Burden of acute otitis media, recurrent otitis media and tympanostomy tube insertion in urban, minority children less than 7 years of age in Boston: Comparison of Pre and Post PCV13 eras Stephen Pelton, MD and Kim Shea, PhD Boston University Schools of Medicine and Public Health

Burden of acute otitis media, recurrent otitis media and tympanostomy tube insertion in urban, minority children less than 7 years of age in Boston: Comparison of Pre and Post PCV13 eras Objective: To evaluate the change in OM disease burden in urban, minority children < 7 yrs. of age, with and without comorbidity, in Boston, MA by comparing AOM, ROM and TT insertion incidence before and after introduction of PCV13*. Add note/focus about comorbidity? We propose to assess the burden of pneumonia in children in the BMC health network and to evaluate the impact of PCV13 introduction on disease incidence and excess risk in children with at-risk and high-risk conditions as defined by 2012 Report of The Committee on Infectious Diseases of the American Academy of Pediatrics (AAP)10 and 2013 recommendations by the Advisory Committee on Immunization Practices. 11 * PCV13 introduced in 2nd quarter of 2010 for all children < 5 years of age Impact of PCV13 vaccination on AOM

NOVEL Study Design and Data Source Impact of PCV13 vaccination on AOM 4 NOVEL Study Design and Data Source Retrospective cohort analysis of children 0-7 years of age who received primary care with the BMC health system between January 1, 2007 – December 31, 2014 Data Source: De-identified electronic medical records included in the Massachusetts Health Disparities Repository (MHDR) Includes patient demographics, visit history, clinical diagnoses, medications, and immunization records

NOVEL Study Design To increase the likelihood the child was part of the practice (and not a transient) a primary care visit was required for each year the child was to be included in the data set [as opposed to ER visit]. A random primary care visit was selected for a given year and the experience with OM events tracked for the subsequent 12 months [this implies that not all OM events are identified as some may have preceded the primary care visit; therefore comparison between years are possible but true incidence is not determined] Outcomes ascertained via physician-entered problem lists and/or ICD-9CM and/or CPT diagnosis codes included in the MHDR OM event frequency was compared for the 2007-2009 and the 2011-2014 time period

AOM Outcomes of Interest: Any AOM Proportion of children with FIRST EPISODE within 12 months of primary care visit AOM episodes occurring within 14 days of a previous diagnosis were assumed to be a follow-up or treatment failure and were excluded Recurrent AOM Identified all children in data base with ROM (3 episodes within 6 months or 4 episodes within 12 months) ROM episodes identified within 12 months after the qualifying primary care visit were included Tympanostomy tube insertion Identify tube insertion within 12 months of qualifying primary care visit

Study population by Year: 2007-2009 vs 2011 vs 2014 No. children 36032 53859 n % <6 months** 7457 15.6 8099 15.0 6<12 months 3473 7.3 3551 6.6 12<24 months 6784 14.2 7228 13.4 24<60 months 18037 37.8 20373 60<84 months 12006 25.1 14608 27.1 Asian 3708 7.8 3922 Black 25013 52.4 26092 48.4 Hispanic 3298 6.9 3218 6.0 White 5700 11.9 5890 10.9 Other 10038 21.0 14737 27.4 Comorbidity 6223 13.0 6690 12.4 No comorbidity 41534 87.0 47169 87.6 Public insurance 35033 74.6 42005 78.8 Private insurance 11906 25.4 11301 21.2

Decline in Proportion of Proportion of urban Boston children with any AOM by year and comparison of prePCV13 (2007-2009) with postPCV13(2011-2014) PCV13 introduced Period % with AOM Decline (%) 95% CI Pre-PCV13 38.5 19.6% (19.1 – 20.1) Post-PCV13 31.0 Decline in Proportion of Children with AOM: 2007-2009 vs 2011-2014

Proportion of Urban Boston Children with AOM by year and age and decline in AOM in children in PCV13 era Year Pre-PCV13 (2007-2009) Post-PCV13 (2011-2014) DECLINE (%) No. children 36032 53859 n AOM n children % <6 months 1249 5543 22.5 1521 8099 18.8 16.7 (15.2-18.1Z) 6<12 months 905 2575 35.1 1101 3551 31.0 11.8 (9.3-14.2) 12<24 months 1420 5146 27.6 1795 7228 24.8 10.0 (8.4-11.6) 24<60 months 2365 13695 17.3 2777 20373 13.6 21.1 (20.3-21.9) 60<84 months 1003 9073 11.1 1148 14608 7.9 28.9 (28.1-29.7) PCV13 Declines observed in ALL AGE GROUPING beginning in 2012

Proportion of Children with Comorbid conditions and List of most common comorbidities Age Comorbidity (%) < 6 mon. 5.3 6 – 11 mon 11.8 12 – 23 mon 10.8 24 – 59 mon 14.2 > 60 mon 16.5 overall 13.6 Comorbidity N % Persistent wheeze/asthma 10930 9.8 Hemoglobinopathy 1407 1.3 Congenital and chronic heart disease 871 0.8 Neuromuscular disorder 686 0.6 Chronic lung disease 615 Diabetes 162 0.15 Congenital immunodeficiency 58 < 0.1 HIV 57 Chronic Renal Disease 32 Liver disease 16 Nephrotic Syndrome 8 Down syndrome 6 Malignancy 2 Neuopathy 1 Prematurity was not included as comorbidity because it is uncommonly carried over after year 2 of life

Proportion of Urban Boston Children with AOM by year and comorbidity and decline in AOM in children with and without comorbidity in PCV13 era Year Pre-PCV13 (2007-2009) Post-PCV13 (2011-2014) DECLINE (%) No. children 36032 53859 n AOM n children % healthy 5884 31311 18.8 7226 47169 15.3 18.5 (17.9-19.0) comorbidity 1058 4721 22.4 1116 6690 16.7 25.6 (24.0-27.1) PCV13 introduced

ROM by year and decline in ROM: 2011-2014 compared to 2007-2009 Pre-PCV13 (2007-2009) Post-PCV13 (2011-2014) DECLINE (%) No. children 36032 53859 number ROM % numberROM Recurrent OM 564 1.6% 529 1.0 37.3 (37.1-37.4)

Proportion of Urban Boston Children with ROM by year and age grouping Pre-PCV13 (2007-2009) Post-PCV13 (2011-2014) DECLINE (%) No. children 36032 53859 n AOM n children % <6 months** 4 5543 0.1 6 8099 +2.7 ( +2.6 - +2.8) 6<12 months 68 2575 2.6 63 3551 1.8 32.8 (32.0-33.6) 12<24 months 227 5146 4.4 234 7228 3.2 26.6 (25.9-27.3) 24<60 months 214 13695 1.6 188 20373 0.9 40.9 (40.7-41.2) 60<84 months 51 9073 0.6 33 14608 0.2 59.8 (59.6-60.0)

Proportion of Urban Boston Children with ROM with and without comorbid conditions and decline in ROM in children in PCV13 era Year Pre-PCV13 (2007-2009) Post-PCV13 (2011-2014) DECLINE N ROM Children % Healthy 395 31311 1.3 415 47169 1 30.3 (30.1-30.4) Comorbidity 179 4721 3.8 109 6690 57.0 (56.4-57.7)

Proportion of Urban Boston Children with Tympanostomy Tube Insertion by year among children with and without comorbidity

Limitations We assumed each child with a primary care visit in a given year remained in the population for at least 12 months; however, some children may stop receiving primary care before the end of their 12- month follow-up period, resulting in under ascertainment of AOM cases We were not able to evaluate the impact of PCV13 on specific pathogens or pneumococcal serotypes PCV13 is potentially only one contributor to the decline in AOM and ROM observed [as there may be unappreciated confounders]. Each child with a primary care visit in a given year is assumed to be part of the annual cohort however

Summary Decline in AOM and ROM in both healthy children and those with comorbid conditions was observed in urban, largely minority children in Boston in 2011-2014 in association with introduction of PCV13. In general that declines were observed across all age groupings The decline in ROM was greater that decline in AOM The decline was observed approximately 2 years after PCV13 introduction 5. It is likely that there are unappreciated confounders that contribute to the decline in addition to PCV13

Acknowledgements Study Team Kimberly Shea Stephen I. Pelton Impact of PCV13 vaccination on all-cause pneumonia IDM Symposium 2017 Acknowledgements Study Team Kimberly Shea Stephen I. Pelton Aaron Legler Laura White Inci Yildirim Emily Welch Funded through an investigator initiated grant from the Thrasher Foundation, and Pfizer Inc.,