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Purpose: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. Methods: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. Results: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. Conclusion: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is an uncommon cause of osteoarticular infections (OAI) in children. The objective of this study was to investigate the clinical and laboratory characteristics of pneumococcal OAI before and after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). Data were retrospectively collected from children aged <16 years who were hospitalized for pneumococcal OAI between 1997 and 2007 in four Parisian teaching hospitals. Forty-three children were included (32 with arthritis and 11 with osteomyelitis) and the median age of these children was 12.5 months (range 3 months to 14 years). Serotypes were available for 19/43 strains (44 %) from 1997 onwards and for 12/13 strains (92 %) from 2005 onwards. Seven unvaccinated children were infected with vaccine serotypes and we observed only one vaccine failure. After the introduction of PCV7, we noted an increase in short-term complications and the emergence of serotype 19A, which was penicillin-intermediate in 86 % of cases. After PCV7 introduction, serotype 19A was the most frequent serotype implicated in pediatric pneumococcal OAI. The 13-valent pneumococcal conjugate vaccine introduced in France in June 2010 should cover the emerging serotype. [ABSTRACT FROM AUTHOR]

Study Design: Outcome study to determine the internal consistency, reproducibility, and concurrent validity of the French-Canadian version of the Scoliosis Research Society 22 (SRS-22 fcv) patient questionnaire in France., Objective: To determine whether the SRS-22 fcv can be used in a population from France., Summary of Background Data: The SRS-22 has been translated and validated in multiple countries, notably in the French-Canadian language in Quebec, Canada. Use of SRS-22 fcv seems appropriate for evaluating adolescent idiopathic scoliosis in France. However, French-Canadian French is noticeably different from the French spoken in France, and no study has investigated the use of a French-Canadian version of a health-quality questionnaire in another French population., Methods: The methods used for validating the SRS-22 fcv in Quebec were adopted for use with a group of 200 adolescents with idiopathic scoliosis and 60 healthy adolescents in France. Reliability and reproducibility were measured by the Cronbach α and intraclass correlation coefficient (ICC), construct validity by factorial analysis, concurrent validity by the Short-Form of the survey, and discriminant validity by analysis of variance and multivariate linear regression., Results: In France, the SRS-22 fcv showed good global internal consistency (Cronbach α = 0.87, intraclass correlation coefficient = 0.92), a coherent factorial structure, and high correlation coefficients between the SRS-22 fcv and Short-Form of the survey (P < 0.001). However, reliability and validity were slightly less than that for the instrument's original validation and the validation of the SRS-22 fcv in Quebec. These differences could be explained by language and cultural differences., Conclusion: The SRS-22 fcv is relevant for use in France, but further development and validation of a specific French questionnaire remain necessary to improve the assessment of functional outcomes of adolescents with scoliosis in France., Level of Evidence: N/A.

Objectives: To evaluate both local outcome and sequelae of non-metastatic spinal Ewing tumours (EWT)., Patients and Methods: A French cohort of patients ≤ 50years with localised spinal EWT treated between 1988 and 2009, was analysed in regard to tumour characteristics (e.g. volume, vertebral compartment, spinal cord compression, paraspinal soft tissue invasion), local treatment modalities (surgery (S) and margin quality, radiotherapy (RT) dose), response to treatment (e.g. histological response to neoadjuvant chemotherapy (CT)), tumour local control (LC) and sequelae., Results: Seventy-five patients treated in successive trials were evaluated for LC: SFOP-EW88 (n=14), SFOP-EW93 (n=17) and EuroEwing99 (n=44). Fifty-seven patients (79%) presented initial neurological compression and 69% had inaugural decompressive S. Local treatment modality was S+RT (n=50), RT alone (n=19) and S alone (n=6). Surgery was mainly intralesional (66%). Local recurrences had occurred in 19 patients (14 local, 5 loco-regional) with a median interval of 25 months (1-50). After a 7 year median follow-up (1-22 years), the 5-year LC, relapse-free survival (RFS) and overall survival (OS) reached 78.0% (95%CI: 62.6-84.6), 57.0% (95%CI: 45.2-68.9) and 70.0% (95%CI: 59.1-81.0), respectively. Vertebral compartment involved was the only prognostic factor (5-year LC rate 100% versus 71% for favourable and unfavourable compartment, p<0.03). Among 41 five-year survivors, we observed spinal curvature deformation (35%), growth retardation (28%), spinal reduction mobility (40%), spinal pain (25%) and neurological sequelae (32%) without any significant association with a particular local procedure., Conclusion: RT is the backbone of a successful local treatment of spinal EWT. The place of S remains a pending question. Its actual benefit will likely evolve with new available RT techniques., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006., Methods: Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death., Results: Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%)., Conclusions: We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.

Patients and Methods: Forty-six patients with localised RMS of the limbs entered the MMT 89 and 95 study in France. We studied potential risk factors that were predictive of relapse and survival to propose a therapeutic approach of surgery and radiotherapy appropriate to the risk of relapse., Results: Median age at diagnosis was 6.5 years [9 months to 15.5 years]. At time of diagnosis, 43% had marginal surgery and only 13% radical intervention. Primary re-excision was performed in 12% of the patients. All patients received chemotherapy, 43% had second look surgery and 37% received radiotherapy. Fifty-four percent of all tumors relapsed: local relapse 36%, nodes l8%, metastatic 40%, local and metastatic 16%. Estimated overall 5-year event-free survival (EFS) and overall survival (OS) were 40 and 57%, respectively., Conclusions: Prognosis of RMS of the limbs is bad but only 37% of the patients had radiotherapy. We could define patients with very high risk among those with limbs RMS as nodal involvement (5 years overall survival OS 22%), alveolar histology (OS 38%) and site of hand and foot (4 survivors out of 10 patients). In further studies, these patients should be treated even more aggressive with early surgery followed by re-excision if necessary, chemotherapy including alkylating agents and systematic radiotherapy.