Abby Li

Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations

Palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the Canadian Registry Database (CARESS) to aid in developing guidelines for potential “at-risk” infants in the future. Infants who received ≥1 dose of palivizumab during the 2006–2010 respiratory syncytial virus (RSV) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (RI) events were collected monthly. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for premature infants ≤35 completed weeks gestational age (GA) who met standard approval criteria (group 1) compared to those with medical disorders (group 2) using Cox proportional hazards regression models with adjustment for potential confounding factors. Of 7,339 registry infants, 4,880 were in group 1 and 952 in group 2, which included those with Down syndrome (20.3%), upper airway anomalies (18.7%), pulmonary diseases (13.3%), and cystic fibrosis (12.3%). Group 2 were older at enrolment (10.2u2009±u20099.2 vs. 3.5u2009±u20093.1xa0months, pu2009<u20090.0005), had higher GA (35.9u2009±u20096.0 vs. 31.0u2009±u20095.4xa0weeks, pu2009<u20090.0005), and were less compliant with treatment intervals (69.4% vs. 72.6%, pu2009=u20090.048). A greater proportion of group 2 infants were hospitalized for RI (9.0% vs. 4.2%, pu2009<u20090.0005) and RSV (2.4% vs. 1.3%, pu2009=u20090.003) (unadjusted). Being in group 2 was associated with an increased risk of RI (HRu2009=u20092.0, 95%CI 1.5–2.5, pu2009<u20090.0005), but not RSV hospitalization (HRu2009=u20091.6, 95%CI 0.9–2.8, pu2009=u20090.106). In infants receiving palivizumab, those with underlying medical disorders, though not currently approved for prophylaxis, are at higher risk for RI events compared with preterm infants. However, risk of RSV hospitalizations is similar.

A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS)

We examined the dosing regimens, compliance, and outcomes of premature infants who received palivizumab within the Canadian Registry of Palivizumab (CARESS). Infants receiving ≥1 dose of palivizumab during the 2006–2011 respiratory syncytial virus (RSV) seasons were recruited across 30 sites. Respiratory illness events were captured monthly. Infants ≤32 completed weeks gestational age (GA) (Group 1) were compared to 33–35 completed weeks GA infants (Group 2) following prophylaxis. In total, 6,654 patients were analyzed (Group 1, nu2009=u20095,183; Group 2, nu2009=u20091,471). The mean GA was 29.9u2009±u20092.9 versus 34.2u2009±u20092.2xa0weeks for Groups 1 and 2, respectively. Group differences were significant (all p-values <0.05) for the following: proportion of males, Caucasians, siblings, multiple births, maternal smoking, smoking during pregnancy, household smokers, >5 household individuals, birth weight, and enrolment age. Overall, infants received 92.6xa0% of expected injections. Group 1 received significantly more injections, but a greater proportion of Group 2 received injections within recommended intervals. The hospitalization rates were similar for Groups 1 and 2 for respiratory illness (4.7xa0% vs. 3.7xa0%, pu2009=u20090.1) and RSV (1.5xa0% vs. 1.4xa0%, pu2009=u20090.3). Neither the time to first respiratory illness [hazard ratiou2009=u20090.9, 95 % confidence interval (CI) 0.7–1.2, pu2009=u20090.5] nor to first RSV hospitalization (hazard ratiou2009=u20091.3, 95 % CI 0.8–2.2, pu2009=u20090.3) were different. Compliance with RSV prophylaxis is high. Despite the higher number of palivizumab doses in infants ≤32 completed weeks GA, the two groups’ respiratory illness and RSV-positive hospitalization rates were similar.

Hospitalization for respiratory syncytial virus illness in Down syndrome following prophylaxis with palivizumab.

Background: Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children. Methods: CARESS is a prospective registry of children who received ≥1 dose of palivizumab during the 2006–2012 RSV seasons across 32 sites in Canada. The objective was to compare respiratory illness hospitalization and RSV hospitalization (RSVH) hazard ratios in DS children aged <2 years who received palivizumab versus children who received prophylaxis for standard indications (SI) and for other medical illnesses (MI). Results: 13,310 children were enrolled; DS (600; 4.5%), SI (11,081; 83.3%) and MI (1629, 12.2%), with DS children increasing over the duration from 0.1% (2006) to 4.5% (2012). Participants were significantly different in mean birth weight, gestational and enrollment age and risk factors. Children in each group received an average of 4.3u2009±u20091.4 (DS), 4.1u2009±u20091.6 (SI) and 4.5u2009±u20091.4 (MI) palivizumab injections per RSV season, with DS, differing significantly from SI [F(2, 13,307) = 43.6, P = 0.01] but not MI [F(2, 13 307) = 43.6, P = 0.07]. Compliance rates were similar across the groups. While a significantly greater proportion of SI children had RIHs compared with DS, [hazard ratio: 0.64 (0.48–0.84); P = 0.001] hazard ratios were similar for DS and MI. RSVH incidence rates were: 1.53%, 1.45% and 2.27% for DS, SI and MI, respectively. Neither group nor compliance affected time to RSVH. Conclusions: The proportion of DS children who received palivizumab in CARESS has increased almost 45-fold. RSVH rates were low in DS following prophylaxis and hazards were similar to those found in SI and MI.

Adherence to Palivizumab for Respiratory Syncytial Virus Prevention in the Canadian Registry of Palivizumab.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants. Palivizumab, a means of passive prophylaxis, relies on patient adherence to ensure therapeutic effectiveness. The objective of this study is to evaluate the association between adherence and the incidence of RSV-associated outcomes and to identify demographic factors that may impact adherence. Methods: Infants were recruited into the Canadian registry of palivizumab (CARESS) with parental consent. Monthly interviews collected information on palivizumab administration and RSV-associated outcomes. An infant was considered adherent if they received all of their expected injections or ≥5 injections within the appropriate interdose intervals. Results: Nineteen thousand two hundred thirty-five infants received a total of 83,447 injections from October 2005 to May 2014. Adherence was more likely in infants with higher maternal education and in those with siblings. Adherence was less likely in infants of aboriginal descent, with mothers who smoke and older infants. Adherence was significantly associated [odds ratio (95% confidence interval), P value] with a lower incidence of RSV infection [0.74 (0.60–0.93), 0.01] but not with RSV-associated hospitalization. However, in those hospitalized for RSV, adherence was significantly associated with the incidence of intubation and duration of hospitalization, intensive care stay and respiratory support. Conclusions: Adherence may have implications in children with less severe RSV infections and those who are already hospitalized for a RSV infection. Our study also identifies subpopulations that are more likely to be nonadherent to palivizumab therapy. Future studies should aim to validate the relationship among adherence, palivizumab levels and RSV-associated outcomes.

First versus second year respiratory syncytial virus prophylaxis in chronic lung disease (2005-2015).

AbstractChildren aged <2xa0years with chronic lung disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29xa0weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all pxa0<xa00.0005. RIH rates were 12.2 (FY) and 18.2 (SY), and RSVH rates were 2.3 (FY) and 3.9 (SY). Cox regression showed similar hazards for both RIH (hazard ratio 0.9, 95% CI 0.6–1.6, pxa0=xa00.812) and RSVH (hazard ratio 1.1, 95% CI 0.4–2.9, pxa0=xa00.920).n Conclusions: SY and FY children had similar risks for RIH and RSVH. The findings imply that SY children with CLD are correctly selected for palivizumab based on neonatal illness severity and merit prophylaxis.What is Known:• Children with chronic lung disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections.• The American Academy of Pediatrics [2] and the Canadian Paediatric Society [30] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those <32xa0weeks gestation or those in the first year of life who are oxygen dependent or require medical therapy for the treatment of their condition.What is New:• Children with chronic lung disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS).• CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity.

Palivizumab Adherence and Outcomes in Canadian Aboriginal Children.

Background: Aboriginal infants are at risk for serious respiratory infection. Objective: To determine the hazard rate (HR) for respiratory-related illness (RIH) and respiratory syncytial virus (RSV) specific infection hospitalization (RSVH) in Aboriginal versus non-Aboriginal children receiving palivizumab and the effect of adherence on hospitalization. Methods: Palivizumab recipients in the Canadian registry from 2005 to 2014 were included. Adherence was determined by the number of palivizumab doses received during the RSV season and interdose time interval. Adherence proportions between groups were compared by &khgr;2 test. Cox proportional hazard analysis determined the effect of Aboriginal status and adherence on the risk of RIH and RSVH. Results: Aboriginal infants comprised 3.6% (701/19,235) of the registry. HR was 1.6 [95% confidence interval (CI): 1.3–2.0, P < 0.001] and 1.2 (95% CI: 0.7–2.2, P = 0.383) for RIH and RSVH. Aboriginal infants were 62.8% and 63.3% adherent with all recommended injections and within stipulated time intervals, respectively, whereas 81.9% (&khgr;2 = 162.45, df = 1, P < 0.001) and 72.4% (&khgr;2 = 27.35, df = 1, P = 0.002) of non-Aboriginal infants were correspondingly adherent. Only 39.9% of Aboriginals were perfectly adherent (adherent to total number and injection intervals), compared with 61.7% of non-Aboriginals (&khgr;2 = 133.89, df = 1, P < 0.001). Even after adjustment for known risk factors, being Aboriginal and nonadherent was associated with higher RIH hazard (HR = 1.4, 95% CI: 1.1–1.8; HR = 1.3, 95% CI: 1.1–1.4, P = 0.004), respectively. Aboriginals nonadherent with interdose intervals had a 2.2-fold increased HR for RSVH (HR = 2.2, 95% CI: 1.2–4.2, P = 0.015). Conclusions: Prophylaxed Aboriginal infants have a significantly increased RIH and RSVH hazard than non-Aboriginal infants. Improving adherence especially interdose frequency may further reduce hospitalizations in this vulnerable population.

Erratum to: Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations

Erratum to: Eur J Pediatr n nDOI 10.1007/s00431-011-1654-8 n nOn page 835, in the first paragraph of the Utilization and Compliance section, the overall average number of injections should be 3.9u2009±u20091.5, not 3.6u2009±u20091.5. As well, the average injections for Special Populations (Group 2) and Premature Infants (Group 1) were reversed. On average, Special Populations (Group 2) had 4.2u2009±u20091.6 injections and Premature Infants (Group 1) had 3.8u2009±u20091.7 injections. n nIn Figure 2B, the caption is missing the following: “Note: In figure b the solid and dotted lines overlap and appear as a single entity.