Bosco Paes

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio‐aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non‐ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 μg) or sidestream jet nebulizer (5 minutes of nebulization with 100 μg/kg) in 10 ventilated (mean birthweight, 1.101 g) and 13 non‐ventilated (mean birthweight, 1,093 g) prematurely born infants. Non‐ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber®). Ventilated infants received aerosol from an MDI + MV15 Aerochamber® or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter‐subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions. Pediatr Pulmonol. 1996; 2:301–309.

Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization and outcomes.

Objective. To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus (RSV) infection. Design. Observational, prospective, longitudinal, multicenter study. Setting. Eighteen hospitals and pediatric clinics located in six provinces across Canada. Patients. Infants enrolled in the palivizumab Special Access Programme of Canada’s Therapeutic Products Programme throughout the 1999 to 2000 RSV season. Most were premature infants born at ≤32 weeks of gestation and/or had bronchopulmonary dysplasia. Methods and main outcome measures. Neonatal and demographic data were recorded for each subject. The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections. Results. There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000. Most subjects received 5 injections with high compliance. Prophylaxis was discontinued in 2% of children. There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children. Eighty-six of these were managed in an outpatient setting, and 30 required hospitalization. The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was 2.4%. Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%). Conclusions. This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings confirm the results of the major randomized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis.

Development and Validation of a Risk Scoring Tool to Predict Respiratory Syncytial Virus Hospitalization in Premature Infants Born at 33 through 35 Completed Weeks of Gestation

Objective. The purpose of the study was to develop and validate a clinical instrument predicting the risk of respiratory syncytial virus (RSV)-associated hospitalization (RSV-H) in premature infants born at 33 through 35 completed weeks of gestation (33—35GA). Design. An RSV risk scoring tool (RSV-RS) was developed by entering risk factors for RSV-H, determined in a Canadian prospective study, into a multiple logistic regression model. The scoring tool was then validated externally with data from a Spanish case-control study (FLIP). The Canadian cohort comprised 1758 RSV-positive infants born 33—35GA, of whom 66 (3.7%) had confirmed RSV-H. The FLIP data set comprised 186 (33.4%) RSV-H cases and 371 (66.7%) controls. Method. The primary outcome measure was RSV-H. The RSV-RS score was the sum of the weighted probabilities for each included risk factor multiplied by 100 and ranged from 0 to 100. Receiver operator characteristic curve analyses determined cutoff points to predict subjects at low, moderate, or high RSV-H risk. Results. The RSV-RS included 7 risk factors and cutoff scores of 0—48, 49—64, and 65— 100 for low-, moderate-, and high-risk subjects, respectively. For the Canadian cohort, RSV-RS sensitivity in predicting RSV-H cases was 68.2%, with 71.9% specificity. With the FLIP data set, the RSV-RS had lower accuracy (61.3% sensitivity; 65.8% specificity) but showed significant positive association with increased risk for RSV-H. Conclusion. The RSV-RS accurately identified 33—35GA infants at increased risk for RSV-H in a Canadian cohort. External validation with Spanish case-control study data further confirmed that the scoring tool is appropriate for the estimation of RSV-H risk.

The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32–35 weeks: a Canadian-based analysis

ABSTRACT Background: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32–35 weeks’ gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown. Objectives: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32–35 weeks’ GA. Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted. Setting: Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis. Participants: Canadian infants born at 32–35 weeks’ GA without chronic lung disease. Interventions: Palivizumab prophylaxis versus no prophylaxis. Main outcome measures: Expected costs and incremental cost–effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars. Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost–effectiveness ratio (ICER) for the base-case scenario was

Closed Suctioning of Intubated Neonates Maintains Better Physiologic Stability: A Randomized Trial

20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than

|[alpha]|2-Macroglobulin Remains as Important as Antithrombin III for Thrombin Regulation in Cord Plasma in the Presence of Endothelial Cell Surfaces

50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range:

Risk-Scoring Tool for respiratory syncytial virus prophylaxis in premature infants born at 33-35 completed weeks' gestational age in Canada.

808–81 331, per QALY). Conclusions: Palivizumab was cost-effective and the authors’ model supports prophylaxis for infants born at 32–35 weeks’ GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool.

Comparison of the cost of hospitalization for respiratory syncytial virus disease versus palivizumab prophylaxis in Canadian Inuit infants.

OBJECTIVE: To evaluate the physiological variance in a closed (CS) vs an open suction (OS) protocol in intubated infants.STUDY DESIGN: Infants were stratified into three weight groups in a randomized crossover trial. Heart rate, respiratory rate, blood pressure, oxygen saturation, transcutaneous oxygen and carbon dioxide, and end-tidal carbon dioxide were recorded prior to suctioning, during suctioning, and recovery to baseline. Following the procedures, recovery time to baseline parameters was measured. Data were analyzed using repeated measures ANOVA.RESULTS: Overall, there was significantly less deviation from baseline physiological parameters with CS. Infants <1000 g had clinically significant decreases in heart rate with the OS method (−18% OS vs −6% CS; p=0.016). Recovery time in the OS group was twice that of the CS cohort (4 vs 2 minutes; p<0.001).CONCLUSION: CS maintains better physiologic stability in intubated infants.

Neonatal Cerebral Sinovenous Thrombosis: Sifting the Evidence for a Diagnostic Plan and Treatment Strategy

ABSTRACT: Infants and children rarely develop thrombotic complications compared with adults, suggesting that there are protective mechanisms in place for the young. Because endothelial cell surfaces regulate thrombin formation and inhibition, we compared thrombin regulation by human umbilical vein endothelial cell surfaces exposed to defibrinated cord and adult plasmas. After activation by either 10% activated partial thromboplastin reagent (strong activator) or coagulant phospholipids (weak activator) the following were measured: free thrombin, thrombin bound to antithrombin III (ATIII), heparin cofactor II, α2-macroglobulin (α2M), and prothrombin concentration. Free thrombin activity was expressed as remaining activity, after subtraction of thrombin-α2M activity. After 10% activated partial thromboplastin reagent, 100% of prothrombin was consumed and significant amounts of thrombin generated by 2 min. Cord plasma generated significantly less thrombin than adult plasma, reflecting the lower initial plasma concentration of prothrombin. Correspondingly, concentrations of thrombin inhibitor complexes were significantly greater in adult plasma than in cord plasma. After coagulant phospholipids, 50% of prothrombin was consumed and negligible thrombin activity measured for both adult and cord plasma. Similar amounts of thrombin inhibitor complexes were formed. ATIII was the predominant inhibitor of thrombin in adult plasma, whereas α2M was as important as ATIII in cord plasma for both activators. When cord plasma concentrations of ATIII were increased to adult values, the proportion complexed to α2M decreased. We conclude that on human umbilical vein endothelial cells, the capacity to generate thrombin is decreased in adult and cord plasmas. Furthermore, α2M is at least as important an inhibitor as ATIII in cord plasma, even in the presence of endothelium.

Are late preterm infants as susceptible to RSV infection as full term infants

ABSTRACT Objective: To study the impact of the Risk-Scoring Tool (RST) as a strategy for targeting prophylaxis effectively in 33–35-week gestational age (GA) Canadian infants who range from low to high risk by evaluating the subsequent incidence of respiratory syncytial virus (RSV) infections resulting in emergency room (ER) visits and hospitalization. Design: Prospective, descriptive study. Setting: McMaster Childrens Hospital and St Josephs Healthcare in Hamilton, Ontario. Participants: Premature infants between 33 and 35 weeks’ completed gestation who were less than 6 months’ chronological age at the start of, or during, the local 2005–2008 RSV winter seasons. Methods: A validated, Canadian RST was used to calculate a total risk score based on seven risk factors. Only infants at moderate (RST score 49–64) and high risk (RST score 65–100) received palivizumab at monthly intervals from November to April and were followed during the respective RSV seasons. All parents received information on RSV prevention at hospital discharge. Parents of all recruited infants were contacted by telephone in May at the end of each season, and medical records were checked to determine ER visits for RSV-related respiratory tract infections and RSV hospitalization. Means, standard deviations, ranges, and percents were used to describe the variables for patients enrolled in the study. Results: Over 3 years, 430 infants were recruited. Of these, 346 (81%), 57 (13%), and 27 (6%) were in the low-, moderate- and high-risk categories, respectively, based on their risk scores. A total of 78 (18.1%) infants received full courses of palivizumab. Six out of 57 (10.5%) infants in the moderate-risk group did not receive prophylaxis, while all 27 high-risk group infants received palivizumab. Seven (1.6%) infants were RSV-positive and five (low-risk) infants were hospitalized. One high-risk, RSV-positive infant, was seen in the ER, and discharged home. There were no statistical differences in the number of infants with RSV-related ER visits and hospitalizations within the risk category groups (p = 0.43). The limitations of this study include the observational design and the relatively small sample size. Conclusions: The RST is a practical, easy-to-use instrument to guide judicious RSV prophylaxis for moderate–high-risk, 33–35-week GA infants. It is cost-effective, reducing hospitalization in infants who are most ‘at-risk’, while avoiding prophylaxis in a large segment (81.9%) of this GA cohort who are considered low risk for RSV infection.