François Alla

Anaphylactic and Anaphylactoid Reactions Occurring during Anesthesia in France in 1999–2000

Background Anaphylactic and anaphylactoid reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. The authors report the results of a 2-yr survey of such reactions observed during anesthesia in France. Methods Between January 1, 1999, and December 31, 2000, 789 patients who experienced immune-mediated (anaphylaxis) or nonimmune-mediated (anaphylactoid) reactions were referred to one of the 40 participating centers. Anaphylaxis was diagnosed on the basis of clinical history, skin tests, and/or specific immunoglobulin E assay. Results Anaphylactic and anaphylactoid reactions were diagnosed in 518 cases (66%) and 271 cases (34%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBAs) (n = 306, 58.2%), latex (n = 88, 16.7%), and antibiotics (n = 79, 15.1%). Rocuronium (n = 132, 43.1%) and succinylcholine (n = 69, 22.6%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 75.1% of cases of anaphylaxis to an NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, asthma, or drug intolerance were compared. However, atopy, asthma, and food allergy were significantly more frequent in the case of latex allergy when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase for the diagnosis of anaphylaxis was 92.6%; the negative predictive value was 54.3%. The diagnostic value of specific NMBA immunoglobulin E assays was confirmed. Conclusions These results further corroborate the need for systematic screening in the case of anaphylactoid reaction during anesthesia and for the constitution of allergoanesthesia centers to provide expert advice to anesthesiologists and allergists.

Pioglitazone and risk of bladder cancer among diabetic patients in France: a population-based cohort study.

Aims/hypothesisPrevious studies have suggested an increased risk of bladder cancer with pioglitazone exposure. We aimed to investigate the association between pioglitazone exposure and bladder cancer in France.MethodsThis cohort study involved use of data from the French national health insurance information system (Système National dInformation Inter-régimes de lAssurance Maladie; SNIIRAM) linked with the French hospital discharge database (Programme de Médicalisation des Systèmes dInformation; PMSI). The cohort included patients aged 40 to 79xa0years who filled a prescription for a glucose-lowering drug in 2006. The cohort was followed for up to 42xa0months. Pioglitazone exposure was modelled as a time-dependent variable and defined by having filled at least two prescriptions over a 6-month period. Incident cases of bladder cancer were identified by a discharge diagnosis of bladder cancer combined with specific aggressive treatment. Statistical analyses involved a multivariate Cox model adjusted for age, sex and exposure to other glucose-lowering drugs.ResultsThe cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone. We found 175 cases of bladder cancer among exposed patients and 1,841 among non-exposed patients. Incidence rates were 49.4 and 42.8 per 100,000 person-years, respectively. Pioglitazone exposure was significantly associated with bladder cancer incidence (adjusted HR 1.22 [95% CI 1.05, 1.43]). We observed a dose–effect relationship, with a significantly increased risk for high cumulative doses (≥28,000xa0mg, adjusted HR 1.75 [95% CI 1.22, 2.50]) and long duration of exposure (≥24xa0months, adjusted HR 1.36 [1.04, 1.79]).Conclusions/interpretationIn this cohort of diabetic patients from France, pioglitazone exposure was significantly associated with increased risk of bladder cancer.

Can acceleromyography detect low levels of residual paralysis? A probability approach to detect a mechanomyographic train-of-four ratio of 0.9

Background: The incidence of residual paralysis, i.e., a mechanomyographic train-of-four (TOF) ratio (T4/T1) less than 0.9, remains frequent. Routine acceleromyography has been proposed to detect residual paralysis in clinical practice. Although acceleromyographic data are easy to obtain, they differ from mechanomyographic data, with which they are not interchangeable. The current study aimed to determine (1) the acceleromyographic TOF ratio that detects residual paralysis with a 95% probability, and (2) the impact of calibration and normalization on this predictive acceleromyographic value. Methods: In 60 patients, recovery from neuromuscular block was assessed simultaneously with mechanomyography and acceleromyography. To obtain calibrated acceleromyographic TOF ratios in group A, the implemented calibration modus 2 was activated in the TOF-Watch S®; to obtain uncalibrated acceleromyographic TOF ratios in group B, the current was manually set at 50 mA (n = 30 for each). In addition, data in group B were normalized (i.e., dividing the final TOF ratio by the baseline value). The agreement between mechanomyography and acceleromyography was assessed by calculating the intraclass correlation coefficient. Negative predictive values were calculated for detecting residual paralysis from acceleromyographic TOFs of 0.9, 0.95, and 1.0. Results: Group A: For a mechanomyographic TOF of 0.9 or greater, the corresponding acceleromyographic TOF was 0.95 (range, 0.86–1.0), and the negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 37% (95% CI, 20–56%), 70% (95% CI, 51–85%), and 97% (95% CI, 83–100%), respectively. Group B: Without normalization, an acceleromyographic TOF of 0.97 (range, 0.68–1.18) corresponded to a mechanomyographic TOF of 0.9 or greater, with negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 being 40% (95% CI, 23–59%), 60% (95% CI, 41–77%), and 77% (95% CI, 58–90%), respectively. After normalization, an acceleromyographic TOF of 0.89 (range, 0.63–1.06) corresponded to a mechanomyographic TOF of 0.9 or greater, and the negative predictive values of acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 89% (95% CI, 70–98%), 92% (95% CI, 75–99%), and 96% (95% CI, 80–100%), respectively. Conclusion: To exclude residual paralysis reliably when using acceleromyography, TOF recovery to 1.0 is mandatory.

Self-rating of quality of life provides additional prognostic information in heart failure. Insights into the EPICAL study.

The relationship between quality of life (QoL) and survival have been poorly investigated. The aim of this study was to determine the value of QoL score as a prognostic factor in a prospective cohort of patients with advanced chronic heart failure (CHF).

Epidemiology of acute heart failure syndromes

Acute Heart Failure is a heterogeneous set of syndromes associated with significant morbidity and mortality. There are several classifications of acute heart failure syndromes (AHFS) based on pathophysiology or clinical presentation. In the USA and in Europe, AHFS are the first cause of hospitalization of the elderly, and the leading health care cost. Despite this clinical and social importance, AHFS have received little attention from clinicians and researchers. Recently published epidemiological studies described clinical presentation, characteristics and treatment of over 100,000 patients hospitalized with AHFS. These studies also underlined the poor, short, and medium term prognosis, especially for the most severe patients admitted to an intensive care unit, with in-hospital mortality of 28%. Further epidemiological and clinical research is needed to improve our understanding of AHFS, thereby enhancing patient care.

Endocarditis in Patients with a Permanent Pacemaker: A 1-Year Epidemiological Survey on Infective Endocarditis due to Valvular and/or Pacemaker Infection

To describe characteristics of infective endocarditis (IE) in pacemaker (PM) recipients, including the annual incidence and exact localization of IE on PM leads, cardiac valves, or both, we prospectively analyzed 45 PM recipients from a group of 559 patients with definite IE who responded to a population-based survey conducted in France in 1999. Thirty-three patients had definite PM-lead IE (group I), and 12 had valvular IE without evidence of PM involvement (group II). The valvular structure was involved in almost two-thirds of IE cases among PM recipients. Of the 28 patients (62%) with valvular IE, 10 group I patients had tricuspid involvement, and 6 group I patients had left heart-valve involvement. The most frequent causative organisms in groups I and II were staphylococci (82%) and streptococci (50%), respectively. The incidence of age- and sex-standardized IE was 550 cases/million PM recipients per year. The incidence of IE with PM involvement is between that of valvular IE in the general population and prosthetic valve IE.

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

Background— The safety and effectiveness of non–vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. Methods and Results— With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched–treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64–1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72–1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64–1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47–1.85) risks were comparable between rivaroxaban and VKA new users. Conclusions— In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Antagonism of low degrees of atracurium-induced neuromuscular blockade: dose-effect relationship for neostigmine.

Background:Low degrees of residual paralysis (i.e., a train-of-four [TOF] ratio > 0.4) are relatively frequent, difficult to detect, and still potentially harmful. Unfortunately, the appropriate dose of anticholinesterase for this situation has not been determined. This may be of clinical interest because a high dose of neostigmine given at a shallow level of neuromuscular block may produce neuromuscular weakness. The purpose of this study was to investigate the dose–effect relationship of neostigmine to antagonize residual paralysis corresponding to a TOF ratio of 0.4 and 0.6. Methods:Recovery after 10, 20, 30 &mgr;g/kg neostigmine or placebo given at either 0.4 or 0.6 TOF ratio was assessed by acceleromyography in 120 patients undergoing intravenous anesthesia. Time to a 0.9 and 1.0 TOF ratio was measured, and the probability of successful reversal within 10 min after the respective neostigmine doses was calculated. In addition, the dose of neostigmine needed to achieve the recovery targets in 5 or 10 min was also determined. Results:When given at a TOF ratio of either 0.4 or 0.6, time to 0.9 and 1.0 TOF ratio was significantly shorter with any dose of neostigmine than without. The probability of successful reversal after 20 &mgr;g/kg neostigmine was 100% when a TOF ratio of 0.9 was the target; for a TOF ratio of 1.0, the probability was 93% and 67%, dependent on whether the dose of neostigmine was given at TOF ratio of 0.6 or 0.4, respectively. With a dose of 30 &mgr;g/kg, a TOF ratio of 1.0 is expected to be reached within approximately 5 min. Low doses of neostigmine are required to reach a TOF ratio of 0.9 or to accept an interval of 10 min. Conclusion:Reduced doses (10–30 &mgr;g/kg) of neostigmine are effective in antagonizing shallow atracurium block. For successful reversal within 10 min, as little as 20 &mgr;g/kg neostigmine may be sufficient. These dose recommendations are specific for atracurium and an intravenous anesthetic background.

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes.

Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals.

Does Insulin Glargine Increase the Risk of Cancer Compared With Other Basal Insulins? A French nationwide cohort study based on national administrative databases

OBJECTIVE To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins. RESEARCH DESIGN AND METHODS Data were extracted from French health insurance information system (Système National dInformation Inter-Régimes de lAssurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes dInformation). Included were 70,027 patients aged 40–79 years who started a basal insulin in 2007–2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites. RESULTS The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87–1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72–1.62). CONCLUSIONS In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.