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Association of Broad- Vs Narrow-Spectrum Antibiotics with Treatment Failure, Adverse Events, and Quality of Life in Children with Acute Respiratory Tract Infections

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Association of Broad- Vs Narrow-Spectrum Antibiotics with Treatment Failure, Adverse Events, and Quality of Life in Children with Acute Respiratory Tract Infections Supplementary Online Content Gerber JS, Ross RK, Bryan M, et al. Association of broad- vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. JAMA. doi:10.1001/jama.2017.18715 eTable 1. Diagnosis codes for acute respiratory tract infections eTable 2. Appropriate antibiotics with classification for treatment of acute respiratory tract infections eTable 3. Assessment of balance after full matching for clinical outcomes (n=30086) eTable 4. Odds ratios for clinical outcomes eTable 5. Clinical outcomes, results stratified by diagnosis eTable 6. Prospective patient-centered outcome cohort: Enrolled stratified enrolled and eligible population (n=10,296): patient characteristics of children included in the final cohort compared to children who were not successfully enrolled eTable 7. Prospective patient-centered outcome cohort: Comparison of patient characteristics of children who did and did not complete the 14-20 day interview eTable 8. Assessment of balance after full matching for PedsQL and secondary outcome difficulty sleeping (n=2430) eTable 9. Assessment of balance after full matching for missed school or daycare (n=1901) eTable 10. Assessment of balance after full matching for need additional childcare (n=1891) eTable 11. Assessment of balance after full matching for patient-reported adverse events (n=2085) eTable 12. Assessment of balance after full matching for patient-reported persistent symptoms at day 3 (n=1775) eTable 13. Odds ratios for patient-centered outcomes eTable 14. Patient-centered outcomes, results stratified by diagnosis eText eFigure. Histogram of PedsQL health related quality of life score (n=2430) This supplementary material has been provided by the authors to give readers additional information about their work. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 1. Diagnosis codes for acute respiratory tract infections Diagnosis ICD-9 ICD-10 Acute otitis media 382.00-382.02, 382.4, 382.9 H66.001-H66.019, H66.40- H66.43, H66.90-H66.93 Acute sinusitis 461.0-461.9 J01.00-J01.91 Group A 034.0, 462, 463 J02.0-J02.9, J03.00-J03.91 streptococcal pharyngitis © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 2. Appropriate antibiotics with classification for treatment of acute respiratory tract infections Diagnosis Narrow spectrum antibiotics Broad spectrum antibiotics Acute otitis media Amoxicillin Amoxicillin-Clavulanate Azithromycin Cefdinir Cefprozil Cefuroxime Axetil Acute sinusitis Amoxicillin Amoxicillin-Clavulanate Azithromycin Cefdinir Cefprozil Cefuroxime Axetil Group A Penicillin Amoxicillin-Clavulanate streptococcal Amoxicillin Azithromycin pharyngitis Cefadroxil Cefdinir Cefprozil Cefuroxime Axetil Cephalexin © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 3. Assessment of balance after full matching for clinical outcomes (n=30 086) Acute otitis media Acute sinusitis Pharyngitis Spectrum Spectrum Spectrum Narrow Broad Std. Narrow Broad Std. Narrow Broad Std. Diff Diff Diff Characteristic n=16437 n=2688 n=3400 n=825 n=5953 n=783 Age (years, weighted mean) 3.48 3.56 -0.028 6.08 6.41 -0.095 7.6 7.53 0.03 Male 53.2% 53.2% 0.00 52.2% 53.9%-0.04 49.2% 49.2% 0.00 Race/ethnicity Latino/Hispanic 8.4% 8.6% -0.01 6.1% 4.6%0.07 6.2% 5.8% 0.02 White 61.2% 62.3% -0.02 67.0% 71.7% -0.10 65.7% 66.9% -0.03 Black 13.2% 11.9% 0.04 9.7% 6.9% 0.10 13.2% 11.3% 0.06 Other and mixed race 17.3% 17.2% 0.00 17.2% 16.8% 0.01 14.9% 16.0% -0.03 Public insurance 27.5% 27.5% 0.00 21.5% 18.3% 0.08 24.3% 26.1% -0.04 Season Winter 40.8% 40.4% 0.01 38.3% 38.6%-0.01 31.5% 31.5% 0.00 Spring 25.2% 25.6% -0.01 18.6% 19.8% -0.03 34.1% 32.9% 0.02 Summer 12.9% 12.8% 0.00 13.0% 13.7% -0.02 15.5% 15.3% 0.00 Fall 21.0% 21.2% -0.01 30.1% 28.0% 0.05 18.9% 20.2% -0.03 Visited urban-teaching practice 89.5% 89.0% 0.02 97.2% 96.9% 0.02 84.1% 84.1% 0.00 Clinician Category Physician with <10 yrs 15.0% 15.2% 0.00 10.7% 11.5% -0.02 16.9% 17.3% -0.01 experience Physician with ≥10 yrs 68.0% 67.6% 0.01 78.0% 77.4% 0.02 64.6% 64.0% 0.01 experience Nurse 17.0% 17.3% -0.01 11.3% 11.1% 0.00 18.5% 18.7% 0.00 Prescribed antibiotic ear drops 3.7% 3.7% 0.00 Note: Numbers are weighted percentages except where otherwise noted. Std diff = standardized difference. Pharyngitis was exactly matched on practice type; AOM was stratified by sex and insurance due to sample size © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 4. Odds ratios for clinical outcomes Stratified analysisa Full matched analysisb Outcome n OR (95% CI) n OR (95% CI) Treatment failure, 14 days 22,900 1.02 (0.84, 1.22) 30,086 1.09 (0.90, 1.32) Treatment failure, 30 days 27,305 1.04 (0.92, 1.18) 30,086 1.08 (0.95, 1.22) Adverse events, 14 days 23,375 1.36 (1.13, 1.63) 30,086 1.42 (1.17, 1.72) Adverse events, 30 days 24,333 1.34 (1.14, 1.58) 30,086 1.39 (1.17, 1.66) Abbreviations: CI, confidence interval; OR, odds ratio Note: An odds ratio more than 1.0 means that the broad-spectrum antibiotics had a higher risk of the adverse outcome than the narrow-spectrum antibiotics. aEstimated using conditional logistic regression, conditioning on the diagnosis clinician strata; analysis dropped patients if a strata did not contain both outcomes (i.e. for these dichotomous outcomes, the strata had to include patients who had the event and patients who did not have the event). bIn the full matched analysis, children prescribed narrow-spectrum antibiotics were optimally matched to children prescribed broad- spectrum antibiotics based on a propensity score estimated from patient-level and clinical-level characteristics creating matched sets of difference sizes using all children. Odds ratios were estimated using weighted logistic regression. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 5. Clinical outcomes, results stratified by diagnosis Raw, n (%) Stratified Matched analysisa analysisb Day 14 Diagnosis Broad Narrow Risk difference, % Risk difference, outcomes (95% CI)a % (95% CI)c Treatment AOM 124 (4.6) 614 (3.7) 0.6 (-0.3, 1.5) 0.8 (-0.2, 1.7) failure Sinusitis 15 (1.8) 51 (1.5) -0.1 (-1.1, 0.9) 0.5 (-0.6, 1.6) Pharyngitis 8 (1.0) 144 (2.4) -1.7 (-2.5, -0.9) -1.3 (-2.2, -0.3) Adverse AOM 125 (4.7) 507 (3.1) 1.4 (0.5, 2.2) 1.8 (0.8, 2.7) events Sinusitis 11 (1.3) 61 (1.8) -0.4 (-1.3, 0.6) -0.4 (-1.3, 0.5) Pharyngitis 21 (2.7) 127 (2.1) 0.5 (-0.6, 1.7) 0.1 (-1.1, 1.3) N: AOM 19125 (2688 broad, 16437 narrow), Sinusitis 4225 (825 broad, 3400 narrow), Pharyngitis 6734 (783 broad, 5953 narrow) Note: Outcomes for clinical outcomes were identified in the electronic health record. Treatment failure was defined as an in-person or telephone encounter with the same ARTI diagnosis and a new systemic antibiotic prescription. Adverse events were encounter for candidiasis, non-candida rash, vomiting, diarrhea, other/unspecified allergic reaction, and other/unspecified adverse event. aIn stratified analysis, contrasts were made within diagnosis and clinician strata. Risk differences were estimated using fixed-effects linear regression (first differencing method); diagnosis clinician strata were included as fixed effects bIn the full matched analysis, children prescribed narrow-spectrum antibiotics were optimally matched to children prescribed broad- spectrum antibiotics based on a propensity score estimated from patient-level and clinical-level characteristics creating matched sets of difference sizes using all children. Risk differences were estimated using weighted logistic regression with marginal standardization. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 6. Prospective patient-centered cohort: enrolled and eligible population (n=10,296) - patient characteristics of children included in the final cohort compared to children who were not successfully enrolled No. (%) In cohort Not in cohort Characteristic n=2472 n=7824 Age yrs, mean (standard deviation) 5.0 (3.5) 4.8 (3.5) Male 1275 (52) 4049 (52) Race White 1437 (58) 4662 (60) Black 636 (26) 1486 (19) Asian 66 (3) 336 (4) Other 38 (2) 140 (2) Unknown 295 (12) 1200 (15) Latino Yes 125 (5) 576 (7) No 2344 (95) 7235 (92) Unknown 3 (0) 13 (0) Public insurance 800 (32) 2402 (31) Visited urban-teaching practice 777 (31) 2066 (26) Note: race and ethnicity were obtained exclusively from the EHR; in the analysis of the enrolled cohort race/ethnicity was derived from both the day 14-20 interview and the EHR © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 7. Prospective patient-centered cohort: Comparison of patient characteristics of children who did and did not complete the 14-20 day interview No.
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