[Congenital thoracic deformities and 3D custom-made implants. New classification based on a series of 789 treated cases]. / Malformations thoraciques congénitales et implants sur mesure 3D. Nouvelle classification basée sur une série de 789 cas traités.

The authors present a new study on 789 cases of congenital thoracic malformations including 638 pectus excavatum and 151 Poland syndromes, according to a new classification which completes Chin's one. All these malformations were treated with silicone elastomer implants. The contribution of computer-aided design and manufacturing (CAD/CAM) since 2008 is essential. The one-stage surgical protocol is precisely described. The results are impressive, permanent, for life, and complications are rare. The authors evoke a common vascular etiopathogenesis theory at the embryonic stage and question the heavy techniques of invasive remodeling that are most often unjustified.

[Two cases of severe pruritus revealing Hodgkin's disease in children]. / Prurit sévère révélant un lymphome de Hodgkin chez l'enfant : deux observations.

BACKGROUND: Pruritus in children is a frequent reason for consultation, most often related to a common dermatosis. Where dermatological investigation fails to reveal a dermatological cause, a general cause may be suspected. We report three cases of pruritus revealing Hodgkin's lymphoma in children. PATIENTS AND METHODS: Case 1: a 14-year-old girl presented pruritus with diffuse scratching lesions present for 6 months, associated with right cervical lymph nodes occurring after the onset of pruritus. Tomodensitometry revealed involvement of the supra- and sub-diaphragmatic lymph nodes as well as pulmonary involvement. Lymph node biopsy confirmed nodular sclerosing Hodgkin's lymphoma. Case 2: a 14-year-old boy was hospitalized for suspected psychogenic pruritus. He presented intense itching, predominantly in the lower extremities and at night, occurring over the previous 6 months as well as night sweats. Examination showed that the patient had lost 5kg in 1 month and had a low-grade fever of 38°C; he presented linear striated scratching lesions on both legs. Cervical and inguinal lymphadenopathy was seen. The chest scan also revealed supra-diaphragmatic adenomegalies. The biopsy confirmed Hodgkin's lymphoma. DISCUSSION: Systemic causes of pruritus in children are poorly described in the literature. In these two cases, pruritus allowed a diagnosis of Hodgkin's lymphoma to be made, emphasizing the important role of dermatologists in the early diagnosis of haematological malignancy.

Counselling on sun protection, a survey of French paediatricians.

BACKGROUND: High sun exposure during childhood is an important risk factor for skin cancers at adulthood. Paediatricians are first in line to provide sun protection (SP) information. OBJECTIVE: To describe paediatricians' attitudes towards SP counselling and compare French and American paediatricians' behaviours. METHODS: Methodology used by the American Academy of Pediatrics in 2001. Validation of the French version of the questionnaire. Survey of all 1108 paediatrician members of the Association Française de Pédiatrie Ambulatoire (AFPA) RESULTS More than 90% of paediatricians agreed that skin cancers are a Public Health concern, that preventing episodic high sun exposures during childhood would reduce the risk of adult melanoma, and that it is a paediatrician's role to educate parents/patients on SP. Three quarters reported counselling all of their patients. The most important SP recommendation was to avoid sun during peak hours, followed by sunscreen use. Only 48.3% of paediatricians rated SP as very important to their patients' health, at the 8th rank among selected preventive care topics. The most frequently identified barrier to SP counselling was cost of sunscreens followed by lack of sufficient time. CONCLUSIONS: The majority of paediatricians believe that prevention of skin cancers is a worthy issue and it is their role to educate patients, but less than half of them consider SP as an important topic among selected preventive care issues. Although paediatricians seem to know SP measures well, their (counselling?) seems to respond to patients' preoccupations more than to expert recommendations. French and American behaviours show some major differences.

High frequency, diversity and severity of skin diseases in a paediatric emergency department.

BACKGROUND: Skin disorders are a major concern in the Paediatric Emergency Department (PED). We provide an accurate evaluation of the incidence, characteristics and severity of skin disorders seen in our PED over a 1-year period. METHODS: A total of 20,652 children's medical notes were reviewed in a single centre, retrospective study in the PED of a University Hospital over a 1-year period. The dermatological disorders were analysed on the basis of different criteria including their incidence, patient age, sex ratio, diagnosis, seasonal variations and hospitalization rates. RESULTS: A total of 1897 (9.2%, F/M: 1.2; mean age: 4.1 ± 3.6 years) children presented with 1999 skin diseases and 69 different diagnoses. This frequency increased in the summer months (more than 14% of all patients). A total of 46.5% of diseases were infectious in nature (27.6% viral and 14.4% bacterial), inflammatory diseases accounted for 26.2% (urticaria and angio-oedema 15.9%, atopic dermatitis 3.5%, Henoch-Schönlein purpura: 2.1%), non-specific focal disease (balanitis, vulvitis, etc.) and insect bites, burns, transient diseases of the newborn and drug reactions for 9.2%, 7.8%, 6.4%, 3.7% and 1.2% respectively. More than 90% of children presented at the hospital for an acute condition and 155 (8.2% of children with skin disorders; F/M: 0.9; age: 4.0 ± 4.0 years) were hospitalized. More than 90% of hospitalizations were for infectious and inflammatory diseases. CONCLUSION: Our data reveal the extremely high frequency, diversity and potential severity of paediatric emergency skin disorders. Specific educational measures and closer co-operation between Dermatologists and Paediatricians are essential if the skin care dispensed to children and teenagers is to be improved.

[Value of a new thickened formula in infants with regurgitations]. / Intérêt d'une nouvelle préparation infantile dans la prise en charge des régurgitations du nourrisson.

OBJECTIVES: The purpose of this open multicenter study was to evaluate the value of a new starch-thickened formula in infants with regurgitations in ambulatory pediatric practice. POPULATION AND METHODS: The study population comprised full-term infants with an age at inclusion of 1-90 days, who were bottle-fed and presented regurgitations. The formula tested was an infant formula-thickened with starch (2g/100mL). The primary endpoint was the frequency of bottles regurgitated, expressed in percentage of meals per day after 15 days of feeding with the preparation studied. Secondary endpoints were the assessment of regurgitations using the Vandenplas' score, as well as the daily increase in weight, height, and cranial circumference, overall and gastrointestinal tolerance, and formula acceptability. RESULTS: Sixty-four infants presenting regurgitation were included. The frequency of bottles regurgitated estimated at 80.3% at inclusion significantly decreased at D3, D15, and D30 to 40.1, 40.2 and 37.2% (P<0.0001), respectively. Thirty percent of infants did not present regurgitations at all at D30. Similarly, a significant decrease in the Vandenplas' score was observed from 1.9 at D0 to 0.9 at D30 (P<0.0001). Infant growth was similar to the French and European growth curves. CONCLUSION: The results showed rapid and lasting improvement in decreasing the frequency of feeding-bottles regurgitated by 50% from the first 3 days of using this new starch-thickened formula (2g/100mL). These satisfying results encourage the use of the tested formula in cases of infant regurgitation, in line with the European Society of Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommendations.

Iatrogenic mediastinitis in bronchiolitis: Importance of avoiding pharyngeal aspiration.

An 11-month-old infant was hospitalized for his first episode of severe bronchiolitis, with pneumomediastinum on the chest x-ray performed in the emergency room before hospitalization. After a few days, the occurrence of a feverish torticollis motivated a CT scan, revealing mediastinitis. An iatrogenic perforation was objectified in the posterior wall of the esophagus, probably caused by nasopharyngeal aspiration. This exceptional case has never been reported before, except in premature infants. This encouraged us to report this case to change systematic aspiration practices and prefer nasal suctioning in healthy infants with bronchiolitis presenting to the emergency department.

[Disseminated BCG infection revealing X-linked severe combined immunodeficiency]. / BCGite disséminée révélant un déficit immunitaire combiné sévère lié à l'X.

BACKGROUND: Live attenuated Bacillus Calmette-Guérin (BCG) vaccine is rarely responsible for disseminated infection. We report a case of X-linked severe combined immunodeficiency (SCID) revealed by a disseminated skin infection. PATIENTS AND METHODS: A 4-month-old baby was hospitalized for prolonged gastroenteritis. He was in poor general condition, with prolonged fever, oral and gluteal candidiasis and purple nodules associated with ulceration of the BCG scar. The absence of a thymus, T-cells and NK-cells, and the presence of nonfunctional B-lymphocytes led to a diagnosis of SCID. Biopsies of nodules revealed a dermal infiltrate without necrosis. A Ziehl-Neelson stain was highly positive and the culture grew Mycobacterium bovis. Treatment consisted of a four-drug antibiotic regimen directed against M. bovis combined with gamma interferon, immunoglobulins and antibiotic prophylaxis by cotrimoxazole and was followed by a haploid-identical bone marrow transplant without rejection at six months. The early death of the child's maternal uncle from sepsis suggested X-linked transmission, which was subsequently confirmed by genetic analysis. DISCUSSION: BCG vaccination can cause serious infections in immunocompromised subjects. Skin involvement is extremely rare but may be the first sign of SCID, of which the X-linked form is the most common and corresponds to a variety of mutations in the gene coding for the gamma chain common to several interleukin receptors. Genetic counselling is essential to identify female carriers and allow early antenatal diagnosis. Bone marrow transplantation is the only treatment.

Non-typhi Salmonella enterica urinary tract infections.

OBJECTIVE: Non-typhi Salmonella enterica urinary tract infections (UTIs) are not frequent and rarely reported in the literature. We aimed to characterize clinical presentations and risk factors for the infection. PATIENTS AND METHODS: We performed a retrospective study of non-typhi Salmonella enterica strains isolated from urine cytobacteriological examinations (UCBE) collected between January 1, 1996 and October 30, 2014 and analyzed by the microbiology laboratories of the university hospitals of the western part of Île-de-France and of Paris, France. RESULTS: Twenty UCBEs positive for non-typhi Salmonella enterica were analyzed. The sex ratio was 0.53 and the average age of patients was 57 years. Clinical presentations were acute pyelonephritis, acute cystitis, and prostatitis. Eight cases of bacteremia were identified. Diarrhea was observed in half of patients, either before the UTI or simultaneously. No patient required to be transferred to the intensive care unit. Immunodeficiency and/or diabetes were observed in eight patients. Three patients presented with a uropathy. Prescribed antibiotics were third generation cephalosporins and fluoroquinolones. The average treatment duration was 20 days. A spondylitis and a purulent pleurisy were observed and deemed related to the UTI. Patient outcome was always favorable following treatment prescription. CONCLUSION: Non-typhi Salmonella enterica UTIs are rare. They are mainly observed in elderly patients presenting with immunodeficiency or an underlying urological disorder.

[Medication errors in pediatric inpatients: a multicentric prospective study]. / Erreurs de prescription médicamenteuse en pédiatrie hospitalière: enquête prospective multicentrique. Implications pour la prévention.

OBJECTIVE: To improve the knowledge of medication errors in paediatrics: rate of occurrence, error characteristics, risk factors. PATIENTS AND METHODS: Our prospective study included nine uninformed teaching paediatric wards (general paediatrics, emergency departments, intensive care units) using a describing questionnaire built from medical reports analysis (event description, medical issues, contributing personal and structural factors) during a two-months period. RESULTS: Seventy-five questionnaires were collected and analysed. Medical errors reported concerned prescription: 21 cases and administration: 45 cases. Ten errors led to adverse effects. An attributable factor was noted in 39 cases. Concerning prescription errors, no respect to protocol: 11 cases, lack of knowledge: 3 cases, personal communication failure: 3 cases were noted. Concerning administration errors, human mistakes (lack of experience, miscommunication, calculation error): 8 cases, unclear prescription: 6 cases and system flaws: 6 cases were noted. Several attribuable causes were reported in 8 cases. CONCLUSIONS: Medication errors in paediatrics inpatients are common and contributing factors intricated. Paediatricians should help hospitals develop effective programs for safety providing medications, reporting medication errors, errors analysis strategy and creating a safe environment of medication for all hospitalised paediatric patients.

[Influenza vaccination coverage rate in children with underlying chronic disorders in 7 French pediatric wards]. / Couverture vaccinale vis-à-vis de la grippe chez les enfants de la région parisienne atteints d'une affection de longue durée.

UNLABELLED: In France, annual influenza vaccination is recommended and free of charge for children with chronic disease (chronic lung, heart or kidney disease, diabetes, haemoglobinopathy, immune deficiency). The national goal is to reach 75% influenza vaccination coverage by 2008, but data on coverage in high risk children are limited. OBJECTIVES: To estimate the influenza vaccination coverage in children with an underlying chronic health condition in the Paris region, during in- or out-patient visit at hospital. METHODS: A multicentre cross-sectional descriptive study was carried out over 2 months before the 2004-2005 flu vaccination campaign in 7 French paediatric hospitals (Paris region). Inclusion criteria for this survey were: children aged 6 months to 18 years, with an underlying chronic disease requiring annual influenza vaccination, with a vaccination card available, so as to check their vaccination status. Reasons for non vaccination were recorded. RESULTS: Data from 239 children were analysed. 56% of patients were males (mean age: 8.1 years). Two patients had 2 separate underlying chronic disorders; 69% had a haemoglobinopathy, 16.3% had a chronic respiratory disease, and 7.5% had diabetes. The influenza vaccination rate for 2003-2004 was 43.7% (haemoglobinopathy: 55.5%; chronic respiratory diseases: 12.8%). This rate increased from 20.4% to 43.7% between 1999 and 2003. Less than 16% of parents remembered having received a voucher for free vaccination from the National Health Insurance Agency. CONCLUSION: Efforts are still needed to achieve the 2008 objectives of 75% coverage.

[Febrile ulceronecrotic Mucha-Habermann disease]. / Maladie de Mucha-Habermann fébrile et ulcéronécrotique.

Pityriasis lichenoides et varioliformis acuta (PLEVA) is an inflammatory skin disease that is unknown to pediatricians. The ulceronecrotic febrile form is a rare and potentially lethal variant. We report the case of a 7-year-old boy with a papulovesicular eruption lasting for 4 weeks, secondarily associated with ulcers and necrotic crusts, fever, and systemic signs. After exploring infectious causes such as chickenpox, we discussed and confirmed PLEVA with histological analysis. Systemic steroids and methotrexate improved the symptoms. It is necessary to mention PLEVA in case of prolonged papulovesicular eruption. Prompt diagnosis allows appropriate treatment, although there is no consensus on therapeutic guidelines.

Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.

PURPOSE: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy. PATIENTS AND METHODS: Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner. RESULTS: Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles. CONCLUSION: Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.

Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer.

PURPOSE: To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide high-dose (FEC-HD) neoadjuvant chemotherapy. PATIENTS AND METHODS: One hundred twenty patients have been enrolled by nine French centers in this double-blind, parallel-group, vehicle-controlled study to compare at each cycle subcutaneous lenograstim (5 micrograms/kg/d) with placebo given from day 6 to day 15 after the induction chemotherapy (day 1 to day 4, fluorouracil 750 mg/m2 continuous intravenous [IV] infusion; day 2 to day 4, epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push). Four cycles were planned every 3 weeks before locoregional treatment. Patients with febrile neutropenia remained blinded for the subsequent cycles. RESULTS: Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days, respectively, as compared with 5 and 7 days in the placebo group. This translated into a statistically significant reduced incidence of microbiologically documented infections, and a decreased need for rehospitalizations for infectious events and antibiotic use. Clinical objective tumor response rate observed after four cycles was 89.6% and 93%, respectively, in the placebo and treated groups. Mild transient bone and injection-site pain, myelemia, and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim. CONCLUSION: Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer. Response rate is not affected.

Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer.

PURPOSE: This trial investigated the toxicity and efficacy of docetaxel as first-line chemotherapy in women with heavily pretreated advanced breast cancer. PATIENTS AND METHODS: From April 1992 to August 1992, 35 patients with advanced breast cancer from 29 to 65 years of age with a performance status of 0 to 2 were entered onto the study. Docetaxel 100 mg/m2 was administered every 3 weeks as a 1-hour infusion on day 1 without routine premedication for hypersensitivity reactions. Thirty-one patients were assessable for response. Previous adjuvant chemotherapy had been given to 11 patients. RESULTS: Five complete responses (CRs) and 16 partial responses (PRs) were observed, for an overall response rate of 67.7% (95% confidence interval, 49% to 83%). A CR occurred at 13 of 45 assessable sites (four liver, two lung, three breast, three lymph node, and one skin). The median duration of response was 44+ weeks, the median time to disease progression 37+ weeks, and the median overall survival time 16+ months. Among 34 patients assessable for toxicity (177 cycles; median, five cycles per patient), the following side effects were reported: nadir neutropenia grade 3 (three patients); grade 4 (31 patients); no grade 3 to 4 infection, acute hypersensitivity-like reaction (10 patients); grade 2 to 3 alopecia (all patients); and grade 2 to 3 nausea and vomiting (six patients). Fluid retention occurred in 26 patients and consisted of weight gain, edema alone (15 patients), or edema associated with serous effusion (11 patients). This side effect led to treatment discontinuation in 16 of 21 responding patients after a median of five cycles and a median cumulative dose of docetaxel of 574 mg/m2. CONCLUSION: Our data suggest that docetaxel has major antitumor activity when used as a single cytotoxic agent as first-line chemotherapy in advanced breast cancer.

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix.

PURPOSE: To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma. PATIENTS AND METHODS: Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (>/= one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field). RESULTS: Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events. CONCLUSION: Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.

Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer.

PURPOSE: The population pharmacokinetic/pharmacodynamic (PK/PD) approach was prospectively integrated in the clinical development of docetaxel to assess the PK profile in a large population of patients and investigate systemic exposure as a prognostic factor for clinical outcome. PATIENTS AND METHODS: PK analysis was performed at first course in 24 phase II studies of docetaxel monotherapy using four randomized limited-sampling schedules. Bayesian estimates of clearance (CL), area under the concentration-time curve (AUC), and peak and duration of plasma levels greater than threshold levels were used as measures of exposure. PD data included for efficacy, response rate, time to first response, and time to progression (TTP) in breast cancer and non-small-cell lung cancer (NSCLC), and for toxicity, grade 4 neutropenia, and febrile neutropenia at first course and time to onset of fluid retention. PK/PD analysis was conducted using logistic and Cox multivariate regression models. RESULTS: PK protocol implementation was successful. Most of the patients registered (721 of 936, 77%) were sampled and 68% were assessable for PK (640 patients). First-course docetaxel AUC was a significant predictor (P = .0232) of TTP in NSCLC (n = 151). Docetaxel CL was a strong independent predictor (P < .0001) of both grade 4 neutropenia and febrile neutropenia (n = 582). Cumulative dose was the strongest predictor (P < .0001) of the time to onset of fluid retention (n = 631). However, the duration of exposure over 0.20 micromol/L (0.16 microg/mL) at first course was an independent predictor (P = .0029). Few patients (n = 25, 4%) received the recommended dexamethasone premedication. CONCLUSION: First-course docetaxel PK is a predictor of first-course hematologic toxicity, but also of fluid retention, which is cumulative in nature. Patients with elevated hepatic enzymes have a 27% reduction in docetaxel CL and are at a higher risk of toxicity. A starting dose of 75 mg/m2 is currently being evaluated in this population. Prospective implementation of large-scale population PK/PD evaluation is feasible in early drug development and this approach generates clinically relevant findings.

Respiratory development of 5- to 6- year-old children experiencing a first bronchiolitis episode before age one.

BACKGROUND: The relationship between early infections due to respiratory syncytial virus (RSV), particularly bronchiolitis in infancy, and the subsequent development of asthma, bronchial hyper-responsiveness, and/or other allergic manifestations, seems increasingly certain, even if the mechanisms involved are not yet quite clear. OBJECTIVES: The objectives of this work were to determine the prevalence of, and risk factors for, asthma and allergy in 5 to 6 year-old children who five years previously, had experienced their first episode of bronchiolitis before the age of twelve months, and to define the possible effect of the age at which the bronchiolitis occurred on the subsequent development of asthma. METHOD: A retrospective cohort survey was conducted, based on the registers of two hospital paediatric emergency units (Unit A: the Ambroise Pare teaching hospital at Boulogne, France and unit B: the General Hospital of Cherbourg, France). The cohort comprised 5-6 years old children who had consulted or been admitted to emergency unit A or B between October 1993 and March 1994 for a first attack of bronchiolitis before the age of 12 months. RESULTS: One hundred and twenty eight children were included in the two centres (centre A: 78; centre B: 50). A familial history of allergy was found in 92 children (71.8%). Fifty-two (40.6%) were exposed to tobacco smoke. One hundred and five children (81.2%) had been hospitalised during the first episode of bronchiolitis, but none had been placed in intensive care. Their mean age at admission was 5.1 months, and 29 children were less than three months old. Ninety seven children (75.8%) had experienced at least one episode of wheezing at some time of their life. In the twelve months before the telephone interview, 40 children (31.3%) had had at least one such episode, 47 (36.7%) an attack of asthma, 32 (25.0%) wheezing after an effort, 43 (39.4%) a dry cough at night, 52 children (40.6%) had exhibited allergic rhinitis signs, and 32 (25.0%) eczema. Among the 47 children who had experienced at least one attack of asthma during the previous twelve months, 27 (57.4%) had a history of familial asthma (p<0.04). This was the only significant relationship observed in this study with regard to risk factors for asthma. No relationship was observed between asthma or recent wheezing on the one hand, and on the others age less than three months during the first bronchiolitis episode (p=0.6), initial hospital admission (p=0.6) tobacco smoke exposure (p=0.27), sex (p=0.10) or day care management until age three (p=0.73). DISCUSSION: This study showed a high prevalence of asthma and other allergic manifestations in children who five years previously, had experienced their first bronchiolitis episode before the age of twelve months. The only risk factor for asthma or chest wheezing identified in this study was a familial history of allergy. These data support the idea that for most children, early acute bronchiolitis, even if severe, is a transient event, with no or very few consequences in the middle or long term. Nevertheless it may be the expression of an interaction between viral infection and atopic familial predisposition leading to lasting bronchial hyper-responsiveness.

[The pediatrician's waiting room: a place for health education?]. / La salle d'attente du pédiatre: lieu d'éducation pour la santé?

OBJECTIVES: To assess the presence and impact of health education messages in pediatricians' waiting rooms. METHODS: In September 2001, 81 pediatricians completed a questionnaire about the furnishings and equipment in their waiting rooms. They also distributed a questionnaire about waiting room health education messages to parents, to be completed at home. RESULTS: The analysis considered 1830 questionnaires. Health education messages were posted in 91% of the waiting rooms and most frequently concerned children's accidents, vaccines, hygiene and nutrition. The best topics that the parents remembered involved child neglect, antibiotic therapy, AIDS and other sexually transmitted diseases, and nutrition. Although memorization of the messages was not influenced by duration of the wait, it was higher among parents who had previously visited the pediatrician. These messages led 14% of the parents to discuss them spontaneously with their pediatrician. CONCLUSION: Health education messages are posted in nearly all the waiting rooms studied; parents remember them in a variable and rather inexplicable order. Posting these messages demonstrates the pediatricians' willingness to be involved - beyond the simple consultation - in the health education of children and families. Identifying the real impact of these messages would require further study.

[Treatment of exacerbation of asthma: what are today's issues?]. / Traitement de la crise d'asthme: où sont aujourd'hui les enjeux?

During past decades, major progress has been accomplished in the management of acute asthma. Most recent recommendations include evidence-based rationale. The improved quality of clinical guidelines makes them efficient models for medical education. The pediatric pharmacopoeia provides a great variety of choices of drugs as well as for asthma medical devices. These innovations dramatically facilitated the medical management of asthmatic children, but they did not solve all problems. Physicians now use higher doses of salbutamol, but the early prescription of systemic glucocorticoids for moderate exacerbation of asthma is still underused, given the most recent clinical guidelines and meta-analysis. Furthermore, repeated emergency department visits to the wards and lack of primary care physician should systematically be appraised when evaluating severity, as they are both major risk factors for severe exacerbations, even though they are not considered in acute asthma severity scores. Finally, initiating (or reinforcing) patient education at the time of exacerbation also presents important challenges, as emergency visits are a favorable moment to commence the therapeutic education of the child and his family. Indeed, framing the controller medications and educating families about how to manage the disease and to improve their domestic environment are the genuine tools available for the prevention of asthma exacerbations, and particularly those most severe.