Introduction / RSV Season. In This Issue: News in Brief / Notices

Transcription

1 Briitiish Collumbiia RSV IImmunoprophyllaxiis Program Monthlly Newslletter IIssssuuee I 55 FFeebbrruuaarryy Introduction / RSV Season In This Issue: News in Brief p. 1 RSV Season As It Happens p. 2 Abstract & Commentary: Maternal Milk Protects from Bronchiolitis during the First Year of Life p. 3-4 RSV Program & Cardiology by Dr. Derek Human p. 5 Upcoming Dates this RSV Season: News in Brief / Notices Farewell to RSV Research Associate Soon we bid adieu to Alison Butler, who has greatly supported the program as a Research Coordinator for the last year. As you all know, the RSV Program is evidence-based and carefully reviews its outcomes. Following the success at previous PAS meetings, this year we have three accepted presentations at the Pediatric Academic Societies meeting. Alison has been an invaluable part of the work that will be presented. We thank her for all her contributions and wish her Alison Butler, an invaluable member of the team, moves on well in her future endeavours. We are now recruiting a successor to her role in the program, and because all of Alison s accomplishments, as for finding her successor we proudly say we have our work cut out for us! Form Submission FEBRUARY 20 Patient Logs & Hospitalization Data Forms due a note by Marianne Tofan, the RSV Program s Coordinator of Distribution With regards to automatic approvals, whenever possible, please complete and submit both the Application form and the Authorization and Patient Log form together to the RSV Desk. This would simplify and reduce the workload associated with processing the forms. Thank you. This Edition s Award for Clinic Excellence goes to Raandi Nesbitt (of the University Hospital of Northern BC), Leah Samson (coordinator for Saskatewan s RSV patients at Royal University Hospital), and Rose Paulley of Manitoba s clinics, for their amazing work liaising and communicating regarding the transferring of patients to and from clinics. With the intense activity of the past six weeks, we credit you that things went so smoothly and give our thanks! BC RSV Immunoprophylaxis Program Administrative Office: Room B203, 4500 Oak Street; Mailbox 157 Vancouver, BC Canada V6H 3N1 Tel: ; or Fax: ; or [email protected] While every attempt has been made to ensure that the information contained herein is clinically accurate and current, the BC RSV Immunoprophylaxis Program acknowledges that this information may change over time as evidence becomes available. Provincial Health Services Authority, 2014

2 RSV Season As It Happens Figure 1.1 (left): compares RSV seasons by showing trends of RSV+ patients each year. The blue diamonds show the progression of the current, 2013/14 season, using November as week one. The yellow triangles and line indicate how the 2012/13 season progressed from beginning to end, starting on Nov , The pink squares indicate an average season. TABLE 1.2 Pre-Approved Indications Approved Denied Under Review BPD / CLD < 29 weeks weeks Tracheotomy / 0 2 / Vent Multiple of approved patient Total Pre-Approved Adjudicated Indications Approved Denied Under Review Congenital Heart Disease Trisomy 21 (Down Syndrome) Cystic Fibrosis Immunodeficiency Pulmonary Other Total Adjudicated Does not meet criteria, not sent to adjudication Total All TABLE 1.4 Report-Back Process Authorization forms received 341 Authorization forms still requested 14 Not needed (DNMC/Refused, etc.) 62 Percentage received 82% TABLE 1.3 C&W Pharmacy Palivizumab Data Over Time /14.(as of Jan 20) Requests Total Requests Approved Denied % difference in requests from previous year 42% 19% 14% 5% 15% 13% Approval Rate 67% 74% 76% 90% 80% 84% 86% Issue 5: Published February 20, 2014 Provincial Health Services Authority Page 2

3 Maternal Milk Protects against Bronchiolitis during the First Year of Life Results from an Italian Cohort of Newborns M. Lanari and Collaborators on behalf of the Italian Neonatology Study Group of RSV Infections Early Human Development 89S1 (2013) S51 S57 Bronchiolitis is one of the primary causes of hospitalization in infancy. The authors of this study evaluated the effect of breastfeeding on the occurrence of hospitalization for bronchiolitis in the first year of life. Methods: In a prospective cohort study, 1,814 newborns of 33 weeks of gestational age (wga) were enrolled in 30 Italian Neonatology Units and followed-up for 1 year to assess hospitalizations for bronchiolitis. Children were grouped as never breastfed and ever breastfed ; these latter were further divided into those exclusively breastfed breastfed with associated milk formula. At 12 months of age, the risk of hospitalization for bronchiolitis was significantly higher in the never breastfed group (HR: 1.57; 95% CI: ). Breastfed associated with formula milk and exclusively breastfed groups were at similar risk of hospitalization for bronchiolitis. This observed protective effect of maternal milk was not explained by the higher prevalence of conditions able to increase the risk of bronchiolitis among never breastfed newborns. Conclusions: Breastfeeding, even in association and breastfed associated with milk formula. The with formula milk, reduces the risk of risk of hospitalization for bronchiolitis was hospitalization for bronchiolitis during the first evaluated with survival analysis, and hazard ratios (HR) with 95% confidence interval [95% CI] were calculated. year of life. Encouraging breastfeeding might be an effective/inexpensive measure of prevention of lower respiratory tract infections in infancy. Results: Among enrolled newborns 22.9% were never breastfed ; in the breastfed group, 65% were exclusively breastfed and 35% were [Commentary by authors on following page] Issue 5: Published February 20, 2014 Provincial Health Services Authority Page 3

4 Maternal Milk Protects against Bronchiolitis during the First Year of Life Commentary by Authors [Continued from Last Page] This result can be explained by the many properties of maternal milk, some of which are non-specific, while others on the contrary are specific to RSV infection. Basically, breast milk has a direct action against pathogenic agents and an indirect action that is mediated by its capacity of impacting on infant s physiology by modulating mucosal immune responses. We found similar risks of hospitalization for bronchiolitis in children fed exclusively maternal milk or fed a combination of maternal and formula milk, which suggests that the protective effect observed is independent of the amount of maternal milk intake. This result implies that, in the case of RSV infection, a direct passive protection by maternal milk (expected to be dose dependent) is less relevant than an indirect strengthening of the newborn s immune system. Breast milk plays an important role in the establishment of the intestinal microbiota, where bifidobacteria constitute the most characteristic microbial group in breast-fed infants, in contrast to formula-fed infants whose microbiota has a more typically adult-like composition. The predominant bifidobacteria microbiota of breastfed infants reduces the risk of infection probably providing appropriate signals for gut and immune system maturation. The colonization of the infant s intestine by bifidobacteria is favored by lactose and other oligosaccharides present in maternal milk, but also by a direct transfer to the newborn of maternal bifidobacteria through the milk. Compared to formula fed infants, breastfed infants have a larger thymus, which suggests a role of breastfeeding in T cell development and thus in activation and stimulation of the adaptive immune system. Human milk contains specific immune components that might facilitate the development and maturation of the infant immune system. Live activated leukocytes go through the mammary epithelium and are found in milk secretion together with other agents with immunomodulatory properties such as prolactin, anti-idiotypic antibodies, nucleotides, pro- and anti-inflammatory cytokines, IGF and chemokines. In particular, among these immune components of maternal milk, IL-10, IFN-g, transforming growth factor-b (TGF-b) and epidermal growth factor (EGF) can modulate the integrity of the epithelial barrier and induce maturation of the intestinal epithelium. In RSV infection a relevant role is played by inflammatory factors since IL-6, IL-8, IL-10 and macrophage inflammatory 1 a protein (MIP-1-a) were found in nasopharyngeal wash and tracheal aspirate from children with RSV disease. Although also human milk reacts to RSV infection with an inflammatory response (increased levels of proinflammatory mediators IL-6, IL-8, IFN-g) breastfeeding seems to reduce the inflammatory activation induced by RSV infection. Issue 5: Published February 20, 2014 Provincial Health Services Authority Page 4

5 RSV Program and Cardiology The group of infants with hemodynamically significant congenital heart disease is a large and relatively constant population who receive Palivizumab each season, 107, 124 and 120 in each of the last 3 years. With our current approach of early and complete repair of most heart lesions, those receiving prophylaxis are nearly all in the first year of life, and include a relatively large number of infants with complex defects, undergoing multiple procedures as part of a strategy of staged repair. How do we identify those who need prophylaxis? We depend mostly on the nurses in the Cardiac Clinic, the Cardiac Nurse Practitioners, and of course Joyce, who keep a list of the likely candidates, which we then review at the start of the season; more cases will be born and diagnosed during the season, and we also rely on the community Pediatricians to keep us informed of those infants outside of BCCH. The adjudication process for hemodynamically significant heart disease has been quite painless, less than a dozen cases have been refused each year. How do we know that prophylaxis is useful? The original MI-CPO48 study enrolled over 600 infants with CHD, and was completed in July This double-blind controlled study showed a 45% reduction in hospitalization rates for those receiving Palivizumab, and positive secondary endpoints in terms of reductions in length of stay. We looked at BCCH data (remembering that 98% of those admitted with RSV do not meet any of the current criteria for prophylaxis), and compared cardiac admissions in the 5 years before 2003, with the years Our findings were strikingly similar: admissions dropped by 42%, and total by Dr. Derek Human Head, Division of Cardiology Clinical Professor, UBC Department of Pediatrics days admitted dropped by 83%. Is this clinical efficacy also cost effective? Kevin Harris completed this study in 2010*, in which we concluded: Our study is the first economic evaluation of palivizumab in children with CHD in a Canadian context. The clinical effect of palivizumab in our cohort was similar or better than previously published results. 9, 22 However, despite this dramatic clinical effect, the economic evaluation 10, 25 of this program was unfavourable. The cost of the drug is a major concern. In our cohort drug cost was the major contributor to a net cost of nearly 2.5 million dollars over 4 years at a single centre. The clinical effects of palivizumab are dramatic and if the cost-effectiveness can be improved, either through more strict patient selection criteria or reduced drug cost, palivizumab prevention programs should be promoted. We believe that we are targeting the prophylaxis appropriately, and will continue to support efforts to maximize cost Happy PVZ recipient effectiveness in the program. with twin and older sister What is special about the cardiac population? The original MI-CPO48 study showed that palivizumab levels are decreased by nearly 60% after cardiopulmonary bypass, meaning that an infant receiving prophylaxis will need a top-up dose after surgery. The importance of this was brought home to us this past year, when an infant did not get this extra dose, and went on to acquire RSV in the post-operative period, fortunately not severely. Respectfully submitted. * (Harris KC, Anis AA, Crosby MC, Cender LM, Potts JE, Human DG. Economic evaluation of Palivizumab in children with congenital heart disease. Can J Cardiol: 2011; 27:523.ell.e15) Issue 5: Published February 20, 2014 Provincial Health Services Authority Page 5

6 Additional Information News items welcome! News, events, educational pieces, and more Submitted content is welcome, from nurses, clinicians, physicians, or anyone else involved with the RSV Program. If you have a news item you would like included in the next issue, please it to [email protected]. We consider both submissions of full news items or interesting facts. Corresponding pictures or diagrams are welcome. Why did I receive this newsletter? This newsletter is issued to a distribution list of those involved with the BC RSV Immunoprophylaxis Program. If you feel you have received this newsletter in error, or do not wish to receive this newsletter, please send an to [email protected] and you will be removed from the distribution list. Where can I find previous editions of this newsletter? The RSV Program s newsletter is regularly uploaded to the RSV section of the Child Health BC website alongside all program documents. You can access the newsletter at: and all other program resources at: rsv-immuno-prophylaxis-guidelines Corrections? If you believe we have made an error and would like to submit a correction or clarification regarding any content in this edition, or you have any questions or concerns about the content of this newsletter, feel free to contact [email protected] and a correction will be added to the following publication. Please include as much information as possible.....report AN ERROR Contributors Patricia Eastman: Dr. Derek Human: Kyle Mallinson: Dr. Alfonso Solimano: Clinical Editor Head, Division of Cardiology Administrative Editor Medical Director BC RSV Immunoprophylaxis Program Administrative Office: Room B203, 4500 Oak Street; Mailbox 157 Vancouver, BC Canada V6H 3N1 Tel: ; or (toll free) Fax: ; or (toll free) [email protected] While every attempt has been made to ensure that the information contained herein is clinically accurate and current, the BC RSV Immunoprophylaxis Program acknowledges that this information may change over time as evidence becomes available. Provincial Health Services Authority, 2014 Issue 5: Published February 20, 2014 Provincial Health Services Authority Page 6