Bronchiolitis: what's next?
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Bronchiolitis↗
Biomedical subjects
Jacques Lacroix
Publications and source records attributed to Jacques Lacroix.
A new generation of N-aryl-N'-(1-alkyl-2-chloroethyl)ureas as microtubule disrupters: synthesis, antiproliferative activity, and beta-tubulin alkylation kinetics.
New N-aryl-N'-2-chloroethylureas (CEUs) with enhanced cytotoxicity were developed as antimitotic agents potentially useful in cancer chemotherapy. Highly potent CEUs were obtained by introduction of a branched alkylating chain, the N'-(1-methyl-2-chloro)ethyl group. Their cytotoxic activity was enantio-dependent and induced through specific alkylation of beta-tubulin, leading to microtubule disruption and mitotic arrest. Overall, the structural modifications of the CEUs described here significantly improved their kinetics of beta-tubulin alkylation. In this new series, CEUs 16a and 18a displayed particularly enhanced antiproliferative activity related to a faster reaction with beta-tubulin and merit further investigation as potential antitumor agents.
Alkylation↗
Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study.
BACKGROUND: Multiple organ dysfunction syndrome is more frequent than death in paediatric intensive care units. Estimation of the severity of this syndrome could be a useful additional outcome measure in clinical trials in such units. We aimed to validate the paediatric logistic organ dysfunction (PELOD) score and estimate its validity when recorded daily (dPELOD). METHODS: We did a prospective, observational, multicentre cohort study in seven multidisciplinary, tertiary-care paediatric intensive care units of university-affiliated hospitals (two French, three Canadian, and two Swiss). We included 1806 consecutive patients (median age 24 months; IQR 5-90). PELOD score includes six organ dysfunctions and 12 variables and was recorded daily. For each variable, the most abnormal value each day and during the whole stay were used in calculating the dPELOD and PELOD scores, respectively. Outcome was vital status at discharge. We used Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration and areas under receiver operating characteristic curve (AUC) to estimate discrimination. FINDINGS: 370 (21%) patients had no organ dysfunction, 471 (26%) had one, 457 (25%) had two, and 508 (28%) had three or more. Case fatality rate was 6.4% (115 deaths). PELOD score was significantly higher in non-survivors (mean 31.0 [SE 1.2]) than survivors (9.4 [0.2]; p<0.0001). Calibration (p=0.54) and discrimination (AUC=0.91, SE=0.01) of PELOD and dPELOD (p> or =0.39; AUC> or =0.79) scores were good. INTERPRETATION: PELOD and dPELOD scores are valid outcome measures of the severity of multiple organ dysfunction syndrome in paediatric intensive care units; their use should significantly reduce the sample size required to complete clinical trials in critically ill children.
Adolescent↗
Evaluation of the pediatric risk of admission score in a pediatric emergency department.
STUDY OBJECTIVES: The pediatric risk of admission (PRISA) score was developed to predict the risk for hospitalization for pediatric emergency department patients. We sought to evaluate prospectively the predictive value of the PRISA score with respect to the risk for hospitalization in a pediatric ED. METHODS: A prospective cohort study was conducted in a pediatric tertiary center ED. From November 1, 2000, to October 31, 2001, 3 periods of 8 hours each were randomly chosen monthly. During these periods, all patients triaged to the ED were evaluated. Data collection was performed by an investigator uninvolved in the patients' treatment. Data were recorded before the decision regarding hospitalization was made. Odds ratios for the risk of hospitalization related to individual criteria and PRISA scores were calculated. Discrimination and calibration of the score were assessed. RESULTS: During the study periods, 1,930 patients were evaluated. Among these, 203 hospitalizations were observed, and the PRISA score predicted 235. The goodness-of-fit test demonstrated that the score had good predictive ability (chi(2)=28.15; P =.78). Receiver operating characteristic curve analysis confirmed the latter findings (area under the curve 0.79 [95% confidence interval 0.72 to 0.86]). Some individual criteria of the score did not significantly predict risk for admission. CONCLUSION: The PRISA score is a good predictor of the risk for hospitalization in a pediatric ED. It seems more accurate for the sicker patients. Some variables of the score could be deleted or modified to optimize its accuracy.
Adolescent↗
The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial.
OBJECTIVE: To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO(2)) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111). STUDY DESIGN: In a crossover randomized double-blind clinical trial, 5 children with SLSJ-COX deficiency, who were stable and old enough to comply with VO(2) measurement, were treated with placebo or DMG for 3 days, and with the alternate treatment after a 2-week washout period. VO(2) was measured by indirect calorimetry before and after treatment. Dietary caloric intake was calculated for 3 days before each measurement. Mean caloric intakes per day were 1562 and 1342 kcal x m(-2) before and during placebo, 1,336 and 1,380 before and during DMG, respectively. RESULTS: DMG was well tolerated and, in all cases, resulted in markedly increased blood DMG levels (617 + 203 mmol x L(-1)), versus 0 to 2 mmol x L(-1) without treatment. Mean VO(2) was lower after administration of either DMG (-1 +/- 3 mL x min(-1) x m(-2)) or placebo (-6 +/- 4), but neither difference was statistically significant. There was no detectable effect of DMG treatment on blood levels of lactate, pyruvate, bicarbonate, or pH. VO(2) values of patients (range, 101-135 mL x min(-1) x m(-2)) were lower than published norms (150-160 mL x min(-1) x m(-2)). CONCLUSION: This study suggests that treatment with DMG does not substantially change VO(2) in children with SLSJ-COX deficiency.
Child↗
Erythropoietin for critically ill children.
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Anemia↗
Ventilator-associated pneumonia in intubated children: comparison of different diagnostic methods.
OBJECTIVES: To compare different methods for diagnosis of ventilator-associated pneumonia in intubated children. DESIGN: Prospective epidemiologic study. SETTING: Pediatric intensive care unit of a tertiary care university hospital. PATIENTS: All consecutive pediatric intensive care unit patients <18 yrs of age with suspected ventilator-associated pneumonia. INTERVENTIONS: For all patients, the following diagnostic methods were compared: 1) clinical data using Centers for Disease Control criteria; 2) blind protected bronchoalveolar lavage, evaluating quantitative cultures, bacterial index of >5, Gram stain, and presence of intracellular bacteria; and 3) nonquantitative cultures of endotracheal secretions. The reference standard used was clinical judgment of three independent experts (Delphi method) who retrospectively established by consensus the presence of ventilator-associated pneumonia based on clinical, microbiological, and radiologic data. Concordance between each diagnostic method and the reference standard was evaluated by concordance percentage and kappa score. Validity was evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and global value. RESULTS: A total of 30 patients were included in the study. According to the reference standard, ventilator-associated pneumonia occurred in 10 of 30 patients (33%). Bacterial index of >5 in bronchoalveolar secretions showed the best concordance compared with the reference standard (concordance, 83%; kappa, 0.61). Bacterial index of >5 also showed the best validity (sensitivity, 78%; specificity, 86%; positive predictive value, 70%; negative predictive value, 90%; global value, 90%). Intracellular bacteria and Gram stain from bronchoalveolar secretions were very specific (95% and 81%, respectively) but not sensitive (30% and 50%, respectively). Clinical criteria and endotracheal cultures were very sensitive (100% and 90%, respectively) but poorly specific (15% and 40%, respectively). CONCLUSION: Our data show that the most reliable diagnostic method for ventilator-associated pneumonia is a bacterial index of >5, using blind protected bronchoalveolar lavage. Further studies should evaluate the validity of all these methods according to the gold standard (autopsy).
Bronchoalveolar Lavage Fluid↗
Reproducibility of blind protected bronchoalveolar lavage in mechanically ventilated children.
Blind protected bronchoalveolar lavage (BAL) could be an interesting tool in the diagnosis of ventilator-associated pneumonia in intubated children, but its reproducibility has never been evaluated. This study evaluates the reproducibility, feasibility, and safety of blind protected BAL in mechanically ventilated children. Two blind protected BAL were done, at a 2-hour interval, in 30 patients. The reproducibility of microbiologic and cytologic results was studied. A total of 60 BALs was analyzed. Bacterial growth was present in 26 of 60 BAL (43%). Reproducibility for the presence of bacteria on quantitative cultures was excellent (concordance, 93%; kappa [kappa], 0.86). Concordance for the type of bacteria isolated was 86% and for the number of bacteria was 79%. Reproducibility for the presence of neutrophils containing bacteria was perfect (concordance, 100%; kappa, 1) although only a few BALs had a positive result (8/60). Blind protected BAL was feasible in all patients and all samples were considered adequate for analysis. Complications were mostly benign and transitory except in two cases: one pneumothorax and one significant increase in intracranial pressure. Overall, blind protected BAL is a reproducible test in mechanically ventilated children, is easily feasible, and is usually well tolerated.
Adolescent↗
Randomized clinical trials in pediatric critical care: Rarely done but desperately needed.
OBJECTIVE: To review the benefits and challenges of using the randomized, controlled trial (RCT) study design to evaluate preventive and therapeutic interventions in pediatric critical care medicine. CONCLUSIONS: The RCT design is able to control for many sources of potential bias that other types of study designs cannot. The findings of RCTs often contradict the findings of less rigorous study designs. Before performing an RCT, there must exist a state of clinical equipoise, a sufficient number of eligible patients must be available, and the epidemiology of the disorder in question must be well studied. There are many challenges to performing high-quality RCTs. Studying multiple element support strategies in the critically ill patient population is more complex than studying a single drug therapy. High patient and practice variability and hazy diagnostic definitions can dilute the signal-to-noise ratio. Most interventions in critical care are expected to have a modest or small effect. This markedly increases the requisite sample size. There is a paucity of accepted clinically important measurements of the outcome of critical care, making mortality a common outcome to evaluate with a not-so-common incidence. Developmental issues, the inability to give informed consent, and the failure to perform the appropriate pharmacokinetic and safety studies are additional challenges facing pediatric investigators. Despite these limitations, a good RCT remains the best way to prove that an intervention is working or not. Indeed, RCTs are and will remain the "gold standard" method to estimate the efficacy of a therapeutic or prophylactic intervention.
Journal Article↗
Survey on transfusion practices of pediatric intensivists.
OBJECTIVE: To describe the red blood cell transfusion practices of pediatric intensivists. DESIGN: Cross-sectional self-administered survey. SETTING: Pediatric intensive care units. PATIENTS: Academic pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Scenario-based survey among English- or French-speaking intensivists from Canada, France, Belgium, or Switzerland, working in tertiary-care pediatric intensive care units. Respondents were asked to report their decisions regarding transfusion practice with respect to four scenarios: cases of bronchiolitis, septic shock, trauma, and the postoperative care of a patient with Fallot's tetrad. The response rate was 71% (163 of 230). The overall baseline hemoglobin transfusion threshold that would have prompted intensivists to transfuse a patient ranged from 7 to 13 g/dL (70-130 g/L) within almost all scenarios. There was a significant difference between scenarios of the average baseline hemoglobin transfusion thresholds (p < .0001). A low Pao2, a high blood lactate concentration, a high Pediatric Risk of Mortality score, active gastric bleeding, emergency surgery, and age (2 wks) were important determinants of red blood cell transfusion, whereas none of the respondents' personal characteristics were. The average volume of packed red blood cells transfused in the four scenarios did not differ significantly. CONCLUSIONS: This survey documented a significant variation in transfusion practice patterns among pediatric critical care practitioners with respect to the threshold hemoglobin concentration for red blood cell transfusion. The volume of packed red blood cells given was not adjusted to the hemoglobin concentration.
Journal Article↗