirmed in larger studies with more detailed dose-response analyses.