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Summary What is known and Objective: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL. Methods: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (Vd) of the drug were estimated by the nonmem computer program and also compared between both groups. Results and Discussion: Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. What is new and Conclusion: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

Background: All recent guidelines recommend a search for asthma utilizing both specific interrogation and pulmonary function tests in patients suffering from allergic rhinitis. Although the mandatory place of spirometry has not been confirmed, a self-questionnaire containing nine specific questions on asthma symptoms in different daily life situations was found to be capable of discriminating asthmatics from nonasthmatics in a rhinitic population. Objective: We addressed the questions of prevalence of asthma using a validated self-questionnaire and what might be the risk factors of being asthmatic according to that specific self-questionnaire. Methods: Between April 2003 and September 2004, nearly 12 000 rhinitis patients were enrolled by more than 2300 physicians (78% general practitioners, 22% ear nose and throat specialists). Patients were consulting for an exacerbation of chronic rhinitis and did not have a previous diagnosis of asthma. Both doctors and patients filled out a specific questionnaire on rhinitis and asthma. Results: Almost 30% of the patients had at least three positive answers to the self-questionnaire and could possibly be considered as asthmatics. We found five independent clinical risk factors for having ≥3 positive answers to the self-questionnaire. Severity of rhinitis (moderate-severe vs mild, OR = 1.84; 95% CI = 1.68–2.00), diagnosis of allergy (yes vs no) (OR = 1.86; 95% CI = 1.68–2.00), body mass index (≤18.5 vs >30) (OR = 0.51; 95% CI = 0.39–0.66), type of rhinitis (persistent vs intermittent) (OR = 1.25; 95% CI = 1.15–1.37), and patient age (≤25 vs >47) (OR = 0.73; 95% CI = 0.65–0.80). Conclusion: Asthma symptoms are frequent in rhinitics without a prior history of asthma. Several variables were shown to be predictive of asthma in these patients.

In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL.Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V(d) ) of the drug were estimated by the NONMEM computer program and also compared between both groups.Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse.Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

Idiopathic scoliosis leads to a three-dimensional thoracic deformity. The purpose of this study is to measure thoracic dimensions and volume related to growth and to verify the influence of moderate and severe scoliosis. 176 children (36 boys, 140 girls; 4-16 years) with scoliosis45 degrees and 17 patients (2 boys, 15 girls) with scoliosis65 degrees were compared to 239 children without spinal deformity (97 boys, 142 girls) using an optical system. Thoracic volume, perimeter, anterior-posterior and transversal diameters, T1-T12 and sternal lengths were calculated. These measurements were related to age and sitting height. Thoracic volume (3-16 dm(3)) did not differ significantly over growth between reference and moderate scoliosis groups. At 4 years, it represents 33%, at 10 years it represents 55% of its volume compared with age 16. It triples from 4-16 years and doubles during puberty. In severe scoliosis, the age related thoracic volume was always lower than volumes in reference and moderate scoliosis groups. During growth, the transversal diameter corresponds to 30%, the anterior-posterior diameter represents 20% and the thoracic perimeter 100% of sitting height. In severe lordoscoliosis the anterior-posterior diameter represents less than 20%. Scoliosis45 degrees does not influence thoracic volume significantly. Severe deformities seem to inhibit volumetric growth. Thoracic parameters should be related to growth parameters such as sitting height rather than age because of possible height variations in one age section. The established relationships offer a reliable orientation of thoracic proportions. They help to understand the global deformity and represent a baseline for surgical treatment using vertical expandable prosthetic titanium ribs.

A patient's knowledge of his disease and its treatment is an essential part of the evaluation of an educational process. It is useful therefore to use a rapid, easy and valid means of collecting the information necessary to produce an educational programme adapted to the needs of the patient.Following a review of the literature an initial questionnaire was constructed. It included four domains: biomedical, signs and symptoms of severity, general knowledge and treatment. The questionnaire was administered to 73 asthmatics in order to assess its clarity and comprehensibility. It was then reviewed and modified in both format and content by 10 French experts. The revised questionnaire was completed by 108 asthmatics distributed throughout 10 French respiratory centres, a group of 83 non-asthmatic subjects and 203 sixth year medical students at the Bordeaux University School of Medicine.The mean scores were: 19 for the non-asthmatics (range 2-36), 25.7 for the asthmatics (range 4-38) and 32.9 for the students (range 17-40), p 0.0001. The questionnaire was shown to be discriminating with good reliability and reproducibility: alpha Cronbach coefficient=0.82; intra-class correlation coefficient=0.70.This study has validated a French language asthma knowledge questionnaire.

Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification.We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service.The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost.This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

A six-month, prospective descriptive study of medical outcomes (including quality of life) and costs was conducted in 20 incident cases of rheumatoid arthritis (RA). Multidisciplinary management was started during an inpatient stay at the beginning of the study. Patients were evaluated on a day-hospital basis three and six months later. The following parameters were studied: quality-of-life scores on a generic scale (the Nottingham Health Profile [NHP]) and two specific scales (Health Assessment Questionnaire [HAQ] and the short-form Arthritis Impact Measurement Scale [AIMS]), pain severity, disease activity assessed by the patient and physician, painful and swollen joint counts, erythrocyte sedimentation rate, and C-reactive protein level. The following costs were evaluated: laboratory tests, plain radiographs, other investigations, physician care (by rheumatologists or other specialists), second-line drug therapy and monitoring for its side effects, care by nurses, physical therapy, and occupational therapy. All patients showed significant improvement three months after initiation of multidisciplinary management. This effect was sustained through the sixth month. Quality-of-life scores improved, with the exceptions of the social isolation subscore on the NHP and the psychological impact, social activity, and occupational activity subscores on the short-form AIMS. Mean total cost for the six-month period was 3429 +/- 880 euros (1 euro = 6.6 FF). Laboratory tests contributed the largest portion of the total cost (39%), followed by rheumatologist care (16%); the other costs accounted for 7.6 to 9.2% of the total cost. This prospective medical and economic study is preliminary. Comparative studies are needed.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.