Physiological Synchrony of the Broad Bean Weevil, Bruchus rufimanus Boh., to the Host Plant Phenology, Vicia faba L.

The aims of the study were to understand the physiological and phenological relationship between Bruchus rufimanus and Vicia faba in the perspective of IPM strategies. V. faba, an important food resource for humans and livestock is the main host plant of B. rufimanus. Adults feed on the pollen, females lay eggs on pods, and larvae develop into the seeds. Pending the blooming phase, the weevil may feed on the pollen from wild plants. Depending on the sowing date, the phenological time lag should lead the plant parts, most utilized by the weevil, less or more available during the key life stages of the pest. The aims of the study were therefore (1) to assess the impact of the sowing date (i.e., cultivars) on the phenological relationship between B. rufimanus and V. faba, and (2) to identify alternative pollen resources during the vegetative phase. Insects were collected weekly on two cultivars: winter-sown and spring-sown fields. Ovarian development, fecundity, and diet were monitored using dissected adults. Results showed that immature adults colonized the blooming winter-sown field and then 2 weeks later, the blooming spring-sown field. Sexual maturity of the weevils is related with V. faba pollen consumption. The sexual maturity of females increased with the growing density of flowers and the first pods were quickly covered with eggs. In spring-sown field, first pods grew 19 days later, while collected females in winter sown field had already laid most of their eggs. Feeding tests were carried using flowers collected from plants growing close to the fields: wild chervil, oilseed rape and wild Prunus. All this pollen were consumed by the weevils. The study showed a perfect synchrony between the host and the pest. Late sowing date and control of the early blooming wild plants surrounding the crops might reduce the attacks in field beans. More broadly, the study helps to understand the eco-ethology of the insect in cultivated areas.

Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation.

Seventy-five percent of patients with beta thalassemia (ß-thalassemia) do not have human leukocyte antigen-matched siblings and until recently had no access to a curative treatment. Gene therapy is a promising treatment that can be proposed to these patients. This study estimates its cost and efficacy. In a monocentric retrospective study and cost-efficacy analysis, this study compared the two-year outcomes and costs of patients with ß-thalassemia treated by gene therapy and hematopoietic stem-cell transplantation (HSCT). Grade III and grade IV complications, hospitalizations, and length of stay were extracted from the hospital discharge data. Costs were estimated from hospital accounting information and national cost studies. A total of seven patients with ß-thalassemia treated between 2009 and 2016 were included, of whom four received gene therapy. Patients treated by gene therapy were older and had fewer complications and hospital admissions. Infectious complications were three times more frequent for patients treated with HSCT than for gene therapy. Average costs were €608,086 for patients treated by gene therapy and €215,571 for HSCT. The total cost of the vector was 48% of the total cost of gene therapy. Gene therapy as a curative alternative for patients lacking human leukocyte antigen-matched donors was costlier but resulted in fewer complications than HSCT.

Response of insect relative growth rate to temperature and host-plant phenology: estimation and validation from field data.

Between 1975 to 2011, aphid Relative Growth Rates (RGR) were modelled as a function of mean outdoor temperature and host plant phenology. The model was applied to the grain aphid Sitobion avenae using data on aphid counts in winter wheat at two different climate regions in France (oceanic climate, Rennes (western France); continental climate, Paris). Mean observed aphid RGR was higher in Paris compared to the Rennes region. RGR increased with mean temperature, which is explained by aphid reproduction, growth and development being dependent on ambient temperature. From the stem extension to the heading stage in wheat, there was either a plateau in RGR values (Rennes) or an increase with a maximum at heading (Paris) due to high intrinsic rates of increase in aphids and also to aphid immigration. From the wheat flowering to the ripening stage, RGR decreased in both regions due to the low intrinsic rate of increase in aphids and high emigration rate linked to reduced nutrient quality in maturing wheat. The model validation process showed that the fitted models have more predictive power in the Paris region than in the Rennes region.

Changes in insulin therapy regimens over 10 yr in children and adolescents with type 1 diabetes attending diabetes camps.

OBJECTIVE: To describe the changes in insulin therapy regimens of children and adolescents with type 1 diabetes over 10 yr and their correlation with hemoglobin A1c (HbA1c). RESEARCH DESIGN AND METHODS: The study included 7206 children and adolescents (age 12.8 ± 2.7 yr, more than 1 yr of diabetes duration) admitted in summer camps between 1998 and 2007 (707-896/yr). Based on injection times (breakfast, lunch, afternoon, dinner, bedtime) and insulin types (short, long and premixed; human or analog), 786 different therapeutic combinations were classified in six main types of regimens. The distribution of the different regimens and their correlation with HbA1c were evaluated as a function of year and age. RESULTS: Over 10 yr, basal bolus increased from 13 to 52% and the pump from <1 to 13%, regimens with two to three injections per day decreased from 50 to 25%, those with only premixed insulins from 33 to 7%, and diverse regimens from 9 to 1%. HbA1c was significantly higher with premixed insulin only, but there were no differences between the other regimens throughout the follow-up. Mean yearly HbA1c (8.21-8.45%) did not show any significant decrease, but the percentage of patients with HbA1c > 9 and 10% decreased significantly, in those treated with two to three injections and the pump, not with basal bolus or premixed only regimens. CONCLUSION: A major trend in intensifying insulin treatment in children and adolescents with type 1 diabetes was accompanied by modest improvements in HbA1c. No insulin regimen has shown any better results, except over premixed insulins.

Do parents understand the medical information provided in paediatric emergency departments? A prospective multicenter study.

AIM: We evaluated the extent to which parents understood the medical information about hospitalization of their child in an emergency department and looked for characteristics likely to increase the risk of poor comprehension. METHODS: Prospective multicenter study in thirteen paediatric emergency departments. The parents and doctors completed questionnaires based on closed-ended questions with a common core of four items: reasons of hospitalization, diagnosis, treatment and seriousness of child condition. We evaluated concordance between parents and doctor answers for these items by comparing their responses. RESULTS: This study included 380 parents. Percentage of concordance was 55% for the reason of hospitalization, 78% for the diagnosis, 92% for the treatment, 48% for the seriousness of the condition and 19% for all four items. The mean number of concordant items was 2.76 (CI 95%, 2.66-2.86). Parents whose children seemed not in pain and parents who received additional information from the nurse showed significantly slightly higher levels of concordance with doctor's answers (2.98 vs 2.66, p = 0.006 and 2.89 vs 2.60, p = 0.004, respectively). CONCLUSION: This study shows that improvements are required in the clarity of the information delivered to the parents. The assistance of nurses and optimal pain management may help to improve communication.

Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood?

Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4(+) and CD3(+) cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5-year overall survival rates were 62% ± 4% after MMRDT and 57% ± 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes.

Decrease of inpatient mortality for hip fracture in France.

OBJECTIVE: Hip fracture is the most devastating osteoporotic fracture, increasing the risk of mortality. Recent data suggest a decrease in incidence of this fracture. Few data are available on potential changes in mortality. We studied the change of inpatient mortality from 2002 to 2008 in France. METHODS: Data were extracted from the French Hospital National Database. The absolute number of inpatient mortality for hip fracture was described as well as the case fatal rate and mortality rate adjusted on age and gender. Risk factors of inpatient mortality were assessed by multiple regressions. RESULTS: Inpatient mortality stay decreased from 3057 to 2350 in patients aged 40 years and over and in both gender. Inpatient mortality stays were more important in women and increased with age, but the case fatal rate was higher in men than in women (5.4 vs. 2.8% in 2008). During the study period, the mortality rate (per 1,000,000) varied from 132 to 88 and from 82 to 64 in women and men, respectively. In the older patients, case fatality and mortality rates decreased significantly during the study period. From 2008 data, age more or equal to 85 years, male gender, stay in intensive care and existence of some chronic or acute disease, especially cardiovascular disease, hepatic disease, renal insufficiency, and infection were significant determinants of inpatient mortality. CONCLUSION: Inpatient mortality after hip fracture decreased in France between 2002 and 2008, although age, male gender and comorbidities were identified as determinants of inpatient mortality.

Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better?

BACKGROUND: Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs). OBJECTIVE: To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005. METHODS: The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival. RESULTS: In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B(+) phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016). CONCLUSION: This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned.

Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.

Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score) used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders) for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.

Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis.

OBJECTIVES: To describe the history, mechanisms, and consequences of cystic fibrosis (CF)-related diabetes, from childhood to early adulthood. STUDY DESIGN: Pancreatic beta-cell function was estimated from the plasma insulin/glucose ratios during oral glucose tolerance test (total area under the curve and deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls). Progression of glucose metabolism abnormalities was evaluated by analysis for interval censored data; rates of pulmonary transplantation and death by Kaplan-Meier analysis. RESULTS: Impaired glucose tolerance was found in 20% of patients at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes, >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at 20 years, 40% at 30 years. Early impairment was associated with lower survival rates and higher rates of lung transplantation. The area under the curve(glucose) correlated with decreased body mass index and height. Decrease in early insulin secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not differ between the groups. Increased inflammation correlated with insulin resistance and impaired glucose tolerance. CONCLUSIONS: CF-related diabetes, mainly because of beta-cell deficiency, is frequent early in life and associated with impaired nutritional state and growth, increased rates of terminal respiratory failure, and death.

Experience in the management of eighty-two newborns with congenital diaphragmatic hernia treated with high-frequency oscillatory ventilation and delayed surgery without the use of extracorporeal membrane oxygenation.

The aim of this study is to analyze neonatal outcome of isolated congenital diaphragmatic hernia and to identify prenatal and postnatal prognosis-related factors. A retrospective single institution series from January 2000 to November 2005 of isolated congenital diaphragmatic hernia neonates was reviewed. Respiratory-care strategy was early high-frequency oscillatory ventilation, nitric oxide in pulmonary hypertension, and delayed surgery after respiratory and hemodynamic stabilization. Survival rate at 1 month was 65.9%. None of the prenatal factors were predictive of neonatal outcome, except an intra-abdominal stomach in left diaphragmatic hernia. Preoperative pulmonary hypertension was more severe in the nonsurvivor group and was predictive of length of ventilation in the survivors. During the first 48 hours of life, the best oxygenation index above 13 and the best PaCO2 above 45 were predictive of poor outcome. When treating isolated congenital diaphragmatic hernia with early high-frequency ventilation and delayed surgery but excluding extracorporeal membrane oxygenation, survival rates compare favorably with other reported series, and the respiratory morbidity is low.

Prenatal prognosis in isolated congenital diaphragmatic hernia.

OBJECTIVE: A monocentric retrospective study of 79 neonates with isolated diaphragmatic hernia antenatally diagnosed was performed to identify prenatal parameters that may characterize the severity of the disease. STUDY DESIGN: Postnatal treatment protocol included early high frequency ventilation, inhaled nitric oxide, and delayed surgery. Postnatal survival rate was 63.3%. RESULTS: Age at diagnosis, polyhydramnios, and left ventricle/right ventricle index were not related with survival. None of the 9 left diaphragmatic hernias with intraabdominal stomach died. Neonatal mortality was significantly related with the side of the defect, intrathoracic position of the liver, the ratio of fetal lung area to head circumference value, and fetal lung volume ratio measured by resonance magnetic imaging. CONCLUSION: No prenatal factor alone firmly predicts neonatal outcome. Clinicians should help stratify the severity of the disease and compare accurately different postnatal therapeutic strategies.

Long-term outcome of children receiving home parenteral nutrition: a 20-year single-center experience in 302 patients.

BACKGROUND: More information is needed regarding the prognosis of children receiving home parenteral nutrition (HPN). This article describes 20-year outcome data in children receiving HPN and provides separate profiles for the major pediatric diagnostic subgroups. PATIENTS AND METHODS: This retrospective study included children who started receiving HPN between January 1, 1980, and December 31, 1999, in a single pediatric HPN center. RESULTS: A total of 302 children were recruited, 230 (76%) with primary digestive disorders and 72 (24%) with nonprimary digestive disorders. Median age at HPN onset was 1.5 years. Median duration of HPN was 1.3 years. By January 1, 2000, 54% had weaned from HPN, 26% were still receiving HPN, 16% had died, and 4% had undergone intestinal transplantation. The survival probabilities at 2, 5, 10, and 15 years were 97%, 89%, 81%, and 72%, respectively. The likelihood and cause of death depended on the underlying diagnosis. Nine percent of children with primary digestive disorders died, 24% from their primary disease and 48% from liver disease or sepsis. Children with intractable diarrhea of infancy had the highest mortality rate (25%) and the highest incidence of liver disease (48%; P = 0.0002). Thirty-eight percent of children with primary nondigestive diseases died, 94% from their primary disease and 6% from liver disease or sepsis. CONCLUSIONS: Outcome and survival of children receiving HPN are mainly determined by their underlying diagnosis. Nearly all children with primary digestive disease survive if referred early to an expert center.

Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype.

We studied T-cell reconstitution in 31 primary T-cell-immunodeficient patients who had undergone hematopoietic stem-cell transplantation (HSCT) over 10 years previously. In 19 patients, there was no evidence of myeloid chimerism because little or no myeloablation had been performed. Given this context, we sought factors associated with good long-term T-cell reconstitution. We found that all patients having undergone full myeloablation had donor myeloid cells and persistent thymopoiesis, as evidenced by the presence of naive T cells carrying T-cell receptor excision circles (TRECs). In 9 patients with host myeloid chimerism, sustained thymic output was also observed and appeared to be associated with gammac deficiency. It is therefore possible that the complete absence of thymic progenitors characterizing this condition created a more favorable environment for thymic seeding by a population of early progenitor cells with the potential for self-renewal, thus enabling long-term (> 10 years) T-cell production.

How emergency departments might alert for prehospital heat-related excess mortality?

INTRODUCTION: A major issue raised by the public health consequences of a heat wave is the difficulty of detecting its direct consequences on patient outcome, particularly because of the delay in obtaining definitive mortality results. Since emergency department (ED) activity reflects the global increase of patients' health problems during this period, the profile of patients referred to EDs might be a basis to detect an excess mortality in the catchment area. Our objective was to develop a real-time surveillance model based on ED data to detect excessive heat-related mortality as early as possible. METHODS: A day-to-day composite indicator was built using simple and easily obtainable variables related to patients referred to the ED during the 2003 heat-wave period. The design involved a derivation and validation study based on a real-time surveillance system of two EDs at Cochin Hospital and Hôtel-Dieu Hospital, Paris, France. The participants were 99,976 adult patients registered from 1 May to 30 September during 2001, 2002 and 2003. Among these participants, 3,297, 3,580 and 3,851 patients were referred to the EDs from 3 August to 19 August for 2001, 2002 and 2003, respectively. Variables retained for the indicator were selected using the receiver operating characteristic curve methodology and polynomial regression. RESULTS: The indicator was composed of only three variables: the percentage of patients older than 70 years, the percentage of patients with body temperature above 39 degrees C, and the percentage of patients admitted to or who died in the ED. The curve of the indicator with time appropriately fitted the overall mortality that occurred in the region of interest. CONCLUSION: A composite and simple index based on real-time surveillance was developed according to the profile of patients who visited the ED. It appeared suitable for determining the overall mortality in the corresponding region submitted to the 2003 heat wave. This index should help early warning of excessive mortality and monitoring the efficacy of public health interventions.

Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial.

BACKGROUND: Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial. In this study, we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome. METHODS: Our prospective, randomised, multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France. Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer. 360 patients were randomised, and the primary endpoint was 60-day survival based on an intention-to-treat analysis. FINDINGS: Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any other time. INTERPRETATION: These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.

Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas.

The incidence of follicular lymphoma (FL) in industrialized countries has been increasing since the 1950s. Polymorphisms in genes encoding key enzymes controlling folate-methionine metabolism, including methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS or MTR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TS or TYMS), modify the risk of various cancers and possibly FL. This study specifically looks for an association between MTHFR, MTR, TYMS, and SHMT polymorphisms and the risk of FL. We carried out a case-control study with 172 patients diagnosed with FL and 206 control subjects. We report that the risk of FL was doubled by the association of one mutant allele at both MTHFR polymorphisms. Individuals with MTR 2756AA had 2-fold higher risk of FL, and subjects not having at least one TYMS 2R allele showed a 2-fold higher risk of FL. The MTR 2756AA genotype conferred a greater multivariate-adjusted relative risk of FL, and the risk was multiplied by almost 5 in the TYMS2R(-)/MTR 2756AA combination. In conclusion, common polymorphisms in key enzymes of the folate-methionine metabolism pathway result in an increased risk of FL and suggest that inadequate intake of dietary folate and other methyl donor nutrients may contribute to the development of this malignancy.

Avoiding doubles in distributed nominative medical databases: optimization of the needleman and wunsch algorithm.

Difficulties in reconstituting patients' trajectory in the public health information systems are raised by errors in patients' identification processes. A crucial issue to achieve is avoiding doubles in distributed web databases. We explored Needleman and Wunsch (N&W) algorithm in order to optimize the properties of string matching. Five variants of the N&W algorithm were developed. The algorithms were implemented for a web Multi-Source Information System. This system was dedicated to tracking patients with End-Stage Renal Disease at both regional and national level. A simulated study database of 73,210 records was created. An insertion or suppression of each character of the original string was simulated. The rate of double entries was 2% given an acceptable distance set to 5 modifications. The search was sensitive and specific with an acceptable detection time. It detected up to 10% of modifications that is above the estimated error rate. A variant of the N&W algorithm designed as "cut-off heuristic", proved to be efficient for the search of double entries occurring in nominative distributed databases.

Prediction model of coronary heart disease in patients with chronic kidney disease: role of plasma fibrinogen as a new prognostic variable.

BACKGROUND: The Framingham-Anderson (FA) risk equation can predict coronary heart disease (CHD) risk in the general population. However, this formula's validity in predicting CHD risk in chronic kidney disease (CKD) patients is not extensively evaluated. METHODS: In a group of 96 patients with CKD stage 2 to 4, free of CHD at the time of the start of follow-up, and prospectively followed for 4 to 12 years (7.4 +/- 2.2 years, mean +/- SD), we calculated the FA index. RESULTS: During the follow-up period, twenty-one patients experienced fatal and non-fatal myocardial infarction (CHDobs+), and 75 remain free of CHD (CHDobs-). The median FA index was 7.1% for CHDobs - patients and 10.3% for CHDobs+ patients. The specificity of the model was acceptable (89%), but the sensitivity was low (24%). Sensitivity analysis by adding fibrinogen led to an improvement in the CHD risk index and the sensitivity of the model (48%) as well. However, despite the addition of fibrinogen to the FA risk factors, full CHD risk in CKD patients remains underestimated. CONCLUSIONS: Our results show that the FA index is a weak predictor of CHD in CKD stage 2 to 4 patients, and emphasized the role of inflammation in predicting the CHD risk.

Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type.

OBJECTIVE: To assess the efficacy of etanercept in patients with juvenile idiopathic arthritis (JIA), and to assess the tolerance of these patients to etanercept. METHODS: All JIA patients with active chronic polyarthritis, who were first treated with etanercept between November 1999 and June 2001 in 18 French centers because of poor response or intolerance to methotrexate, were included in this open-label, prospective, multicenter study. A standardized questionnaire was sent to the treating physicians. We assessed the validated international core-set score for JIA activity every 3 months and performed an intent-to-treat analysis. We also compared the risk of treatment failure in patients defined as having systemic-onset, oligoarticular-onset, or polyarticular-onset JIA. RESULTS: Sixty-one patients were enrolled and were followed up for a median of 13 months. Treatment had to be stopped in 1 patient who became pregnant and in 12 patients due to severe side effects, including neurologic or psychiatric disorders, retrobulbar optic neuropathy, major weight gain, severe infection, cutaneous vasculitis with systemic symptoms, hemorrhagic diarrhea, uveitis flare, and pancytopenia. All of these side effects disappeared after discontinuation of etanercept. Crohn's disease was subsequently diagnosed in 1 child. Scores improved by > or =30% in 73% of patients after 3 months, but this proportion decreased to 39% after 12 months. The response rate was significantly lower in patients with systemic-onset JIA than in those with oligoarticular- or polyarticular-onset JIA. CONCLUSION: Treatment of JIA with etanercept may be associated with a wide spectrum of severe side effects. Although most patients initially respond to etanercept, this initial response is not always followed by sustained improvement over longer periods of time. In addition, the higher rate of treatment failure in the group with systemic-onset JIA indicates that these patients in particular may require alternative treatments.