Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood.

BACKGROUND: It is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT) before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are not informative and no spermogram can be done. METHODS: We classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH). RESULTS: Ten (26%) boys had normal testicular function, 16 (42%) had isolated tubular failure and 12 (32%) also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B.Seven (21%) girls had normal ovarian function, 11 (32%) had partial and 16 (47%) complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls.FSH and inhibin B were negatively correlated in boys (P < 0.0001) and girls (P = 0.0006). Neither the age at HCT nor the interval between HCT and evaluation influenced gonadal function. CONCLUSION: The concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.

Serious adverse reactions of bupropion for smoking cessation: analysis of the French Pharmacovigilance Database from 2001 to 2004.

BACKGROUND: Bupropion was the first alternative to nicotine replacement therapy in the pharmacological treatment for smoking cessation. Its safety profile has been monitored in France via spontaneous reporting. OBJECTIVE: To describe all serious adverse reactions (SARs) reported in France since the marketing authorization for bupropion in September 2001, and to analyse risk factors for these SARs. DESIGN: We collected all spontaneous reports of adverse reactions to bupropion received by all French Regional Pharmacovigilance Centres and by GlaxoSmithKline, the manufacturer of bupropion, during the first 3 years of marketing of this agent. We identified the characteristics of the population to whom bupropion was prescribed from the Thales database, which contains information obtained from a representative sample of general practitioners in France. We then compared the population with SARs with the population prescribed the drug (exposed population) to identify possible risk factors such as sex, age and daily dose for the most frequent SARs. RESULTS: Bupropion was prescribed to 698 000 patients during the first 3 years of marketing in France. In these patients, 1682 cases of adverse reactions were reported; 28% of these involved SARs, mainly cutaneous or allergic reactions (31.2%), including angioedema and serum sickness-like reactions. Serious neurological reactions were frequent (22.5%), mostly comprising seizures; however, questioning revealed that almost half of these patients had a history of seizures or other risk factors. Of the serious neuropsychiatric adverse events reported (17.3%), suicide attempts/suicides were a cause for concern, although risk factors (history of depression, suicide attempts, etc.) were described for 66% of patients experiencing these events. Patients reporting angioedema and serum sickness-like reactions, and those involved in suicide attempts/suicides, were significantly younger than the exposed population. A dose-dependent effect was also apparent for angioedema and for seizures. Cardiovascular SARs, such as ischaemic heart disease (10.1%) or sudden death (2.3%), were very often associated with pre-existing coronary artery disease induced by smoking. All these SARs occurred within a median of 12-14 days after drug initiation. CONCLUSION: To ensure safer use of bupropion, health professionals must respect the strict contraindications and warnings about use of this drug in patients with a history of seizures. Seizures, angioedema and serum sickness-like reactions were the most frequently reported SARs to bupropion treatment in our study. Moreover, younger people appeared to be more at risk for cutaneous SARs generally, and younger women for angioedema in particular, perhaps because of weight-related differences in pharmacokinetics. A dose-dependent effect for angioedema and the results of skin tests were suggestive of a histamine liberation mechanism. Our analysis showed that taking more notice of the contraindications to use of bupropion could have prevented half the seizures reported to the database. The sex and age characteristics of patients with ischaemic heart disease and suicide attempts in the study population were similar to those of the French population as a whole. Whether bupropion is associated with an increase in these potential adverse effects of therapy can be determined only by epidemiological studies that take into account specific risk factors in the smoking population. Finally, the median time to onset of the SARs identified in this study suggests that prescribers should monitor patients exposed to bupropion more carefully during the first 2 weeks of treatment.

Can emergency physicians identify a high mortality subgroup of patients with sepsis: role of procalcitonin.

OBJECTIVE: To assess the potential role of procalcitonin and tumor necrosis factor-alpha, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis. DESIGN: Prospective study. SETTING: The emergency unit of a teaching hospital. PATIENTS: We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis. MEASUREMENTS AND MAIN RESULTS: Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%. CONCLUSIONS: Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Fatal vascular outcomes following major orthopedic surgery.

Major orthopedic surgery is known to be associated with potentially serious arterial and venous vascular complications, although uncertainty exists about current event rates. Using electronic databases and investigator contact, we identified randomized and cohort studies reporting overall mortality and fatal vascular events. Where possible, studies reporting high autopsy rates (>60%) were examined. Pooled incidences were calculated from eligible studies. For Autopsy studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis could not be calculated, while with prophylaxis they were 0.44% (95% confidence interval 0.02 to 0.87%) and 0.43% (0.01 to 0.85%). For patients undergoing hip fracture surgery, the corresponding rates without prophylaxis were 15.9% (14.5 to 17.3%) and 1.9% (1.4 to 2.4%). With prophylaxis, mortality and fatal pulmonary embolismrates were 8.5% (7.3 to 9.7%) and 1.0% (0.6 to 1.5%). Among Cohort studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis were 0.93% (0.57 to 1.29%) and 0.36% (0.14 to 0.59%). For patients receiving prophylaxis (7 to 14 days), mortality and fatal pulmonary embolism were 0.57% (0.51 to 0.62%) and 0.18% (0.14 to 0.21%). Patients undergoing hip fracture surgery receiving prophylaxis hadmortality and fatal pulmonary embolismrates of 3.2% (2.8 to 3.6%) and 0.30% (0 to 0.61%). Vascular events contributed towards approximately 50% of all deaths with similar proportions due to ischemic heart disease, cardiac failure and pulmonary embolism. In conclusion, although prophylaxis results in a reduction in overall mortality and fatal pulmonary embolism, vascular events continue to be a common cause of mortality.

Use of the Delphi method to facilitate antithrombotics prescription during pregnancy.

INTRODUCTION: Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis. MATERIALS AND METHODS: A Delphi exercise was conducted to collect 19 French experts' opinions on pregnancy-related VTE. RESULTS: Experts with an active interest in clinical research and care of VTE and placental vascular complications were selected. The risk score was classified by an anonymous computer vote. A scoring system for VTE risk in pregnant women was developed, each score being associated with a specific treatment: graduated elastic compression stockings, aspirin, prophylactic Low Molecular Weight Heparin (LMWH: variable durations), or adjusted-dose of LMWH through pregnancy and postpartum. CONCLUSIONS: Our simple consensual scoring system offers an individual estimation of thrombosis risk during pregnancy together with its related therapeutic strategy, in accordance with most of the new international recommendations. The accuracy of our individual risk score-based therapeutic guidance is currently being prospectively evaluated in a multicenter trial.

Comparison of the efficacy of cooled-tip and 8-mm-tip catheters for radiofrequency catheter ablation of the cavotricuspid isthmus: a meta-analysis.

BACKGROUND: Cooled-tip RFA (cRFA) and conventional 8-mm-tip catheters were found to be more effective and as safe as conventional 4-mm-tip catheters for atrial flutter (AFL) radiofrequency ablation (RFA), facilitating the rapid achievement of bi-directional isthmus block (BIB), but studies comparing cRFA and 8-mm-tip catheters are not randomized or results are discussed. Thus, we performed a meta-analysis of available randomized trials to evaluate the effectiveness in terms of primary success and procedure parameters. METHODS: Reports of trials were identified through a Medline, Embase, Current Contents, Cardline, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, and open trials; (2) patients assigned to an 8-mm-tip or a cRFA catheter for AFL RFA; (3) endpoints events related to primary success rate (BIB achievement), and procedure parameters (number of RF applications, x-ray exposure and ablation duration). RESULTS: Seven trials met the inclusion criteria. They included 603 patients with established AFL randomized to an 8-mm-tip or cRFA catheter group. Comparing 8-mm groups with cRFA groups, the meta-analysis showed similar BIB achievement relative risk (RR) 0.96, 95% confidence interval (CI): 0.92 to 1.01, (P = 0.13); total RF application time weighted mean difference (WMD) 0.88, 95% CI: -0.36 to 2.12, (P = 0.16); duration of x-ray exposure (min) (WMD = 1.07, 95% CI: -0.81 to 0.295, (P = 0.26); ablation procedure duration (min) (WMD = 0.68, 95% CI: -3.37 to 4.73; P = 0.74). CONCLUSION: The present meta-analysis confirms that cooled-tip and large-tip catheters are equally efficient for cavotricuspid isthmus ablation with both similar primary success rates and procedure parameters.