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Confidential: For Review Only Examining the effects of excess pre-pregnancy weight and gestational weight gain on allergic disease development in offspring: a protocol for a population-based study using health administrative databases in Ontario, Canada
Journal: BMJ Paediatrics Open
Manuscript ID bmjpo-2020-000893
Article Type: Protocol
Date Submitted by the 29-Sep-2020 Author:
Complete List of Authors: Srugo, Sebastian; University of Ottawa, School of Epidemiology and Public Health Gaudet, Laura; Queen's University, Department of Obstetrics and Gynecology; Kingston Health Sciences Centre, Department of Obstetrics and Gynecology Corsi, Daniel; Ottawa Hospital Research Institute, OMNI Research Group;
University of Ottawa, School of Epidemiology and Public Health http://bmjpaedsopen.bmj.com/ Fakhraei, Romina; Ottawa Hospital Research Institute, OMNI Research Group; Children's Hospital of Eastern Ontario Research Institute Guo, Yanfang; Better Outcomes Registry and Network; University of Ottawa, School of Epidemiology and Public Health Fell, Deshayne B.; University of Ottawa, School of Epidemiology and Public Health; Children's Hospital of Eastern Ontario Research Institute
Keywords: Epidemiology, Obesity, Pathology
on September 25, 2021 by guest. Protected copyright.
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https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 2 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from Running head: MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 TITLE 4 5 Examining the effects of excess pre-pregnancy weight and gestational weight gain on allergic disease 6 development in offspring: a protocol for a population-based study using health administrative databases in 7 8 Ontario, Canada 9 10 Confidential: For Review Only 11 AUTHORS 12 1 1,2,3,4 1,2,5,7 2,5 1,2,5,7 13 Sebastian A. Srugo, Laura Gaudet, Daniel Corsi, Romina Fakhraei, Yanfang Guo, and 14 Deshayne B. Fell1,5,6* 15 16 17 1School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada; 18 19 [email protected] (S.A.S.) 20 2 21 OMNI Research Group, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; 22 [email protected] (D.C.) 23 24 3Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON, Canada; 25 [email protected] (L.G.) 26 27 4Department of Obstetrics and Gynecology, Kingston Health Sciences Center, Kingston, ON, Canada 28 5Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; [email protected] 29 30 (R.F.) http://bmjpaedsopen.bmj.com/ 31 6 32 ICES, Ottawa, ON, Canada 33 7Better Outcomes Registry & Network Ontario, Ottawa, ON, Canada; [email protected] (Y.G.) 34 35 36 *Correspondence to: Dr. Deshayne Fell, Children’s Hospital of Eastern Ontario Research Institute, Centre 37 38 for Practice Changing Research Building, Room L-1154, 401 Smyth Road, Ottawa, ON K1H 8L1, 39 40 Canada; Email: [email protected]; Telephone: +1 613-737-7600 Ext. 6033 on September 25, 2021 by guest. Protected copyright. 41 42 43 Abstract word count: 334 44 Body word count: 2247 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo Page 3 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 ABSTRACT 4 5 Introduction 6 Over the last 20 years, excess maternal pre-pregnancy weight (overweight and obesity) and gestational 7 8 weight gain have become the most common morbidities in pregnancy. These morbidities may pose a 9 threat to fetal immunological development through associated metabolic dysfunction and inflammation 10 Confidential: For Review Only 11 and, as such, may partly explain the concurrent rise of pediatric allergic disease. We will examine the 12 13 effect of excess maternal pre-pregnancy weight and gestational weight gain during pregnancy on the 14 incidence of allergic diseases among offspring in Canada’s most populous province. 15 16 17 Methods and analysis 18 19 We will conduct a retrospective, population-based cohort study of all singleton live births to residents of 20 21 Ontario, Canada in 2012–13 and 2013–14. The study population will be defined using maternal-newborn 22 records from the provincial birth registry, which captures information on maternal pre-pregnancy weight 23 24 and gestational weight gain. The cohort will be linked with provincial health administrative databases, 25 allowing for follow-up of neonates through early childhood until 2019 (5–7 years of age). Allergic disease 26 27 development (asthma, rhinitis, atopic dermatitis, and anaphylaxis) will be ascertained using diagnostic 28 codes from healthcare encounters. Potential confounders have been identified a priori through a directed 29 30 acyclic graph. Cox proportional-hazards regression models will be employed to assess the associations http://bmjpaedsopen.bmj.com/ 31 32 between excess maternal pre-pregnancy weight, gestational weight gain, and incident pediatric allergic 33 disease. Several pre-planned sensitivity analyses will be conducted, including a probabilistic bias analysis 34 35 of outcome misclassification. 36 37 38 Ethics and dissemination 39 40 Ethics approval was obtained from the Research Ethics Board of the Children’s Hospital of Eastern on September 25, 2021 by guest. Protected copyright. 41 Ontario and the ICES Privacy Office. Findings will be disseminated in scientific conference presentations 42 43 and peer-reviewed publications. 44 45 46 Keywords: Pregnancy; Allergic disease; Pre-pregnancy weight; Gestational weight gain; Ontario 47 48 49 50 51 52 53 54 55 56 57 58 59 2 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 4 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 ARTICLE SUMMARY 4 5 What is known on this subject 6 Excess maternal pre-pregnancy weight and gestational weight gain are common morbidities in 7 8 pregnancy and may impact fetal immunological development. 9 10 SeveralConfidential: studies have suggested these morbiditiesFor Reviewincrease the risk of asthma Only among offspring, 11 though their impact on other common allergic diseases is unclear. 12 13 Further, most previous studies have been limited by small sample sizes and self-reported 14 measures of the exposure or outcome. 15 16 17 18 What this study adds 19 This protocol details a large and extensive study to evaluate the impact of maternal pre-pregnancy 20 21 weight and gestational weight gain on several pediatric allergic diseases. 22 23 This study will employ a population-based approach and objective measures, increasing the 24 generalizability and validity of the study findings. 25 26 To ensure the robustness of results, several pre-specified sensitivity analyses will be undertaken 27 to measure the impact of selection biases, residual confounding, and misclassification. 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 3 60 https://mc.manuscriptcentral.com/bmjpo Page 5 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 INTRODUCTION 4 5 In 1997, the World Health Organization declared obesity a global epidemic.1 Since then, excess maternal 6 pre-pregnancy weight (body mass index [BMI]≥25kg/m2) and gestational weight gain (GWG) have 7 8 become the most common morbidities in pregnancy.2,3 A recent analysis of perinatal registry data from 9 four Canadian provinces found that 35–55% of singleton live births are born to overweight or obese 10 Confidential: For Review Only 11 mothers, while 50–66% are born to mothers who exceed GWG recommendations.3 These morbidities are 12 13 associated with metabolic dysfunction and inflammation, which pose a threat to the homeostasis of the 14 fetal compartment and could result in impaired fetal immunological development and increased chronic 15 16 disease susceptibility in later life.2 Therefore, the rise of excess weight and GWG during pregnancy may 17 partially explain the concurrent rise in pediatric allergic disease,4 which is now one of the most common 18 19 and earliest-onset morbidities in childhood.5 One 2016 study conducted in Ontario found that 44% of 20 21 toddlers suffered from food allergies, environmental allergies (wheezing, asthma, eczema, or rhinitis), 22 atopy, or a combination thereof.6 Though one cross-sectional and several longitudinal studies have 23 24 assessed the early-life programming of allergic diseases by maternal weight or GWG, they have been 25 limited by small sample sizes (<1000)7,8 and self-reported measures of the exposure or outcome,7–19 which 26 27 have reduced their generalizability and validity. Further, most have focussed on asthma alone,7–14 none 28 have examined anaphylaxis, and none have calculated risk by the length of follow-up time, opting instead 29 30 8,13,17 7,9–12,14–16,18 for aggregate rates (log-linear model), odds (logistic model), or prevalence ratios (log- http://bmjpaedsopen.bmj.com/ 31 19 32 binomial model). As well, none of these studies have been undertaken in Canada, which has a unique 33 multicultural population. This proposed research will attempt to address these evidence gaps by carrying 34 35 out a large population-based study in Canada’s most populous province. 36 37 38 Aims 39 40 We will assess the impact of excess maternal pre-pregnancy weight (overweight and obesity) and GWG on September 25, 2021 by guest. Protected copyright. 41 on the incidence of childhood allergic diseases (asthma, rhinitis, atopic dermatitis, and anaphylaxis). 42 43 Based on previous literature, we hypothesize that maternal overweight, obesity, and excess GWG will all 44 increase the risk of allergic diseases in offspring, with GWG incurring the greatest risk. This work may 45 46 help inform public health initiatives for high-risk groups and increase early prevention, identification, and 47 treatment of early childhood morbidity. 48 49 50 51 METHODS AND ANALYSIS 52 Design and Setting 53 54 We will conduct a population-based retrospective cohort study of all singleton live births to residents of 55 Ontario, Canada between 1 April 2012 and 31 March 2014, with follow-up of children to 31 March 2019 56 57 58 59 4 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 6 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 (Figure 1). The study will be conducted using multiple linked province-wide health databases within the 4 5 secure network environment of ICES (https://www.ices.on.ca/). This protocol was developed following 6 the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) 7 8 guidelines.20 9 10 Confidential: For Review Only 11 Data Sources and Population 12 13 The birth cohort will be defined using maternal-newborn records from the provincial birth registry, the 14 Better Outcomes Registry & Network (BORN) Information System (BIS). The BIS captures all hospital 15 16 births ≥500g or ≥20 weeks of gestation in Ontario, as well as detailed clinical and demographic 17 information about the birth and the mother. Deterministic and probabilistic methods have been used to 18 19 link the BIS database to health administrative databases at ICES, enabling follow-up of offspring health 20 21 outcomes into early childhood (5–7 years of age). All residents of Ontario are covered by publicly funded 22 universal healthcare and are eligible to access the services captured in the health administrative databases. 23 24 The health administrative databases at ICES to be used in this study include: the Canadian Institute for 25 Health Information (CIHI) Discharge Abstract Database (DAD); the CIHI National Ambulatory Care 26 27 Reporting System (NACRS); the Ontario Health Insurance Plan (OHIP) database; the Ontario Asthma 28 Surveillance Information System (ASTHMA); the Ontario Drug Benefit (ODB) database; the Ontario 29 30 portion of the federal Immigration, Refugees and Citizenship Canada (IRCC) Permanent Resident http://bmjpaedsopen.bmj.com/ 31 32 Database; and the Ontario Marginalization Index (ON-Marg). All data sources and reasons for use are 33 displayed in Figure 2. The study population will be restricted by sample exclusions (non-Ontario resident; 34 35 stillbirth; twin or higher-order multiple birth; mother’s age outside probable range [i.e., <12 years or >50 36 years]; and infant died on date of birth) and administrative exclusions (duplicate records in BORN; 37 38 invalid linkages and linkage warnings; invalid infant and mother identifiers; mothers without continuous 39 40 OHIP eligibility throughout pregnancy; and infants who did not have records of health care eligibility on September 25, 2021 by guest. Protected copyright. 41 within 90 days of birth). Figure 3 displays temporal aspects of the study design relating to eligibility, 42 43 variable measurement, and follow-up; this figure was previously proposed by Schneeweiss and 44 colleagues.21 45 46 47 Exposures 48 49 The primary exposures of interest will be maternal pre-pregnancy BMI and GWG. Ascertainment. Pre- 50 51 pregnancy BMI will be calculated by dividing pre-pregnancy weight (kg) by height (m), squared. For 52 approximately 70% of participants, data on maternal weight will be available from the first prenatal 53 54 screening visit at around 12 weeks of gestation (available from the Prenatal Screening Ontario [PSO] 55 encounter within the BIS database), where it is likely to have been objectively measured. From this, pre- 56 57 58 59 5 60 https://mc.manuscriptcentral.com/bmjpo Page 7 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 pregnancy weight will be estimated by subtracting the typical first trimester weight gain.22 For subjects 4 5 with no record in the PSO database (due to no prenatal screening), maternal pre-pregnancy weight will be 6 captured from the Labour & Birth encounter within the BIS database, where the data may be based on 7 8 either self-report or objective measurement. GWG will be calculated by subtracting maternal pre- 9 pregnancy weight from weight recorded at delivery. Measures. Pre-pregnancy BMI will be classified 10 Confidential: For Review Only 11 according to World Health Organization categories: underweight (<18.5 kg/m2), normal weight (18.5– 12 2 2 2 1 13 24.9 kg/m ), overweight (25.0–29.9 kg/m ) or obese (≥30.0 kg/m ). The Institute of Medicine (IOM) 14 recommendations for weight gain during pregnancy suggest total weight gain for singleton pregnancies 15 16 should not exceed 12.5–18 kg, 11.5–16 kg, 7–11.5 kg, or 5–9 kg based on pre-pregnancy BMI category, 17 respectively.23 However, these recommendations do not account for gestational length. To do so, we will 18 19 follow previously published methods24 to establish expected GWG based on IOM recommendations for 20 21 weight gain by trimester and pre-pregnancy BMI and calculate the ratio of actual to expected GWG. We 22 will then employ the recommended ratio ranges calculated by Guo and colleagues24 to classify GWG into 23 24 three categories: inadequate, adequate, or excess weight gain. These ratio ranges were determined by 25 dividing the lower and upper limits of the IOM GWG recommendations by the expected GWG within 26 27 each pre-pregnancy BMI category. 28 29 30 Outcomes http://bmjpaedsopen.bmj.com/ 31 32 Asthma, rhinitis, atopic dermatitis, and anaphylaxis will be examined separately during follow-up based 33 on International Classification of Diseases (ICD)-9 and ICD-10 diagnostic codes in health administrative 34 35 datasets (DAD, NACRS, and OHIP). ICD codes and algorithms can be found in Supplementary File A. 36 We will employ a time-to-first-event analysis for all outcomes, in which the follow-up period will begin 37 38 at birth and continue until either the outcome occurs, the infant dies or becomes ineligible to receive 39 40 healthcare services (with a 90 day grace period), or until the end of the study period, whichever comes on September 25, 2021 by guest. Protected copyright. 41 first. Follow-up time (person-days) will be calculated for each event separately. Asthma. Using a 42 43 validated algorithm, the ASTHMA database will identify infants with asthma diagnoses. The algorithm 44 requires ≥1 hospitalization and/or ≥2 ambulatory care visits for asthma within two years, where the 45 46 earliest claim is deemed the date of diagnosis.25 The algorithm was first validated among children in 2006 47 (ages 1–8; sensitivity: 91%, specificity: 83%),26 and was recently re-validated in 2019 among younger 48 49 children (ages 1–5; sensitivity: 81%, specificity: 90%).27 Since the accuracy of asthma diagnoses among 50 51 young infants is debated, records fulfilling the algorithm for asthma diagnosis before the age of 6 months 52 will be disregarded unless a further hospitalization or ambulatory care visit for asthma is detected after 12 53 54 months of age.28 Rhinitis and atopic dermatitis. Rhinitis and atopic dermatitis cases will be captured by 55 an algorithm from Hill and colleagues, which requires ≥2 care visits occurring ≥6 months apart and where 56 57 58 59 6 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 8 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 the date of diagnosis is the first visit. These algorithms displayed positive predictive values of 100% and 4 5 90% based on chart review, respectively (no sensitivity or specificity measures were published).29 6 Anaphylaxis. We will employ criteria A and B from the algorithm by Walsh and colleagues30 to detect 7 8 anaphylaxis in inpatient, emergency department, and outpatient encounters using ICD codes for diagnoses 9 and symptoms. In a validation study, this algorithm performed better than those of previous studies, with 10 Confidential: For Review Only 11 a sensitivity of 91% and positive predictive value of 67%.30 Some modifications were made to the 12 13 algorithm for our study, including the removal of the three procedure/intervention codes which are not 14 available in our outpatient dataset and the inclusion of an ICD code for anaphylactic shock due to food 15 16 reaction due its high prevalence in childhood. 17 18 19 Covariates and Confounders 20 21 The following covariates and potential confounders will be examined: maternal characteristics (maternal 22 country of birth [for recent immigrants, otherwise Canada], maternal age at birth, maternal smoking, 23 24 parity, maternal asthma and other pre-existing medical conditions, and use of drugs, alcohol, or 25 medications during pregnancy); neighbourhood characteristics, using residential postal codes linked to 26 27 Census data (neighbourhood marginalization index and rural residence); and birth or infant characteristics 28 (mode of delivery, complications of pregnancy, season of birth, sex of infant, gestational age, birth 29 30 weight, and exclusive breastfeeding at time of hospital discharge). Causal assumptions are presented in a http://bmjpaedsopen.bmj.com/ 31 11,13 32 directed acyclic graph (DAG; Figure 4), adapted from two published DAGs and supplemented for our 33 study through a review of the literature. Before statistical analysis, 10 multiple imputation datasets will be 34 35 generated to deal with missing values. The results from the imputed datasets will be combined to produce 36 final estimates, following best practices.31 37 38 39 40 Statistical Analyses on September 25, 2021 by guest. Protected copyright. 41 Sample characteristics will be presented as frequencies and proportions for categorical variables and 42 43 means or medians for continuous variables (with measures of spread, such as standard deviation or inter- 44 quartile range), overall and stratified by exposure group to present potential confounding.32 Between 45 46 group-differences will be assessed by standardized differences, which denote differences in units of 47 standard deviation. Standardized differences greater than 10% indicate an imbalance between the 48 49 exposure groups.33 Crude incidence rates (per 100,000 person-days of follow-up) for each study outcome 50 51 will be calculated for each exposure group and graphically presented using cumulative incidence curves. 52 53 54 For the primary analyses, Cox proportional-hazards regression models will be employed to produce 55 hazard ratios (HR) with 95% confidence intervals (95% CI). Crude and adjusted analyses (utilizing 56 57 58 59 7 60 https://mc.manuscriptcentral.com/bmjpo Page 9 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 multivariable analysis methods) will assess differences in pediatric allergic disease incidence: 1) between 4 5 infants born to underweight, overweight, or obese mothers compared to those born to mothers with 6 normal pre-pregnancy weight; and 2) between infants born to mothers who fell below or exceeded 7 8 recommended GWG guidelines compared to those who met the GWG recommendation. Models will be 9 adjusted for maternal age, maternal birth country, maternal pre-pregnancy health conditions, maternal 10 Confidential: For Review Only 11 medication and substance use during pregnancy, neighbourhood characteristics, and parity—the minimal 12 13 sufficient adjustment set identified in the DAG (Figure 4). Cox models will account for repeated 14 pregnancies during the 2012–2014 period by adjusting the variance through generalized estimating 15 16 equation (GEE) methods.34 The following effect measure modifiers have been selected a priori: pre- 17 pregnancy BMI (when GWG is the exposure), GWG (when pre-pregnancy BMI is the exposure), and 18 19 infant sex. If estimates between strata are qualitatively different, we will introduce an interaction term or 20 35 21 report strata-specific estimates based on published guidelines. The proportional hazards assumption of 22 the Cox models will be assessed through Schoenfeld residual plots and Wald tests for interaction between 23 24 exposure status and time. All analyses will be conducted using SAS version 9.4 (SAS Institute, Cary, 25 NC). 26 27 28 Pre-planned Sensitivity Analyses 29 30 Assessment of Potential Selection Biases and Residual Confounding http://bmjpaedsopen.bmj.com/ 31 32 1. A complete case analysis will be conducted. 33 2. To understand the impact of exclusion criteria on selection bias, sociodemographic information of 34 35 response, complete-case, and imputed samples will be compared.32 36 3. To account for potential residual confounding by maternal propensity to access healthcare 37 38 services, we will assess typical maternal healthcare utilization through outpatient visits in the 39 40 OHIP database during a one-year look-back period before pregnancy and adjust for this in our on September 25, 2021 by guest. Protected copyright. 41 models. Only mothers who were continuously eligible for OHIP during the look-back period will 42 43 be included. 44 45 46 Assessment of Potential Exposure Misclassification 47 4. To ensure that self-reported maternal weight does not bias our results, a subgroup analysis will be 48 49 undertaken among the subset of participants with pre-pregnancy weight recorded in the prenatal 50 encounter of the BIS database. 51 52 53 Assessment of Potential Outcome Misclassification 54 55 56 57 58 59 8 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 10 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 5. Researchers from Denmark created36 and validated37 algorithms that employ hospital diagnoses 4 5 and dispensed prescription medications to identify cases of rhinitis (sensitivity: 84%, specificity: 6 82%) and atopic dermatitis (sensitivity: 74%, specificity: 73%) in childhood compared to parental 7 8 reports of physician diagnoses. In our study, data on prescription medications dispensed can only 9 be ascertained for the subset of participants who were covered by the provincial drug funding 10 Confidential: For Review Only 11 system (Ontario Drug Benefit, ODB). Residents of Ontario qualify for ODB if they are either ≥65 12 13 years old or are enrolled in one of the following provincial programs: home care and community 14 services, employment assistance, assistance for persons with disabilities, or assistance with 15 16 prescription-drug costs for those in financial need; starting on 1 January 2018, ODB was 17 extended to any resident of Ontario covered by OHIP+: Children and Youth Pharmacare (≤24 18 19 years old). We will run a sensitivity analysis using these derived algorithms for rhinitis and atopic 20 21 dermatitis in the subgroup of children whose families qualified for ODB (see Supplementary File 22 A for algorithms and codes). 23 24 6. We believe that the algorithms employed may result in non-differential outcome 25 misclassification, which usually produces bias towards the null or, in some circumstances, no 26 27 bias.38 A probabilistic bias analysis will be conducted to evaluate the influence of this 28 misclassification, following published methods.39 29 30 http://bmjpaedsopen.bmj.com/ 31 32 PATIENT AND PUBLIC INVOLVEMENT 33 Patients and the public were not involved in the development of the protocol. 34 35 36 ETHICS AND DISSEMINATION 37 38 Approval was obtained from the Research Ethics Board of the Children’s Hospital of Eastern Ontario 39 40 (protocol No 19/14PE) and the ICES Privacy Office (protocol No 2020 0901 237 000). Individual patient on September 25, 2021 by guest. Protected copyright. 41 consent is not required for secondary analyses of routinely collected data, pursuant to privacy legislation 42 43 in Ontario (Personal Health Information Protection Act, 2004). Further, under the same legislation, 44 BORN and CIHI can collect, use, and disclose personal health information without consent. Research 45 46 finding will be disseminated to public health audiences through presentations at scientific conferences and 47 publications in peer-reviewed journals. 48 49 50 51 FOOTNOTES 52 Author Contributions 53 54 55 56 57 58 59 9 60 https://mc.manuscriptcentral.com/bmjpo Page 11 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 Conceptualization—SAS, DBF, RF, LG; Funding acquisition—SAS, DBF, LG; Methodology—SAS, 4 5 DBF, DC, YG, RF, LG; Supervision—DBF, LG; Writing, original draft—SAS; Writing, review & 6 editing—SAS, DBF, RF, DC, YG, LG. 7 8 9 Funding 10 Confidential: For Review Only 11 This work was supported by a Canadian Institutes of Health Research (CIHR) Foundation Grant (grant 12 13 No FDN-148438) to LG, a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship – 14 Master’s Award and an Ontario Graduate Scholarship to SAS, and by ICES, which is funded by an annual 15 16 grant from the Ontario Ministry of Health and Long term Care (MOHLTC). The funders had no role in 17 the study design or manuscript preparation or publication decisions. The opinions, results and conclusions 18 19 reported in this article are those of the authors and are independent from the funding sources. No 20 21 endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material 22 are based on data and/or information compiled and provided by CIHI. However, the analyses, 23 24 conclusions, opinions and statements expressed in the material are those of the author(s), and not 25 necessarily those of CIHI. This Study is based in part on data provided by Better Outcomes Registry and 26 27 Network (“BORN”), part of the Children’s Hospital of Eastern Ontario. The interpretation and 28 conclusions contained herein do not necessarily represent those of BORN Ontario. 29 30 http://bmjpaedsopen.bmj.com/ 31 32 Competing Interests 33 None declared. 34 35 36 Patient consent for publication 37 38 None required. 39 40 on September 25, 2021 by guest. Protected copyright. 41 Ethical Approval 42 43 Research Ethics Board of the Children’s Hospital of Eastern Ontario (protocol No 19/14PE) and the ICES 44 Privacy Office (protocol No 2020 0901 237 000). 45 46 47 Data Sharing 48 49 The data set from this study is held securely in coded form at ICES. While data sharing agreements 50 51 prohibit ICES from making the data set publicly available, access may be granted to those who meet pre- 52 specified criteria for confidential access, available at www.ices.on.ca/DAS. The full data set creation plan 53 54 and underlying analytic code are available from the authors upon request, understanding that the 55 programs may rely upon coding templates or macros that are unique to ICES. 56 57 58 59 10 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 12 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 4 5 REFERENCES 6 1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO 7 consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1–253. 8 9 2. Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse 10 11 consequencesConfidential: for mother and child. BMJ For. 2017;356:j1. Review Only 12 13 3. McDonald SD, Woolcott C, Chapinal N, Guo Y, Murphy P, Dzakpasu S. Interprovincial variation in 14 pre-pregnancy body mass index and gestational weight gain and their impact on neonatal birth 15 weight with respect to small and large for gestational age. Can J Public Health. 2018;109(4):527– 16 38. 17 18 4. Hersoug L-G, Linneberg A. The link between the epidemics of obesity and allergic diseases: does 19 obesity induce decreased immune tolerance? Allergy. 2007;62(10):1205–13. 20 21 5. Prescott SL. Early-life environmental determinants of allergic diseases and the wider pandemic of 22 inflammatory noncommunicable diseases. J Allergy Clin Immunol. 2013;131(1):23–30. 23 24 6. Batool T, Reece PL, Schulze KM, Morrison KM, Atkinson SA, Anand SS, et al. Prenatal and early-life 25 predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis 26 Monitoring In earLY life (FAMILY) Study. J Dev Orig Health Dis. 2016;7(6):665–71. 27 28 7. Halonen M, Lohman IC, Stern DA, Ellis WL, Rothers J, Wright AL. Perinatal tumor necrosis factor-α 29 production, influenced by maternal pregnancy weight gain, predicts childhood asthma. Am J Respir 30 Crit Care Med. 2013;188(1):35–41. http://bmjpaedsopen.bmj.com/ 31 32 8. Pike KC, Inskip HM, Robinson SM, Cooper C, Godfrey KM, Roberts G, et al. The relationship 33 between maternal adiposity and infant weight gain, and childhood wheeze and atopy. Thorax. 34 2013;68(4):372–9. 35 36 9. Reichman NE, Nepomnyaschy L. Maternal Pre-Pregnancy Obesity and Diagnosis of Asthma in 37 38 Offspring at Age 3 Years. Matern Child Health J. 2008;12(6):725–33. 39 40 10. Polinski KJ, Liu J, Boghossian NS, McLain AC. Maternal Obesity, Gestational Weight Gain, and on September 25, 2021 by guest. Protected copyright. 41 Asthma in Offspring. Prev Chronic Dis. 2017;14:E109. 42 43 11. Dumas O, Varraso R, Gillman MW, Field AE, Camargo CA. Longitudinal study of maternal body 44 mass index, gestational weight gain, and offspring asthma. Allergy. 2016;71(9):1295–304. 45 46 12. Scholtens S, Wijga AH, Brunekreef B, Kerkhof M, Postma DS, Oldenwening M, et al. Maternal 47 overweight before pregnancy and asthma in offspring followed for 8 years. Int J Obes. 48 2010;34(4):606–13. 49 50 13. Harskamp-van Ginkel MW, London SJ, Magnus MC, Gademan MG, Vrijkotte TG. A Study on 51 Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory 52 Outcomes in the Amsterdam Born and Their Development Study Cohort. PloS One. 53 2015;10(10):e0140641. 54 55 56 57 58 59 11 60 https://mc.manuscriptcentral.com/bmjpo Page 13 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 14. Patel SP, Rodriguez A, Little MP, Elliott P, Pekkanen J, Hartikainen A-L, et al. Associations between 4 pre-pregnancy obesity and asthma symptoms in adolescents. J Epidemiol Community Health. 5 2012;66(9):809–14. 6 7 15. Harpsøe MC, Basit S, Bager P, Wohlfahrt J, Benn CS, Nøhr EA, et al. Maternal obesity, gestational 8 weight gain, and risk of asthma and atopic disease in offspring: a study within the Danish National 9 Birth Cohort. J Allergy Clin Immunol. 2013;131(4):1033–40. 10 11 Confidential: For Review Only 12 16. Ekström S, Magnusson J, Kull I, Lind T, Almqvist C, Melén E, et al. Maternal body mass index in 13 early pregnancy and offspring asthma, rhinitis and eczema up to 16 years of age. Clin Exp Allergy J 14 Br Soc Allergy Clin Immunol. 2015;45(1):283–91. 15 16 17. Goudarzi H, Konno S, Kimura H, Araki A, Miyashita C, Itoh S, et al. Contrasting associations of 17 maternal smoking and pre-pregnancy BMI with wheeze and eczema in children. Sci Total Environ. 18 2018;639:1601–9. 19 20 18. Drucker AM, Pope EI, Field AE, Qureshi AA, Dumas O, Camargo CA. Association Between 21 Maternal Pre-Pregnancy Body Mass Index, Gestational Weight Gain, and Offspring Atopic 22 Dermatitis: A Prospective Cohort Study. J Allergy Clin Immunol Pract. 2019;7(1):96-102.e2. 23 24 19. Chen Y, Zhu J, Lyu J, Xia Y, Ying Y, Hu Y, et al. Association of Maternal Prepregnancy Weight and 25 Gestational Weight Gain With Children’s Allergic Diseases. JAMA Netw Open. 26 2020;3(9):e2015643. 27 28 20. Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of 29 studies Conducted using Observational Routinely-collected health Data (RECORD) statement. 30 PLoS Med. 2015;12(10):e1001885. http://bmjpaedsopen.bmj.com/ 31 32 21. Schneeweiss S, Rassen JA, Brown JS, Rothman KJ, Happe L, Arlett P, et al. Graphical Depiction of 33 Longitudinal Study Designs in Health Care Databases. Ann Intern Med. 2019;170(6):398–406. 34 35 22. Dayan N, Fell DB, Guo Y, Wang H, Velez MP, Spitzer K, et al. Severe maternal morbidity in women 36 with high BMI in IVF and unassisted singleton pregnancies. Hum Reprod. 2018;33(8):1548–56. 37 38 39 23. Institute of Medicine and National Research Council. Weight Gain During Pregnancy: Reexamining 40 the Guidelines [Internet]. Washington, DC: The National Academies Press; 2009. Available from: on September 25, 2021 by guest. Protected copyright. 41 https://doi.org/10.17226/12584 42 43 24. Guo Y, Miao Q, Huang T, Fell DB, Harvey ALJ, Wen SW, et al. Racial/ethnic variations in 44 gestational weight gain: a population-based study in Ontario. Can J Public Health. 45 2019;110(5):657–67. 46 47 25. Gershon AS, Wang C, Guan J, Vasilevska-Ristovska J, Cicutto L, To T. Identifying patients with 48 physician-diagnosed asthma in health administrative databases. Can Respir J. 2009;16(6):183–8. 49 50 26. To T, Dell S, Dick PT, Cicutto L, Harris JK, MacLusky IB, et al. Case verification of children with 51 asthma in Ontario. Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol. 52 2006;17(1):69–76. 53 54 55 56 57 58 59 12 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 14 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 27. Omand JA, Maguire JL, O’Connor DL, Parkin PC, Birken CS, Thorpe KE, et al. Agreement between 4 a health claims algorithm and parent-reported asthma in young children. Pediatr Pulmonol. 5 2019;54(10):1547–56. 6 7 28. Radhakrishnan DK, Dell SD, Guttmann A, Shariff SZ, Liu K, To T. Trends in the age of diagnosis of 8 childhood asthma. J Allergy Clin Immunol. 2014;134(5):1057-1062.e5. 9 10 29. Hill DA, Grundmeier RW, Ram G, Spergel JM. The epidemiologic characteristics of healthcare 11 Confidential: For Review Only 12 provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: a retrospective 13 cohort study. BMC Pediatr. 2016;16:133. 14 15 30. Walsh KE, Cutrona SL, Foy S, Baker MA, Forrow S, Shoaibi A, et al. Validation of anaphylaxis in 16 the Food and Drug Administration’s Mini-Sentinel. Pharmacoepidemiol Drug Saf. 17 2013;22(11):1205–13. 18 19 31. Sterne JAC, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, et al. Multiple imputation for 20 missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393. 21 22 32. Hayes-Larson E, Kezios KL, Mooney SJ, Lovasi G. Who is in this study, anyway? Guidelines for a 23 useful Table 1. J Clin Epidemiol. 2019;114:125–32. 24 25 33. Austin PC. Using the Standardized Difference to Compare the Prevalence of a Binary Variable 26 Between Two Groups in Observational Research. Commun Stat - Simul Comput. 2009;38(6):1228– 27 34. 28 29 34. Louis GB, Dukic V, Heagerty PJ, Louis TA, Lynch CD, Ryan LM, et al. Analysis of repeated 30 pregnancy outcomes. Stat Methods Med Res. 2006;15(2):103–26. http://bmjpaedsopen.bmj.com/ 31 32 35. Knol MJ, VanderWeele TJ. Recommendations for presenting analyses of effect modification and 33 interaction. Int J Epidemiol. 2012;41(2):514–20. 34 35 36. Henriksen L, Simonsen J, Haerskjold A, Linder M, Kieler H, Thomsen SF, et al. Incidence rates of 36 atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy 37 Clin Immunol. 2015;136(2):360-366.e2. 38 39 40 37. Stensballe LG, Klansø L, Jensen A, Hærskjold A, Thomsen SF, Simonsen J. The validity of register on September 25, 2021 by guest. Protected copyright. 41 data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis. Pediatr 42 Allergy Immunol. 2017;28(6):535–42. 43 44 38. Rothman KJ, Greenland S, Lash TL. Section II: Study Design and Conduct. In: Modern 45 Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. 46 47 39. Fox MP, Lash TL, Greenland S. A method to automate probabilistic sensitivity analyses of 48 misclassified binary variables. Int J Epidemiol. 2005;34(6):1370–6. 49 50 51 52 53 54 55 56 57 58 59 13 60 https://mc.manuscriptcentral.com/bmjpo Page 15 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 4 5 6 Birth years Study end 7 8 9 6–7 years old at end of study period 10 11 Confidential: For Review Only 12 5–6 years old at end of study period 13 14 15 2012–13 2013–14 2018–19 16 17 Figure 1. Length of study period for two two-year birth cohorts. Each birth cohort starts onst April 1st and ends st Figure 1. Length stof study period for two two-year birth cohorts. Each birth cohort starts on April 1 and ends March 31 of the 18 followingMarch calendar 31 ofyear. the following calendar year. 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 14 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 16 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 4 5 6 Better Outcomes Registry & Network (BORN) 7 To define birth cohort and Information System (BIS) include detailed clinical and 8 demographic information about Provincial birth registry; includes clinical and 9 the birth and the mother demographic information from the Prenatal Screening 10 Ontario (PSO) and Labour & Birth encounters 11 Confidential: For Review Only 12 Canadian Institute for Health Information (CIHI) 13 Discharge Abstract Database (DAD) 14 Includes hospital admissions 15 16 CIHI National Ambulatory Care Reporting System 17 To ascertain outcomes from (NACRS) clinical encounters 18 Includes emergency department visits 19 20 Ontario Health Insurance Plan (OHIP) Database 21 22 Includes ambulatory physician visits 23 24 Ontario Asthma Surveillance Information System 25 (ASTHMA) 26 Includes prevalent or incident cases of asthma among 27 Data Sources mothers and offspring 28 29 Ontario Drug Benefit (ODB) 30 Includes dispensed prescription medications for outcome http://bmjpaedsopen.bmj.com/ 31 sensitivity analyses 32 To include additional 33 information on the mother or infant Ontario portion of the federal Immigration, Refugees 34 and Citizenship Canada (IRCC) Permanent Resident 35 Database 36 Includes information on maternal country of birth 37 38 39 Ontario Marginalization Index (ON-Marg) 40 Includes information on economic, ethno-racial, age- based, and social marginalization of the mother’s on September 25, 2021 by guest. Protected copyright. 41 neighbourhood 42 43 44 45 Figure 2. DataFigure sources 2. Data to be sources used atin ICESthis study. to be used in this study. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 15 60 https://mc.manuscriptcentral.com/bmjpo Page 17 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 4 5 6 Maternal Entry Date Infant Entry Date (Last menstrual period) (Date of birth) 7 Day -280 a Day 0 8 9 PREGNANCY 10 Confidential:Exclusion Assessment Window For Review OnlyLEGEND 11 (Administrative and sample exclusions b) 12 Days [-280, -280] Maternal 13 Exclusion Assessment Window 14 (Ineligible to receive health care) Infant 15 Days [-280, 0] 16 Exposure Assessment Window (Pre-pregnancy BMI) 17 Days [-280, -280] 18 Exposure Assessment Window 19 (GWG) 20 Days [-280, 0] 21 Covariate Assessment Window 22 (Maternal characteristics and pre-existing conditions c) 23 Days [-280, -280]
24 Sensitivity Analysis 25 Covariate Assessment Window 26 (Health-care utilization d) Days [-645, -280] 27 28 Exclusion Assessment Window 29 (Not singleton live birth; invalid infant identification code) Days [0, 0] 30 http://bmjpaedsopen.bmj.com/ 31 Exclusion Assessment Window (ineligible to receive health care) 32 Days [0, 60] 33 Covariate Assessment Window 34 (Infant characteristics) 35 Days [0, 0] 36 37 Follow-up Window Days [0, Censor] 38 39 40 Time on September 25, 2021 by guest. Protected copyright. 41 42 Figure 3. Study design and cohort structure. Adapted from Schneeweiss et al, 2019. Abbreviations: BMI, body-mass index; GWG, gestational Figure 3. Studyweight design gain. Numbers and cohort in square structure. brackets Adapted represent from date ranges Schneeweiss relative to et the al date, 2019. of birth Abbreviations: (day 0). BMI, body-mass index; 43 GWG, gestational weight gain. Numbers in square brackets represent date ranges relative to the date of birth (day 0). 44 a For the purposes of illustrating the temporal relationship between maternal and infant study variables, the date of the LMP is shown as day -280 a 45 For the purposes(i.e. 40 completedof illustrating weeks the of gestation). temporal In relationship the study, this between will depend maternal on the actual and infant length ofstudy gestation. variables, the date of the LMP is shown basSample day -280 exclusions (i.e. 40 include: completed non-Ontario weeks resident; of gestation). stillbirth; In twin the or study, higher-order this will multiple depend birth; on mother’s the actual age outside length probable of gestation. range (i.e. <12 46 b Sample exclusionsyears or >50 include: years); andnon-Ontario infant died onresident; date of birth.stillbirth; Administrative twin or higher-order exclusions include: multiple duplicate birth; records mother’s in BORN; age invalidoutside linkages probable and linkage 47 range (i.e.warnings; <12 years invalid or infant >50 andyears); mother and identifiers; infant died mothers on date without of continuousbirth. Administrative OHIP eligibility exclusions throughout include: pregnancy; duplicate and infants records who did innot have records of health care eligibility within 90 days of birth. BORN; invalid linkages and linkage warnings; invalid infant and mother identifiers; mothers without continuous OHIP 48 c Pre-existing maternal conditions are ascertained on delivery record but reflect previous history. 49 eligibilityd Only throughout mothers who pregnancy; were continuously and infants eligible who to receivedid not health have care records (OHIP) of during health the care one-year eligibility period within will be included.90 days of birth. c Pre-existing maternal conditions are ascertained on delivery record but reflect previous history. 50 d Only mothers who were continuously eligible to receive health care (OHIP) during the one-year period will be included. 51 52 53 54 55 56 57 58 59 16 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 18 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 4 5 LEGEND 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32
33 Figure 3. Directed acyclic graph (DAG) of causal assumptions. Adapted from Dumas et al., 2016 and Harskamp-van Ginkel et al., 2015. 34 Figure 4. Directed acyclic graph (DAG) of causal assumptions. Adapted from Dumas et al., 2016 and Harskamp-van Ginkel et 35 al., 2015. 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 17 60 https://mc.manuscriptcentral.com/bmjpo Page 19 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 !%')$&+#!'( )*"+&#&" 25 26 27 'B($A3/<=$:82$/>$392$:4$=>?2A$;3<7:2 28 29 30 &B'$A3/<=$:82$/>$392$:4$=>?2A$;3<7:2 http://bmjpaedsopen.bmj.com/ 31 32 33 #!"#B"$ #!"$B"% #!")B"* 34 35 !$#&%"' ) -395>6$:4$=>?2A$;3<7:2$4:<$>@:$>@:?A3/<$07<>6$1:6:<>= $,/16$07<>6$1:6:<>$=>/<>=$:9$+;<78$"! /92$392=$ 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
BMJ Paediatrics Open Page 20 of 91 Better Outcomes Registry & Network (BORN) To define birth cohort and Information System (BIS) include detailed clinical and 1 Confidential:demographic information about For ReviewProvincial birth registry; includesOnly clinical and 2 the birth and the mother demographic information from the Prenatal Screening 3 Ontario (PSO) and Labour & Birth encounters 4 5 6 Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) 7 8 Includes hospital admissions 9 10 CIHI National Ambulatory Care Reporting System 11 To ascertain outcomes from (NACRS) clinical encounters 12 Includes emergency department visits 13 14 15 Ontario Health Insurance Plan (OHIP) Database 16 Includes ambulatory physician visits 17 18 19 Ontario Asthma Surveillance Information System 20 (ASTHMA)
21 Includes prevalent or incident cases of asthma among http://bmjpaedsopen.bmj.com/ 22 Sources Data mothers and offspring 23 24 Ontario Drug Benefit (ODB) 25 26 Includes dispensed prescription medications for outcome 27 sensitivity analyses 28 To include additional information on the mother or 29 infant Ontario portion of the federal Immigration, Refugees 30 and Citizenship Canada (IRCC) Permanent Resident Database
31 on September 25, 2021 by guest. Protected copyright. 32 Includes information on maternal country of birth 33 34 35 Ontario Marginalization Index (ON-Marg) 36 Includes information on economic, ethno-racial, age- 37 https://mc.manuscriptcentral.com/bmjpobased, and social marginalization of the mother’s 38 neighbourhood 39 40 41 42 Figure 2. Data sources at ICES to be used in this study. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
Page 21 of 91 Maternal Entry Date BMJ PaediatricsInfant Entry Date Open (Last menstrual period) (Date of birth) Confidential:Day -280 a ForDay 0 Review Only 1 2 PREGNANCY
3 Exclusion Assessment Window LEGEND 4 (Administrative and sample exclusions b) Days [-280, -280] 5 Maternal 6 Exclusion Assessment Window (Ineligible to receive health care) Infant 7 Days [-280, 0] 8 Exposure Assessment Window 9 (Pre-pregnancy BMI) 10 Days [-280, -280] 11 Exposure Assessment Window 12 (GWG) 13 Days [-280, 0]
14 Covariate Assessment Window 15(Maternal characteristics and pre-existing conditions c) 16 Days [-280, -280]
17 Sensitivity Analysis
18 Covariate Assessment Window http://bmjpaedsopen.bmj.com/ (Health-care utilization d) 19 Days [-645, -280] 20 21 Exclusion Assessment Window 22 (Not singleton live birth; invalid infant identification code) Days [0, 0] 23 24 Exclusion Assessment Window (ineligible to receive health care) 25 Days [0, 60] 26 Covariate Assessment Window 27 (Infant characteristics)
28 Days [0, 0] on September 25, 2021 by guest. Protected copyright. 29 30 Follow-up Window 31 Days [0, Censor] https://mc.manuscriptcentral.com/bmjpo 32 33 Time 34 35 Figure 3. Study design and cohort structure. Adapted from Schneeweiss et al, 2019. Abbreviations: BMI, body-mass index; GWG, gestational 36 weight gain. Numbers in square brackets represent date ranges relative to the date of birth (day 0). 37 a For the purposes of illustrating the temporal relationship between maternal and infant study variables, the date of the LMP is shown as day -280 38 (i.e. 40 completed weeks of gestation). In the study, this will depend on the actual length of gestation. 39 b Sample exclusions include: non-Ontario resident; stillbirth; twin or higher-order multiple birth; mother’s age outside probable range (i.e. <12 years or >50 years); and infant died on date of birth. Administrative exclusions include: duplicate records in BORN; invalid linkages and linkage 40 warnings; invalid infant and mother identifiers; mothers without continuous OHIP eligibility throughout pregnancy; and infants who did not have 41 records of health care eligibility within 90 days of birth. c Pre-existing maternal conditions are ascertained on delivery record but reflect previous history. 42 d Only mothers who were continuously eligible to receive health care (OHIP) during the one-year period will be included. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
BMJ Paediatrics Open Page 22 of 91 Confidential: For Review LEGENDOnly 1 2 3 4 5 6 7 8 9 10 11 12 13 14 http://bmjpaedsopen.bmj.com/ 15 16 17 18 19 20 21 22 23 24 https://mc.manuscriptcentral.com/bmjpo on September 25, 2021 by guest. Protected copyright. 25 26 27 Figure 4. Directed acyclic graph (DAG) of causal assumptions. Adapted from Dumas et al., 2016 and Harskamp-van Ginkel et al., 2015. 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 23 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 2 Original Algorithm: Gershon et al, 2009 3 Uses ICD-10 4 5 Algorithm Original ICD Code Disease/Disorder Mapped ICD Disease/Disorder 6 ≥1 hospitaliza on J45 Asthma 493Code Asthma 7 and/or ≥2 8 ambulatory care 9 visits for asthma 10 within two years 11 Confidential: For Review Only 12 J46 Status asthma cus 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 BMJ Paediatrics Open Page 24 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Hill et al, 2016 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD Code Disease/Disorder 3 ≥2 care visits occurring ≥6 477 Allergic Rhini s J301–J304 Allergic Rhini s 4 months apart
5 SENSITIVITY ANALYSIS Original Algorithm: Stensballe et al, 2017 6 Uses ICD-10
7 Algorithm Original ICD/DIN Code Disease/Disorder Mapped ICD/DIN Code Disease/Disorder ≥1 hospital contact for: J30 Hay Fever and Allergic Rhini s 477 Allergic Rhini s 8 J30.0 Vasomotor Rhini s J30.1 Allergic Rhini s due to Pollen 9 J30.2 Other Seasonal Allergic Rhini s J30.3 Other Allergic Rhini s 10 J30.4 Allergic Rhini s, Unspecified 11 J31.0Confidential:Chronic Rhini s For Review Only OR ≥2 filled prescrip ons of: Inhaled Cor costeroids for Rhini s Inhaled Cor costeroids for Rhini s Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 12 Excluding: J33 Nasal Polyps 471 Nasal Polyps J330 Polyps in Nasal Cavity 13 J331 Polyp Related Sinus Degenera on 14 J331A Woakes' Ethmoidi s J338 Nasal Polyps, Other 15 J338A Polypus Sinus Sphenoidalis J339 Nasal Polyps, Unspecified 16 J010-J019 Acute Sinusi s 461 Acute Sinusi s J320-J3290 Chronic Sinusi s 473 Chronic Sinusi s 17 OR ≥2 filled prescrip ons of: An histamines for Systemic Use An histamines for Systemic Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 18 Excluding: L29 Pruritus 698 Pruritus and related condi ons L50 Allergic Ur caria 708 Ur caria 19 OR ≥1 filled prescrip ons of: Specific Immune Therapy, Allergen Specific Immune Therapy, Allergen Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 20 Substract Therapy Substract Therapy Medica on for Allergic Conjunc vi s Medica on for Allergic Conjunc vi s Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 Page 25 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Hill et al, 2016 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD Code Disease/Disorder 3 ≥2 care visits occurring ≥6 691 Atopic derma s and related condi ons L20 Atopic Derma s and Related Condi ons 4 months apart 5 SENSITIVITY ANALYSIS Original Algorithm: Stensballe et al, 2017 6 Uses ICD-10 Algorithm Original ICD/DIN Code Disease/Disorder Mapped ICD/DIN Code Disease/Disorder 7 ≥1 hospital contact for: L20 Atopic Derma s 691 Atopic derma s and related condi ons Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 8 Excluding: 691.0 Diaper or Napkin Rash Added this exclusion since L20 doesn't include diaper rash but 691 does 9 OR ≥1 filled prescrip ons of: Agents for Derma s: Tacrolimus, Pimecrolimus Agents for Derma s: Tacrolimus, Pimecrolimus Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Excluding: Exclusion criteria below 10 OR ≥2 filled prescrip ons of Cor costeroids for Topical Use Cor costeroids for Topical Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 11 the code within 12 months: Confidential: For Review Only If above prescrip on is: Cor costeroids, very potent (group IV) Cor costeroids, very potent (group IV) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 12 Then also with either (as Cor costeroids, weak (group I) Cor costeroids, weak (group I) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab atopic derma s is never 13 treated alone with group IV): Cor costeroids, moderately potent (group II) Cor costeroids, moderately potent (group II) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 14 Cor costeroids, potent (group III) Cor costeroids, potent (group III) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Excluding: Exclusion criteria below 15
16 Exclusion Criteria 17 Exclude those without: L20 Atopic Derma s 691 Atopic derma s and related condi ons Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes AND with: L21 Seborrhoeic Derma s 690.1 Seborrheic derma s L22 Diaper Derma s 691.0 Diaper or Napkin Rash 18 L23 Allergic Contact Derma s 692 Contact derma s and other eczema L24 Irritant Contact Derma s 19 L25 Unspecified Contact Derma s L26 Exfolia ve Derma s 695.89 Other Specified Erythematous Condi ons 20 L27 Derma s due to Substances Taken Internally 693 Derma s due to Substances Taken Internally L28 Lichen Simplex Chronicus and Prurigo 698.2, 698.3 Prurigo & Lichenifica on 21 L29 Pruritus 698.0, 698.1, 698.8, Pruritus ani, Pruritus of genitalia, Pruri c 698.9 condi ons NEC & Pruri c disorder NOS 22 L30 Other Derma s 692.9, 705.81, 690.8, Derma s NOS, Dyshidrosis, Erythmtsquamous Removed 'except Winter Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 696.5 derm NEC & Pityriasis NEC & NOS 23 L40 – L45 Papulosquamous Disorders 696.0 - 696.4, 696.8, Psoria c arthropathy, Other psoriasis, 694.3, 697.0, 697.1, Parapsoriasis, Pityriasis rosea, Pityriasis rubra 697.8, 057.8, 709.8 pilaris, Psorias related dis NEC, Impe go 24 herpe formis, Lichen planus, Lichen ni dus, Lichen NEC, Viral exanthemata NEC & Skin 25 disorders NEC L53 Other Erythematosus Condi ons 695.0, 695.89, 695.9 Toxic erythema, Erythematous cond NEC & 26 Erythematous cond NOS L55 Sunburn 692.71, 692.76, 692.77 Sunburn, 2nd degree sunburn & 3rd degree 27 sunburn L56 Other Acute Skin Changes due to Ultraviolet 692.72, 692.82, 692.75, Acute derma s due to solar radia on, Derma s 28 Radia on 692.79 due to other radia on, Disseminated superficial ac nic porokeratosis (DSAP) & Other derma s 29 due to solar radia on L80 Vi ligo 709.01 Vi ligo 30 L90 Atrophic Disorders of the Skin 701.0, 701.3, 701.8, Circumscribe scleroderma, Striae atrophicae, 701.9, 709.2 Other specified hypertrophic and atrophic http://bmjpaedsopen.bmj.com/ condi ons of skin, Unspecified hypertrophic and 31 atrophic condi ons of skin & Scar condi ons and fibrosis of skin
32 L93 Lupus Erythematosus 695.4 Lupus Erythematosus
33 OR ≥1 filled prescrip on of: An psoriasics An psoriasics Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Salicylates for Dermatological Use Salicylates for Dermatological Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 34 Cor costeroids Moderately Potent Other Cor costeroids Moderately Potent Other Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Combina ons Combina ons 35 Cor costeroids Potent Other Combina ons Cor costeroids Potent Other Combina ons Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Cor costeroids (Group IV) Clobetasol Cor costeroids (Group IV) Clobetasol Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 36 Clobetasol and An bio cs Clobetasol and An bio cs Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab AND with: An fungals (implies cor costeroid (group IV) use for An fungals (implies cor costeroid (group IV) use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 37 vaginal fungal infec on) for vaginal fungal infec on) 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 BMJ Paediatrics Open Page 26 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Walsh et al, 2013 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD/CCI Code Disease/Disorder 3 In an inpa ent or 995.0 Other Anaphylac c Shock T78.2 Anaphylac c Shock, Unspecified emergency department 4 encounter (i.e. DAD 5 or NACRS) either: 999.4 Anaphylac c Shock due to Serum T80.5 Anaphylac c Shock due to Serum 995.6 Anaphylac c Shock due to Adverse Food Reac on T78.0 Anaphylac c Shock due to Adverse Food Added this code due to high prevalence food-induced anaphylaxis among 6 Reac on young children. First-author of original paper said that they didn't include the code since they were mostly interested in anaphylaxis due to medica ons, but that the addi on of this code was a good approach if food-induced anaphylaxis 7 was important to our study. 8 T886 Anaphylac c shock due to adverse effect of correct drug or medicament properly 9 administered
10 OR in an outpa ent 995.0 Other Anaphylac c Shock T78.2 Anaphylac c Shock, Unspecified encounter (i.e. OHIP) 11 either: Confidential: For Review Only 999.4 Anaphylac c Shock due to Serum T80.5 Anaphylac c Shock due to Serum
12 995.6 Anaphylac c Shock due to Adverse Food Reac on T78.0 Anaphylac c Shock due to Adverse Food Same comment as above Reac on 13 T88.6 Anaphylac c shock due to adverse effect of correct drug or medicament properly 14 administered AND at least one of: 519.11 Bronchospasm J98.01 Acute Bronchospasm 15 786.1 Stridor R06.1 Stridor 458.9 Hypotension I95.9 Hypotension, Unspecified The three interven on codes in the original algorithm (epinephrine, injec on 16 of diphenhydramine, and CPR) did not have analogous OHIP fee codes. As such, 17 we could not include these in our algorithm. 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 Page 27 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Mapped using the WHO ATC/DDD Index 2020 (h ps://www.whocc.no/atc_ddd_index/) and the ICES DRUGLIST excel 2 Original Name Original ATC Code Drug DIN 3 For Rhini s Algorithm Inhaled R01AD01 – R01AD60 Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 4 Cor costeroids for 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 Rhini s 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 5 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 6 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 00237663 00237698 7 00806994 00807001 01934546 01944819 Prednisolone + combina ons 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00194875 00030739 00030740 00030759 00030767 00031062 8 00386847 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00895962 00194867 00806935 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 9 02063700 02063719 02063727 02230210 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00194859 00021679 00031003 00178926 00210692 00544817 00993610 00813680 00028118 00093602 00250376 00252492 00278912 10 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 Confidential:00961264 01916181 01916203 For 02023768 99100258 Review99100485 99100550 99113742 00042617 00042625Only 00042633 00045632 00177024 00307246 11 00395145 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00218812 00281824 00527998 00760056 00808199 00843741 00903477 02133342 00544833 01924400 12 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 00003603 00007668 00010197 00021687 00021695 00093629 00153710 00156876 00178934 00210188 00232092 00232378 00252417 00271373 00271381 00280852 00312770 00508586 13 00550957 00589194 00598194 00607517 00610623 00868426 00868434 00868442 00901425 00999108 06623833 09857797 09857798 09857799 14 99100988 00154008 00023833 15 Dexamethasone + 00229652 00778907 00016217 00379689 00778915 02252716 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 16 combina ons 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 17 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00140449 00173592 00173606 00228052 01987712 01987720 02224623 02224631 02247920 00285110 00626597 00140732 00042668 18 00042676 00358177 02023806 02023849 00229679 00308455 00617199 00874582 00800767 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 19 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 00016268 20 21 Flunisolide 00421456 00588997 00790486 00878790 01927187 02162687 02230306 02239288 02240956 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 22 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 23 Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 24 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 25 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 26 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 27 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 28 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 29 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 30 95000467 99113736 99900015 http://bmjpaedsopen.bmj.com/ 31 32 xocortol + combina ons 00609110 x Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 33 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 02460513 34 02467895 02467909 02467917 77700002 77700003 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 35 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 36 Triamcinolone § 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 37 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 38 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 39 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 40 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 on September 25, 2021 by guest. Protected copyright. 09857128 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 41 02470632 42 flu casone furoate + 02432889 02446561 02446588 02474522 02408872 02444186 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 43 combina ons 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 44 02298589 02336405 02453738 02460513 02467895 02467909 02467917 77700002 77700003 02240835 02240836 02240837 02245125 02245126 02245127 02474611 02474638 02474646 02494507 02494515 02494523 02495597 02495600 02495619 45 46 ciclesonide None found. 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 BMJ Paediatrics Open Page 28 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 hydrocor sone, combina ons 02242485 00068772 00068780 00243124 00243132 00520322 00666246 00701904 00091820 00662461 00086096 00426350 00568074 00806099 2 00900737 01937979 00578533 00578541 00856711 00768069 00155977 00156175 00163511 00163538 00438669 00704555 00704563 00750670 00763543 00837350 01980572 01980580 02240035 00074489 00074497 00074500 00074527 00193410 00193429 00245399 00338605 00774489 3 00807079 00807087 00807095 00807109 00811467 00091448 00215686 00216828 00521205 00521213 00521221 00449768 00456403 00203378 00445045 00476439 00229679 00387592 00448710 00530085 00530093 00807656 00807664 02226383 02226391 02247882 00173614 00173615 4 00173622 00807621 00813060 01988549 01988573 02223252 02223260 02242527 02242528 02247322 00534838 00534846 02463512 02238578 00209465 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 5 00157880 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 6 00461903 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 7 00740330 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 8 00960535 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 9 66123379 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 10 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00990313 00216941 Confidential:00216968 00216976 00801666 For 00145718 00390748 Review00390798 00068667 00068675 00191282 00243140Only 00243159 00281816 00530611 00626600 11 00666211 00694401 00813559 00912828 01912828 02025736 02230386 00158046 00158178 00443298 00770957 01954210 00192678 00241067 00364134 00681989 00681997 00733083 00895911 02010720 80061502 80073645 80073689 00000671 00016276 00020818 00020826 00024775 12 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 13 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00063312 00063313 00576514 00194883 00194891 00194913 00194921 00194948 00194956 14 00806897 00807346 00363014 00203505 00203513 00395765 00427497 00476226 00476242 00505781 00811513 02234466 02240851 02242797 02247692 00503134 00560022 66894419 80061501 00203483 00319848 00395757 00461717 00476277 00476285 00505773 00511781 00607789 15 An histamines for R06A Bromazine None00811505 found. 00894761 00897434 00898325 00363847 00385700 00404411 00607797 00885738 02128446 02179547 02209764 02210517 02236399 16 Systemic Use Diphenhydramine + 02246449 02246450 02358689 02289407 00022756 00022757 00022764 00022918 00023191 00023205 00130974 00155276 00271411 00304387 17 combina ons 00337404 00337412 00370517 00421197 00439118 00443441 00450839 00479764 00487791 00489867 00504653 00509345 00554294 00556726 00583332 00596612 00610755 00622796 00622818 00728152 00728160 00728162 00754889 00757683 00757691 00792705 00804193 00804401 18 00811432 00833266 00843482 00843490 00878200 00878634 00880043 00960314 01900005 01907034 01933434 01933442 01933450 01934414 01944290 01944347 01946986 01949454 01957996 01959395 01991086 01994247 01997025 02017849 02019671 02019698 02019701 02019728 19 02019736 02019744 02061287 02061597 02087588 02097575 02097583 02141728 02141736 02146142 02153165 02164574 02171279 02176483 02176580 02176883 02210657 02219298 02219336 02229492 02229958 02229959 02229960 02230398 02230485 02237169 02237788 02237789 20 02238644 02239029 02239030 02239138 02239548 02241167 02241734 02244203 02245778 02246936 02247037 02247560 02247659 02247762 02248858 02248859 02249529 02251817 02254425 02254433 02257548 02257556 02258250 02258994 02261286 02263882 02270900 02284170 21 02292734 02297701 02297728 02298503 02304244 02304252 02306352 02309629 02309742 02311232 02311240 02311771 02312352 02312360 02318849 02320789 02321076 02321270 02323346 02328895 02348608 02354578 02361256 02365685 02367939 02368374 02369567 02369656 22 02373300 02376202 02383268 02396599 02401932 02404869 02409224 02409240 02409259 02410214 02411415 02419769 02427427 02431181 02431203 02431599 02432129 02434385 02436884 02436930 02445182 02446170 02447827 02447835 02453711 02456303 02464683 02465108 23 02470144 02474867 02478242 02478757 02479710 02483122 02490943 02491850 02492318 02492326 09850791 09850805 66999121 80757683 88907502 99100522 99101300 99101367 02369672 00633917 00258350 00270695 00362611 00454494 02401193 02410583 02430770 02226626 24 02230939 00173568 00173576 02444593 02278170 02280612 02294354 02323915 00466069 00568473 01944789 02280868 02280876 02301717 02376148 02376156 02429721 02478072 02484838 02424630 02355841 22123333 00286710 02246391 02278693 02167670 02279150 02291371 25 02305666 02416050 02362643 02368528 02384175 02387697 01979124 02383357 02385244 02469960 02469944 02238183 02359944 02385619 02356457 02273934 02275961 02276232 02319195 02322099 02326884 02409178 02413280 02420929 02420937 02423200 02432498 02462265 26 02487233 02487276 02487322 02488574 02490498 02046784 02203424 02215241 02215861 02229367 02230424 02237483 02237707 02239514 02240560 02241043 02241995 02242691 02245017 02248700 02250993 02255472 02256576 02258633 02261014 02263874 02294370 02298171 27 02303833 02305305 02322269 02365766 02366797 02368196 02404974 02438348 00156345 00469122 00503215 00806781 00156337 00361909 00420026 00464686 00535230 00659142 00690074 00792160 02190575 02244010 02245019 02245592 02486903 01905635 02005395 02242999 28 00156264 00361887 00361888 00370975 00710822 00766380 00156086 00156094 00156108 00358452 00358460 00462683 00538493 00609188 29 00730556 01945874 01945882 01962507 01962515 02241462 02246696 02310783 00889865 00156116 30 Clemas ne + combina ons 00035971 00349046 00458570 01925946 00728500 01906577 http://bmjpaedsopen.bmj.com/ 31 Chlorphenoxamine + 00006491 x combina ons 32 Diphenylpyraline + 00492744 00524980 00230200 00425125 00462055 00462071 00412651 00242977 00425133 00425141 00467073 00133264 00449024 00449032 combina ons 00462063 00462039 00462047 00522058 00091626 00091634 00091642 00425168 00214027 00425117 01940783 00763527 00091847 00145815 33 00581771 00299596 00299561 00299588 02422964 02437953 00145963 00213543 00218227 34 Carbinoxamine None found. Doxylamine + combina ons 00134155 00545449 00550477 00749052 02048183 02230769 02244662 02485443 00507407 00713465 01946994 00435619 00134104 00460850 35 00373850 00481394 00609129 00806331 02304503 02406187 02413248 02383365 00566829 02047667 02409542 02410737 01982532 01996215 02198924 02248371 02272792 02291339 02293927 02374277 02378655 02380315 02438305 02449188 02492857 02494027 02276879 02291444 36 02458462 02481928 02482401 02483351 02492865 02493322 00237760 00758558 01900501 02050684 02148315 02218836 02239041 02239061 02241706 02248905 02254913 02254921 02258285 02258625 02258927 02260271 02262320 02272369 02273071 02293242 02298414 02307014 37 02335239 02426315 02427923 02472864 02472872 02368536 02427958 02273810 02380307 02437201 02459876 02240302 02245016 02380404 38 02385260 02383608 02388537 02246847 02253267 02255014 Trimethobenzamide 00012769 00013102 00115568 39 Brompheniramine + 02241814 02241813 00295450 00295469 02245301 01900559 01934724 02243945 00026395 00026484 00172227 00172235 00172537 01932535 combina ons 01932543 01932551 01933582 02052482 02229557 00493082 01934716 02244079 00172545 00656828 01934694 02244078 02215314 00172529 40 00533963 00810711 00933620 01933574 01933620 02243969 02245076 02266466 02266474 02267446 02267454 02315483 02315491 02328658 on September 25, 2021 by guest. Protected copyright. 02468204 00172650 01934708 02244080 01933590 00172383 00172391 00172405 00933647 01932608 01933604 01933647 02012146 02024616 41 02243980 02245075 02266180 02266199 02267411 02267438 02277239 02307316 02315475 02468212 00588229 01933639 02043947 02125714 42 02198916 00342718 00589292 00589306 01934686 Dexchlorpheniramine + 00028142 00028207 00176893 00225533 02273330 43 combina ons 44 Dime ndene None found. Chlorphenamine + None found. 45 combina ons Pheniramine None found. 46 Dexbrompheniramine + 00298433 00616869 00411892 00471348 00746304 00808059 00808253 00810577 00905755 02154285 combina ons 47 Talas ne None found. 48 Mepyramine None found. Histapyrrodine + None found. 49 combina ons Chloropyramine + None found. 50 combina ons 51 Tripelennamine 00005703 00074306 00488461 00584096 00623504 00659673 02239338 Methapyrilene None found. 52 Thonzylamine None found. Alimemazine None found. 53 Promethazine + combina ons 00164291 00385948 01937561 02162199 00164267 00385964 01937545 02162180 00209449 00209457 00232920 00236276 00450561 00450588 00518336 00518344 02043459 02043467 02225654 02225662 00164283 00385956 00811211 01937588 02162172 00164186 01927736 00164259 54 00385972 00811203 01937553 02162164 00025380 00025402 00025046 00025429 00025712 00025739 00164038 00164046 00213896 00236764 00248754 00567434 00575178 00575186 00583979 00627607 00911311 01927566 01937685 01937693 01937707 01937715 01937723 02068591 55 02162156 02162202 02162210 02162229 02162237 99101319 99101320 99101340 56 Thiethylperazine 00027324 00027367 00027510 Methdilazine 00003158 00003514 57 Hydroxyethylpromethazine + None found. 58 combina ons 59 60 https://mc.manuscriptcentral.com/bmjpo2 Page 29 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Thiazinam None found. 2 Mequitazine None found. Oxomemazine None found. 3 Isothipendyl None found. Buclizine + combina ons None found. 4 Cyclizine + combina ons 00068586 00318809 00985562 00318795 00004448 00318817 5 Chlorcyclizine None found. Meclizine + combina ons 00901069 00024724 00216151 00220442 02368838 22123148 66903076 90220442 00158127 00221850 6 Oxatomide None found. Ce rizine 01900978 02315963 02427192 00900986 00980986 01900986 02145782 02145790 02223546 02223554 02231603 02238337 02240265 02240266 7 02240910 02241912 02241913 02295059 02295067 02315947 02315955 02316609 02318873 02318881 02318903 02344572 02355868 02358352 02363844 02364689 02368064 02375087 02375095 02408732 02427133 02427141 02432722 02450526 02451751 02451778 02453363 02466171 8 02467577 02486954 02491125 41900986 9 Levoce rizine None found. Bamipine None found. 10 Cyproheptadine 00009989 00010073 00016314 00016454 00757713 02245667 02245668 02332248 09850775 09991029 Confidential:Thenalidine + combina ons None found. For Review Only 11 Phenindamine None found. 12 Antazoline 00005436 x Triprolidine 00004812 00235768 13 Pyrrobutamine + None found. combina ons 14 Astemizole 00610070 00610089 02182912 02184656 02239669 Terfenadine 00590908 00614394 00641774 00786624 00870927 00881694 00893528 00893536 00893552 01905058 01913395 02034433 02034441 02103575 15 02103621 02103648 02130882 02130890 16 Loratadine 00782696 02019973 02237734 02241523 02242957 02243880 02244691 02244692 02251795 02280159 02284669 02366444 02375990 02379481 02390388 02404494 02418959 17 Mebhydrolin None found. Deptropine None found. 18 Keto fen 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 02231680 02242324 02279223 02400871 02489651 19 99400864 Acrivas ne None found. 20 Azelas ne None found. Tritoqualine None found. 21 Ebas ne None found. Pimethixene None found. 22 Epinas ne None found. 23 Mizolas ne None found. Fexofenadine 02231462 02231463 02237296 02237633 02242818 02242819 24 Desloratadine 02243919 02247192 02247193 02298155 02338424 02408740 Rupatadine 02456451 02456478 25 Bilas ne 02454130 x 26 Quifenadine None found. Sequifenadine None found. 27 Specific Immune V01A Allergen extracts and 00006144 00061379 00061387 00061395 00061409 00061441 00099902 00286273 00286281 00499625 00499633 00499641 00499668 00499676 Therapy, Allergen prepara ons 00504572 00514713 00541427 00541435 00541443 00541451 00541478 00583448 00602752 00602760 00602779 00602787 00602795 00602809 28 Substract Therapy 00603384 00605263 00605298 00605301 00605328 00614424 00662283 00705300 00800227 00861081 00861111 00861138 00861162 00861170 00861189 00861219 00861227 00861251 00861286 00861308 00861316 00861332 00861359 00861367 00861375 00861405 00886831 00886912 29 00886920 00888540 00888559 00888613 00888648 00888656 00888796 00888818 00888826 00888834 00888842 00888850 00888877 00888885 00888893 00888915 00888958 00889601 00889628 00889636 00889644 00889709 00889717 00889725 00889733 00889741 00889768 00889776 30 00889784 00889792 00889814 00889822 00889849 00889857 00894346 00894354 00894362 00894524 00894583 00895245 00895296 00895334 00895423 00895431 00895458 00895466 00896853 00896934 00896942 00896950 00897752 00897817 00898422 00898430 00898449 00898465 http://bmjpaedsopen.bmj.com/ 31 00898473 00898481 00898503 00898511 00898538 00898546 00898589 00898597 00898619 00899828 00899836 00899844 00899852 00899895 00899968 00900702 00900818 00906115 00906271 00907529 00907545 00908614 00911496 00967483 00967823 00969702 00990303 00998885 32 00999900 01948873 01959123 01959131 01959133 01959157 01959158 01959166 01959182 02217104 02223961 02226219 02226251 02226286 02226294 02226928 02226944 02230863 02238472 02238473 02238485 02238497 02241328 02242672 02242713 02242714 02242715 02242716 33 02242717 02247755 02247756 02247757 02325470 02325543 09850724 11135717 14048555 66861073 66889210 66889695 66889830 66894699 66895318 66895326 66969680 66969699 66969818 95000650 99000350 99000407 99000415 99000423 99000431 99000458 99000466 99003651 34 99003678 99003686 99003694 99003708 99003716 99003724 99003732 99003740 99003759 99003767 99003775 99003791 99003805 99003813 99003821 99003848 99003856 99003864 99003872 99003880 99003899 99003902 99003910 99003929 99003937 99003945 99003953 99003961 35 99003988 99003996 99004003 99004097 99004100 99100018 99100062 99100225 99100226 99100227 99100228 99100229 99100230 99100267 99100268 99100269 99100270 99100278 99100279 99100280 99100281 99100282 99100284 99100625 99101105 99101106 99101107 99101108 36 99101109 99101110 99101111 99101112 99101113 99101114 99101115 99101117 99101118 99101119 99101120 99101121 99101122 99101123 99101124 99101125 00350245 00966134 00999652 00999938 00999981 09999938 11044212 99100026 02230860 99100021 02220075 01948903 37 01948911 02239410 02217082 02223953 02223988 02231321 02231322 02369737 01959174 02223996 02231325 02270919 02223937 02223945 02231323 02231324 02369745 01948938 01948946 01948881 01948997 01949004 02242666 00504564 02221314 00286303 00299979 00522457 38 00662275 02372428 02238486 02242674 02238501 02242676 00155233 02230864 99100017 01948970 01948989 00299987 00522465 02372444 00648122 00648922 00464988 02241327 02247754 99000547 02238489 02242670 02217457 02235299 02136074 02217465 02238493 02238494 39 02242668 02238500 01948954 01948962 02220091 02220105 99004607 99100016 99100266 02230862 00605271 02220083 02220113 99004593 40 02247753 02247758 99100061 99100063 99100064 99100065 99100066 99100067 99100068 99100070 99100072 99100073 99100074 99100075
99100076 99100077 99100078 99100079 99100080 99100082 99101141 99101142 99101143 99101144 99101145 99101146 99101147 99101148 on September 25, 2021 by guest. Protected copyright. 41 Medica on for S01GX Cromoglicic acid + None99101149 found. 99101150 99101151 99101153 99101155 00888023 02423723 02242669 02432889 02451778 02467577 02240953 02242675 02447231 Allergic combina ons 42 Conjunc vi s Levocabas ne 01945130 02020017 02123363 02131625 43 Spaglumic acid None found. 44 Nedocromil 00766038 02230543 02229636 02230446 02241407 Lodoxamide 00893560 x 45 Emedas ne 02237355 x Azelas ne None found. 46 Keto fen 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 02231680 02242324 02279223 02400871 02489651 99400864 47 Olopatadine 02233143 02305054 02358913 02362171 02402823 02403986 02404095 02420171 02422727 02458411 02458551 48 Epinas ne None found. Alca adine None found. 49 For derma s algorithm 50 Agents for D11AH Tacrolimus 00903944 00950645 00950653 00960039 00960632 00960634 02175983 02175991 02176009 02243144 02244148 02244149 02296462 02296470 Derma s: 02296489 02331667 02416816 02416824 02416832 02454068 02456095 02456109 02485877 02485885 02485893 09851984 09852069 09852662 51 Tacrolimus, 09854786 66123987 66124086 66990973 99108093 99109293 52 Pimecrolimus Pimecrolimus 02247238 x 53 Cromoglicic acid None found. Alitre noin 02240328 02337630 02337649 02477432 02477440 54 Dupilumab 02470365 02492504 Crisaborole 02476991 x 55 Cor costeroids for D07 Methylprednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 56 Topical Use 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 57 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 58 59 60 https://mc.manuscriptcentral.com/bmjpo3 BMJ Paediatrics Open Page 30 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Hydrocor sone 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 2 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 00461903 3 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 00740330 4 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 5 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 6 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 80071959 7 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 8 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 9 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 10 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 11 Confidential: For Review Only 12 Prednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 13 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 14 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 00278912 00299405 00300373 00301175 00622931 00700401 00727466 15 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 16 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 17 Clobetasone 00456543 00456551 00889938 00889946 00894591 02214415 02214423 18 Hydrocor sone butyrate None found. 19 Flumetasone 00005134 00005789 Fluocor n None found. 20 Fluperolone None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 21 Fluprednidene None found. Desonide 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 00889563 02048639 02115514 02115522 02154862 22 02154870 02229315 02229323 02348489 23 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 24 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 25 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 26 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 27 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 28 Alclometasone 02070855 02070871 29 Hydrocor sone buteprate None found. 30 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 http://bmjpaedsopen.bmj.com/ 31 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 32 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 33 00016268 34 Clocortolone None found. Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 35 02048124 02060868 99100868 00028096 02237835 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 36 00895768 00899291 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 37 02122073 02122081 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 99100521 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 38 00027944 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 39 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 40 00889504 00895873 00895881 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 on September 25, 2021 by guest. Protected copyright. 41 02449773 66887323 66907960 95000467 99113736 99900015 42
43 Fluclorolone None found. Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 44 02221934 02239068 02239069 02241887 66889318 45 Fluocinolone acetonide 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 00464627 46 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 00806951 00862347 47 00862355 00862371 00862398 00873292 00886998 00887005 00887013 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 00895105 00895113 00897868 48 00897884 00897892 00897906 00899976 02129078 02162504 02162512 02162520 02162539 02162547 02163470 02163489 02242738 02300559 49 02306980 66030236 66894257 90716790 99100878 99100879 99100883
50 Fluocortolone None found. Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 51 Fludroxycor de None found. 52 Fluocinonide 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 00908282 53 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 02187663 02187671 02236996 02236997 02240269 22369960 66887102 66887129 66887137 54 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 55 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 56 Diflorasone 00481793 00481807 00889377 00889385 00889407 Amcinonide 00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 00894621 00894656 02052881 02154838 02170175 57 02192268 02192276 02192284 02219719 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 02242542 58 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 02257416 02370557 66894648 59 60 https://mc.manuscriptcentral.com/bmjpo4 Page 31 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Halometasone None found. 2 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 3 Methylprednisolone None found. 4 aceponate 5 Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 6 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 7 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 8 9 Hydrocor sone aceponate None found. Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 10 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 Confidential:02237246 02237247 02241752 For 02243646 02244291 Review02244292 02244293 02248307 02294745 02296071Only 02298589 02336405 02453738 02460513 11 02467895 02467909 02467917 77700002 77700003 12 Prednicarbate 02059754 02227517 02230642 Difluprednate 02415534 x 13 Ulobetasol None found. Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 14 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 15 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 16 02490706 66888389 66895083 Halcinonide 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02010283 02010291 02010305 02011921 02200945 17 66887803 66887811 Prednisolone and an sep cs None found. 18 Hydrocor sone and 00063312 00063313 00449768 00456403 00091448 00215686 00216828 00521205 00521213 00521221 00203378 00534838 00534846 00990313 19 an sep cs 00216941 00216968 00216976 00801666 Flumetasone and an sep cs 00074454 00806870 00806889 20 Desonide and an sep cs None found. 21 Triamcinolone and an sep cs 00128031 00128058 Hydrocor sone butyrate and None found. 22 an sep cs 23 Betamethasone and 00271012 00575194 00611174 00813087 00417254 00417262 00811521 00811548 00586692 00586706 00614270 00682217 02244999 00177016 an sep cs 00813036 00813052 02244766 02238818 02238819 02247446 02244126 02457393 02319012 02474883 00177017 00232352 00807052 24 Fluocinolone acetonide and None found. 25 an sep cs 26 Fluocortolone and an sep cs None found. Diflucortolone and an sep cs 02028719 x 27 Hydrocor sone and 02238578 00445045 00155977 00429090 00807478 02038242 02224542 02242485 00243124 00243132 00520322 00666246 00701904 00156175 28 an bio cs 00163511 00163538 00438669 00704555 00704563 00750670 00763543 00837350 01980572 01980580 00476439 00145718 00390748 00390798 00068667 00191282 00243140 00243159 00666211 00694401 00813559 00912828 01912828 02025736 02230386 00194883 00194891 00194913 29 00194921 00194948 00194956 00806897 00807346 00622249 00068772 00068780 00091820 00203378 00534838 00534846 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 00068675 00281816 00530611 00158046 00158178 00443298 00192678 00241067 30 00885738 00828947 http://bmjpaedsopen.bmj.com/ 31 Methylprednisolone and 00195057 00806919 00806927 00252395 00194867 00806935 00194859 00260428 00880787 00194875 an bio cs 32 Prednisolone and an bio cs 00813680 00195057 00806919 00806927 00194867 00806935 00194859 00177121 00042617 00042625 00042633 00045632 00177024 00307246 00395145 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00218812 00281824 00527998 00760056 00808199 33 00843741 00903477 02133342 00194875 34 Triamcinolone and an bio cs 00128066 00128031 00128058 00184659 00184667 00199850 00245259 00245267 00382620 00433527 00464554 00464562 00464589 00492760 00501107 00562173 00562181 00717002 00717029 00774659 00774667 00806846 00806854 00806862 00808083 00808091 00808105 00808113 35 00808555 00810959 00810975 00811440 00811459 00960101 01999826 01999834 01999842 01999850 00960128 00903365 00960497 66960500 00192627 00128090 00128112 36 Fluprednidene and an bio cs None found. Fluorometholone and 00395153 x 37 an bio cs 38 Dexamethasone and 00778907 00778915 00173592 00173606 00228052 01987712 01987720 02224623 02224631 02247920 00626597 00140732 00042668 00042676 an bio cs 00358177 02023806 02023849 39 Flumetasone and an bio cs None found. Betamethasone and 02474883 x 40 an bio cs on September 25, 2021 by guest. Protected copyright. 41 Fluocinolone acetonide and 00189499 x an bio cs 42 Fludroxycor de and None found. an bio cs 43 Beclometasone and None found. 44 an bio cs Fluocinonide and an bio cs 00492442 00808393 00808407 07090343 45 Fluocortolone and an bio cs None found. Clobetasol and an bio cs None found. 46 Cor costeroids, D07AD Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 very potent (group 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 47 IV) 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 48 02490706 66888389 66895083 49 Halcinonide 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02010283 02010291 02010305 02011921 02200945 66887803 66887811 50 Cor costeroids, D07AA Methylprednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 weak (group I) 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 51 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 52 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo5 BMJ Paediatrics Open Page 32 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 Hydrocor sone 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 2 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 00461903 3 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 00740330 4 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 5 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 6 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 80071959 7 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 8 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 9 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 10 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 11 Confidential: For Review Only 12 Prednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 13 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 14 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 00278912 00299405 00300373 00301175 00622931 00700401 00727466 15 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 16 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 17 Cor costeroids, D07AB Clobetasone 00456543 00456551 00889938 00889946 00894591 02214415 02214423 18 moderately potent 19 (group II) Hydrocor sone butyrate None found. 20 Flumetasone 00005134 00005789 Fluocor n None found. 21 Fluperolone None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 22 Fluprednidene None found. 23 Desonide 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 00889563 02048639 02115514 02115522 02154862 02154870 02229315 02229323 02348489 24 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 25 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 26 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 27 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 28 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 29 30 Alclometasone 02070855 02070871 Hydrocor sone buteprate None found. http://bmjpaedsopen.bmj.com/ 31 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 32 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 33 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 34 00016268
35 Clocortolone None found. Cor costeroids, D07AC Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 36 potent (group III) 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 37 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 38 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 39 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 40 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650
00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 on September 25, 2021 by guest. Protected copyright. 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 41 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 42 95000467 99113736 99900015 43 44 Fluclorolone None found. 45 Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 66889318 46 Fluocinolone acetonide 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 00464627 47 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 00806951 00862347 48 00862355 00862371 00862398 00873292 00886998 00887005 00887013 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 00895105 00895113 00897868 49 00897884 00897892 00897906 00899976 02129078 02162504 02162512 02162520 02162539 02162547 02163470 02163489 02242738 02300559 50 02306980 66030236 66894257 90716790 99100878 99100879 99100883
51 Fluocortolone None found. 52 Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 Fludroxycor de None found. 53 Fluocinonide 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 00908282 54 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 02187663 02187671 02236996 02236997 02240269 22369960 55 66887102 66887129 66887137 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 56 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 57 Diflorasone 00481793 00481807 00889377 00889385 00889407 58 59 60 https://mc.manuscriptcentral.com/bmjpo6 Page 33 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Amcinonide 00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 00894621 00894656 02052881 02154838 02170175 2 02192268 02192276 02192284 02219719 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 02242542 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 02257416 02370557 66894648 3 Halometasone None found. Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 4 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 5 Methylprednisolone None found. 6 aceponate Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 7 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 8 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 9 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 10 Confidential:Hydrocor sone aceponate None found. For Review Only 11 Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 12 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 02460513 13 02467895 02467909 02467917 77700002 77700003 Prednicarbate 02059754 02227517 02230642 14 Difluprednate 02415534 x Ulobetasol None found. 15 An psoriasics D05 Tars 02241506 00023237 00035815 00085871 00086126 00090948 00208132 00238252 00241075 00245631 00246948 00251372 00276456 00280747 00342769 00343447 00358494 00358495 00423203 00426415 00426423 00509310 00517879 00530492 00539063 00577359 00579963 00621137 16 00623237 00632295 00632309 00644994 00645001 00710962 00776415 00810363 00811157 00811165 00812978 00860964 00864706 00875279 17 00894516 00897302 00897361 00899712 00900974 00903450 00905321 00908169 00972339 00982407 00999972 01908855 01918087 01918974 01918982 01918990 01921983 01937642 01937650 01981021 01981293 02143941 02184672 02184680 02220350 02220393 02238310 02238311 18 02238642 02240151 02240152 02240645 02241910 02245737 02246735 02246736 02246802 02246974 02293978 02307146 02392046 02403854 02439085 02439093 02448963 02458837 66899704 66901032 66903256 88901121 00090905 00249866 00329231 00344508 00419133 00489271 19 00501832 00505765 00632260 00632279 00770428 00810401 00810428 00067229 00157562 00234206 00167800 00167819 00351881 00625280 00810886 00899704 02023075 00961043 01931121 02230134 00659703 00773492 00288640 00784753 01931237 01931245 01932446 01942379 20 02285703 02285711 02432366 02432439 00509302 00090891 00632244 01936980 02106299 00800694 00866601 00550434 00812226 00379727 00594792 00628042 00807133 00811076 00812889 02240942 01981307 02403862 00344494 00509906 00510335 00560448 00744298 00748269 21 00894508 00181757 00208205 00232890 00362204 00444448 00525383 01909118 01981315 02030462 02403846 00266493 00332801 00373222 00506966 00652326 00740314 01909185 00090913 00091006 00579955 00579971 00234141 00907308 22 23 Dithranol + combina ons None found. 24 Trioxysalen 00331171 01966383 Methoxsalen 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 01907476 01946374 02406233 09852247 09852905 25 09991125 22123043 49007269 99100699 99100916 99100917 99100918 26 Fumaric acid None found. Calcipotriol 01971633 x 27 Calcitriol 02338572 00481815 00481823 00824291 00891738 00891746 02245686 02245687 02399334 02399342 02431637 02431645 02485710 02485729 02495899 02495902 28 Tacalcitol None found. Tazarotene 02230784 02230785 02243894 02243895 29 Calcipotriol + combina ons None found. 30 Methoxsalen 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 01907476 01946374 02406233 09852247 09852905 09991125 22123043 49007269 99100699 99100916 99100917 99100918 http://bmjpaedsopen.bmj.com/ 31 Bergapten None found. Etre nate 00616400 00616419 66123914 32 Acitre n 02070847 02070863 02080863 02466074 02466082 02468840 02468859 Fumaric acid deriva ves + None found. 33 combina ons 34 Salicylates for D02AF Salicylic acid prepara ons 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 Dermatological 00813346 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 02248196 02248197 66903051 80027681 35 Use 00961043 01931121 02230134 00181757 00208205 00232890 00362204 00444448 00525383 01909118 01981315 02030462 02403846 00266493 00234141 00907308 00075973 00203297 00208175 00208183 00232882 00355607 00428752 00506974 00534854 00739316 00807958 00810312 36 00810320 00810991 00972584 01909096 01988239 00180076 Cor costeroids D07XB Flumetasone 00005134 00005789 37 Moderately Potent 38 Other Combina ons 39 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 40 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 on September 25, 2021 by guest. Protected copyright. 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 41 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 42 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 43 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 44 45 Fluprednidene None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 46 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 47 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 48 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 49 00016268 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo7 BMJ Paediatrics Open Page 34 of 91 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 Cor costeroids D07XC Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 2 Potent Other 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 Combina ons 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 3 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 4 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 5 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 6 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 7 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 8 95000467 99113736 99900015 9
10 Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 Confidential:02221934 02239068 02239069 For 02241887 66889318 Review Only 11 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 12 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 13 Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 Fluocortolone None found. 14 Cor costeroids D07AD01 Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 (Group IV) 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 15 Clobetasol 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 16 02490706 66888389 66895083 17 An fungals D01 Nysta n 00014850 00014974 00029319 00029416 00248169 00248170 00270113 00282219 00779121 00785709 00792667 00894834 00894893 00895210 (implies 00898953 00903212 00904479 00984671 02125145 02194198 02194201 02229852 02238544 02433443 09850457 09857764 40079266 49248169 18 cor costeroid 66898929 66907472 66988170 00015067 00029092 00029491 00029556 00270091 00278793 00288195 00288209 00288217 00295973 00382639 (group IV) use for 00422592 00444383 00449792 00449806 00480819 00510297 00522864 00716871 00716898 00716901 00811084 00870552 00870560 00882607 19 vaginal fungal 00885126 00888761 00908053 00912972 00929092 00985074 00999954 00999958 02004674 02194163 02194171 02194228 02194236 02195704 20 infec on) 09852921 09857765 09857767 50237469 66908061 99113755 99900006 00464597 00811091 00885096
21 Natamycin None found. Hachimycin None found. 22 Pecilocin None found. 23 Mepartricin None found. Pyrrolnitrin None found. 24 Griseofulvin 00012246 00012254 00012262 00028266 00028274 00028282 00513229 00513237 00901061 02100266 02100274 02100282 09991069 99100253
25 Clotrimazole 00903037 00903061 00001403 00139035 00325465 00325473 00353833 00420301 00513903 00513904 00513911 00513938 00513946 00516805 00516806 00516813 00516821 00516848 00567388 00576492 00629243 00731307 00731707 00759457 00810045 00810967 00812366 00812374 26 00812382 00874043 00874051 00874078 00895571 00895598 00896845 00898112 00899046 00899054 00899399 00901412 00903184 00904279 00908045 00908495 02029480 02029499 02029502 02029510 02126818 02126826 02130203 02130211 02130238 02130254 02130262 02130920 27 02131633 02131641 02131668 02131676 02150667 02150832 02150840 02150859 02150867 02150875 02150883 02150891 02150905 02150921 02150948 02180723 02229378 02229379 02229380 02230447 02230509 02232395 02236746 02239432 02240847 02264099 02264102 02311720 28 02462397 02490927 49812382 66894788 66999474 99113693 99113695
29 Miconazole 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 00685917 00771035 00771036 00807605 00807613 30 00895237 00895628 00900958 00980617 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 02231533 02239600 02239601 02244005 02245546 66894796 http://bmjpaedsopen.bmj.com/ 31 92085852 95003840 95023947 Econazole 00452114 00561002 00895997 02010267 02011948 32 Chlormidazole None found. Isoconazole None found. 33 Tiabendazole None found. 34 Tioconazole 00657395 00791725 02095009 02095017 02095025 02171902 02171910 02217406 02218283 02218291 02241700 Ketoconazole 00967343 00633836 00788813 00903341 02122197 02231061 02237235 02237882 00703974 00803588 02182920 02245662 02292661 35 Sulconazole None found. Bifonazole None found. 36 Oxiconazole 02230452 02230453 37 Fen conazole None found. Omoconazole None found. 38 Sertaconazole None found. Fluconazole 00891800 00891819 00891827 00891835 00891900 00901418 02024152 02091216 02091372 02091380 02141442 02236978 02236979 02236980 39 02237370 02237371 02237372 02241895 02243645 02245292 02245293 02245294 02245643 02245644 02245697 02246108 02246109 02246620 02246942 02247749 02247922 02248443 02248731 02249294 02249308 02249316 02255510 02261472 02271516 02273632 02273640 02273659 40 02281260 02281279 02282348 02282453 02287242 02287250 02287269 02294036 02294044 02301938 02301946 02301954 02309432 02310686 02310694 02311690 02312686 02312694 02323419 02336162 02339560 02340038 02340046 02340798 02340801 02340828 02352133 02357496 on September 25, 2021 by guest. Protected copyright. 41 02378302 02388448 02428792 02432471 02433702 02462168 22123126 22123127 99101272 42 Flutrimazole None found. 43 Eberconazole None found. 44 Luliconazole None found. Efinaconazole 02413388 x 45 Imidazoles/triazoles in 00611174 00813087 02244766 combina on with 46 cor costeroids Miconazole + combina ons 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 00685917 00771035 00771036 00807605 00807613 47 00895237 00895628 00900958 00980617 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 02231533 02239600 02239601 02244005 02245546 66894796 48 92085852 95003840 95023947 02382628 49 Bifonazole + combina ons None found. Bromochlorosalicylanilide None found. 50 Methylrosaniline None found. Tribromometacresol None found. 51 Undecylenic acid + 00240664 00829315 02222736 02239048 02243662 80041595 80041596 80043930 00240656 00030163 00030201 00373443 00373478 00376906 52 combina ons 00519898 00595926 00829145 00829153 00829307 00864137 00864145 02021838 02021846 02021862 02021900 02021919 02154552 80041594 00373451 00829285 02021803 00228796 00374598 00484334 00501840 00146013 00522074 00145661 00145831 00213497 00464651 53 Polynoxylin None found. 54 2-(4-chlorphenoxy)-ethanol None found. 55 Chlorphenesin 00253065 00253073 02089637 02091496 Ticlatone None found. 56 Sulben ne None found. Ethyl hydroxybenzoate None found. 57 Haloprogin 00291021 00291048 00800953 01910094 01910108 58 59 60 https://mc.manuscriptcentral.com/bmjpo8 Page 35 of 91 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Salicylic acid 00187542 00438294 00636347 00685186 00740292 00764361 00766216 00766240 00805300 00807583 00896063 00900796 00967548 00967556 2 00968978 00990141 00990244 00999036 00999081 01908553 01908561 01914847 01915185 01930575 01939513 01939521 01947451 01947494 01978861 01999540 02015358 02025868 02044412 02044471 02047403 02069725 02074257 02074265 02139073 02139081 02147076 02147114 3 02156172 02163055 02199009 02199017 02221349 02222442 02227266 02230960 02230961 02230963 02231101 02231619 02236775 02236983 02237796 02238309 02238314 02238418 02238573 02238815 02238816 02239079 02240447 02240758 02240763 02240902 02240903 02241153 4 02241420 02243321 02243578 02243590 02243615 02243939 02244191 02244449 02245611 02245763 02245873 02245984 02246380 02246604 02246681 02246710 02246712 02247218 02248036 02248585 02248586 02248587 02248711 66898848 66900788 66900818 66900893 66901164 5 80002908 80005358 80006363 80007324 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 00813346 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 6 02248196 02248197 66903051 80027681 00764310 02211203 02231218 02243011 02245989 02247262 00075914 00075957 00273104 00281891 00555967 00652342 00652350 02149044 02149052 02240107 00792020 00794759 02032945 00230081 00465976 00903371 01915177 02047764 7 02230957 02230959 02241590 80005624 80008630 80011794 80073326 66908029 00307580 00307904 00355828 00355895 00413356 00413372 00454893 00505978 00609501 00614246 00625353 00690333 00740276 00754951 00813044 00815861 00837733 00889598 00895059 00895067 8 00895075 00895083 00895091 00899372 00906018 00987034 01909029 01909037 01909134 01911384 01914456 01915258 01918729 01929429 01939645 01948156 01967878 01974335 01977725 01981463 02022915 02035553 02050285 02050293 02060493 02123045 02223821 02229957 9 02229990 02230131 02230132 02230691 02231570 02237019 02239055 02239299 02240322 02241129 02241465 02241621 02241738 02243332 10 02244054 02244850 02245445 80063216 00903056 00999082 11 Confidential: For Review Only Selenium sulfide 00243000 00353809 00418293 00443581 00457086 00457094 00483788 00483796 00594601 00709069 00808466 00811181 01950487 01951653 12 02242871 02245007 13 Ciclopirox 00001516 02250535 02349086 02353288 02410346 02413574 00593362 00811688 00836281 00895741 01987569 01989626 02221802 02221810 02247228 02298953 49593362 14 Terbinafine 02242735 02254727 02320134 02352818 02353121 02357070 02385279 02299275 09991323 00903384 02031108 02031116 02239893 02240345 02240346 02240807 02242503 02247530 02262177 02262924 02286580 02294273 02297973 02320126 02341190 02343452 02352796 02363836 15 02372762 02031094 02238703 02239876 02241815 02241816 02248845 02332612 16 Amorolfine None found. Dimazole None found. 17 Tolna ate 00027936 00027960 00028088 00415782 00458163 00549185 00576026 00576034 00576042 00576050 00576057 00596361 00614211 00614238 00658731 00716928 00810584 00810592 01918826 01919245 01942263 01942573 01942581 02029081 02078341 02220733 02226707 02239066 18 02239497 02240064 02243064 02243663 02244939 02295873 02311801 02319276 02319314 02375397 02378248 02380765 02396785 02401584 19 02413760 02417715 02431718 02434113 02475324 02476703 02480166 Tolciclate + combina ons None found. 20 Flucytosine 00990256 66123998 00384895 66128023 66124323 Na ifine 02011255 02011263 21 Butenafine 02231063 02238762 02244312 22 Tavaborole None found. 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo9 BMJ Paediatrics Open Page 36 of 91
1 2 Original Algorithm: Gershon et al, 2009 3 Uses ICD-10 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Algorithm Original ICD Code Disease/Disorder 7 8 ≥1 hospitalization J45 Asthma 9 and/or ≥2 10 ambulatory care 11 visits for asthma 12 Confidential: For Review Only 13 within two years 14 J46 Status asthmaticus 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Mapped ICD Code Disease/Disorder 7 8 493 Asthma 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Original Algorithm: Hill et al, 2016 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code 7 8 ≥2 care visits occurring ≥6 477 9 months apart 10 11 12 Confidential: For Review Only 13 SENSITIVITY ANALYSIS 14 15 Original Algorithm: Stensballe et al, 2017 16 Uses ICD-10 17 18 19 Algorithm Original ICD/DIN Code 20 ≥1 hospital contact for: J30 21 22 J30.0 23 J30.1 24 25 J30.2 26 J30.3 27 J30.4 28 29 J31.0 30 31 OR ≥2 filled prescriptions of: 32 33 Excluding: J33 34
J330 http://bmjpaedsopen.bmj.com/ 35 36 J331 37 J331A 38 J338 39 40 J338A 41 J339 42 43 J010-J019 44 J320-J3290 45 on September 25, 2021 by guest. Protected copyright. 46 47 OR ≥2 filled prescriptions of: 48 Excluding: L29 49 50 L50 51 52 OR ≥1 filled prescriptions of: 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder Mapped ICD Code 7 8 Allergic Rhinitis J301–J304 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder Mapped ICD/DIN Code 20 Hay Fever and Allergic Rhinitis 477 21 22 Vasomotor Rhinitis 23 Allergic Rhinitis due to Pollen 24 25 Other Seasonal Allergic Rhinitis 26 Other Allergic Rhinitis 27 Allergic Rhinitis, Unspecified 28 29 Chronic Rhinitis 30 31 Inhaled Corticosteroids for Rhinitis 32 33 Nasal Polyps 471 34
Polyps in Nasal Cavity http://bmjpaedsopen.bmj.com/ 35 36 Polyp Related Sinus Degeneration 37 Woakes' Ethmoiditis 38 Nasal Polyps, Other 39 40 Polypus Sinus Sphenoidalis 41 Nasal Polyps, Unspecified 42 43 Acute Sinusitis 461 44 Chronic Sinusitis 473 45 on September 25, 2021 by guest. Protected copyright. 46 47 Antihistamines for Systemic Use 48 Pruritus 698 49 50 Allergic Urticaria 708 51 52 Specific Immune Therapy, Allergen Substract 53 54 Therapy 55 Medication for Allergic Conjunctivitis 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder 7 8 Allergic Rhinitis 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder 20 Allergic Rhinitis 21 22 23 24 25 26 27 28 29 30 31 Inhaled Corticosteroids for Rhinitis Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 32 33 Nasal Polyps 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 Acute Sinusitis 44 Chronic Sinusitis 45 on September 25, 2021 by guest. Protected copyright. 46 47 Antihistamines for Systemic Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 48 Pruritus and related conditions 49 50 Urticaria 51 52 Specific Immune Therapy, Allergen Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 53 54 Substract Therapy 55 Medication for Allergic Conjunctivitis Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Original ATC codes were mapped31 to Canadian Drug Identification Numbers (DIN) on the last tab 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 Original ATC codes were mapped47 to Canadian Drug Identification Numbers (DIN) on the last tab 48 49 50 51 Original ATC codes were mapped52 to Canadian Drug Identification Numbers (DIN) on the last tab 53 54 Original ATC codes were mapped55 to Canadian Drug Identification Numbers (DIN) on the last tab 56 57 58 59 60
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1 2 Original Algorithm: Hill et al, 2016 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code 7 8 ≥2 care visits occurring ≥6 691 9 months apart 10 11 12 Confidential: For Review Only 13 SENSITIVITY ANALYSIS 14 15 Original Algorithm: Stensballe et al, 2017 16 Uses ICD-10 17 18 19 Algorithm Original ICD/DIN Code 20 ≥1 hospital contact for: L20 21 22 Excluding: 23 24 OR ≥1 filled prescriptions of: 25 26 27 Excluding: Exclusion criteria below 28 29 30 OR ≥2 filled prescriptions of 31 the code within 12 months: 32 33 If above prescription is: 34 35 Then also with either (as atopic http://bmjpaedsopen.bmj.com/ 36 dermatitis is never treated 37 38 alone with group IV): 39 40 41 42 Excluding: Exclusion criteria below 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 Exclusion Criteria 48 49 Exclude those without: L20 50 51 AND with: L21 52 L22 53 54 L23 55 L24 56 L25 57 58 L26 59 L27 60 L28
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1 2 L29 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 L30 6 7 8 L40 – L45 9 10 11 12 Confidential: For Review Only 13 14 15 16 L53 17 18 19 L55 20 21 22 L56 23 24 25 26 27 L80 28 29 L90 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 L93 37 38 OR ≥1 filled prescription of: 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 AND with: 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder Mapped ICD Code 7 8 Atopic dermatitis and related conditions L20 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder Mapped ICD/DIN Code 20 Atopic Dermatitis 691 21 22 691.0 23 24 Agents for Dermatitis: Tacrolimus, Pimecrolimus 25 26 27 28 29 30 Corticosteroids for Topical Use 31 32 33 Corticosteroids, very potent (group IV) 34 35 Corticosteroids, weak (group I) http://bmjpaedsopen.bmj.com/ 36 37 38 39 Corticosteroids, moderately potent (group II) 40 41 Corticosteroids, potent (group III) 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 Atopic Dermatitis 691 50 51 Seborrhoeic Dermatitis 690.1 52 Diaper Dermatitis 691.0 53 54 Allergic Contact Dermatitis 692 55 Irritant Contact Dermatitis 56 Unspecified Contact Dermatitis 57 58 Exfoliative Dermatitis 695.89 59 Dermatitis due to Substances Taken Internally 693 60 Lichen Simplex Chronicus and Prurigo 698.2, 698.3
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1 2 Pruritus 698.0, 698.1, 698.8, 3
698.9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Other Dermatitis 692.9, 705.81, 690.8, 6 696.5 7 8 Papulosquamous Disorders 696.0 - 696.4, 696.8, 9 694.3, 697.0, 697.1, 10 697.8, 057.8, 709.8 11 12 Confidential: For Review Only 13 14 15 16 Other Erythematosus Conditions 695.0, 695.89, 695.9 17 18 19 Sunburn 692.71, 692.76, 692.77 20 21 22 Other Acute Skin Changes due to Ultraviolet Radiation 692.72, 692.82, 692.75, 23 692.79 24 25 26 27 Vitiligo 709.01 28 29 Atrophic Disorders of the Skin 701.0, 701.3, 701.8, 30 701.9, 709.2 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Lupus Erythematosus 695.4 37 38 Antipsoriasics 39 40 Salicylates for Dermatological Use 41 Corticosteroids Moderately Potent Other 42 43 Combinations 44 Corticosteroids Potent Other Combinations 45 on September 25, 2021 by guest. Protected copyright. 46 Corticosteroids (Group IV) Clobetasol 47 Clobetasol and Antibiotics 48 Antifungals (implies corticosteroid (group IV) use for 49 50 vaginal fungal infection) 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder 7 8 Atopic Dermatitis and Related Conditions 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder 20 Atopic dermatitis and related conditions Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 21 22 Diaper or Napkin Rash Added this exclusion since L20 doesn't include diaper rash but 691 does 23 24 Agents for Dermatitis: Tacrolimus, Pimecrolimus Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 25 26 27 28 29 30 Corticosteroids for Topical Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 31 32 33 Corticosteroids, very potent (group IV) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 34 35 Corticosteroids, weak (group I) Original ATC codes were mapped to Canadian http://bmjpaedsopen.bmj.com/ Drug Identification Numbers (DIN) on the last tab 36 37 38 39 Corticosteroids, moderately potent (group II) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 40 41 Corticosteroids, potent (group III) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 Atopic dermatitis and related conditions Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 50 51 Seborrheic dermatitis 52 Diaper or Napkin Rash 53 54 Contact dermatitis and other eczema 55 56 57 58 Other Specified Erythematous Conditions 59 Dermatitis due to Substances Taken Internally 60 Prurigo & Lichenification
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1 2 Pruritus ani, Pruritus of genitalia, Pruritic 3
conditions NEC & Pruritic disorder NOS bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Dermatitis NOS, Dyshidrosis, Erythmtsquamous Removed 'except Winter Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 6 derm NEC & Pityriasis NEC & NOS 7 8 Psoriatic arthropathy, Other psoriasis, 9 Parapsoriasis, Pityriasis rosea, Pityriasis rubra 10 pilaris, Psorias related dis NEC, Impetigo 11 12 herpetiformis,Confidential: Lichen planus, Lichen nitidus, ForLichen Review Only 13 NEC, Viral exanthemata NEC & Skin disorders NEC 14 15 16 Toxic erythema, Erythematous cond NEC & 17 Erythematous cond NOS 18 19 Sunburn, 2nd degree sunburn & 3rd degree 20 sunburn 21 22 Acute dermatitis due to solar radiation, Dermatitis 23 due to other radiation, Disseminated superficial 24 actinic porokeratosis (DSAP) & Other dermatitis 25 26 due to solar radiation 27 Vitiligo 28 29 Circumscribe scleroderma, Striae atrophicae, Other 30 specified hypertrophic and atrophic conditions of 31 skin, Unspecified hypertrophic and atrophic 32 33 conditions of skin & Scar conditions and fibrosis of 34 skin 35 http://bmjpaedsopen.bmj.com/ 36 Lupus Erythematosus 37 38 Antipsoriasics Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 39 40 Salicylates for Dermatological Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 41 Corticosteroids Moderately Potent Other Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 Combinations 44 Corticosteroids Potent Other Combinations Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 45 on September 25, 2021 by guest. Protected copyright. 46 Corticosteroids (Group IV) Clobetasol Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 47 Clobetasol and Antibiotics Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 48 Antifungals (implies corticosteroid (group IV) use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 49 50 for vaginal fungal infection) 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Removed L308C "Winter20 Feet" since not in Canadian ICD-10-CA codes 21 Added this exclusion22 since L20 doesn't include diaper rash but 691 does 23 Original ATC codes24 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 25 26 27 28 29 Original ATC codes30 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 31 32 Original ATC codes33 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 34 Original ATC codes35 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab http://bmjpaedsopen.bmj.com/ 36 37 38 Original ATC codes39 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 40 Original ATC codes41 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 Removed L308C "Winter49 Feet" since not in Canadian ICD-10-CA codes 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from Removed 'except Winter5 Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Original ATC codes38 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 39 Original ATC codes40 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes41 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 Original ATC codes44 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 45 on September 25, 2021 by guest. Protected copyright. Original ATC codes46 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes47 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes48 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Original Algorithm: Walsh et al, 2013 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code Disease/Disorder 7 8 In an inpatient or 995.0 Other Anaphylactic Shock 9 emergency 10 department 11 12 encounter (i.e.Confidential: DAD For Review Only 13 or NACRS) either: 14 15 999.4 Anaphylactic Shock due to Serum 16 17 995.6 Anaphylactic Shock due to Adverse Food Reaction 18 19 20 21 22 23 24 25 26 27 28 29 30 31 OR in an outpatient 995.0 Other Anaphylactic Shock 32 encounter (i.e. OHIP) 33 either: 34 35 999.4 Anaphylactic Shock due to Serum http://bmjpaedsopen.bmj.com/ 36 37 995.6 Anaphylactic Shock due to Adverse Food Reaction 38 39 40 41 42 43 44 45 AND at least one of: 519.11 Bronchospasm on September 25, 2021 by guest. Protected copyright. 46 786.1 Stridor 47 48 458.9 Hypotension 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Mapped ICD/CCI Code Disease/Disorder 7 8 T78.2 Anaphylactic Shock, Unspecified 9 10 11 12 Confidential: For Review Only 13 14 15 T80.5 Anaphylactic Shock due to Serum 16 17 T78.0 Anaphylactic Shock due to Adverse Food 18 Reaction 19 20 21 22 23 24 T886 Anaphylactic shock due to adverse effect of 25 correct drug or medicament properly 26 administered 27 28 29 30 31 T78.2 Anaphylactic Shock, Unspecified 32 33 34 35 T80.5 Anaphylactic Shock due to Serum http://bmjpaedsopen.bmj.com/ 36 37 T78.0 Anaphylactic Shock due to Adverse Food 38 39 Reaction 40 41 T88.6 Anaphylactic shock due to adverse effect of 42 correct drug or medicament properly 43 administered 44 45 J98.01 Acute Bronchospasm on September 25, 2021 by guest. Protected copyright. 46 R06.1 Stridor 47 48 I95.9 Hypotension, Unspecified 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 Added this code due to high prevalence food-induced anaphylaxis among young 18 children. First-author of original paper said that they didn't include the code 19 since they were mostly interested in anaphylaxis due to medications, but that 20 21 the addition of this code was a good approach if food-induced anaphylaxis was 22 important to our study. 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Same comment as above 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 The three intervention codes in the original algorithm (epinephrine, injection of 50 diphenhydramine, and CPR) did not have analogous OHIP fee codes. As such, we 51 52 could not include these in our algorithm. 53 54 55 56 57 58 59 60
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1 2 Mapped using the WHO ATC/DDD Index 2020 (https://www.whocc.no/atc_ddd_index/) and the ICES DRUGLIST excel 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 Original Name Original ATC Code Drug 6 For Rhinitis Algorithm 7 Inhaled R01AD01 – R01AD60 Beclomethasone 8 9 Corticosteroids for 10 Rhinitis 11 12 Confidential: For Review Only 13 14 15 16 17 Prednisolone + combinations 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Dexamethasone + 38 combinations 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 Flunisolide 51 Budesonide 52 53 54 55 56 57 58 59 60
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1 2 Betamethasone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 tixocortol + combinations 24 25 Fluticasone 26 27 28 29 30 Mometasone 31 32 33 34 Triamcinolone http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 fluticasone furoate + 49 50 combinations 51 52 53 54 55 56 57 ciclesonide 58 59 60
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1 2 hydrocortisone, combinations 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Antihistamines for R06A Bromazine 37 Systemic Use 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Diphenhydramine + 3
combinations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Clemastine + combinations 37 Chlorphenoxamine + 38 39 combinations 40 Diphenylpyraline + 41 combinations 42 43 44
Carbinoxamine on September 25, 2021 by guest. Protected copyright. 45 46 Doxylamine + combinations 47 48 49 50 51 52 53 54 55 56 Trimethobenzamide 57 58 59 60
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1 2 Brompheniramine + 3
combinations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 Dexchlorpheniramine + 11 12 Confidential: Forcombinations Review Only 13 Dimetindene 14 15 Chlorphenamine + 16 combinations 17 Pheniramine 18 19 Dexbrompheniramine + 20 combinations 21 22 Talastine 23 Mepyramine 24 25 Histapyrrodine + combinations 26 27 Chloropyramine + 28 29 combinations 30 Tripelennamine 31 32 Methapyrilene 33 Thonzylamine 34 Alimemazine http://bmjpaedsopen.bmj.com/ 35 36 Promethazine + combinations 37 38 39 40 41 42 43 Thiethylperazine 44
Methdilazine on September 25, 2021 by guest. Protected copyright. 45 46 Hydroxyethylpromethazine + 47 combinations 48 Thiazinam 49 50 Mequitazine 51 Oxomemazine 52 53 Isothipendyl 54 Buclizine + combinations 55 Cyclizine + combinations 56 57 Chlorcyclizine 58 Meclizine + combinations 59 60 Oxatomide
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1 2 Cetirizine 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Levocetirizine 9 Bamipine 10 Cyproheptadine 11 12 Confidential: ForThenalidine Review + combinations Only 13 Phenindamine 14 15 Antazoline 16 Triprolidine 17 Pyrrobutamine + combinations 18 19 20 Astemizole 21 22 Terfenadine 23 24 25 Loratadine 26 27 Mebhydrolin 28 29 Deptropine 30 Ketotifen 31 32 33 Acrivastine 34 Azelastine http://bmjpaedsopen.bmj.com/ 35 36 Tritoqualine 37 Ebastine 38 39 Pimethixene 40 Epinastine 41 Mizolastine 42 43 Fexofenadine 44
Desloratadine on September 25, 2021 by guest. Protected copyright. 45 46 Rupatadine 47 Bilastine 48 Quifenadine 49 50 Sequifenadine 51 52 53 54 55 56 57 58 59 60
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1 2 Specific Immune V01A Allergen extracts and 3
Therapy, Allergen preparations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Substract Therapy 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Medication for S01GX Cromoglicic acid + 37 Allergic combinations 38 Conjunctivitis 39 40 Levocabastine 41 Spaglumic acid 42 43 Nedocromil 44
Lodoxamide on September 25, 2021 by guest. Protected copyright. 45 46 Emedastine 47 Azelastine 48 49 Ketotifen 50 51 Olopatadine 52 53 Epinastine 54 Alcaftadine 55 56 57 For dermatitis algorithm 58 59 60
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1 2 Agents for D11AH Tacrolimus 3
Dermatitis: bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Tacrolimus, 6 Pimecrolimus 7 8 Pimecrolimus 9 Cromoglicic acid 10 Alitretinoin 11 12 Confidential: ForDupilumab Review Only 13 Crisaborole 14 15 Corticosteroids for D07 Methylprednisolone 16 Topical Use 17 18 19 20 21 22 Hydrocortisone 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 Prednisolone 49 50 51 52 53 54 55 56 57 58 59 60 Clobetasone
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1 2 Hydrocortisone butyrate 3
Flumetasone bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Fluocortin 6 Fluperolone 7 8 Fluorometholone 9 Fluprednidene 10 Desonide 11 12 Confidential: For Review Only 13 Triamcinolone 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Alclometasone 28 29 Hydrocortisone buteprate 30 Dexamethasone 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 Clocortolone 41 Betamethasone 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Fluclorolone 3
Desoximetasone bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Fluocinolone acetonide 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Fluocortolone 20 Diflucortolone 21 22 Fludroxycortide 23 Fluocinonide 24 25 26 27 28 29 Budesonide 30 31 32 33 Diflorasone 34 Amcinonide http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Halometasone 40 Mometasone 41 42 43 44
Methylprednisolone on September 25, 2021 by guest. Protected copyright. 45 aceponate 46 47 Beclomethasone 48 49 50 51 52 53 54 55 56 57 Hydrocortisone aceponate 58 59 60
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1 2 Fluticasone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Prednicarbate 9 Difluprednate 10 Ulobetasol 11 12 Confidential: ForClobetasol Review Only 13 14 15 16 17 18 19 Halcinonide 20 21 22 Prednisolone and antiseptics 23 Hydrocortisone and antiseptics 24 25 26 Flumetasone and antiseptics 27 Desonide and antiseptics 28 29 Triamcinolone and antiseptics 30 31 32 Hydrocortisone butyrate and 33 antiseptics 34 Betamethasone and http://bmjpaedsopen.bmj.com/ 35 36 antiseptics 37 38 39 Fluocinolone acetonide and 40 antiseptics 41 Fluocortolone and antiseptics 42 43 Diflucortolone and antiseptics 44 45 on September 25, 2021 by guest. Protected copyright. 46 Hydrocortisone and antibiotics 47 48 49 50 51 52 53 54 Methylprednisolone and 55 antibiotics 56 57 Prednisolone and antibiotics 58 59 60
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1 2 Triamcinolone and antibiotics 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Fluprednidene and antibiotics 9 Fluorometholone and 10 antibiotics 11 12 Confidential: ForDexamethasone Review and Only 13 antibiotics 14 15 Flumetasone and antibiotics 16 Betamethasone and antibiotics 17 18 19 Fluocinolone acetonide and 20 antibiotics 21 22 Fludroxycortide and antibiotics 23 24 25 Beclometasone and antibiotics 26 27 Fluocinonide and antibiotics 28 29 Fluocortolone and antibiotics 30 Clobetasol and antibiotics 31 32 Corticosteroids, D07AD Clobetasol 33 very potent (group 34
IV) http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Halcinonide 40 41 Corticosteroids, D07AA Methylprednisolone 42 43 weak (group I) 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Hydrocortisone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Prednisolone 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 Corticosteroids, D07AB Clobetasone 42 43 moderately potent 44 (group II) 45 on September 25, 2021 by guest. Protected copyright. 46 Hydrocortisone butyrate 47 Flumetasone 48 Fluocortin 49 50 Fluperolone 51 Fluorometholone 52 53 Fluprednidene 54 Desonide 55 56 57 58 59 60
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1 2 Triamcinolone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Alclometasone 17 Hydrocortisone buteprate 18 19 Dexamethasone 20 21 22 23 24 25 26 27 28 29 Clocortolone 30 Corticosteroids, D07AC Betamethasone 31 potent (group III) 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 Fluclorolone 52 53 Desoximetasone 54 55 56 57 58 59 60
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1 2 Fluocinolone acetonide 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 Fluocortolone 16 Diflucortolone 17 Fludroxycortide 18 19 Fluocinonide 20 21 22 23 24 25 Budesonide 26 27 28 29 Diflorasone 30 Amcinonide 31 32 33 34 Halometasone http://bmjpaedsopen.bmj.com/ 35 36 Mometasone 37 38 39 40 Methylprednisolone 41 aceponate 42 43 Beclomethasone 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 Hydrocortisone aceponate 54 Fluticasone 55 56 57 58 59 60 Prednicarbate Difluprednate
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1 2 Ulobetasol 3
Antipsoriasics D05 Tars bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 Dithranol + combinations 24 25 Trioxysalen 26 Methoxsalen 27 28 29 Fumaric acid 30 Calcipotriol 31 32 Calcitriol 33 34 Tacalcitol http://bmjpaedsopen.bmj.com/ 35 36 Tazarotene 37 Calcipotriol + combinations 38 39 Methoxsalen 40 41 Bergapten 42 43 Etretinate 44
Acitretin on September 25, 2021 by guest. Protected copyright. 45 46 Fumaric acid derivatives + 47 combinations 48 Salicylates for D02AF Salicylic acid preparations 49 50 Dermatological Use 51 52 53 54 55 Corticosteroids D07XB Flumetasone 56 57 Moderately Potent 58 Other 59 Combinations 60
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1 2 Triamcinolone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Fluprednidene 17 Fluorometholone 18 19 Dexamethasone 20 21 22 23 24 25 26 27 28 29 Corticosteroids D07XC Betamethasone 30 Potent Other 31 Combinations 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 Desoximetasone 51 52 53 Mometasone 54 55 56 57 Diflucortolone 58 Fluocortolone 59 60
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1 2 Corticosteroids D07AD01 Clobetasol 3
(Group IV) bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Clobetasol 6 7 8 9 Antifungals (implies D01 Nystatin 10 corticosteroid 11 12 (group IV) useConfidential: for For Review Only 13 vaginal fungal 14 infection) 15 16 17 18 19 Natamycin 20 Hachimycin 21 22 Pecilocin 23 Mepartricin 24 25 Pyrrolnitrin 26 Griseofulvin 27 28 29 Clotrimazole 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 Miconazole 40 41 42 43 44
Econazole on September 25, 2021 by guest. Protected copyright. 45 46 Chlormidazole 47 Isoconazole 48 Tiabendazole 49 50 Tioconazole 51 Ketoconazole 52 53 Sulconazole 54 Bifonazole 55 Oxiconazole 56 57 Fenticonazole 58 Omoconazole 59 60 Sertaconazole
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1 2 Fluconazole 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: ForFlutrimazole Review Only 13 Eberconazole 14 15 Luliconazole 16 Efinaconazole 17 Imidazoles/triazoles in 18 19 combination with 20 corticosteroids 21 22 Miconazole + combinations 23 24 25 26 27 Bifonazole + combinations 28 29 Bromochlorosalicylanilide 30 Methylrosaniline 31 32 Tribromometacresol 33 Undecylenic acid + 34
combinations http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Polynoxylin 40 2-(4-chlorphenoxy)-ethanol 41 Chlorphenesin 42 43 Ticlatone 44
Sulbentine on September 25, 2021 by guest. Protected copyright. 45 46 Ethyl hydroxybenzoate 47 Haloprogin 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Salicylic acid 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Selenium sulfide 28 29 30 Ciclopirox 31 32 33 Terbinafine 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Amorolfine 38 39 Dimazole 40 Tolnaftate 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 Tolciclate + combinations 47 Flucytosine 48 Naftifine 49 50 Butenafine 51 Tavaborole 52 53 54 55 56 57 58 59 60
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1 Mapped using the WHO ATC/DDD Index 2020 (https://www.whocc.no/atc_ddd_index/)2 and the ICES DRUGLIST excel 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 DIN 6 7 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 8 9 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 10 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 11 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 12 Confidential: For Review Only 13 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 14 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 15 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 16 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 17 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00194875 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 18 00030739 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 19 99100392 00237663 00237698 00806994 00807001 01934546 01944819 20 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 21 02245407 02245408 00895962 00194867 00806935 00030791 00030643 00030651 00030678 22 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 23 24 02230210 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 25 02367955 02367963 02367971 00194859 00021679 00031003 00178926 00210692 00544817 26 00993610 00813680 00028118 00093602 00250376 00252492 00278912 00299405 00300373 27 28 00301175 00622931 00700401 00727466 00764639 00801186 00809152 00894958 00896144 29 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 30 99100550 99113742 00042617 00042625 00042633 00045632 00177024 00307246 00395145 31 32 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00281735 33 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00218812 34
00281824 00527998 00760056 00808199 00843741 00903477 02133342 00544833 01924400 http://bmjpaedsopen.bmj.com/ 35 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 36 37 0022965299101412 00778907 00003603 00016217 00007668 00379689 00010197 00778915 00021687 02252716 00021695 00000698 00093629 00016462 00153710 00016470 00156876 38 0002250000178934 0002251900210188 0004256000232092 0004257900232378 0026902600252417 0028547100271373 0029509400271381 0034910000280852 0035430900312770 39 0048915800508586 0050105000550957 0050106900589194 0050113100598194 0050441600607517 0052528600610623 0072414900868426 0073288500868434 0073289300868442 40 41 0073983900901425 0090306200999108 0090421706623833 0190883909857797 0193096609857798 0194689709857799 0196406899100988 0196407000154008 0196496800023833 42 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 43 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 44 45 19649760 66901352 99503007 00140449 00173592 00173606 00228052 01987712 01987720 on September 25, 2021 by guest. Protected copyright. 46 02224623 02224631 02247920 00285110 00626597 00140732 00042668 00042676 00358177 47 02023806 02023849 00229679 00308455 00617199 00874582 00800767 00213624 00732907 48 49 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 50 0075186300421456 0078390000588997 0078526100790486 0091174200878790 0091174501927187 0091174602162687 0194704402230306 0197754702239288 0199502202240956 51 0202386500634530 0220426600634549 0220427400636460 0221297800814091 0237884300817228 0238567800851752 0238568600851760 0238774300852074 0241288800904059 52 0241289600911730 0001626800969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 53 54 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 55 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 56 49636460 49851752 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 74 of 91
1 2 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 3 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 6 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 7 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 8 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 9 10 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 11 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 12 02217856 02217864Confidential: 02217872 02217880 For66899798 Review 00012181 00036366 Only 00176834 00212385 13 14 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 15 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 16 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 17 18 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 19 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 20 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 21 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 22 23 0060911000887439 00887455 x 00887471 00888494 00888672 00889024 00889490 00889504 00895873 24 0244656100895881 0244658800897728 02048043 00897833 02089912 00897841 0209001500897949 0217469300899550 0217470700904937 0217471500908355 0217472300908363 25 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 26 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 27 0221361302100193 0221362102106264 0221364802214350 0221365602357844 0221366402357852 0221367202357860 0221368002357879 0221369902366924 0223724402449773 28 0223724566887323 0223724666907960 0223724795000467 0224175299113736 0224364699900015 02244291 02244292 02244293 02248307 29 30 0080090202294745 0081364802296071 0085173602298589 0085174402336405 0087109502453738 0223846502460513 0224302102467895 0224302202467909 0224359502467917 31 0224359677700002 0224476777700003 02244768 02244769 02248130 02264749 02266385 02270862 02367157 32 33 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 34
. 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 000146 http://bmjpaedsopen.bmj.com/ 35 36 13 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 000295 37 64 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 003851 38 82 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 004725 39 81 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 005352 40 41 49 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 007169 42 87 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 008877 43 73 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 008884 44 45 51 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 008951 on September 25, 2021 by guest. Protected copyright. 46 48 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 019133 47 28 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 021940 48 02432889 02446561 02446588 02474522 02408872 02444186 02048043 02089912 02090015 49 31 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 022365 50 6902174693 02368676 02174707 02417510 02174715 02437635 02174723 09857128 02174731 66887889 02174738 00014834 02174758 00014842 02174766 00499846 02174774 0071699 51 502213581 00903208 02213583 01977555 02213591 02194120 02213605 02194147 02213613 66494240 02213621 00297151 02213648 00903175 02213656 02194155 02213664 0247063 52 202213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 53 54 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 55 02460513 02467895 02467909 02467917 77700002 77700003 02240835 02240836 02240837 56 02245125 02245126 02245127 02474611 02474638 02474646 02494507 02494515 02494523 None found. 57 02495597 02495600 02495619 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 75 of 91 BMJ Paediatrics Open
1 2 02242485 00068772 00068780 00243124 00243132 00520322 00666246 00701904 00091820 3 00662461 00086096 00426350 00568074 00806099 00900737 01937979 00578533 00578541 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00856711 00768069 00155977 00156175 00163511 00163538 00438669 00704555 00704563 6 00750670 00763543 00837350 01980572 01980580 02240035 00074489 00074497 00074500 7 00074527 00193410 00193429 00245399 00338605 00774489 00807079 00807087 00807095 8 00807109 00811467 00091448 00215686 00216828 00521205 00521213 00521221 00449768 9 10 00456403 00203378 00445045 00476439 00229679 00387592 00448710 00530085 00530093 11 00807656 00807664 02226383 02226391 02247882 00173614 00173615 00173622 00807621 12 00813060 01988549Confidential: 01988573 02223252 For02223260 Review 02242527 02242528 Only 02247322 00534838 13 14 00534846 02463512 02238578 00209465 00003719 00003727 00006351 00016527 00021083 15 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 16 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 17 18 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 19 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 20 00461903 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 21 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 22 23 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 24 00728837 00740330 00748811 00748889 00756679 00763470 00804533 00824435 00862770 25 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 26 27 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 28 00907065 00907073 00960535 00967564 00967572 00968951 00990137 00990253 00990841 29 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 30 31 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 32 09857120 10502200 49513288 66123379 66123732 66123756 66896071 66903124 66903132 33 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 34 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 http://bmjpaedsopen.bmj.com/ 35 36 80066165None found. 80066167 80066168 80066699 80071959 80073687 80076663 80076664 80078409 37 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00990313 00216941 38 00216968 00216976 00801666 00145718 00390748 00390798 00068667 00068675 00191282 39 40 00243140 00243159 00281816 00530611 00626600 00666211 00694401 00813559 00912828 41 01912828 02025736 02230386 00158046 00158178 00443298 00770957 01954210 00192678 42 00241067 00364134 00681989 00681997 00733083 00895911 02010720 80061502 80073645 43 44 80073689 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 45 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 on September 25, 2021 by guest. Protected copyright. 46 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 47 48 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 49 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 50 02099179 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00063312 51 00063313 00576514 00194883 00194891 00194913 00194921 00194948 00194956 00806897 52 53 00807346 00363014 00203505 00203513 00395765 00427497 00476226 00476242 00505781 54 00811513 02234466 02240851 02242797 02247692 00503134 00560022 66894419 80061501 55 00203483 00319848 00395757 00461717 00476277 00476285 00505773 00511781 00607789 56 57 00811505 00894761 00897434 00898325 00363847 00385700 00404411 00607797 00885738 58 02128446 02179547 02209764 02210517 02236399 02240112 02242798 02247691 02387239 59 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 60 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 00622249 02240658 00090808 00090824 00355038 02404044 https://mc.manuscriptcentral.com/bmjpo 00429090 00807478 02038242 02224542 00062251 00062278 02062251 BMJ Paediatrics Open Page 76 of 91
1 2 02246449 02246450 02358689 02289407 00022756 00022757 00022764 00022918 00023191 3 00023205 00130974 00155276 00271411 00304387 00337404 00337412 00370517 00421197 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00439118 00443441 00450839 00479764 00487791 00489867 00504653 00509345 00554294 6 00556726 00583332 00596612 00610755 00622796 00622818 00728152 00728160 00728162 7 00754889 00757683 00757691 00792705 00804193 00804401 00811432 00833266 00843482 8 00843490 00878200 00878634 00880043 00960314 01900005 01907034 01933434 01933442 9 10 01933450 01934414 01944290 01944347 01946986 01949454 01957996 01959395 01991086 11 01994247 01997025 02017849 02019671 02019698 02019701 02019728 02019736 02019744 12 02061287 02061597Confidential: 02087588 02097575 For02097583 Review 02141728 02141736 Only 02146142 02153165 13 14 02164574 02171279 02176483 02176580 02176883 02210657 02219298 02219336 02229492 15 02229958 02229959 02229960 02230398 02230485 02237169 02237788 02237789 02238644 16 02239029 02239030 02239138 02239548 02241167 02241734 02244203 02245778 02246936 17 18 02247037 02247560 02247659 02247762 02248858 02248859 02249529 02251817 02254425 19 02254433 02257548 02257556 02258250 02258994 02261286 02263882 02270900 02284170 20 02292734 02297701 02297728 02298503 02304244 02304252 02306352 02309629 02309742 21 02311232 02311240 02311771 02312352 02312360 02318849 02320789 02321076 02321270 22 23 02323346 02328895 02348608 02354578 02361256 02365685 02367939 02368374 02369567 24 02369656 02373300 02376202 02383268 02396599 02401932 02404869 02409224 02409240 25 02409259 02410214 02411415 02419769 02427427 02431181 02431203 02431599 02432129 26 27 02434385 02436884 02436930 02445182 02446170 02447827 02447835 02453711 02456303 28 02464683 02465108 02470144 02474867 02478242 02478757 02479710 02483122 02490943 29 02491850 02492318 02492326 09850791 09850805 66999121 80757683 88907502 99100522 30 31 99101300 99101367 02369672 00633917 00258350 00270695 00362611 00454494 02401193 32 02410583 02430770 02226626 02230939 00173568 00173576 02444593 02278170 02280612 33 02294354 02323915 00466069 00568473 01944789 02280868 02280876 02301717 02376148 34 02376156 02429721 02478072 02484838 02424630 02355841 22123333 00286710 02246391 http://bmjpaedsopen.bmj.com/ 35 36 0003597102278693 0216767000349046 02279150 00458570 02291371 01925946 0230566600728500 0241605001906577 02362643 02368528 02384175 37 0000649102387697 01979124 x 02383357 02385244 02469960 02469944 02238183 02359944 02385619 38 02356457 02273934 02275961 02276232 02319195 02322099 02326884 02409178 02413280 39 40 0049274402420929 0052498002420937 00230200 02423200 00425125 02432498 0046205502462265 0046207102487233 0041265102487276 00242977 02487322 00425133 02488574 41 0042514102490498 0046707302046784 0013326402203424 0044902402215241 0044903202215861 0046206302229367 0046203902230424 0046204702237483 0052205802237707 42 02239514 02240560 02241043 02241995 02242691 02245017 02248700 02250993 02255472 43 00091626 00091634 00091642 00425168 00214027 00425117 01940783 00763527 00091847 44 0014581502256576 00581771 02258633 00299596 02261014 00299561 02263874 00299588 02294370 02422964 02298171 02437953 02303833 00145963 02305305 00213543 02322269
None found. on September 25, 2021 by guest. Protected copyright. 45 02365766 02366797 02368196 02404974 02438348 00156345 00469122 00503215 00806781 0013415500218227 00545449 00550477 00749052 02048183 02230769 02244662 02485443 00507407 46 00156337 00361909 00420026 00464686 00535230 00659142 00690074 00792160 02190575 47 00713465 01946994 00435619 00134104 00460850 00373850 00481394 00609129 00806331 02244010 02245019 02245592 02486903 01905635 02005395 02242999 00156264 00361887 48 02304503 02406187 02413248 02383365 00566829 02047667 02409542 02410737 01982532 49 00361888 00370975 00710822 00766380 00156086 00156094 00156108 00358452 00358460 01996215 02198924 02248371 02272792 02291339 02293927 02374277 02378655 02380315 50 00462683 00538493 00609188 00730556 01945874 01945882 01962507 01962515 02241462 02438305 02449188 02492857 02494027 02276879 02291444 02458462 02481928 02482401 51 02246696 02310783 00889865 00156116 52 02483351 02492865 02493322 00237760 00758558 01900501 02050684 02148315 02218836 53 02239041 02239061 02241706 02248905 02254913 02254921 02258285 02258625 02258927 54 55 02260271 02262320 02272369 02273071 02293242 02298414 02307014 02335239 02426315 00012769 00013102 00115568 56 02427923 02472864 02472872 02368536 02427958 02273810 02380307 02437201 02459876 57 02240302 02245016 02380404 02385260 02383608 02388537 02246847 02253267 02255014 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 77 of 91 BMJ Paediatrics Open
1 2 02241814 02241813 00295450 00295469 02245301 01900559 01934724 02243945 00026395 3 00026484 00172227 00172235 00172537 01932535 01932543 01932551 01933582 02052482 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02229557 00493082 01934716 02244079 00172545 00656828 01934694 02244078 02215314 6 00172529 00533963 00810711 00933620 01933574 01933620 02243969 02245076 02266466 7 02266474 02267446 02267454 02315483 02315491 02328658 02468204 00172650 01934708 8 02244080 01933590 00172383 00172391 00172405 00933647 01932608 01933604 01933647 9 02012146 02024616 02243980 02245075 02266180 02266199 02267411 02267438 02277239 10 00028142 00028207 00176893 00225533 02273330 11 02307316 02315475 02468212 00588229 01933639 02043947 02125714 02198916 00342718 12 00589292 00589306Confidential: 01934686 For Review Only 13 None found. 14 15 None found. 16 17 None found. 18 19 00298433 00616869 00411892 00471348 00746304 00808059 00808253 00810577 00905755 20 02154285 21 22 None found. 23 None found. 24 25 None found. 26 27 None found. 28 29 30 00005703 00074306 00488461 00584096 00623504 00659673 02239338 31 32 None found. 33 None found. 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 00164291 00385948 01937561 02162199 00164267 00385964 01937545 02162180 00209449 37 00209457 00232920 00236276 00450561 00450588 00518336 00518344 02043459 02043467 38 02225654 02225662 00164283 00385956 00811211 01937588 02162172 00164186 01927736 39 40 00164259 00385972 00811203 01937553 02162164 00025380 00025402 00025046 00025429 41 00025712 00025739 00164038 00164046 00213896 00236764 00248754 00567434 00575178 42 00575186 00583979 00627607 00911311 01927566 01937685 01937693 01937707 01937715 00027324 00027367 00027510 43 01937723 02068591 02162156 02162202 02162210 02162229 02162237 99101319 99101320 44
00003158 00003514 on September 25, 2021 by guest. Protected copyright. 45 99101340 46 None found. 47 48 None found. 49 50 None found. 51 None found. 52 53 None found. 54 None found. 55 00068586 00318809 00985562 00318795 00004448 00318817 56 57 None found. 58 00901069 00024724 00216151 00220442 02368838 22123148 66903076 90220442 00158127 59 00221850 60 None found.
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 78 of 91
1 2 01900978 02315963 02427192 00900986 00980986 01900986 02145782 02145790 02223546 3 02223554 02231603 02238337 02240265 02240266 02240910 02241912 02241913 02295059 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02295067 02315947 02315955 02316609 02318873 02318881 02318903 02344572 02355868 6 02358352 02363844 02364689 02368064 02375087 02375095 02408732 02427133 02427141 7 None02432722 found. 02450526 02451751 02451778 02453363 02466171 02467577 02486954 02491125 8 41900986 9 None found. 10 00009989 00010073 00016314 00016454 00757713 02245667 02245668 02332248 09850775 11 12 None09991029 found.Confidential: For Review Only 13 None found. 14 15 00005436 x 16 00004812 00235768 17 None found. 18 19 20 00610070 00610089 02182912 02184656 02239669 21 22 00590908 00614394 00641774 00786624 00870927 00881694 00893528 00893536 00893552 23 01905058 01913395 02034433 02034441 02103575 02103621 02103648 02130882 02130890 24 25 00782696 02019973 02237734 02241523 02242957 02243880 02244691 02244692 02251795 26 02280159 02284669 02366444 02375990 02379481 02390388 02404494 02418959 27 None found. 28 29 None found. 30 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 31 02231680 02242324 02279223 02400871 02489651 99400864 32 33 None found. 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 None found. 37 None found. 38 39 None found. 40 None found. 41 None found. 42 43 02231462 02231463 02237296 02237633 02242818 02242819 44
02243919 02247192 02247193 02298155 02338424 02408740 on September 25, 2021 by guest. Protected copyright. 45 46 02456451 02456478 47 02454130 x 48 None found. 49 50 None found. 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 79 of 91 BMJ Paediatrics Open
1 2 00006144 00061379 00061387 00061395 00061409 00061441 00099902 00286273 00286281 3 00499625 00499633 00499641 00499668 00499676 00504572 00514713 00541427 00541435 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00541443 00541451 00541478 00583448 00602752 00602760 00602779 00602787 00602795 6 00602809 00603384 00605263 00605298 00605301 00605328 00614424 00662283 00705300 7 00800227 00861081 00861111 00861138 00861162 00861170 00861189 00861219 00861227 8 00861251 00861286 00861308 00861316 00861332 00861359 00861367 00861375 00861405 9 10 00886831 00886912 00886920 00888540 00888559 00888613 00888648 00888656 00888796 11 00888818 00888826 00888834 00888842 00888850 00888877 00888885 00888893 00888915 12 00888958 00889601Confidential: 00889628 00889636 For00889644 Review 00889709 00889717 Only 00889725 00889733 13 14 00889741 00889768 00889776 00889784 00889792 00889814 00889822 00889849 00889857 15 00894346 00894354 00894362 00894524 00894583 00895245 00895296 00895334 00895423 16 00895431 00895458 00895466 00896853 00896934 00896942 00896950 00897752 00897817 17 18 00898422 00898430 00898449 00898465 00898473 00898481 00898503 00898511 00898538 19 00898546 00898589 00898597 00898619 00899828 00899836 00899844 00899852 00899895 20 00899968 00900702 00900818 00906115 00906271 00907529 00907545 00908614 00911496 21 00967483 00967823 00969702 00990303 00998885 00999900 01948873 01959123 01959131 22 23 01959133 01959157 01959158 01959166 01959182 02217104 02223961 02226219 02226251 24 02226286 02226294 02226928 02226944 02230863 02238472 02238473 02238485 02238497 25 02241328 02242672 02242713 02242714 02242715 02242716 02242717 02247755 02247756 26 27 02247757 02325470 02325543 09850724 11135717 14048555 66861073 66889210 66889695 28 66889830 66894699 66895318 66895326 66969680 66969699 66969818 95000650 99000350 29 99000407 99000415 99000423 99000431 99000458 99000466 99003651 99003678 99003686 30 31 99003694 99003708 99003716 99003724 99003732 99003740 99003759 99003767 99003775 32 99003791 99003805 99003813 99003821 99003848 99003856 99003864 99003872 99003880 33 99003899 99003902 99003910 99003929 99003937 99003945 99003953 99003961 99003988 34 99003996 99004003 99004097 99004100 99100018 99100062 99100225 99100226 99100227 http://bmjpaedsopen.bmj.com/ 35 36 None99100228 found. 99100229 99100230 99100267 99100268 99100269 99100270 99100278 99100279 37 99100280 99100281 99100282 99100284 99100625 99101105 99101106 99101107 99101108 38 99101109 99101110 99101111 99101112 99101113 99101114 99101115 99101117 99101118 39 40 0194513099101119 0202001799101120 0212336399101121 0213162599101122 99101123 99101124 99101125 00350245 00966134 41 None00999652 found. 00999938 00999981 09999938 11044212 99100026 02230860 99100021 02220075 42 01948903 01948911 02239410 02217082 02223953 02223988 02231321 02231322 02369737 43 00766038 02230543 02229636 02230446 02241407 44 01959174 02223996 02231325 02270919 02223937 02223945 02231323 02231324 02369745
00893560 x on September 25, 2021 by guest. Protected copyright. 45 01948938 01948946 01948881 01948997 01949004 02242666 00504564 02221314 00286303 46 0029997902237355 00522457 x 00662275 02372428 02238486 02242674 02238501 02242676 00155233 47 None found. 48 02230864 99100017 01948970 01948989 00299987 00522465 02372444 00648122 00648922 49 0046498802172585 0224132702230799 0224775400577308 9900054700600784 0223848902176084 0224267002218305 0221745702221330 0223529902230730 0213607402231679 50 0221746502231680 0223849302242324 0223849402279223 0224266802400871 0223850002489651 0194895499400864 01948962 02220091 02220105 51 9900460702233143 9910001602305054 9910026602358913 0223086202362171 0060527102402823 0222008302403986 0222011302404095 9900459302420171 02247753 02422727 52 53 None0224775802458411 found. 9910006102458551 99100063 99100064 99100065 99100066 99100067 99100068 99100070 54 None99100072 found. 99100073 99100074 99100075 99100076 99100077 99100078 99100079 99100080 55 99100082 99101141 99101142 99101143 99101144 99101145 99101146 99101147 99101148 56 57 99101149 99101150 99101151 99101153 99101155 00888023 02423723 02242669 02432889 58 02451778 02467577 02240953 02242675 02447231 02463644 02239030 02245778 02247659 59 02248858 02249529 02258250 02258994 02263882 02270900 02284170 02292734 02297728 60 02309629 02311771 02312352 02318849 02361256 02368374 02396599 02409259 02410214 02411415 02431181 02431203 02431599 02434385 02436884 02436930 02447827 02447835 02453711 02456303 02470144 02230865 02381885 02381893 02404494 02418959 02242665 https://mc.manuscriptcentral.com/bmjpo 02242673 02160501 02447304 02238502 02242677 02325500 02238498 02242664 02242667 BMJ Paediatrics Open Page 80 of 91
1 2 00903944 00950645 00950653 00960039 00960632 00960634 02175983 02175991 02176009 3
02243144 02244148 02244149 02296462 02296470 02296489 02331667 02416816 02416824 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 02416832 02454068 02456095 02456109 02485877 02485885 02485893 09851984 09852069 6 09852662 09854786 66123987 66124086 66990973 99108093 99109293 7 8 02247238 x 9 None found. 10 02240328 02337630 02337649 02477432 02477440 11 12 02470365 02492504Confidential: For Review Only 13 02476991 x 14 15 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 16 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 17 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 18 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 19 20 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 21 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 22 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 23 00093637 00093645 00133426 00151475 00157880 00177571 00192562 00192570 00192589 24 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 25 26 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 27 00303887 00303895 00338591 00341606 00341614 00461903 00461911 00477680 00479098 28 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 29 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 30 31 00595802 00641154 00661856 00716855 00728829 00728837 00740330 00748811 00748889 32 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 33 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 34 35 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 00967564 http://bmjpaedsopen.bmj.com/ 36 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 37 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 38 39 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 40 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 41 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 42 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 43 44 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 45 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 on September 25, 2021 by guest. Protected copyright. 46 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 47 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 48 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 49 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 50 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 51 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 52 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 53 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 54 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 55 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 56 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 02242984 02242985 66888338 66895075 57 00278912 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 58 59 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 60 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 0075616400456543 0075617200456551 0090762600889938 0213329600889946 0213331800894591 00544833 02214415 01924400 02214423 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 https://mc.manuscriptcentral.com/bmjpo Page 81 of 91 BMJ Paediatrics Open
1 2 None found. 3
00005134 00005789 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 None found. 6 None found. 7 8 00259454 00432814 00707511 00897469 02238568 00756784 9 None found. 10 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 11 12 00889563 02048639Confidential: 02115514 02115522 For02154862 Review 02154870 02229315 Only 02229323 02348489 13 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 14 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 15 16 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 17 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 18 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 19 20 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 21 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 22 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 23 24 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 25 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 26 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 27 02070855 02070871 28 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 29 02368676None found. 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 30 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 31 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 32 33 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 34 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 http://bmjpaedsopen.bmj.com/ 35 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 36 37 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 38 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 39 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 40 01977547None found. 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 41 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 42 02387743 02412888 02412896 00016268 43 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00028096 44 02237835 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 on September 25, 2021 by guest. Protected copyright. 45 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 46 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 00899305 47 48 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 49 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 50 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 51 52 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 53 00176834 00212385 02060876 02060884 02063190 00900516 99100521 00011916 00011924 54 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 55 56 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 57 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 58 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 59 60 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024
00889490 00889504 00895873 https://mc.manuscriptcentral.com/bmjpo 00895881 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 95000467 99113736 99900015 BMJ Paediatrics Open Page 82 of 91
1 2 None found. 3
00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 6 0003022866889318 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 7 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 8 9 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 10 00464627 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 11 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 12 Confidential: For Review Only 13 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 14 00806951 00862347 00862355 00862371 00862398 00873292 00886998 00887005 00887013 15 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 16 17 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 18 00895105 00895113 00897868 00897884 00897892 00897906 00899976 02129078 02162504 19 02162512None found. 02162520 02162539 02162547 02163470 02163489 02242738 02300559 02306980 20 6603023600527818 6689425700587818 9071679000587826 9910087800587834 9910087900777818 9910088300811017 00811025 00811033 00896012 21 22 None00896020 found. 00896047 00896055 02070995 23 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 24 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 25 26 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 27 00908282 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 28 02187663 02187671 02236996 02236997 02240269 22369960 66887102 66887129 66887137 29 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 30 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 31 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 32 33 0048179302483874 0048180709857675 0088937709857676 0088938509857677 0088940709857679 09857680 09857681 09857682 09991294 34 49636460 49851752
00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 http://bmjpaedsopen.bmj.com/ 35 36 00894621 00894656 02052881 02154838 02170175 02192268 02192276 02192284 02219719 37 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 38 None02242542 found. 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 39 02257416 02370557 66894648 40 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 41 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 42 43 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 44
None found. on September 25, 2021 by guest. Protected copyright. 45 46 47 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 48 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 49 50 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 51 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 52 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 53 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 54 55 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 56 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 57 02241299None found. 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 58 59 99100392 60
https://mc.manuscriptcentral.com/bmjpo Page 83 of 91 BMJ Paediatrics Open
1 2 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 3 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 6 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 7 0205975402294745 0222751702296071 0223064202298589 02336405 02453738 02460513 02467895 02467909 02467917 8 77700002 77700003 9 02415534 x 10 None found. 11 12 02216213 00234408Confidential: 00359718 00359726 For00479012 Review 00878707 00878723 Only 00881678 00887242 13 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 14 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 15 16 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 17 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 18 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 19 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02475162 02489619 02490706 66888389 66895083 20 02010283 02010291 02010305 02011921 02200945 66887803 66887811 21 22 None found. 23 00063312 00063313 00449768 00456403 00091448 00215686 00216828 00521205 00521213 24 00521221 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 25 26 00074454 00806870 00806889 27 None found. 28 29 00128031 00128058 30 31 32 None found. 33 34 00271012 00575194 00611174 00813087 00417254 00417262 00811521 00811548 00586692 http://bmjpaedsopen.bmj.com/ 35 36 00586706 00614270 00682217 02244999 00177016 00813036 00813052 02244766 02238818 37 02238819 02247446 02244126 02457393 02319012 02474883 00177017 00232352 00807052 38 39 None found. 40 41 None found. 42 43 02028719 x 44 45 on September 25, 2021 by guest. Protected copyright. 46 02238578 00445045 00155977 00429090 00807478 02038242 02224542 02242485 00243124 47 00243132 00520322 00666246 00701904 00156175 00163511 00163538 00438669 00704555 48 00704563 00750670 00763543 00837350 01980572 01980580 00476439 00145718 00390748 49 00390798 00068667 00191282 00243140 00243159 00666211 00694401 00813559 00912828 50 51 01912828 02025736 02230386 00194883 00194891 00194913 00194921 00194948 00194956 52 00806897 00807346 00622249 00068772 00068780 00091820 00203378 00534838 00534846 53 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 00068675 54 00195057 00806919 00806927 00252395 00194867 00806935 00194859 00260428 00880787 00281816 00530611 00158046 00158178 00443298 00192678 00241067 00885738 00828947 55 00194875 56 57 00813680 00195057 00806919 00806927 00194867 00806935 00194859 00177121 00042617 58 00042625 00042633 00045632 00177024 00307246 00395145 00630640 00806617 00807788 59 00807982 00810894 00903124 02023784 02023814 00218812 00281824 00527998 00760056 60 00808199 00843741 00903477 02133342 00194875
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 84 of 91
1 2 00128066 00128031 00128058 00184659 00184667 00199850 00245259 00245267 00382620 3 00433527 00464554 00464562 00464589 00492760 00501107 00562173 00562181 00717002 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00717029 00774659 00774667 00806846 00806854 00806862 00808083 00808091 00808105 6 00808113 00808555 00810959 00810975 00811440 00811459 00960101 01999826 01999834 7 01999842 01999850 00960128 00903365 00960497 66960500 00192627 00128090 00128112 8 None found. 9 00395153 x 10 11 12 00778907 00778915Confidential: 00173592 00173606 For00228052 Review 01987712 01987720 Only 02224623 02224631 13 02247920 00626597 00140732 00042668 00042676 00358177 02023806 02023849 14 15 None found. 16 02474883 x 17 18 19 00189499 x 20 21 22 None found. 23 24 25 None found. 26 27 00492442 00808393 00808407 07090343 28 29 None found. 30 None found. 31 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 32 33 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 34 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 http://bmjpaedsopen.bmj.com/ 35 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 36 37 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 38 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 39 02475162 02489619 02490706 66888389 66895083 40 02010283 02010291 02010305 02011921 02200945 66887803 66887811 41 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 42 43 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 44 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 on September 25, 2021 by guest. Protected copyright. 45 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 46 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 47 48 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 49 50 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 85 of 91 BMJ Paediatrics Open
1 2 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 3 00093637 00093645 00133426 00151475 00157880 00177571 00192562 00192570 00192589 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 6 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 7 00303887 00303895 00338591 00341606 00341614 00461903 00461911 00477680 00479098 8 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 9 10 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 11 00595802 00641154 00661856 00716855 00728829 00728837 00740330 00748811 00748889 12 00756679 00763470Confidential: 00804533 00824435 For00862770 Review 00862789 00880671 Only 00887153 00887161 13 14 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 15 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 00967564 16 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 17 18 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 19 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 20 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 21 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 22 23 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 24 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 25 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 26 27 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 28 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 29 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 30 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 31 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 32 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 33 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 34 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 http://bmjpaedsopen.bmj.com/ 35 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 36 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 37 02242984 02242985 66888338 66895075 38 00278912 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 39 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 40 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 41 00456543 00456551 00889938 00889946 00894591 02214415 02214423 42 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 02148498 43 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 44 45 on September 25, 2021 by guest. Protected copyright. 46 None found. 47 00005134 00005789 48 None found. 49 50 None found. 51 00259454 00432814 00707511 00897469 02238568 00756784 52 53 None found. 54 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 55 00889563 02048639 02115514 02115522 02154862 02154870 02229315 02229323 02348489 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 86 of 91
1 2 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 3 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 6 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 7 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 8 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 9 10 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 11 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 12 00888702 00888729Confidential: 00889288 00889296 For00889458 Review 00889466 00893463 Only 00895121 00895148 13 14 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 15 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 16 0219405802070855 0219406602070871 02194074 02213834 02219271 02229540 02229550 02236568 02236569 17 None found. 18 02368676 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 19 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 20 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 21 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 22 23 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 24 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 25 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 26 27 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 28 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 29 01977547None found. 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 30 0238774300012173 0241288800012211 0241289600028185 0001626800726486 00779822 00804541 00907820 00907839 00990333 31 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 32 33 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 34 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 http://bmjpaedsopen.bmj.com/ 35 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 36 37 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 38 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 39 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 40 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 41 42 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 43 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 44
00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 on September 25, 2021 by guest. Protected copyright. 45 46 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 47 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 48 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 49 50 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 51 None00887439 found. 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 52 0042027100895881 0048645000897728 0075254100897833 0079717000897841 0088665300897949 0090809600899550 0096107800904937 0198752600908355 0198784400908363 53 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 54 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 55 6688931802100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 56 66887323 66907960 95000467 99113736 99900015 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 87 of 91 BMJ Paediatrics Open
1 2 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 3 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 6 00464627 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 7 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 8 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 9 10 00806951 00862347 00862355 00862371 00862398 00873292 00886998 00887005 00887013 11 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 12 00889083 00889261Confidential: 00889474 00889482 For00894303 Review 00894311 00894338 Only 00894451 00894478 13 14 00895105 00895113 00897868 00897884 00897892 00897906 00899976 02129078 02162504 15 02162512None found. 02162520 02162539 02162547 02163470 02163489 02242738 02300559 02306980 16 6603023600527818 6689425700587818 9071679000587826 9910087800587834 9910087900777818 9910088300811017 00811025 00811033 00896012 17 None00896020 found. 00896047 00896055 02070995 18 19 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 20 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 21 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 22 23 00908282 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 24 0063453002187663 0063454902187671 0063646002236996 0081409102236997 0081722802240269 0085175222369960 0085176066887102 0085207466887129 0090405966887137 25 26 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 27 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 28 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 29 00481793 00481807 00889377 00889385 00889407 30 0044382449636460 0055923749851752 00571016 00575046 00591629 00810029 00810037 00888311 00889032 31 00894621 00894656 02052881 02154838 02170175 02192268 02192276 02192284 02219719 32 33 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 34 02242542 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 None found. http://bmjpaedsopen.bmj.com/ 35 02257416 02370557 66894648 36 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 37 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 38 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 39 40 None found. 41 42 43 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 44 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 on September 25, 2021 by guest. Protected copyright. 45 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 46 47 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 48 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 49 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 50 51 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 52 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 53 02241299None found. 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 54 9910039202446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 55 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 56 57 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 58 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 59 0205975402294745 0222751702296071 0223064202298589 02336405 02453738 02460513 02467895 02467909 02467917 60 77700002 77700003 02415534 x
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 88 of 91
1 2 None found. 3
02241506 00023237 00035815 00085871 00086126 00090948 00208132 00238252 00241075 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 00245631 00246948 00251372 00276456 00280747 00342769 00343447 00358494 00358495 6 00423203 00426415 00426423 00509310 00517879 00530492 00539063 00577359 00579963 7 00621137 00623237 00632295 00632309 00644994 00645001 00710962 00776415 00810363 8 9 00811157 00811165 00812978 00860964 00864706 00875279 00894516 00897302 00897361 10 00899712 00900974 00903450 00905321 00908169 00972339 00982407 00999972 01908855 11 01918087 01918974 01918982 01918990 01921983 01937642 01937650 01981021 01981293 12 Confidential: For Review Only 02143941 02184672 02184680 02220350 02220393 02238310 02238311 02238642 02240151 13 14 02240152 02240645 02241910 02245737 02246735 02246736 02246802 02246974 02293978 15 02307146 02392046 02403854 02439085 02439093 02448963 02458837 66899704 66901032 16 66903256 88901121 00090905 00249866 00329231 00344508 00419133 00489271 00501832 17 18 00505765 00632260 00632279 00770428 00810401 00810428 00067229 00157562 00234206 19 00167800 00167819 00351881 00625280 00810886 00899704 02023075 00961043 01931121 20 02230134 00659703 00773492 00288640 00784753 01931237 01931245 01932446 01942379 21 22 02285703 02285711 02432366 02432439 00509302 00090891 00632244 01936980 02106299 23 None00800694 found. 00866601 00550434 00812226 00379727 00594792 00628042 00807133 00811076 24 0033117100812889 0196638302240942 01981307 02403862 00344494 00509906 00510335 00560448 00744298 25 00748269 00894508 00181757 00208205 00232890 00362204 00444448 00525383 01909118 26 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 27 0190747601981315 0194637402030462 0240623302403846 0985224700266493 0985290500332801 0999112500373222 2212304300506966 4900726900652326 9910069900740314 28 9910091601909185 0009091399100917 0009100699100918 00579955 00579971 00234141 00907308 29 None found. 30 01971633 x 31 32 02338572 00481815 00481823 00824291 00891738 00891746 02245686 02245687 02399334 33 02399342 02431637 02431645 02485710 02485729 02495899 02495902 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 02230784 02230785 02243894 02243895 37 None found. 38 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 39 40 01907476 01946374 02406233 09852247 09852905 09991125 22123043 49007269 99100699 41 None99100916 found. 99100917 99100918 42 43 00616400 00616419 66123914 44
02070847 02070863 02080863 02466074 02466082 02468840 02468859 on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 48 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 49 50 00748277 00774232 00775238 00808202 00811306 00813346 02016447 02227274 02231520 51 02238910 02241695 02243936 02243937 02243938 02245006 02248196 02248197 66903051 52 80027681 00961043 01931121 02230134 00181757 00208205 00232890 00362204 00444448 53 54 00525383 01909118 01981315 02030462 02403846 00266493 00234141 00907308 00075973 00203297 00208175 00208183 00232882 00355607 00428752 00506974 00534854 00739316 55 00005134 00005789 56 00807958 00810312 00810320 00810991 00972584 01909096 01988239 00180076 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 89 of 91 BMJ Paediatrics Open
1 2 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 3 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 6 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 7 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 8 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 9 10 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 11 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 12 00888702 00888729Confidential: 00889288 00889296 For00889458 Review 00889466 00893463 Only 00895121 00895148 13 14 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 15 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 16 02194058None found. 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 17 00259454 00432814 00707511 00897469 02238568 00756784 18 02368676 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 19 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 20 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 21 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 22 23 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 24 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 25 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 26 27 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 28 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 29 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 30 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 02387743 02412888 02412896 00016268 31 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 32 33 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 34 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 http://bmjpaedsopen.bmj.com/ 35 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 36 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 37 38 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 39 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 40 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 41 42 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 43 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 44
00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 on September 25, 2021 by guest. Protected copyright. 45 46 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 47 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 48 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 49 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 50 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 51 0199094200895881 0199506500897728 0222189600897833 0222191800897841 0222192600897949 0222193400899550 0223906800904937 0223906900908355 0224188700908363 52 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 0080090266889318 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 53 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 54 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 66887323 66907960 95000467 99113736 99900015 55 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 56 57 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 58 None00896020 found. 00896047 00896055 02070995 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 90 of 91
1 2 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 3 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 6 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 7 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 8 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 9 00014850 00014974 00029319 00029416 00248169 00248170 00270113 00282219 00779121 02475162 02489619 02490706 66888389 66895083 10 00785709 00792667 00894834 00894893 00895210 00898953 00903212 00904479 00984671 11 12 02125145 02194198Confidential: 02194201 02229852 For02238544 Review 02433443 09850457 Only 09857764 40079266 13 49248169 66898929 66907472 66988170 00015067 00029092 00029491 00029556 00270091 14 00278793 00288195 00288209 00288217 00295973 00382639 00422592 00444383 00449792 15 00449806 00480819 00510297 00522864 00716871 00716898 00716901 00811084 00870552 16 17 00870560 00882607 00885126 00888761 00908053 00912972 00929092 00985074 00999954 18 00999958 02004674 02194163 02194171 02194228 02194236 02195704 09852921 09857765 19 09857767None found. 50237469 66908061 99113755 99900006 00464597 00811091 00885096 20 None found. 21 22 None found. 23 None found. 24 25 None found. 26 00012246 00012254 00012262 00028266 00028274 00028282 00513229 00513237 00901061 27 02100266 02100274 02100282 09991069 99100253 28 29 00903037 00903061 00001403 00139035 00325465 00325473 00353833 00420301 00513903 30 00513904 00513911 00513938 00513946 00516805 00516806 00516813 00516821 00516848 31 00567388 00576492 00629243 00731307 00731707 00759457 00810045 00810967 00812366 32 33 00812374 00812382 00874043 00874051 00874078 00895571 00895598 00896845 00898112 34 00899046 00899054 00899399 00901412 00903184 00904279 00908045 00908495 02029480 http://bmjpaedsopen.bmj.com/ 35 02029499 02029502 02029510 02126818 02126826 02130203 02130211 02130238 02130254 36 02130262 02130920 02131633 02131641 02131668 02131676 02150667 02150832 02150840 37 02150859 02150867 02150875 02150883 02150891 02150905 02150921 02150948 02180723 38 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 39 02229378 02229379 02229380 02230447 02230509 02232395 02236746 02239432 02240847 00685917 00771035 00771036 00807605 00807613 00895237 00895628 00900958 00980617 40 02264099 02264102 02311720 02462397 02490927 49812382 66894788 66999474 99113693 41 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 99113695 42 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 43 44 02231533 02239600 02239601 02244005 02245546 66894796 92085852 95003840 95023947
00452114 00561002 00895997 02010267 02011948 on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 None found. 48 None found. 49 50 00657395 00791725 02095009 02095017 02095025 02171902 02171910 02217406 02218283 51 0096734302218291 0063383602241700 00788813 00903341 02122197 02231061 02237235 02237882 00703974 52 00803588 02182920 02245662 02292661 53 None found. 54 None found. 55 02230452 02230453 56 57 None found. 58 None found. 59 60 None found.
https://mc.manuscriptcentral.com/bmjpo Page 91 of 91 BMJ Paediatrics Open
1 2 00891800 00891819 00891827 00891835 00891900 00901418 02024152 02091216 02091372 3 02091380 02141442 02236978 02236979 02236980 02237370 02237371 02237372 02241895 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02243645 02245292 02245293 02245294 02245643 02245644 02245697 02246108 02246109 6 02246620 02246942 02247749 02247922 02248443 02248731 02249294 02249308 02249316 7 02255510 02261472 02271516 02273632 02273640 02273659 02281260 02281279 02282348 8 02282453 02287242 02287250 02287269 02294036 02294044 02301938 02301946 02301954 9 10 02309432 02310686 02310694 02311690 02312686 02312694 02323419 02336162 02339560 11 02340038 02340046 02340798 02340801 02340828 02352133 02357496 02378302 02388448 12 02428792None found. 02432471Confidential: 02433702 02462168 For22123126 Review 22123127 99101272 Only 13 None found. 14 15 None found. 16 02413388 x 17 00611174 00813087 02244766 18 19 20 21 22 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 23 00685917 00771035 00771036 00807605 00807613 00895237 00895628 00900958 00980617 24 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 25 26 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 27 None02231533 found. 02239600 02239601 02244005 02245546 66894796 92085852 95003840 95023947 28 02382628 29 None found. 30 None found. 31 32 None found. 33 00240664 00829315 02222736 02239048 02243662 80041595 80041596 80043930 00240656 34
00030163 00030201 00373443 00373478 00376906 00519898 00595926 00829145 00829153 http://bmjpaedsopen.bmj.com/ 35 00829307 00864137 00864145 02021838 02021846 02021862 02021900 02021919 02154552 36 37 80041594 00373451 00829285 02021803 00228796 00374598 00484334 00501840 00146013 38 00522074 00145661 00145831 00213497 00464651 39 None found. 40 None found. 41 00253065 00253073 02089637 02091496 42 43 None found. 44
None found. on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 00291021 00291048 00800953 01910094 01910108 48 49 50 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 92 of 91
1 2 00187542 00438294 00636347 00685186 00740292 00764361 00766216 00766240 00805300 3 00807583 00896063 00900796 00967548 00967556 00968978 00990141 00990244 00999036 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00999081 01908553 01908561 01914847 01915185 01930575 01939513 01939521 01947451 6 01947494 01978861 01999540 02015358 02025868 02044412 02044471 02047403 02069725 7 02074257 02074265 02139073 02139081 02147076 02147114 02156172 02163055 02199009 8 02199017 02221349 02222442 02227266 02230960 02230961 02230963 02231101 02231619 9 10 02236775 02236983 02237796 02238309 02238314 02238418 02238573 02238815 02238816 11 02239079 02240447 02240758 02240763 02240902 02240903 02241153 02241420 02243321 12 02243578 02243590Confidential: 02243615 02243939 For02244191 Review 02244449 02245611 Only 02245763 02245873 13 14 02245984 02246380 02246604 02246681 02246710 02246712 02247218 02248036 02248585 15 02248586 02248587 02248711 66898848 66900788 66900818 66900893 66901164 80002908 16 80005358 80006363 80007324 00054232 00475238 00505757 00509914 00666106 00666108 17 18 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 00813346 19 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 20 02248196 02248197 66903051 80027681 00764310 02211203 02231218 02243011 02245989 21 02247262 00075914 00075957 00273104 00281891 00555967 00652342 00652350 02149044 22 23 02149052 02240107 00792020 00794759 02032945 00230081 00465976 00903371 01915177 24 02047764 02230957 02230959 02241590 80005624 80008630 80011794 80073326 66908029 25 00307580 00307904 00355828 00355895 00413356 00413372 00454893 00505978 00609501 26 00614246 00625353 00690333 00740276 00754951 00813044 00815861 00837733 00889598 27 00243000 00353809 00418293 00443581 00457086 00457094 00483788 00483796 00594601 28 00895059 00895067 00895075 00895083 00895091 00899372 00906018 00987034 01909029 00709069 00808466 00811181 01950487 01951653 02242871 02245007 29 01909037 01909134 01911384 01914456 01915258 01918729 01929429 01939645 01948156 30 0196787800001516 0197433502250535 0197772502349086 0198146302353288 0202291502410346 0203555302413574 0205028500593362 0205029300811688 0206049300836281 31 00895741 01987569 01989626 02221802 02221810 02247228 02298953 49593362 32 02123045 02223821 02229957 02229990 02230131 02230132 02230691 02231570 02237019 33 0223905502242735 0223929902254727 0224032202320134 0224112902352818 0224146502353121 0224162102357070 0224173802385279 0224333202299275 0224405409991323 34 0224485000903384 0224544502031108 8006321602031116 0090305602239893 0099908202240345 02240346 02240807 02242503 02247530 http://bmjpaedsopen.bmj.com/ 35 02262177 02262924 02286580 02294273 02297973 02320126 02341190 02343452 02352796 36 37 None02363836 found. 02372762 02031094 02238703 02239876 02241815 02241816 02248845 02332612 38 39 None found. 40 00027936 00027960 00028088 00415782 00458163 00549185 00576026 00576034 00576042 41 00576050 00576057 00596361 00614211 00614238 00658731 00716928 00810584 00810592 42 01918826 01919245 01942263 01942573 01942581 02029081 02078341 02220733 02226707 43 44 02239066 02239497 02240064 02243064 02243663 02244939 02295873 02311801 02319276 45 on September 25, 2021 by guest. Protected copyright. None02319314 found. 02375397 02378248 02380765 02396785 02401584 02413760 02417715 02431718 46 02434113 02475324 02476703 02480166 47 00990256 66123998 00384895 66128023 66124323 48 02011255 02011263 49 50 02231063 02238762 02244312 51 None found. 52 53 54 55 56 57 58 59 60
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Confidential: For Review Only Examining the effects of pre-pregnancy weight and gestational weight gain on allergic disease development in offspring: a protocol for a population-based study using health administrative databases in Ontario, Canada
Journal: BMJ Paediatrics Open
Manuscript ID bmjpo-2020-000893.R1
Article Type: Protocol
Date Submitted by the 18-Nov-2020 Author:
Complete List of Authors: Srugo, Sebastian; University of Ottawa, School of Epidemiology and Public Health Gaudet, Laura; Queen's University, Department of Obstetrics and Gynecology; Kingston Health Sciences Centre, Department of Obstetrics and Gynecology Corsi, Daniel; Ottawa Hospital Research Institute, OMNI Research Group;
University of Ottawa, School of Epidemiology and Public Health http://bmjpaedsopen.bmj.com/ Fakhraei, Romina; Ottawa Hospital Research Institute, OMNI Research Group; Children's Hospital of Eastern Ontario Research Institute Guo, Yanfang; Better Outcomes Registry and Network; University of Ottawa, School of Epidemiology and Public Health Fell, Deshayne B.; University of Ottawa, School of Epidemiology and Public Health; Children's Hospital of Eastern Ontario Research Institute
Keywords: Epidemiology, Obesity, Pathology
on September 25, 2021 by guest. Protected copyright.
https://mc.manuscriptcentral.com/bmjpo Page 1 of 88 BMJ Paediatrics Open
1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 I, the Submitting Author has the right to grant and does grant on behalf of all authors of the Work (as defined 10 in the below author licence), an exclusive licence and/or a non-exclusive licence for contributions from authors 11 who are: i) UK Crown employees; ii) where BMJ has agreed a CC-BY licence shall apply, and/or iii) in accordance 12 with the termsConfidential: applicable for US Federal Government For officers Review or employees actingOnly as part of their official 13 duties; on a worldwide, perpetual, irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its 14 licensees and where the relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the 15 Work in this journal and any other BMJ products and to exploit all rights, as set out in our licence. 16 17 The Submitting Author accepts and understands that any supply made under these terms is made by BMJ to 18 the Submitting Author unless you are acting as an employee on behalf of your employer or a postgraduate 19 student of an affiliated institution which is paying any applicable article publishing charge (“APC”) for Open 20 Access articles. Where the Submitting Author wishes to make the Work available on an Open Access basis (and 21 intends to pay the relevant APC), the terms of reuse of such Open Access shall be governed by a Creative 22 Commons licence – details of these licences and which Creative Commons licence will apply to this Work are set 23 out in our licence referred to above. 24 25 Other than as permitted in any relevant BMJ Author’s Self Archiving Policies, I confirm this Work has not been 26 accepted for publication elsewhere, is not being considered for publication elsewhere and does not duplicate 27 material already published. I confirm all authors consent to publication of this Work and authorise the granting 28 of this licence. 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 2 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 TITLE 4 5 Examining the effects of pre-pregnancy weight and gestational weight gain on allergic disease 6 development in offspring: a protocol for a population-based study using health administrative databases in 7 8 Ontario, Canada 9 10 Confidential: For Review Only 11 AUTHORS 12 1 1,2,3,4 1,2,5,7 2,5 1,2,5,7 13 Sebastian A. Srugo, Laura Gaudet, Daniel Corsi, Romina Fakhraei, Yanfang Guo, and 14 Deshayne B. Fell1,5,6* 15 16 17 1School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada; 18 19 [email protected] (S.A.S.) 20 2 21 OMNI Research Group, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; 22 [email protected] (D.C.) 23 24 3Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON, Canada; 25 [email protected] (L.G.) 26 27 4Department of Obstetrics and Gynecology, Kingston Health Sciences Center, Kingston, ON, Canada 28 5Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; [email protected] 29 30 (R.F.) http://bmjpaedsopen.bmj.com/ 31 6 32 ICES, Ottawa, ON, Canada 33 7Better Outcomes Registry & Network Ontario, Ottawa, ON, Canada; [email protected] (Y.G.) 34 35 36 *Correspondence to: Dr. Deshayne Fell, Children’s Hospital of Eastern Ontario Research Institute, Centre 37 38 for Practice Changing Research Building, Room L-1154, 401 Smyth Road, Ottawa, ON K1H 8L1, 39 40 Canada; Email: [email protected]; Telephone: +1 613-737-7600 Ext. 6033 on September 25, 2021 by guest. Protected copyright. 41 42 43 Abstract word count: 334 44 Body word count: 2247 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 60 https://mc.manuscriptcentral.com/bmjpo Page 3 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 ABSTRACT 4 5 Introduction 6 Over the last 20 years, excess maternal pre-pregnancy weight (overweight and obesity) and gestational 7 8 weight gain have become the most common morbidities in pregnancy. These morbidities may pose a 9 threat to fetal immunological development through associated metabolic dysfunction and inflammation 10 Confidential: For Review Only 11 and, as such, may partly explain the concurrent rise of pediatric allergic disease. We will examine the 12 13 effect of maternal pre-pregnancy weight and gestational weight gain during pregnancy on the incidence of 14 allergic diseases among offspring in Canada’s most populous province. 15 16 17 Methods and analysis 18 19 We will conduct a retrospective, population-based cohort study of all singleton live births to residents of 20 21 Ontario, Canada in 2012–13 and 2013–14. The study population will be defined using maternal-newborn 22 records from the provincial birth registry, which captures information on maternal pre-pregnancy weight 23 24 and gestational weight gain. The cohort will be linked with provincial health administrative databases, 25 allowing for follow-up of neonates through early childhood until 2019 (5–7 years of age). Allergic disease 26 27 development (asthma, rhinitis, atopic dermatitis, and anaphylaxis) will be ascertained using diagnostic 28 codes from healthcare encounters. Potential confounders have been identified a priori through a directed 29 30 acyclic graph. Cox proportional-hazards regression models will be employed to assess the associations http://bmjpaedsopen.bmj.com/ 31 32 between maternal pre-pregnancy weight, gestational weight gain, and incident pediatric allergic disease. 33 Several pre-planned sensitivity analyses will be conducted, including a probabilistic bias analysis of 34 35 outcome misclassification. 36 37 38 Ethics and dissemination 39 40 Ethics approval was obtained from the Research Ethics Board of the Children’s Hospital of Eastern on September 25, 2021 by guest. Protected copyright. 41 Ontario and the ICES Privacy Office. Findings will be disseminated in scientific conference presentations 42 43 and peer-reviewed publications. 44 45 46 Keywords: Pregnancy; Allergic disease; Pre-pregnancy weight; Gestational weight gain; Ontario 47 48 49 50 51 52 53 54 55 56 57 58 59 2 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 4 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 ARTICLE SUMMARY 4 5 What is known on this subject 6 Excess maternal pre-pregnancy weight and gestational weight gain are common morbidities in 7 8 pregnancy and may impact fetal immunological development. 9 10 SeveralConfidential: studies have suggested these morbiditiesFor Reviewincrease the risk of asthma Only among offspring, 11 though their impact on other common allergic diseases is unclear. 12 13 Further, most previous studies have been limited by small sample sizes and self-reported 14 measures of the exposure or outcome. 15 16 17 18 What this study hopes to add 19 This protocol details a large and extensive study to evaluate the impact of maternal pre-pregnancy 20 21 weight and gestational weight gain on several pediatric allergic diseases. 22 23 This study will employ a population-based approach and objective measures, increasing the 24 generalizability and validity of the study findings. 25 26 To ensure the robustness of results, several pre-specified sensitivity analyses will be undertaken 27 to measure the impact of selection biases, residual confounding, and misclassification. 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 3 60 https://mc.manuscriptcentral.com/bmjpo Page 5 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 INTRODUCTION 4 5 In 1997, the World Health Organization declared obesity a global epidemic.1 Since then, excess maternal 6 pre-pregnancy weight (body mass index [BMI]≥25kg/m2) and gestational weight gain (GWG) have 7 8 become the most common morbidities in pregnancy.2,3 A recent analysis of perinatal registry data from 9 four Canadian provinces found that 35–55% of singleton live births are born to overweight or obese 10 Confidential: For Review Only 11 mothers, while 50–66% are born to mothers who exceed GWG recommendations.3 These morbidities are 12 13 associated with metabolic dysfunction and inflammation, which pose a threat to the homeostasis of the 14 fetal compartment and could result in impaired fetal immunological development and increased chronic 15 16 disease susceptibility in later life.2 Therefore, the rise of excess weight and GWG during pregnancy may 17 partially explain the concurrent rise in pediatric allergic disease,4 which is now one of the most common 18 19 and earliest-onset morbidities in childhood.5 One 2016 study conducted in Ontario found that 44% of 20 21 toddlers suffered from food allergies, environmental allergies (wheezing, asthma, eczema, or rhinitis), 22 atopy, or a combination thereof.6 Though one cross-sectional and several longitudinal studies have 23 24 assessed the early-life programming of allergic diseases by maternal weight or GWG, they have been 25 limited by small sample sizes (<1000)7,8 and self-reported measures of the exposure or outcome,7–19 which 26 27 have reduced their generalizability and validity. Further, most have focussed on asthma alone,7–14 none 28 have examined anaphylaxis, and none have calculated risk by the length of follow-up time, opting instead 29 30 8,13,17 7,9–12,14–16,18 for aggregate rates (log-linear model), odds (logistic model), or prevalence ratios (log- http://bmjpaedsopen.bmj.com/ 31 19 32 binomial model). As well, none of these studies have been undertaken in Canada, which has a unique 33 multicultural population. This proposed research will attempt to address these evidence gaps by carrying 34 35 out a large population-based study in Canada’s most populous province. 36 37 38 Aims 39 40 We will assess the impact of maternal pre-pregnancy BMI and GWG on the incidence of childhood on September 25, 2021 by guest. Protected copyright. 41 allergic diseases (asthma, rhinitis, atopic dermatitis, and anaphylaxis). Based on previous literature, we 42 43 hypothesize that maternal overweight, obesity, and excess GWG will all increase the risk of allergic 44 diseases in offspring, with GWG incurring the greatest risk. This work may help inform public health 45 46 initiatives for high-risk groups and increase early prevention, identification, and treatment of early 47 childhood morbidity. 48 49 50 51 METHODS AND ANALYSIS 52 Design and Setting 53 54 We will conduct a population-based retrospective cohort study of all singleton live births to residents of 55 Ontario, Canada between 1 April 2012 and 31 March 2014, with follow-up of children to 31 March 2019 56 57 58 59 4 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 6 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 (Figure 1). The study will be conducted using multiple linked province-wide health databases within the 4 5 secure network environment of ICES (https://www.ices.on.ca/). This protocol was developed following 6 the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) 7 8 guidelines.20 9 10 Confidential: For Review Only 11 Data Sources and Population 12 13 The birth cohort will be defined using maternal-newborn records from the provincial birth registry, the 14 Better Outcomes Registry & Network (BORN) Information System (BIS). The BIS captures all hospital 15 16 births ≥500g or ≥20 weeks of gestation in Ontario, as well as detailed clinical and demographic 17 information about the birth and the mother. Deterministic and probabilistic methods have been used to 18 19 link the BIS database to health administrative databases at ICES, enabling follow-up of offspring health 20 21 outcomes into early childhood (5–7 years of age). All residents of Ontario are covered by publicly funded 22 universal healthcare and are eligible to access the services captured in the health administrative databases. 23 24 The health administrative databases at ICES to be used in this study include: the Canadian Institute for 25 Health Information (CIHI) Discharge Abstract Database (DAD); the CIHI National Ambulatory Care 26 27 Reporting System (NACRS); the Ontario Health Insurance Plan (OHIP) database; the Ontario Asthma 28 Surveillance Information System (ASTHMA); the Ontario Drug Benefit (ODB) database; the Ontario 29 30 portion of the federal Immigration, Refugees and Citizenship Canada (IRCC) Permanent Resident http://bmjpaedsopen.bmj.com/ 31 32 Database; and the Ontario Marginalization Index (ON-Marg). All data sources and reasons for use are 33 displayed in Figure 2. The study population will be restricted by sample exclusions (non-Ontario resident; 34 35 stillbirth; twin or higher-order multiple birth; mother’s age outside probable range [i.e., <12 years or >50 36 years]; and infant died on date of birth) and administrative exclusions (duplicate records in BORN; 37 38 invalid linkages and linkage warnings; invalid infant and mother identifiers; mothers without continuous 39 40 OHIP eligibility throughout pregnancy; and infants who did not have records of health care eligibility on September 25, 2021 by guest. Protected copyright. 41 within 90 days of birth). Figure 3 displays temporal aspects of the study design relating to eligibility, 42 43 variable measurement, and follow-up; this figure was previously proposed by Schneeweiss and 44 colleagues.21 45 46 47 Exposures 48 49 The primary exposures of interest will be maternal pre-pregnancy BMI and GWG. Ascertainment. Pre- 50 51 pregnancy BMI will be calculated by dividing pre-pregnancy weight (kg) by height (m), squared. For 52 approximately 70% of participants, data on maternal weight will be available from the first prenatal 53 54 screening visit at around 12 weeks of gestation (available from the Prenatal Screening Ontario [PSO] 55 encounter within the BIS database), where it is likely to have been objectively measured. From this, pre- 56 57 58 59 5 60 https://mc.manuscriptcentral.com/bmjpo Page 7 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 pregnancy weight will be estimated by subtracting the typical first trimester weight gain (1.64kg),22 as 4 5 done previously.23 Ideally pre-pregnancy measurements, which are rare in health administrative database 6 studies, would be available; still, it has been recently noted that weight at first prenatal screening offers a 7 8 valid estimate of pre-pregnancy weight after adjustment for first trimester weight gain.24 For subjects with 9 no record in the PSO database (due to no prenatal screening), maternal pre-pregnancy weight will be 10 Confidential: For Review Only 11 captured from the Labour & Birth encounter within the BIS database, where the data may be based on 12 13 either self-report or objective measurement. GWG will be calculated by subtracting maternal pre- 14 pregnancy weight from weight recorded at delivery. Measures. Pre-pregnancy BMI will be classified 15 16 according to World Health Organization categories: underweight (<18.5 kg/m2), normal weight (18.5– 17 24.9 kg/m2), overweight (25.0–29.9 kg/m2) or obese (≥30.0 kg/m2).1 The Institute of Medicine (IOM) 18 19 recommendations for weight gain during pregnancy suggest total weight gain for singleton pregnancies 20 21 should not exceed 12.5–18 kg, 11.5–16 kg, 7–11.5 kg, or 5–9 kg based on pre-pregnancy BMI category, 22 respectively.25 However, these recommendations do not account for gestational length. To do so, we will 23 24 follow previously published methods26 to establish expected GWG based on IOM recommendations for 25 weight gain by trimester and pre-pregnancy BMI, and calculate the ratio of actual to expected GWG. We 26 27 will then employ the recommended ratio ranges calculated by Guo and colleagues26 to classify GWG into 28 three categories: inadequate, adequate, or excess weight gain. These ratio ranges were determined by 29 30 dividing the lower and upper limits of the IOM GWG recommendations by the expected GWG within http://bmjpaedsopen.bmj.com/ 31 32 each pre-pregnancy BMI category. Pre-pregnancy BMI and GWG (calculated as the difference between 33 observed and expected weight gain, based on the above methods) will also be examined as continuous 34 35 variables. 36 37 38 Outcomes 39 40 Asthma, rhinitis, atopic dermatitis, and anaphylaxis will be examined separately during follow-up based on September 25, 2021 by guest. Protected copyright. 41 on International Classification of Diseases (ICD)-9 and ICD-10 diagnostic codes in health administrative 42 43 datasets (DAD, NACRS, and OHIP). ICD codes and algorithms can be found in Supplementary File A. 44 We will employ a time-to-first-event analysis for all outcomes, in which the follow-up period will begin 45 46 at birth and continue until either the outcome occurs, the infant dies or becomes ineligible to receive 47 healthcare services (with a 90-day grace period), or until the end of the study period, whichever comes 48 49 first. Follow-up time (person-days) will be calculated for each event separately. Asthma. Using a 50 51 validated algorithm, the ASTHMA database will identify infants with asthma diagnoses. The algorithm 52 requires ≥1 hospitalization and/or ≥2 ambulatory care visits for asthma within two years, where the 53 54 earliest claim is deemed the date of diagnosis.27 The algorithm was first validated among children in 2006 55 (ages 1–8; sensitivity: 91%, specificity: 83%),28 and was recently re-validated in 2019 among younger 56 57 58 59 6 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 8 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 children (ages 1–5; sensitivity: 81%, specificity: 90%).29 Since the accuracy of asthma diagnoses among 4 5 young infants is debated, records fulfilling the algorithm for asthma diagnosis before the age of 6 months 6 will be disregarded unless a further hospitalization or ambulatory care visit for asthma is detected after 12 7 8 months of age.30 Rhinitis and atopic dermatitis. Rhinitis and atopic dermatitis cases will be captured by 9 an algorithm from Hill and colleagues, which requires ≥2 care visits occurring ≥6 months apart and where 10 Confidential: For Review Only 11 the date of diagnosis is the first visit. These algorithms displayed positive predictive values of 100% and 12 31 13 90% based on chart review, respectively (no sensitivity or specificity measures were published). 14 Anaphylaxis. We will employ criteria A and B from the algorithm by Walsh and colleagues32 to detect 15 16 anaphylaxis in inpatient, emergency department, and outpatient encounters using ICD codes for diagnoses 17 and symptoms. In a validation study, this algorithm performed better than those of previous studies, with 18 19 a sensitivity of 91% and positive predictive value of 67%.32 Some modifications were made to the 20 21 algorithm for our study, including the removal of the three procedure/intervention codes which are not 22 available in our outpatient dataset and the inclusion of an ICD code for anaphylactic shock due to food 23 24 reaction due its high prevalence in childhood. 25 26 27 Covariates and Confounders 28 The following covariates and potential confounders will be examined: maternal characteristics (maternal 29 30 country of birth [for recent immigrants, otherwise Canada], maternal age at birth, maternal smoking, http://bmjpaedsopen.bmj.com/ 31 32 parity, maternal asthma and other pre-existing medical conditions, and use of drugs, alcohol, or 33 medications during pregnancy); neighbourhood characteristics, using residential postal codes linked to 34 35 Census data (neighbourhood marginalization index and rural residence); and birth or infant characteristics 36 (mode of delivery, complications of pregnancy, season of birth, sex of infant, gestational age, birth 37 38 weight, and exclusive breastfeeding at time of hospital discharge). Causal assumptions are presented in a 39 11,13 40 directed acyclic graph (DAG; Figure 4), adapted from two published DAGs and supplemented for our on September 25, 2021 by guest. Protected copyright. 41 study through a review of the literature. Before statistical analysis, 10 multiple imputation datasets will be 42 43 generated to deal with missing values. The results from the imputed datasets will be combined to produce 44 final estimates, following best practices.33 45 46 47 Statistical Analyses 48 49 Sample characteristics will be presented as frequencies and proportions for categorical variables and 50 51 means or medians for continuous variables (with measures of spread, such as standard deviation or inter- 52 quartile range), overall and stratified by exposure group to present potential confounding.34 Between 53 54 group-differences will be assessed by standardized differences, which denote differences in units of 55 standard deviation. Standardized differences greater than 10% indicate an imbalance between the 56 57 58 59 7 60 https://mc.manuscriptcentral.com/bmjpo Page 9 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 exposure groups.35 Crude incidence rates (per 100,000 person-days of follow-up) for each study outcome 4 5 will be calculated for each exposure group and graphically presented using cumulative incidence curves. 6 7 8 For the primary analyses, Cox proportional-hazards regression models will be employed to produce 9 hazard ratios (HR) with 95% confidence intervals (95% CI). Crude and adjusted analyses (utilizing 10 Confidential: For Review Only 11 multivariable analysis methods) will assess differences in pediatric allergic disease incidence: 1) between 12 13 infants born to underweight, overweight, or obese mothers compared to those born to mothers with 14 normal pre-pregnancy weight; and 2) between infants born to mothers who fell below or exceeded 15 16 recommended GWG guidelines compared to those who met the GWG recommendation. Models will be 17 adjusted for maternal age, maternal birth country, maternal pre-pregnancy health conditions, maternal 18 19 medication and substance use during pregnancy, neighbourhood characteristics, and parity—the minimal 20 21 sufficient adjustment set identified in the DAG (Figure 4). Cox models will account for repeated 22 pregnancies during the 2012–2014 period by adjusting the variance through generalized estimating 23 24 equation (GEE) methods.36 The following effect measure modifiers have been selected a priori: pre- 25 pregnancy BMI (when GWG is the exposure), GWG (when pre-pregnancy BMI is the exposure), and 26 27 infant sex. If estimates between strata are qualitatively different, we will introduce an interaction term or 28 report strata-specific estimates based on published guidelines.37 The proportional hazards assumption of 29 30 the Cox models will be assessed through Schoenfeld residual plots and Wald tests for interaction between http://bmjpaedsopen.bmj.com/ 31 32 exposure status and time. In secondary analyses, continuous measures of the exposures will be used and 33 restricted cubic splines will be added to the Cox proportional-hazards models to account for non-linear 34 35 associations between exposures and outcomes.38 All analyses will be conducted using SAS version 9.4 36 (SAS Institute, Cary, NC). 37 38 39 40 Pre-planned Sensitivity Analyses on September 25, 2021 by guest. Protected copyright. 41 Assessment of Potential Selection Biases and Residual Confounding 42 43 1. A complete case analysis will be conducted. 44 2. To understand the impact of exclusion criteria on selection bias, sociodemographic information of 45 46 response, complete-case, and imputed samples will be compared.34 47 3. To account for potential residual confounding by maternal propensity to access healthcare 48 49 services, we will assess typical maternal healthcare utilization through outpatient visits in the 50 51 OHIP database during a one-year look-back period before pregnancy and adjust for this in our 52 models. Only mothers who were continuously eligible for OHIP during the look-back period will 53 54 be included. 55 56 57 58 59 8 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 10 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 Assessment of Potential Exposure Misclassification 4 4. To ensure that self-reported maternal weight does not bias our results, a subgroup analysis will be 5 6 undertaken among the subset of participants with pre-pregnancy weight recorded in the prenatal 7 encounter of the BIS database. 8 9 10 11 AssessmentConfidential: of Potential Outcome Misclassification For Review Only 12 5. Researchers from Denmark created39 and validated40 algorithms that employ hospital diagnoses 13 14 and dispensed prescription medications to identify cases of rhinitis (sensitivity: 84%, specificity: 15 82%) and atopic dermatitis (sensitivity: 74%, specificity: 73%) in childhood compared to parental 16 17 reports of physician diagnoses. In our study, data on prescription medications dispensed can only 18 be ascertained for the subset of participants who were covered by the provincial drug funding 19 20 system (Ontario Drug Benefit, ODB). Residents of Ontario qualify for ODB if they are either ≥65 21 22 years old or are enrolled in one of the following provincial programs: home care and community 23 services, employment assistance, assistance for persons with disabilities, or assistance with 24 25 prescription-drug costs for those in financial need; starting on 1 January 2018, ODB was 26 extended to any resident of Ontario covered by OHIP+: Children and Youth Pharmacare (≤24 27 28 years old). We will run a sensitivity analysis using these derived algorithms for rhinitis and atopic 29 30 dermatitis in the subgroup of children whose families qualified for ODB (see Supplementary File http://bmjpaedsopen.bmj.com/ 31 A for algorithms and codes). 32 33 6. We believe that the algorithms employed may result in non-differential outcome 34 misclassification, which usually produces bias towards the null or, in some circumstances, no 35 36 bias.41 A probabilistic bias analysis will be conducted to evaluate the influence of this 37 misclassification, following published methods.42 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 PATIENT AND PUBLIC INVOLVEMENT 42 Patients and the public were not involved in the development of the protocol. 43 44 45 ETHICS AND DISSEMINATION 46 47 Approval was obtained from the Research Ethics Board of the Children’s Hospital of Eastern Ontario 48 49 (protocol No 19/14PE) and the ICES Privacy Office (protocol No 2020 0901 237 000). Individual patient 50 consent is not required for secondary analyses of routinely collected data, pursuant to privacy legislation 51 52 in Ontario (Personal Health Information Protection Act, 2004). Further, under the same legislation, 53 BORN and CIHI can collect, use, and disclose personal health information without consent. Research 54 55 56 57 58 59 9 60 https://mc.manuscriptcentral.com/bmjpo Page 11 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 finding will be disseminated to public health audiences through presentations at scientific conferences and 4 5 publications in peer-reviewed journals. 6 7 8 FOOTNOTES 9 Author Contributions 10 Confidential: For Review Only 11 Conceptualization—SAS, DBF, RF, LG; Funding acquisition—SAS, DBF, LG; Methodology—SAS, 12 13 DBF, DC, YG, RF, LG; Supervision—DBF, LG; Writing, original draft—SAS; Writing, review & 14 editing—SAS, DBF, RF, DC, YG, LG. 15 16 17 Funding 18 19 This work was supported by a Canadian Institutes of Health Research (CIHR) Foundation Grant (grant 20 21 No FDN-148438) to LG, a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship – 22 Master’s Award and an Ontario Graduate Scholarship to SAS, and by ICES, which is funded by an annual 23 24 grant from the Ontario Ministry of Health and Long-term Care (MOHLTC). The funders had no role in 25 the study design or manuscript preparation or publication decisions. The opinions, results and conclusions 26 27 reported in this article are those of the authors and are independent from the funding sources. No 28 endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material 29 30 are based on data and/or information compiled and provided by CIHI. However, the analyses, http://bmjpaedsopen.bmj.com/ 31 32 conclusions, opinions and statements expressed in the material are those of the author(s), and not 33 necessarily those of CIHI. This Study is based in part on data provided by Better Outcomes Registry and 34 35 Network (“BORN”), part of the Children’s Hospital of Eastern Ontario. The interpretation and 36 conclusions contained herein do not necessarily represent those of BORN Ontario. 37 38 39 40 Competing Interests on September 25, 2021 by guest. Protected copyright. 41 None declared. 42 43 44 Patient consent for publication 45 46 None required. 47 48 49 Ethical Approval 50 51 Research Ethics Board of the Children’s Hospital of Eastern Ontario (protocol No 19/14PE) and the ICES 52 Privacy Office (protocol No 2020 0901 237 000). 53 54 55 Data Sharing 56 57 58 59 10 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 12 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 The data set from this study is held securely in coded form at ICES. While data sharing agreements 4 5 prohibit ICES from making the data set publicly available, access may be granted to those who meet pre- 6 specified criteria for confidential access, available at www.ices.on.ca/DAS. The full data set creation plan 7 8 and underlying analytic code are available from the authors upon request, understanding that the 9 10 programs may rely upon coding templates or macros that are unique to ICES. 11 Confidential: For Review Only 12 13 REFERENCES 14 1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO 15 consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1–253. 16 17 2. Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse 18 consequences for mother and child. BMJ. 2017;356:j1. 19 20 3. McDonald SD, Woolcott C, Chapinal N, Guo Y, Murphy P, Dzakpasu S. Interprovincial variation in 21 22 pre-pregnancy body mass index and gestational weight gain and their impact on neonatal birth 23 weight with respect to small and large for gestational age. Can J Public Health. 2018;109(4):527– 24 38. 25 26 4. Hersoug L-G, Linneberg A. 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The relationship on September 25, 2021 by guest. Protected copyright. 41 between maternal adiposity and infant weight gain, and childhood wheeze and atopy. Thorax. 42 2013;68(4):372–9. 43 44 9. Reichman NE, Nepomnyaschy L. Maternal Pre-Pregnancy Obesity and Diagnosis of Asthma in 45 Offspring at Age 3 Years. Matern Child Health J. 2008;12(6):725–33. 46 47 48 10. Polinski KJ, Liu J, Boghossian NS, McLain AC. Maternal Obesity, Gestational Weight Gain, and 49 Asthma in Offspring. Prev Chronic Dis. 2017;14:E109. 50 51 11. Dumas O, Varraso R, Gillman MW, Field AE, Camargo CA. Longitudinal study of maternal body 52 mass index, gestational weight gain, and offspring asthma. Allergy. 2016;71(9):1295–304. 53 54 12. Scholtens S, Wijga AH, Brunekreef B, Kerkhof M, Postma DS, Oldenwening M, et al. Maternal 55 overweight before pregnancy and asthma in offspring followed for 8 years. 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Chen Y, Zhu J, Lyu J, Xia Y, Ying Y, Hu Y, et al. Association of Maternal Prepregnancy Weight and 30 Gestational Weight Gain With Children’s Allergic Diseases. JAMA Netw Open. http://bmjpaedsopen.bmj.com/ 31 2020;3(9):e2015643. 32 33 20. Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of 34 studies Conducted using Observational Routinely-collected health Data (RECORD) statement. 35 PLoS Med. 2015;12(10):e1001885. 36 37 38 21. Schneeweiss S, Rassen JA, Brown JS, Rothman KJ, Happe L, Arlett P, et al. Graphical Depiction of 39 Longitudinal Study Designs in Health Care Databases. Ann Intern Med. 2019;170(6):398–406. 40 on September 25, 2021 by guest. Protected copyright. 41 22. Ismail LC, Bishop DC, Pang R, Ohuma EO, Kac G, Abrams B, et al. Gestational weight gain 42 standards based on women enrolled in the Fetal Growth Longitudinal Study of the 43 INTERGROWTH-21st Project: a prospective longitudinal cohort study. BMJ. 2016;352. 44 45 23. Dayan N, Fell DB, Guo Y, Wang H, Velez MP, Spitzer K, et al. Severe maternal morbidity in women 46 with high BMI in IVF and unassisted singleton pregnancies. Hum Reprod. 2018;33(8):1548–56. 47 48 24. Inskip H, Crozier S, Baird J, Hammond J, Robinson S, Cooper C, et al. Measured weight in early 49 pregnancy is a valid method for estimating pre-pregnancy weight. J Dev Orig Health Dis. 2020;1–9. 50 51 25. Institute of Medicine and National Research Council. Weight Gain During Pregnancy: Reexamining 52 the Guidelines. Washington, DC: The National Academies Press; 2009. 53 54 55 56 57 58 59 12 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 14 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 26. Guo Y, Miao Q, Huang T, Fell DB, Harvey ALJ, Wen SW, et al. Racial/ethnic variations in 4 gestational weight gain: a population-based study in Ontario. Can J Public Health. 5 2019;110(5):657–67. 6 7 27. Gershon AS, Wang C, Guan J, Vasilevska-Ristovska J, Cicutto L, To T. Identifying patients with 8 physician-diagnosed asthma in health administrative databases. Can Respir J. 2009;16(6):183–8. 9 10 28. To T, Dell S, Dick PT, Cicutto L, Harris JK, MacLusky IB, et al. Case verification of children with 11 Confidential: For Review Only 12 asthma in Ontario. Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol. 13 2006;17(1):69–76. 14 15 29. Omand JA, Maguire JL, O’Connor DL, Parkin PC, Birken CS, Thorpe KE, et al. Agreement between 16 a health claims algorithm and parent-reported asthma in young children. Pediatr Pulmonol. 17 2019;54(10):1547–56. 18 19 30. Radhakrishnan DK, Dell SD, Guttmann A, Shariff SZ, Liu K, To T. Trends in the age of diagnosis of 20 childhood asthma. J Allergy Clin Immunol. 2014;134(5):1057-1062.e5. 21 22 31. Hill DA, Grundmeier RW, Ram G, Spergel JM. The epidemiologic characteristics of healthcare 23 provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: a retrospective 24 cohort study. BMC Pediatr. 2016;16:133. 25 26 32. Walsh KE, Cutrona SL, Foy S, Baker MA, Forrow S, Shoaibi A, et al. Validation of anaphylaxis in 27 the Food and Drug Administration’s Mini-Sentinel. Pharmacoepidemiol Drug Saf. 28 2013;22(11):1205–13. 29 30 33. Sterne JAC, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, et al. Multiple imputation for http://bmjpaedsopen.bmj.com/ 31 missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393. 32 33 34. Hayes-Larson E, Kezios KL, Mooney SJ, Lovasi G. Who is in this study, anyway? Guidelines for a 34 useful Table 1. J Clin Epidemiol. 2019;114:125–32. 35 36 35. Austin PC. Using the Standardized Difference to Compare the Prevalence of a Binary Variable 37 Between Two Groups in Observational Research. Commun Stat - Simul Comput. 2009;38(6):1228– 38 39 34. 40 on September 25, 2021 by guest. Protected copyright. 41 36. Louis GB, Dukic V, Heagerty PJ, Louis TA, Lynch CD, Ryan LM, et al. Analysis of repeated 42 pregnancy outcomes. Stat Methods Med Res. 2006;15(2):103–26. 43 44 37. Knol MJ, VanderWeele TJ. Recommendations for presenting analyses of effect modification and 45 interaction. Int J Epidemiol. 2012;41(2):514–20. 46 47 38. Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic 48 Regression, and Survival Analysis. New York: Springer International Publishing; 2015. 49 50 39. Henriksen L, Simonsen J, Haerskjold A, Linder M, Kieler H, Thomsen SF, et al. Incidence rates of 51 atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy 52 Clin Immunol. 2015;136(2):360-366.e2. 53 54 55 56 57 58 59 13 60 https://mc.manuscriptcentral.com/bmjpo Page 15 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from MATERNAL WEIGHT AND PEDIATRIC ALLERGIC DISEASE 1 2 3 40. Stensballe LG, Klansø L, Jensen A, Hærskjold A, Thomsen SF, Simonsen J. The validity of register 4 data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis. Pediatr 5 Allergy Immunol. 2017;28(6):535–42. 6 7 41. Rothman KJ, Greenland S, Lash TL. Section II: Study Design and Conduct. In: Modern 8 Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. 9 10 42. Fox MP, Lash TL, Greenland S. A method to automate probabilistic sensitivity analyses of 11 Confidential: For Review Only 12 misclassified binary variables. Int J Epidemiol. 2005;34(6):1370–6. 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 14 60 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 16 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 !%')$&+#!'( )*"+&#&" 25 26 27 'B($A3/<=$:82$/>$392$:4$=>?2A$;3<7:2 28 29 30 &B'$A3/<=$:82$/>$392$:4$=>?2A$;3<7:2 http://bmjpaedsopen.bmj.com/ 31 32 33 #!"#B"$ #!"$B"% #!")B"* 34 35 !$#&%"' ) -395>6$:4$=>?2A$;3<7:2$4:<$>@:$>@:?A3/<$07<>6$1:6:<>= $,/16$07<>6$1:6:<>$=>/<>=$:9$+;<78$"! /92$392=$ 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
Page 17 of 88 BMJ Paediatrics Open Better Outcomes Registry & Network (BORN) To define birth cohort and Information System (BIS) include detailed clinical and 1 Confidential:demographic information about For ReviewProvincial birth registry; includesOnly clinical and 2 the birth and the mother demographic information from the Prenatal Screening 3 Ontario (PSO) and Labour & Birth encounters 4 5 6 Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) 7 8 Includes hospital admissions 9 10 CIHI National Ambulatory Care Reporting System 11 To ascertain outcomes from (NACRS) clinical encounters 12 Includes emergency department visits 13 14 15 Ontario Health Insurance Plan (OHIP) Database 16 Includes ambulatory physician visits 17 18 19 Ontario Asthma Surveillance Information System 20 (ASTHMA)
21 Includes prevalent or incident cases of asthma among http://bmjpaedsopen.bmj.com/ 22 Sources Data mothers and offspring 23 24 Ontario Drug Benefit (ODB) 25 26 Includes dispensed prescription medications for outcome 27 sensitivity analyses 28 To include additional information on the mother or 29 infant Ontario portion of the federal Immigration, Refugees 30 and Citizenship Canada (IRCC) Permanent Resident Database
31 on September 25, 2021 by guest. Protected copyright. 32 Includes information on maternal country of birth 33 34 35 Ontario Marginalization Index (ON-Marg) 36 Includes information on economic, ethno-racial, age- 37 https://mc.manuscriptcentral.com/bmjpobased, and social marginalization of the mother’s 38 neighbourhood 39 40 41 42 Figure 2. Data sources at ICES to be used in this study. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
Maternal Entry Date BMJ PaediatricsInfant Entry Date Open Page 18 of 88 (Last menstrual period) (Date of birth) Confidential:Day -280 a ForDay 0 Review Only 1 2 PREGNANCY
3 Exclusion Assessment Window LEGEND 4 (Administrative and sample exclusions b) Days [-280, -280] 5 Maternal 6 Exclusion Assessment Window (Ineligible to receive health care) Infant 7 Days [-280, 0] 8 Exposure Assessment Window 9 (Pre-pregnancy BMI) 10 Days [-280, -280] 11 Exposure Assessment Window 12 (GWG) 13 Days [-280, 0]
14 Covariate Assessment Window 15(Maternal characteristics and pre-existing conditions c) 16 Days [-280, -280]
17 Sensitivity Analysis
18 Covariate Assessment Window http://bmjpaedsopen.bmj.com/ (Health-care utilization d) 19 Days [-645, -280] 20 21 Exclusion Assessment Window 22 (Not singleton live birth; invalid infant identification code) Days [0, 0] 23 24 Exclusion Assessment Window (ineligible to receive health care) 25 Days [0, 60] 26 Covariate Assessment Window 27 (Infant characteristics)
28 Days [0, 0] on September 25, 2021 by guest. Protected copyright. 29 30 Follow-up Window 31 Days [0, Censor] https://mc.manuscriptcentral.com/bmjpo 32 33 Time 34 35 Figure 3. Study design and cohort structure. Adapted from Schneeweiss et al, 2019. Abbreviations: BMI, body-mass index; GWG, gestational 36 weight gain. Numbers in square brackets represent date ranges relative to the date of birth (day 0). 37 a For the purposes of illustrating the temporal relationship between maternal and infant study variables, the date of the LMP is shown as day -280 38 (i.e. 40 completed weeks of gestation). In the study, this will depend on the actual length of gestation. 39 b Sample exclusions include: non-Ontario resident; stillbirth; twin or higher-order multiple birth; mother’s age outside probable range (i.e. <12 years or >50 years); and infant died on date of birth. Administrative exclusions include: duplicate records in BORN; invalid linkages and linkage 40 warnings; invalid infant and mother identifiers; mothers without continuous OHIP eligibility throughout pregnancy; and infants who did not have 41 records of health care eligibility within 90 days of birth. c Pre-existing maternal conditions are ascertained on delivery record but reflect previous history. 42 d Only mothers who were continuously eligible to receive health care (OHIP) during the one-year period will be included. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
Page 19 of 88 BMJ Paediatrics Open Confidential: For Review LEGENDOnly 1 2 3 4 5 6 7 8 9 10 11 12 13 14 http://bmjpaedsopen.bmj.com/ 15 16 17 18 19 20 21 22 23 24 https://mc.manuscriptcentral.com/bmjpo on September 25, 2021 by guest. Protected copyright. 25 26 27 Figure 4. Directed acyclic graph (DAG) of causal assumptions. Adapted from Dumas et al., 2016 and Harskamp-van Ginkel et al., 2015. 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Paediatrics Open Page 20 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 2 Original Algorithm: Gershon et al, 2009 3 Uses ICD-10 4 5 Algorithm Original ICD Code Disease/Disorder Mapped ICD Disease/Disorder 6 ≥1 hospitaliza on J45 Asthma 493Code Asthma 7 and/or ≥2 8 ambulatory care 9 visits for asthma 10 within two years 11 Confidential: For Review Only 12 J46 Status asthma cus 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 Page 21 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Hill et al, 2016 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD Code Disease/Disorder 3 ≥2 care visits occurring ≥6 477 Allergic Rhini s J301–J304 Allergic Rhini s 4 months apart
5 SENSITIVITY ANALYSIS Original Algorithm: Stensballe et al, 2017 6 Uses ICD-10
7 Algorithm Original ICD/DIN Code Disease/Disorder Mapped ICD/DIN Code Disease/Disorder ≥1 hospital contact for: J30 Hay Fever and Allergic Rhini s 477 Allergic Rhini s 8 J30.0 Vasomotor Rhini s J30.1 Allergic Rhini s due to Pollen 9 J30.2 Other Seasonal Allergic Rhini s J30.3 Other Allergic Rhini s 10 J30.4 Allergic Rhini s, Unspecified 11 J31.0Confidential:Chronic Rhini s For Review Only OR ≥2 filled prescrip ons of: Inhaled Cor costeroids for Rhini s Inhaled Cor costeroids for Rhini s Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 12 Excluding: J33 Nasal Polyps 471 Nasal Polyps J330 Polyps in Nasal Cavity 13 J331 Polyp Related Sinus Degenera on 14 J331A Woakes' Ethmoidi s J338 Nasal Polyps, Other 15 J338A Polypus Sinus Sphenoidalis J339 Nasal Polyps, Unspecified 16 J010-J019 Acute Sinusi s 461 Acute Sinusi s J320-J3290 Chronic Sinusi s 473 Chronic Sinusi s 17 OR ≥2 filled prescrip ons of: An histamines for Systemic Use An histamines for Systemic Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 18 Excluding: L29 Pruritus 698 Pruritus and related condi ons L50 Allergic Ur caria 708 Ur caria 19 OR ≥1 filled prescrip ons of: Specific Immune Therapy, Allergen Specific Immune Therapy, Allergen Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 20 Substract Therapy Substract Therapy Medica on for Allergic Conjunc vi s Medica on for Allergic Conjunc vi s Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 BMJ Paediatrics Open Page 22 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Hill et al, 2016 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD Code Disease/Disorder 3 ≥2 care visits occurring ≥6 691 Atopic derma s and related condi ons L20 Atopic Derma s and Related Condi ons 4 months apart 5 SENSITIVITY ANALYSIS Original Algorithm: Stensballe et al, 2017 6 Uses ICD-10 Algorithm Original ICD/DIN Code Disease/Disorder Mapped ICD/DIN Code Disease/Disorder 7 ≥1 hospital contact for: L20 Atopic Derma s 691 Atopic derma s and related condi ons Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 8 Excluding: 691.0 Diaper or Napkin Rash Added this exclusion since L20 doesn't include diaper rash but 691 does 9 OR ≥1 filled prescrip ons of: Agents for Derma s: Tacrolimus, Pimecrolimus Agents for Derma s: Tacrolimus, Pimecrolimus Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Excluding: Exclusion criteria below 10 OR ≥2 filled prescrip ons of Cor costeroids for Topical Use Cor costeroids for Topical Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 11 the code within 12 months: Confidential: For Review Only If above prescrip on is: Cor costeroids, very potent (group IV) Cor costeroids, very potent (group IV) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 12 Then also with either (as Cor costeroids, weak (group I) Cor costeroids, weak (group I) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab atopic derma s is never 13 treated alone with group IV): Cor costeroids, moderately potent (group II) Cor costeroids, moderately potent (group II) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 14 Cor costeroids, potent (group III) Cor costeroids, potent (group III) Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Excluding: Exclusion criteria below 15
16 Exclusion Criteria 17 Exclude those without: L20 Atopic Derma s 691 Atopic derma s and related condi ons Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes AND with: L21 Seborrhoeic Derma s 690.1 Seborrheic derma s L22 Diaper Derma s 691.0 Diaper or Napkin Rash 18 L23 Allergic Contact Derma s 692 Contact derma s and other eczema L24 Irritant Contact Derma s 19 L25 Unspecified Contact Derma s L26 Exfolia ve Derma s 695.89 Other Specified Erythematous Condi ons 20 L27 Derma s due to Substances Taken Internally 693 Derma s due to Substances Taken Internally L28 Lichen Simplex Chronicus and Prurigo 698.2, 698.3 Prurigo & Lichenifica on 21 L29 Pruritus 698.0, 698.1, 698.8, Pruritus ani, Pruritus of genitalia, Pruri c 698.9 condi ons NEC & Pruri c disorder NOS 22 L30 Other Derma s 692.9, 705.81, 690.8, Derma s NOS, Dyshidrosis, Erythmtsquamous Removed 'except Winter Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 696.5 derm NEC & Pityriasis NEC & NOS 23 L40 – L45 Papulosquamous Disorders 696.0 - 696.4, 696.8, Psoria c arthropathy, Other psoriasis, 694.3, 697.0, 697.1, Parapsoriasis, Pityriasis rosea, Pityriasis rubra 697.8, 057.8, 709.8 pilaris, Psorias related dis NEC, Impe go 24 herpe formis, Lichen planus, Lichen ni dus, Lichen NEC, Viral exanthemata NEC & Skin 25 disorders NEC L53 Other Erythematosus Condi ons 695.0, 695.89, 695.9 Toxic erythema, Erythematous cond NEC & 26 Erythematous cond NOS L55 Sunburn 692.71, 692.76, 692.77 Sunburn, 2nd degree sunburn & 3rd degree 27 sunburn L56 Other Acute Skin Changes due to Ultraviolet 692.72, 692.82, 692.75, Acute derma s due to solar radia on, Derma s 28 Radia on 692.79 due to other radia on, Disseminated superficial ac nic porokeratosis (DSAP) & Other derma s 29 due to solar radia on L80 Vi ligo 709.01 Vi ligo 30 L90 Atrophic Disorders of the Skin 701.0, 701.3, 701.8, Circumscribe scleroderma, Striae atrophicae, 701.9, 709.2 Other specified hypertrophic and atrophic http://bmjpaedsopen.bmj.com/ condi ons of skin, Unspecified hypertrophic and 31 atrophic condi ons of skin & Scar condi ons and fibrosis of skin
32 L93 Lupus Erythematosus 695.4 Lupus Erythematosus
33 OR ≥1 filled prescrip on of: An psoriasics An psoriasics Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Salicylates for Dermatological Use Salicylates for Dermatological Use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 34 Cor costeroids Moderately Potent Other Cor costeroids Moderately Potent Other Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Combina ons Combina ons 35 Cor costeroids Potent Other Combina ons Cor costeroids Potent Other Combina ons Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab Cor costeroids (Group IV) Clobetasol Cor costeroids (Group IV) Clobetasol Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 36 Clobetasol and An bio cs Clobetasol and An bio cs Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab AND with: An fungals (implies cor costeroid (group IV) use for An fungals (implies cor costeroid (group IV) use Original ATC codes were mapped to Canadian Drug Iden fica on Numbers (DIN) on the last tab 37 vaginal fungal infec on) for vaginal fungal infec on) 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 Page 23 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Original Algorithm: Walsh et al, 2013 2 Uses ICD-9 Algorithm Original ICD Code Disease/Disorder Mapped ICD/CCI Code Disease/Disorder 3 In an inpa ent or 995.0 Other Anaphylac c Shock T78.2 Anaphylac c Shock, Unspecified emergency department 4 encounter (i.e. DAD 5 or NACRS) either: 999.4 Anaphylac c Shock due to Serum T80.5 Anaphylac c Shock due to Serum 995.6 Anaphylac c Shock due to Adverse Food Reac on T78.0 Anaphylac c Shock due to Adverse Food Added this code due to high prevalence food-induced anaphylaxis among 6 Reac on young children. First-author of original paper said that they didn't include the code since they were mostly interested in anaphylaxis due to medica ons, but that the addi on of this code was a good approach if food-induced anaphylaxis 7 was important to our study. 8 T886 Anaphylac c shock due to adverse effect of correct drug or medicament properly 9 administered
10 OR in an outpa ent 995.0 Other Anaphylac c Shock T78.2 Anaphylac c Shock, Unspecified encounter (i.e. OHIP) 11 either: Confidential: For Review Only 999.4 Anaphylac c Shock due to Serum T80.5 Anaphylac c Shock due to Serum
12 995.6 Anaphylac c Shock due to Adverse Food Reac on T78.0 Anaphylac c Shock due to Adverse Food Same comment as above Reac on 13 T88.6 Anaphylac c shock due to adverse effect of correct drug or medicament properly 14 administered AND at least one of: 519.11 Bronchospasm J98.01 Acute Bronchospasm 15 786.1 Stridor R06.1 Stridor 458.9 Hypotension I95.9 Hypotension, Unspecified The three interven on codes in the original algorithm (epinephrine, injec on 16 of diphenhydramine, and CPR) did not have analogous OHIP fee codes. As such, 17 we could not include these in our algorithm. 18 19 20 21 22 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 BMJ Paediatrics Open Page 24 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Mapped using the WHO ATC/DDD Index 2020 (h ps://www.whocc.no/atc_ddd_index/) and the ICES DRUGLIST excel 2 Original Name Original ATC Code Drug DIN 3 For Rhini s Algorithm Inhaled R01AD01 – R01AD60 Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 4 Cor costeroids for 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 Rhini s 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 5 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 6 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 00237663 00237698 7 00806994 00807001 01934546 01944819 Prednisolone + combina ons 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00194875 00030739 00030740 00030759 00030767 00031062 8 00386847 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00895962 00194867 00806935 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 9 02063700 02063719 02063727 02230210 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00194859 00021679 00031003 00178926 00210692 00544817 00993610 00813680 00028118 00093602 00250376 00252492 00278912 10 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 Confidential:00961264 01916181 01916203 For 02023768 99100258 Review99100485 99100550 99113742 00042617 00042625Only 00042633 00045632 00177024 00307246 11 00395145 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00218812 00281824 00527998 00760056 00808199 00843741 00903477 02133342 00544833 01924400 12 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 00003603 00007668 00010197 00021687 00021695 00093629 00153710 00156876 00178934 00210188 00232092 00232378 00252417 00271373 00271381 00280852 00312770 00508586 13 00550957 00589194 00598194 00607517 00610623 00868426 00868434 00868442 00901425 00999108 06623833 09857797 09857798 09857799 14 99100988 00154008 00023833 15 Dexamethasone + 00229652 00778907 00016217 00379689 00778915 02252716 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 16 combina ons 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 17 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00140449 00173592 00173606 00228052 01987712 01987720 02224623 02224631 02247920 00285110 00626597 00140732 00042668 18 00042676 00358177 02023806 02023849 00229679 00308455 00617199 00874582 00800767 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 19 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 00016268 20 21 Flunisolide 00421456 00588997 00790486 00878790 01927187 02162687 02230306 02239288 02240956 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 22 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 23 Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 24 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 25 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 26 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 27 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 28 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 29 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 30 95000467 99113736 99900015 http://bmjpaedsopen.bmj.com/ 31 32 xocortol + combina ons 00609110 x Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 33 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 02460513 34 02467895 02467909 02467917 77700002 77700003 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 35 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 36 Triamcinolone § 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 37 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 38 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 39 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 40 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 on September 25, 2021 by guest. Protected copyright. 09857128 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 41 02470632 42 flu casone furoate + 02432889 02446561 02446588 02474522 02408872 02444186 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 43 combina ons 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 44 02298589 02336405 02453738 02460513 02467895 02467909 02467917 77700002 77700003 02240835 02240836 02240837 02245125 02245126 02245127 02474611 02474638 02474646 02494507 02494515 02494523 02495597 02495600 02495619 45 46 ciclesonide None found. 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo1 Page 25 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 hydrocor sone, combina ons 02242485 00068772 00068780 00243124 00243132 00520322 00666246 00701904 00091820 00662461 00086096 00426350 00568074 00806099 2 00900737 01937979 00578533 00578541 00856711 00768069 00155977 00156175 00163511 00163538 00438669 00704555 00704563 00750670 00763543 00837350 01980572 01980580 02240035 00074489 00074497 00074500 00074527 00193410 00193429 00245399 00338605 00774489 3 00807079 00807087 00807095 00807109 00811467 00091448 00215686 00216828 00521205 00521213 00521221 00449768 00456403 00203378 00445045 00476439 00229679 00387592 00448710 00530085 00530093 00807656 00807664 02226383 02226391 02247882 00173614 00173615 4 00173622 00807621 00813060 01988549 01988573 02223252 02223260 02242527 02242528 02247322 00534838 00534846 02463512 02238578 00209465 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 5 00157880 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 6 00461903 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 7 00740330 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 8 00960535 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 9 66123379 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 10 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00990313 00216941 Confidential:00216968 00216976 00801666 For 00145718 00390748 Review00390798 00068667 00068675 00191282 00243140Only 00243159 00281816 00530611 00626600 11 00666211 00694401 00813559 00912828 01912828 02025736 02230386 00158046 00158178 00443298 00770957 01954210 00192678 00241067 00364134 00681989 00681997 00733083 00895911 02010720 80061502 80073645 80073689 00000671 00016276 00020818 00020826 00024775 12 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 13 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00063312 00063313 00576514 00194883 00194891 00194913 00194921 00194948 00194956 14 00806897 00807346 00363014 00203505 00203513 00395765 00427497 00476226 00476242 00505781 00811513 02234466 02240851 02242797 02247692 00503134 00560022 66894419 80061501 00203483 00319848 00395757 00461717 00476277 00476285 00505773 00511781 00607789 15 An histamines for R06A Bromazine None00811505 found. 00894761 00897434 00898325 00363847 00385700 00404411 00607797 00885738 02128446 02179547 02209764 02210517 02236399 16 Systemic Use Diphenhydramine + 02246449 02246450 02358689 02289407 00022756 00022757 00022764 00022918 00023191 00023205 00130974 00155276 00271411 00304387 17 combina ons 00337404 00337412 00370517 00421197 00439118 00443441 00450839 00479764 00487791 00489867 00504653 00509345 00554294 00556726 00583332 00596612 00610755 00622796 00622818 00728152 00728160 00728162 00754889 00757683 00757691 00792705 00804193 00804401 18 00811432 00833266 00843482 00843490 00878200 00878634 00880043 00960314 01900005 01907034 01933434 01933442 01933450 01934414 01944290 01944347 01946986 01949454 01957996 01959395 01991086 01994247 01997025 02017849 02019671 02019698 02019701 02019728 19 02019736 02019744 02061287 02061597 02087588 02097575 02097583 02141728 02141736 02146142 02153165 02164574 02171279 02176483 02176580 02176883 02210657 02219298 02219336 02229492 02229958 02229959 02229960 02230398 02230485 02237169 02237788 02237789 20 02238644 02239029 02239030 02239138 02239548 02241167 02241734 02244203 02245778 02246936 02247037 02247560 02247659 02247762 02248858 02248859 02249529 02251817 02254425 02254433 02257548 02257556 02258250 02258994 02261286 02263882 02270900 02284170 21 02292734 02297701 02297728 02298503 02304244 02304252 02306352 02309629 02309742 02311232 02311240 02311771 02312352 02312360 02318849 02320789 02321076 02321270 02323346 02328895 02348608 02354578 02361256 02365685 02367939 02368374 02369567 02369656 22 02373300 02376202 02383268 02396599 02401932 02404869 02409224 02409240 02409259 02410214 02411415 02419769 02427427 02431181 02431203 02431599 02432129 02434385 02436884 02436930 02445182 02446170 02447827 02447835 02453711 02456303 02464683 02465108 23 02470144 02474867 02478242 02478757 02479710 02483122 02490943 02491850 02492318 02492326 09850791 09850805 66999121 80757683 88907502 99100522 99101300 99101367 02369672 00633917 00258350 00270695 00362611 00454494 02401193 02410583 02430770 02226626 24 02230939 00173568 00173576 02444593 02278170 02280612 02294354 02323915 00466069 00568473 01944789 02280868 02280876 02301717 02376148 02376156 02429721 02478072 02484838 02424630 02355841 22123333 00286710 02246391 02278693 02167670 02279150 02291371 25 02305666 02416050 02362643 02368528 02384175 02387697 01979124 02383357 02385244 02469960 02469944 02238183 02359944 02385619 02356457 02273934 02275961 02276232 02319195 02322099 02326884 02409178 02413280 02420929 02420937 02423200 02432498 02462265 26 02487233 02487276 02487322 02488574 02490498 02046784 02203424 02215241 02215861 02229367 02230424 02237483 02237707 02239514 02240560 02241043 02241995 02242691 02245017 02248700 02250993 02255472 02256576 02258633 02261014 02263874 02294370 02298171 27 02303833 02305305 02322269 02365766 02366797 02368196 02404974 02438348 00156345 00469122 00503215 00806781 00156337 00361909 00420026 00464686 00535230 00659142 00690074 00792160 02190575 02244010 02245019 02245592 02486903 01905635 02005395 02242999 28 00156264 00361887 00361888 00370975 00710822 00766380 00156086 00156094 00156108 00358452 00358460 00462683 00538493 00609188 29 00730556 01945874 01945882 01962507 01962515 02241462 02246696 02310783 00889865 00156116 30 Clemas ne + combina ons 00035971 00349046 00458570 01925946 00728500 01906577 http://bmjpaedsopen.bmj.com/ 31 Chlorphenoxamine + 00006491 x combina ons 32 Diphenylpyraline + 00492744 00524980 00230200 00425125 00462055 00462071 00412651 00242977 00425133 00425141 00467073 00133264 00449024 00449032 combina ons 00462063 00462039 00462047 00522058 00091626 00091634 00091642 00425168 00214027 00425117 01940783 00763527 00091847 00145815 33 00581771 00299596 00299561 00299588 02422964 02437953 00145963 00213543 00218227 34 Carbinoxamine None found. Doxylamine + combina ons 00134155 00545449 00550477 00749052 02048183 02230769 02244662 02485443 00507407 00713465 01946994 00435619 00134104 00460850 35 00373850 00481394 00609129 00806331 02304503 02406187 02413248 02383365 00566829 02047667 02409542 02410737 01982532 01996215 02198924 02248371 02272792 02291339 02293927 02374277 02378655 02380315 02438305 02449188 02492857 02494027 02276879 02291444 36 02458462 02481928 02482401 02483351 02492865 02493322 00237760 00758558 01900501 02050684 02148315 02218836 02239041 02239061 02241706 02248905 02254913 02254921 02258285 02258625 02258927 02260271 02262320 02272369 02273071 02293242 02298414 02307014 37 02335239 02426315 02427923 02472864 02472872 02368536 02427958 02273810 02380307 02437201 02459876 02240302 02245016 02380404 38 02385260 02383608 02388537 02246847 02253267 02255014 Trimethobenzamide 00012769 00013102 00115568 39 Brompheniramine + 02241814 02241813 00295450 00295469 02245301 01900559 01934724 02243945 00026395 00026484 00172227 00172235 00172537 01932535 combina ons 01932543 01932551 01933582 02052482 02229557 00493082 01934716 02244079 00172545 00656828 01934694 02244078 02215314 00172529 40 00533963 00810711 00933620 01933574 01933620 02243969 02245076 02266466 02266474 02267446 02267454 02315483 02315491 02328658 on September 25, 2021 by guest. Protected copyright. 02468204 00172650 01934708 02244080 01933590 00172383 00172391 00172405 00933647 01932608 01933604 01933647 02012146 02024616 41 02243980 02245075 02266180 02266199 02267411 02267438 02277239 02307316 02315475 02468212 00588229 01933639 02043947 02125714 42 02198916 00342718 00589292 00589306 01934686 Dexchlorpheniramine + 00028142 00028207 00176893 00225533 02273330 43 combina ons 44 Dime ndene None found. Chlorphenamine + None found. 45 combina ons Pheniramine None found. 46 Dexbrompheniramine + 00298433 00616869 00411892 00471348 00746304 00808059 00808253 00810577 00905755 02154285 combina ons 47 Talas ne None found. 48 Mepyramine None found. Histapyrrodine + None found. 49 combina ons Chloropyramine + None found. 50 combina ons 51 Tripelennamine 00005703 00074306 00488461 00584096 00623504 00659673 02239338 Methapyrilene None found. 52 Thonzylamine None found. Alimemazine None found. 53 Promethazine + combina ons 00164291 00385948 01937561 02162199 00164267 00385964 01937545 02162180 00209449 00209457 00232920 00236276 00450561 00450588 00518336 00518344 02043459 02043467 02225654 02225662 00164283 00385956 00811211 01937588 02162172 00164186 01927736 00164259 54 00385972 00811203 01937553 02162164 00025380 00025402 00025046 00025429 00025712 00025739 00164038 00164046 00213896 00236764 00248754 00567434 00575178 00575186 00583979 00627607 00911311 01927566 01937685 01937693 01937707 01937715 01937723 02068591 55 02162156 02162202 02162210 02162229 02162237 99101319 99101320 99101340 56 Thiethylperazine 00027324 00027367 00027510 Methdilazine 00003158 00003514 57 Hydroxyethylpromethazine + None found. 58 combina ons 59 60 https://mc.manuscriptcentral.com/bmjpo2 BMJ Paediatrics Open Page 26 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Thiazinam None found. 2 Mequitazine None found. Oxomemazine None found. 3 Isothipendyl None found. Buclizine + combina ons None found. 4 Cyclizine + combina ons 00068586 00318809 00985562 00318795 00004448 00318817 5 Chlorcyclizine None found. Meclizine + combina ons 00901069 00024724 00216151 00220442 02368838 22123148 66903076 90220442 00158127 00221850 6 Oxatomide None found. Ce rizine 01900978 02315963 02427192 00900986 00980986 01900986 02145782 02145790 02223546 02223554 02231603 02238337 02240265 02240266 7 02240910 02241912 02241913 02295059 02295067 02315947 02315955 02316609 02318873 02318881 02318903 02344572 02355868 02358352 02363844 02364689 02368064 02375087 02375095 02408732 02427133 02427141 02432722 02450526 02451751 02451778 02453363 02466171 8 02467577 02486954 02491125 41900986 9 Levoce rizine None found. Bamipine None found. 10 Cyproheptadine 00009989 00010073 00016314 00016454 00757713 02245667 02245668 02332248 09850775 09991029 Confidential:Thenalidine + combina ons None found. For Review Only 11 Phenindamine None found. 12 Antazoline 00005436 x Triprolidine 00004812 00235768 13 Pyrrobutamine + None found. combina ons 14 Astemizole 00610070 00610089 02182912 02184656 02239669 Terfenadine 00590908 00614394 00641774 00786624 00870927 00881694 00893528 00893536 00893552 01905058 01913395 02034433 02034441 02103575 15 02103621 02103648 02130882 02130890 16 Loratadine 00782696 02019973 02237734 02241523 02242957 02243880 02244691 02244692 02251795 02280159 02284669 02366444 02375990 02379481 02390388 02404494 02418959 17 Mebhydrolin None found. Deptropine None found. 18 Keto fen 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 02231680 02242324 02279223 02400871 02489651 19 99400864 Acrivas ne None found. 20 Azelas ne None found. Tritoqualine None found. 21 Ebas ne None found. Pimethixene None found. 22 Epinas ne None found. 23 Mizolas ne None found. Fexofenadine 02231462 02231463 02237296 02237633 02242818 02242819 24 Desloratadine 02243919 02247192 02247193 02298155 02338424 02408740 Rupatadine 02456451 02456478 25 Bilas ne 02454130 x 26 Quifenadine None found. Sequifenadine None found. 27 Specific Immune V01A Allergen extracts and 00006144 00061379 00061387 00061395 00061409 00061441 00099902 00286273 00286281 00499625 00499633 00499641 00499668 00499676 Therapy, Allergen prepara ons 00504572 00514713 00541427 00541435 00541443 00541451 00541478 00583448 00602752 00602760 00602779 00602787 00602795 00602809 28 Substract Therapy 00603384 00605263 00605298 00605301 00605328 00614424 00662283 00705300 00800227 00861081 00861111 00861138 00861162 00861170 00861189 00861219 00861227 00861251 00861286 00861308 00861316 00861332 00861359 00861367 00861375 00861405 00886831 00886912 29 00886920 00888540 00888559 00888613 00888648 00888656 00888796 00888818 00888826 00888834 00888842 00888850 00888877 00888885 00888893 00888915 00888958 00889601 00889628 00889636 00889644 00889709 00889717 00889725 00889733 00889741 00889768 00889776 30 00889784 00889792 00889814 00889822 00889849 00889857 00894346 00894354 00894362 00894524 00894583 00895245 00895296 00895334 00895423 00895431 00895458 00895466 00896853 00896934 00896942 00896950 00897752 00897817 00898422 00898430 00898449 00898465 http://bmjpaedsopen.bmj.com/ 31 00898473 00898481 00898503 00898511 00898538 00898546 00898589 00898597 00898619 00899828 00899836 00899844 00899852 00899895 00899968 00900702 00900818 00906115 00906271 00907529 00907545 00908614 00911496 00967483 00967823 00969702 00990303 00998885 32 00999900 01948873 01959123 01959131 01959133 01959157 01959158 01959166 01959182 02217104 02223961 02226219 02226251 02226286 02226294 02226928 02226944 02230863 02238472 02238473 02238485 02238497 02241328 02242672 02242713 02242714 02242715 02242716 33 02242717 02247755 02247756 02247757 02325470 02325543 09850724 11135717 14048555 66861073 66889210 66889695 66889830 66894699 66895318 66895326 66969680 66969699 66969818 95000650 99000350 99000407 99000415 99000423 99000431 99000458 99000466 99003651 34 99003678 99003686 99003694 99003708 99003716 99003724 99003732 99003740 99003759 99003767 99003775 99003791 99003805 99003813 99003821 99003848 99003856 99003864 99003872 99003880 99003899 99003902 99003910 99003929 99003937 99003945 99003953 99003961 35 99003988 99003996 99004003 99004097 99004100 99100018 99100062 99100225 99100226 99100227 99100228 99100229 99100230 99100267 99100268 99100269 99100270 99100278 99100279 99100280 99100281 99100282 99100284 99100625 99101105 99101106 99101107 99101108 36 99101109 99101110 99101111 99101112 99101113 99101114 99101115 99101117 99101118 99101119 99101120 99101121 99101122 99101123 99101124 99101125 00350245 00966134 00999652 00999938 00999981 09999938 11044212 99100026 02230860 99100021 02220075 01948903 37 01948911 02239410 02217082 02223953 02223988 02231321 02231322 02369737 01959174 02223996 02231325 02270919 02223937 02223945 02231323 02231324 02369745 01948938 01948946 01948881 01948997 01949004 02242666 00504564 02221314 00286303 00299979 00522457 38 00662275 02372428 02238486 02242674 02238501 02242676 00155233 02230864 99100017 01948970 01948989 00299987 00522465 02372444 00648122 00648922 00464988 02241327 02247754 99000547 02238489 02242670 02217457 02235299 02136074 02217465 02238493 02238494 39 02242668 02238500 01948954 01948962 02220091 02220105 99004607 99100016 99100266 02230862 00605271 02220083 02220113 99004593 40 02247753 02247758 99100061 99100063 99100064 99100065 99100066 99100067 99100068 99100070 99100072 99100073 99100074 99100075
99100076 99100077 99100078 99100079 99100080 99100082 99101141 99101142 99101143 99101144 99101145 99101146 99101147 99101148 on September 25, 2021 by guest. Protected copyright. 41 Medica on for S01GX Cromoglicic acid + None99101149 found. 99101150 99101151 99101153 99101155 00888023 02423723 02242669 02432889 02451778 02467577 02240953 02242675 02447231 Allergic combina ons 42 Conjunc vi s Levocabas ne 01945130 02020017 02123363 02131625 43 Spaglumic acid None found. 44 Nedocromil 00766038 02230543 02229636 02230446 02241407 Lodoxamide 00893560 x 45 Emedas ne 02237355 x Azelas ne None found. 46 Keto fen 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 02231680 02242324 02279223 02400871 02489651 99400864 47 Olopatadine 02233143 02305054 02358913 02362171 02402823 02403986 02404095 02420171 02422727 02458411 02458551 48 Epinas ne None found. Alca adine None found. 49 For derma s algorithm 50 Agents for D11AH Tacrolimus 00903944 00950645 00950653 00960039 00960632 00960634 02175983 02175991 02176009 02243144 02244148 02244149 02296462 02296470 Derma s: 02296489 02331667 02416816 02416824 02416832 02454068 02456095 02456109 02485877 02485885 02485893 09851984 09852069 09852662 51 Tacrolimus, 09854786 66123987 66124086 66990973 99108093 99109293 52 Pimecrolimus Pimecrolimus 02247238 x 53 Cromoglicic acid None found. Alitre noin 02240328 02337630 02337649 02477432 02477440 54 Dupilumab 02470365 02492504 Crisaborole 02476991 x 55 Cor costeroids for D07 Methylprednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 56 Topical Use 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 57 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 58 59 60 https://mc.manuscriptcentral.com/bmjpo3 Page 27 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Hydrocor sone 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 2 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 00461903 3 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 00740330 4 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 5 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 6 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 80071959 7 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 8 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 9 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 10 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 11 Confidential: For Review Only 12 Prednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 13 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 14 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 00278912 00299405 00300373 00301175 00622931 00700401 00727466 15 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 16 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 17 Clobetasone 00456543 00456551 00889938 00889946 00894591 02214415 02214423 18 Hydrocor sone butyrate None found. 19 Flumetasone 00005134 00005789 Fluocor n None found. 20 Fluperolone None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 21 Fluprednidene None found. Desonide 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 00889563 02048639 02115514 02115522 02154862 22 02154870 02229315 02229323 02348489 23 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 24 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 25 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 26 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 27 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 28 Alclometasone 02070855 02070871 29 Hydrocor sone buteprate None found. 30 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 http://bmjpaedsopen.bmj.com/ 31 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 32 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 33 00016268 34 Clocortolone None found. Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 35 02048124 02060868 99100868 00028096 02237835 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 36 00895768 00899291 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 37 02122073 02122081 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 99100521 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 38 00027944 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 39 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 40 00889504 00895873 00895881 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 on September 25, 2021 by guest. Protected copyright. 41 02449773 66887323 66907960 95000467 99113736 99900015 42
43 Fluclorolone None found. Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 44 02221934 02239068 02239069 02241887 66889318 45 Fluocinolone acetonide 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 00464627 46 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 00806951 00862347 47 00862355 00862371 00862398 00873292 00886998 00887005 00887013 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 00895105 00895113 00897868 48 00897884 00897892 00897906 00899976 02129078 02162504 02162512 02162520 02162539 02162547 02163470 02163489 02242738 02300559 49 02306980 66030236 66894257 90716790 99100878 99100879 99100883
50 Fluocortolone None found. Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 51 Fludroxycor de None found. 52 Fluocinonide 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 00908282 53 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 02187663 02187671 02236996 02236997 02240269 22369960 66887102 66887129 66887137 54 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 55 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 56 Diflorasone 00481793 00481807 00889377 00889385 00889407 Amcinonide 00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 00894621 00894656 02052881 02154838 02170175 57 02192268 02192276 02192284 02219719 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 02242542 58 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 02257416 02370557 66894648 59 60 https://mc.manuscriptcentral.com/bmjpo4 BMJ Paediatrics Open Page 28 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Halometasone None found. 2 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 3 Methylprednisolone None found. 4 aceponate 5 Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 6 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 7 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 8 9 Hydrocor sone aceponate None found. Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 10 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 Confidential:02237246 02237247 02241752 For 02243646 02244291 Review02244292 02244293 02248307 02294745 02296071Only 02298589 02336405 02453738 02460513 11 02467895 02467909 02467917 77700002 77700003 12 Prednicarbate 02059754 02227517 02230642 Difluprednate 02415534 x 13 Ulobetasol None found. Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 14 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 15 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 16 02490706 66888389 66895083 Halcinonide 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02010283 02010291 02010305 02011921 02200945 17 66887803 66887811 Prednisolone and an sep cs None found. 18 Hydrocor sone and 00063312 00063313 00449768 00456403 00091448 00215686 00216828 00521205 00521213 00521221 00203378 00534838 00534846 00990313 19 an sep cs 00216941 00216968 00216976 00801666 Flumetasone and an sep cs 00074454 00806870 00806889 20 Desonide and an sep cs None found. 21 Triamcinolone and an sep cs 00128031 00128058 Hydrocor sone butyrate and None found. 22 an sep cs 23 Betamethasone and 00271012 00575194 00611174 00813087 00417254 00417262 00811521 00811548 00586692 00586706 00614270 00682217 02244999 00177016 an sep cs 00813036 00813052 02244766 02238818 02238819 02247446 02244126 02457393 02319012 02474883 00177017 00232352 00807052 24 Fluocinolone acetonide and None found. 25 an sep cs 26 Fluocortolone and an sep cs None found. Diflucortolone and an sep cs 02028719 x 27 Hydrocor sone and 02238578 00445045 00155977 00429090 00807478 02038242 02224542 02242485 00243124 00243132 00520322 00666246 00701904 00156175 28 an bio cs 00163511 00163538 00438669 00704555 00704563 00750670 00763543 00837350 01980572 01980580 00476439 00145718 00390748 00390798 00068667 00191282 00243140 00243159 00666211 00694401 00813559 00912828 01912828 02025736 02230386 00194883 00194891 00194913 29 00194921 00194948 00194956 00806897 00807346 00622249 00068772 00068780 00091820 00203378 00534838 00534846 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 00068675 00281816 00530611 00158046 00158178 00443298 00192678 00241067 30 00885738 00828947 http://bmjpaedsopen.bmj.com/ 31 Methylprednisolone and 00195057 00806919 00806927 00252395 00194867 00806935 00194859 00260428 00880787 00194875 an bio cs 32 Prednisolone and an bio cs 00813680 00195057 00806919 00806927 00194867 00806935 00194859 00177121 00042617 00042625 00042633 00045632 00177024 00307246 00395145 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00218812 00281824 00527998 00760056 00808199 33 00843741 00903477 02133342 00194875 34 Triamcinolone and an bio cs 00128066 00128031 00128058 00184659 00184667 00199850 00245259 00245267 00382620 00433527 00464554 00464562 00464589 00492760 00501107 00562173 00562181 00717002 00717029 00774659 00774667 00806846 00806854 00806862 00808083 00808091 00808105 00808113 35 00808555 00810959 00810975 00811440 00811459 00960101 01999826 01999834 01999842 01999850 00960128 00903365 00960497 66960500 00192627 00128090 00128112 36 Fluprednidene and an bio cs None found. Fluorometholone and 00395153 x 37 an bio cs 38 Dexamethasone and 00778907 00778915 00173592 00173606 00228052 01987712 01987720 02224623 02224631 02247920 00626597 00140732 00042668 00042676 an bio cs 00358177 02023806 02023849 39 Flumetasone and an bio cs None found. Betamethasone and 02474883 x 40 an bio cs on September 25, 2021 by guest. Protected copyright. 41 Fluocinolone acetonide and 00189499 x an bio cs 42 Fludroxycor de and None found. an bio cs 43 Beclometasone and None found. 44 an bio cs Fluocinonide and an bio cs 00492442 00808393 00808407 07090343 45 Fluocortolone and an bio cs None found. Clobetasol and an bio cs None found. 46 Cor costeroids, D07AD Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 very potent (group 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 47 IV) 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 48 02490706 66888389 66895083 49 Halcinonide 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02010283 02010291 02010305 02011921 02200945 66887803 66887811 50 Cor costeroids, D07AA Methylprednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 weak (group I) 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 51 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 52 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo5 Page 29 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 Hydrocor sone 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 2 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 00461903 3 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 00728837 00740330 4 00748811 00748889 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 5 00967564 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 6 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 80071959 7 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 8 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 02099179 9 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 10 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 11 Confidential: For Review Only 12 Prednisolone 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 00030740 00030759 00030767 00031062 00386847 13 00696617 00770759 00828912 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 02230210 14 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 00278912 00299405 00300373 00301175 00622931 00700401 00727466 15 00764639 00801186 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 16 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 17 Cor costeroids, D07AB Clobetasone 00456543 00456551 00889938 00889946 00894591 02214415 02214423 18 moderately potent 19 (group II) Hydrocor sone butyrate None found. 20 Flumetasone 00005134 00005789 Fluocor n None found. 21 Fluperolone None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 22 Fluprednidene None found. 23 Desonide 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 00889563 02048639 02115514 02115522 02154862 02154870 02229315 02229323 02348489 24 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 25 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 26 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 27 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 28 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 29 30 Alclometasone 02070855 02070871 Hydrocor sone buteprate None found. http://bmjpaedsopen.bmj.com/ 31 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 32 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 33 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 34 00016268
35 Clocortolone None found. Cor costeroids, D07AC Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 36 potent (group III) 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 37 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 38 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 39 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 40 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650
00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 on September 25, 2021 by guest. Protected copyright. 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 41 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 42 95000467 99113736 99900015 43 44 Fluclorolone None found. 45 Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 66889318 46 Fluocinolone acetonide 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 00464627 47 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 00806951 00862347 48 00862355 00862371 00862398 00873292 00886998 00887005 00887013 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 00895105 00895113 00897868 49 00897884 00897892 00897906 00899976 02129078 02162504 02162512 02162520 02162539 02162547 02163470 02163489 02242738 02300559 50 02306980 66030236 66894257 90716790 99100878 99100879 99100883
51 Fluocortolone None found. 52 Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 Fludroxycor de None found. 53 Fluocinonide 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 00908282 54 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 02187663 02187671 02236996 02236997 02240269 22369960 55 66887102 66887129 66887137 Budesonide 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 00911730 00969112 00999717 01974432 01978918 56 01978926 02035324 02052431 02229099 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 49636460 49851752 57 Diflorasone 00481793 00481807 00889377 00889385 00889407 58 59 60 https://mc.manuscriptcentral.com/bmjpo6 BMJ Paediatrics Open Page 30 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Amcinonide 00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 00894621 00894656 02052881 02154838 02170175 2 02192268 02192276 02192284 02219719 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 02242542 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 02257416 02370557 66894648 3 Halometasone None found. Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 4 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 5 Methylprednisolone None found. 6 aceponate Beclomethasone 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 00545333 00638617 00768707 00774407 00812951 7 00828521 00828548 00872318 00872326 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 00905771 00908320 00908347 00923242 00923935 00969400 8 00973025 00986445 01923242 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 02215055 02216531 02228300 02229998 02237258 02237379 02238577 9 02238796 02239211 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 99100392 10 Confidential:Hydrocor sone aceponate None found. For Review Only 11 Flu casone 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 02237245 12 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 02460513 13 02467895 02467909 02467917 77700002 77700003 Prednicarbate 02059754 02227517 02230642 14 Difluprednate 02415534 x Ulobetasol None found. 15 An psoriasics D05 Tars 02241506 00023237 00035815 00085871 00086126 00090948 00208132 00238252 00241075 00245631 00246948 00251372 00276456 00280747 00342769 00343447 00358494 00358495 00423203 00426415 00426423 00509310 00517879 00530492 00539063 00577359 00579963 00621137 16 00623237 00632295 00632309 00644994 00645001 00710962 00776415 00810363 00811157 00811165 00812978 00860964 00864706 00875279 17 00894516 00897302 00897361 00899712 00900974 00903450 00905321 00908169 00972339 00982407 00999972 01908855 01918087 01918974 01918982 01918990 01921983 01937642 01937650 01981021 01981293 02143941 02184672 02184680 02220350 02220393 02238310 02238311 18 02238642 02240151 02240152 02240645 02241910 02245737 02246735 02246736 02246802 02246974 02293978 02307146 02392046 02403854 02439085 02439093 02448963 02458837 66899704 66901032 66903256 88901121 00090905 00249866 00329231 00344508 00419133 00489271 19 00501832 00505765 00632260 00632279 00770428 00810401 00810428 00067229 00157562 00234206 00167800 00167819 00351881 00625280 00810886 00899704 02023075 00961043 01931121 02230134 00659703 00773492 00288640 00784753 01931237 01931245 01932446 01942379 20 02285703 02285711 02432366 02432439 00509302 00090891 00632244 01936980 02106299 00800694 00866601 00550434 00812226 00379727 00594792 00628042 00807133 00811076 00812889 02240942 01981307 02403862 00344494 00509906 00510335 00560448 00744298 00748269 21 00894508 00181757 00208205 00232890 00362204 00444448 00525383 01909118 01981315 02030462 02403846 00266493 00332801 00373222 00506966 00652326 00740314 01909185 00090913 00091006 00579955 00579971 00234141 00907308 22 23 Dithranol + combina ons None found. 24 Trioxysalen 00331171 01966383 Methoxsalen 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 01907476 01946374 02406233 09852247 09852905 25 09991125 22123043 49007269 99100699 99100916 99100917 99100918 26 Fumaric acid None found. Calcipotriol 01971633 x 27 Calcitriol 02338572 00481815 00481823 00824291 00891738 00891746 02245686 02245687 02399334 02399342 02431637 02431645 02485710 02485729 02495899 02495902 28 Tacalcitol None found. Tazarotene 02230784 02230785 02243894 02243895 29 Calcipotriol + combina ons None found. 30 Methoxsalen 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 01907476 01946374 02406233 09852247 09852905 09991125 22123043 49007269 99100699 99100916 99100917 99100918 http://bmjpaedsopen.bmj.com/ 31 Bergapten None found. Etre nate 00616400 00616419 66123914 32 Acitre n 02070847 02070863 02080863 02466074 02466082 02468840 02468859 Fumaric acid deriva ves + None found. 33 combina ons 34 Salicylates for D02AF Salicylic acid prepara ons 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 Dermatological 00813346 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 02248196 02248197 66903051 80027681 35 Use 00961043 01931121 02230134 00181757 00208205 00232890 00362204 00444448 00525383 01909118 01981315 02030462 02403846 00266493 00234141 00907308 00075973 00203297 00208175 00208183 00232882 00355607 00428752 00506974 00534854 00739316 00807958 00810312 36 00810320 00810991 00972584 01909096 01988239 00180076 Cor costeroids D07XB Flumetasone 00005134 00005789 37 Moderately Potent 38 Other Combina ons 39 Triamcinolone 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 00385204 40 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 00488976 00488984 00494240 00501034 00501042 00502928 on September 25, 2021 by guest. Protected copyright. 00509663 00509671 00535249 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 00769983 00887684 41 00887692 00887706 00887722 00887730 00887749 00887757 00887773 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 00897957 00897965 00897973 42 00897981 00913328 00969206 00977653 00990876 01913328 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 02368676 02417510 02437635 09857128 43 66887889 00014834 00014842 00499846 00716995 00903208 01977555 02194120 02194147 66494240 00297151 00903175 02194155 02470632 44 45 Fluprednidene None found. Fluorometholone 00259454 00432814 00707511 00897469 02238568 00756784 46 Dexamethasone 00000698 00016462 00016470 00022500 00022519 00042560 00042579 00269026 00285471 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 01964068 47 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 00213624 00732907 48 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 02387743 02412888 02412896 49 00016268 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo7 Page 31 of 88 BMJ Paediatrics Open bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. 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1 Cor costeroids D07XC Betamethasone 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 00999157 01925350 01944436 01944444 02048116 2 Potent Other 02048124 02060868 99100868 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 00769614 Combina ons 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 3 00899305 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 4 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 5 00028364 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 6 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 00895881 7 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 8 95000467 99113736 99900015 9
10 Desoximetasone 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 01990942 01995065 02221896 02221918 02221926 Confidential:02221934 02239068 02239069 For 02241887 66889318 Review Only 11 Mometasone 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 02243596 02244767 02244768 02244769 02248130 12 02264749 02266385 02270862 02367157 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 13 Diflucortolone 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 00896020 00896047 00896055 02070995 Fluocortolone None found. 14 Cor costeroids D07AD01 Clobetasol 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 00887250 00888397 00910272 00961345 00961361 (Group IV) 00961388 00961396 00961418 00964093 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 02093162 15 Clobetasol 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 02475162 02489619 16 02490706 66888389 66895083 17 An fungals D01 Nysta n 00014850 00014974 00029319 00029416 00248169 00248170 00270113 00282219 00779121 00785709 00792667 00894834 00894893 00895210 (implies 00898953 00903212 00904479 00984671 02125145 02194198 02194201 02229852 02238544 02433443 09850457 09857764 40079266 49248169 18 cor costeroid 66898929 66907472 66988170 00015067 00029092 00029491 00029556 00270091 00278793 00288195 00288209 00288217 00295973 00382639 (group IV) use for 00422592 00444383 00449792 00449806 00480819 00510297 00522864 00716871 00716898 00716901 00811084 00870552 00870560 00882607 19 vaginal fungal 00885126 00888761 00908053 00912972 00929092 00985074 00999954 00999958 02004674 02194163 02194171 02194228 02194236 02195704 20 infec on) 09852921 09857765 09857767 50237469 66908061 99113755 99900006 00464597 00811091 00885096
21 Natamycin None found. Hachimycin None found. 22 Pecilocin None found. 23 Mepartricin None found. Pyrrolnitrin None found. 24 Griseofulvin 00012246 00012254 00012262 00028266 00028274 00028282 00513229 00513237 00901061 02100266 02100274 02100282 09991069 99100253
25 Clotrimazole 00903037 00903061 00001403 00139035 00325465 00325473 00353833 00420301 00513903 00513904 00513911 00513938 00513946 00516805 00516806 00516813 00516821 00516848 00567388 00576492 00629243 00731307 00731707 00759457 00810045 00810967 00812366 00812374 26 00812382 00874043 00874051 00874078 00895571 00895598 00896845 00898112 00899046 00899054 00899399 00901412 00903184 00904279 00908045 00908495 02029480 02029499 02029502 02029510 02126818 02126826 02130203 02130211 02130238 02130254 02130262 02130920 27 02131633 02131641 02131668 02131676 02150667 02150832 02150840 02150859 02150867 02150875 02150883 02150891 02150905 02150921 02150948 02180723 02229378 02229379 02229380 02230447 02230509 02232395 02236746 02239432 02240847 02264099 02264102 02311720 28 02462397 02490927 49812382 66894788 66999474 99113693 99113695
29 Miconazole 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 00685917 00771035 00771036 00807605 00807613 30 00895237 00895628 00900958 00980617 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 02231533 02239600 02239601 02244005 02245546 66894796 http://bmjpaedsopen.bmj.com/ 31 92085852 95003840 95023947 Econazole 00452114 00561002 00895997 02010267 02011948 32 Chlormidazole None found. Isoconazole None found. 33 Tiabendazole None found. 34 Tioconazole 00657395 00791725 02095009 02095017 02095025 02171902 02171910 02217406 02218283 02218291 02241700 Ketoconazole 00967343 00633836 00788813 00903341 02122197 02231061 02237235 02237882 00703974 00803588 02182920 02245662 02292661 35 Sulconazole None found. Bifonazole None found. 36 Oxiconazole 02230452 02230453 37 Fen conazole None found. Omoconazole None found. 38 Sertaconazole None found. Fluconazole 00891800 00891819 00891827 00891835 00891900 00901418 02024152 02091216 02091372 02091380 02141442 02236978 02236979 02236980 39 02237370 02237371 02237372 02241895 02243645 02245292 02245293 02245294 02245643 02245644 02245697 02246108 02246109 02246620 02246942 02247749 02247922 02248443 02248731 02249294 02249308 02249316 02255510 02261472 02271516 02273632 02273640 02273659 40 02281260 02281279 02282348 02282453 02287242 02287250 02287269 02294036 02294044 02301938 02301946 02301954 02309432 02310686 02310694 02311690 02312686 02312694 02323419 02336162 02339560 02340038 02340046 02340798 02340801 02340828 02352133 02357496 on September 25, 2021 by guest. Protected copyright. 41 02378302 02388448 02428792 02432471 02433702 02462168 22123126 22123127 99101272 42 Flutrimazole None found. 43 Eberconazole None found. 44 Luliconazole None found. Efinaconazole 02413388 x 45 Imidazoles/triazoles in 00611174 00813087 02244766 combina on with 46 cor costeroids Miconazole + combina ons 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 00685917 00771035 00771036 00807605 00807613 47 00895237 00895628 00900958 00980617 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 02231533 02239600 02239601 02244005 02245546 66894796 48 92085852 95003840 95023947 02382628 49 Bifonazole + combina ons None found. Bromochlorosalicylanilide None found. 50 Methylrosaniline None found. Tribromometacresol None found. 51 Undecylenic acid + 00240664 00829315 02222736 02239048 02243662 80041595 80041596 80043930 00240656 00030163 00030201 00373443 00373478 00376906 52 combina ons 00519898 00595926 00829145 00829153 00829307 00864137 00864145 02021838 02021846 02021862 02021900 02021919 02154552 80041594 00373451 00829285 02021803 00228796 00374598 00484334 00501840 00146013 00522074 00145661 00145831 00213497 00464651 53 Polynoxylin None found. 54 2-(4-chlorphenoxy)-ethanol None found. 55 Chlorphenesin 00253065 00253073 02089637 02091496 Ticlatone None found. 56 Sulben ne None found. Ethyl hydroxybenzoate None found. 57 Haloprogin 00291021 00291048 00800953 01910094 01910108 58 59 60 https://mc.manuscriptcentral.com/bmjpo8 BMJ Paediatrics Open Page 32 of 88 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from
1 Salicylic acid 00187542 00438294 00636347 00685186 00740292 00764361 00766216 00766240 00805300 00807583 00896063 00900796 00967548 00967556 2 00968978 00990141 00990244 00999036 00999081 01908553 01908561 01914847 01915185 01930575 01939513 01939521 01947451 01947494 01978861 01999540 02015358 02025868 02044412 02044471 02047403 02069725 02074257 02074265 02139073 02139081 02147076 02147114 3 02156172 02163055 02199009 02199017 02221349 02222442 02227266 02230960 02230961 02230963 02231101 02231619 02236775 02236983 02237796 02238309 02238314 02238418 02238573 02238815 02238816 02239079 02240447 02240758 02240763 02240902 02240903 02241153 4 02241420 02243321 02243578 02243590 02243615 02243939 02244191 02244449 02245611 02245763 02245873 02245984 02246380 02246604 02246681 02246710 02246712 02247218 02248036 02248585 02248586 02248587 02248711 66898848 66900788 66900818 66900893 66901164 5 80002908 80005358 80006363 80007324 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 00813346 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 6 02248196 02248197 66903051 80027681 00764310 02211203 02231218 02243011 02245989 02247262 00075914 00075957 00273104 00281891 00555967 00652342 00652350 02149044 02149052 02240107 00792020 00794759 02032945 00230081 00465976 00903371 01915177 02047764 7 02230957 02230959 02241590 80005624 80008630 80011794 80073326 66908029 00307580 00307904 00355828 00355895 00413356 00413372 00454893 00505978 00609501 00614246 00625353 00690333 00740276 00754951 00813044 00815861 00837733 00889598 00895059 00895067 8 00895075 00895083 00895091 00899372 00906018 00987034 01909029 01909037 01909134 01911384 01914456 01915258 01918729 01929429 01939645 01948156 01967878 01974335 01977725 01981463 02022915 02035553 02050285 02050293 02060493 02123045 02223821 02229957 9 02229990 02230131 02230132 02230691 02231570 02237019 02239055 02239299 02240322 02241129 02241465 02241621 02241738 02243332 10 02244054 02244850 02245445 80063216 00903056 00999082 11 Confidential: For Review Only Selenium sulfide 00243000 00353809 00418293 00443581 00457086 00457094 00483788 00483796 00594601 00709069 00808466 00811181 01950487 01951653 12 02242871 02245007 13 Ciclopirox 00001516 02250535 02349086 02353288 02410346 02413574 00593362 00811688 00836281 00895741 01987569 01989626 02221802 02221810 02247228 02298953 49593362 14 Terbinafine 02242735 02254727 02320134 02352818 02353121 02357070 02385279 02299275 09991323 00903384 02031108 02031116 02239893 02240345 02240346 02240807 02242503 02247530 02262177 02262924 02286580 02294273 02297973 02320126 02341190 02343452 02352796 02363836 15 02372762 02031094 02238703 02239876 02241815 02241816 02248845 02332612 16 Amorolfine None found. Dimazole None found. 17 Tolna ate 00027936 00027960 00028088 00415782 00458163 00549185 00576026 00576034 00576042 00576050 00576057 00596361 00614211 00614238 00658731 00716928 00810584 00810592 01918826 01919245 01942263 01942573 01942581 02029081 02078341 02220733 02226707 02239066 18 02239497 02240064 02243064 02243663 02244939 02295873 02311801 02319276 02319314 02375397 02378248 02380765 02396785 02401584 19 02413760 02417715 02431718 02434113 02475324 02476703 02480166 Tolciclate + combina ons None found. 20 Flucytosine 00990256 66123998 00384895 66128023 66124323 Na ifine 02011255 02011263 21 Butenafine 02231063 02238762 02244312 22 Tavaborole None found. 23 24 25 26 27 28 29 30 http://bmjpaedsopen.bmj.com/ 31 32 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmjpo9 Page 33 of 88 BMJ Paediatrics Open
1 2 Original Algorithm: Gershon et al, 2009 3 Uses ICD-10 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Algorithm Original ICD Code Disease/Disorder 7 8 ≥1 hospitalization J45 Asthma 9 and/or ≥2 10 ambulatory care 11 visits for asthma 12 Confidential: For Review Only 13 within two years 14 J46 Status asthmaticus 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Mapped ICD Code Disease/Disorder 7 8 493 Asthma 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Original Algorithm: Hill et al, 2016 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code 7 8 ≥2 care visits occurring ≥6 477 9 months apart 10 11 12 Confidential: For Review Only 13 SENSITIVITY ANALYSIS 14 15 Original Algorithm: Stensballe et al, 2017 16 Uses ICD-10 17 18 19 Algorithm Original ICD/DIN Code 20 ≥1 hospital contact for: J30 21 22 J30.0 23 J30.1 24 25 J30.2 26 J30.3 27 J30.4 28 29 J31.0 30 31 OR ≥2 filled prescriptions of: 32 33 Excluding: J33 34
J330 http://bmjpaedsopen.bmj.com/ 35 36 J331 37 J331A 38 J338 39 40 J338A 41 J339 42 43 J010-J019 44 J320-J3290 45 on September 25, 2021 by guest. Protected copyright. 46 47 OR ≥2 filled prescriptions of: 48 Excluding: L29 49 50 L50 51 52 OR ≥1 filled prescriptions of: 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder Mapped ICD Code 7 8 Allergic Rhinitis J301–J304 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder Mapped ICD/DIN Code 20 Hay Fever and Allergic Rhinitis 477 21 22 Vasomotor Rhinitis 23 Allergic Rhinitis due to Pollen 24 25 Other Seasonal Allergic Rhinitis 26 Other Allergic Rhinitis 27 Allergic Rhinitis, Unspecified 28 29 Chronic Rhinitis 30 31 Inhaled Corticosteroids for Rhinitis 32 33 Nasal Polyps 471 34
Polyps in Nasal Cavity http://bmjpaedsopen.bmj.com/ 35 36 Polyp Related Sinus Degeneration 37 Woakes' Ethmoiditis 38 Nasal Polyps, Other 39 40 Polypus Sinus Sphenoidalis 41 Nasal Polyps, Unspecified 42 43 Acute Sinusitis 461 44 Chronic Sinusitis 473 45 on September 25, 2021 by guest. Protected copyright. 46 47 Antihistamines for Systemic Use 48 Pruritus 698 49 50 Allergic Urticaria 708 51 52 Specific Immune Therapy, Allergen Substract 53 54 Therapy 55 Medication for Allergic Conjunctivitis 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder 7 8 Allergic Rhinitis 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder 20 Allergic Rhinitis 21 22 23 24 25 26 27 28 29 30 31 Inhaled Corticosteroids for Rhinitis Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 32 33 Nasal Polyps 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 Acute Sinusitis 44 Chronic Sinusitis 45 on September 25, 2021 by guest. Protected copyright. 46 47 Antihistamines for Systemic Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 48 Pruritus and related conditions 49 50 Urticaria 51 52 Specific Immune Therapy, Allergen Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 53 54 Substract Therapy 55 Medication for Allergic Conjunctivitis Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Original ATC codes were mapped31 to Canadian Drug Identification Numbers (DIN) on the last tab 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 Original ATC codes were mapped47 to Canadian Drug Identification Numbers (DIN) on the last tab 48 49 50 51 Original ATC codes were mapped52 to Canadian Drug Identification Numbers (DIN) on the last tab 53 54 Original ATC codes were mapped55 to Canadian Drug Identification Numbers (DIN) on the last tab 56 57 58 59 60
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1 2 Original Algorithm: Hill et al, 2016 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code 7 8 ≥2 care visits occurring ≥6 691 9 months apart 10 11 12 Confidential: For Review Only 13 SENSITIVITY ANALYSIS 14 15 Original Algorithm: Stensballe et al, 2017 16 Uses ICD-10 17 18 19 Algorithm Original ICD/DIN Code 20 ≥1 hospital contact for: L20 21 22 Excluding: 23 24 OR ≥1 filled prescriptions of: 25 26 27 Excluding: Exclusion criteria below 28 29 30 OR ≥2 filled prescriptions of 31 the code within 12 months: 32 33 If above prescription is: 34 35 Then also with either (as atopic http://bmjpaedsopen.bmj.com/ 36 dermatitis is never treated 37 38 alone with group IV): 39 40 41 42 Excluding: Exclusion criteria below 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 Exclusion Criteria 48 49 Exclude those without: L20 50 51 AND with: L21 52 L22 53 54 L23 55 L24 56 L25 57 58 L26 59 L27 60 L28
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1 2 L29 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 L30 6 7 8 L40 – L45 9 10 11 12 Confidential: For Review Only 13 14 15 16 L53 17 18 19 L55 20 21 22 L56 23 24 25 26 27 L80 28 29 L90 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 L93 37 38 OR ≥1 filled prescription of: 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 AND with: 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder Mapped ICD Code 7 8 Atopic dermatitis and related conditions L20 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder Mapped ICD/DIN Code 20 Atopic Dermatitis 691 21 22 691.0 23 24 Agents for Dermatitis: Tacrolimus, Pimecrolimus 25 26 27 28 29 30 Corticosteroids for Topical Use 31 32 33 Corticosteroids, very potent (group IV) 34 35 Corticosteroids, weak (group I) http://bmjpaedsopen.bmj.com/ 36 37 38 39 Corticosteroids, moderately potent (group II) 40 41 Corticosteroids, potent (group III) 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 Atopic Dermatitis 691 50 51 Seborrhoeic Dermatitis 690.1 52 Diaper Dermatitis 691.0 53 54 Allergic Contact Dermatitis 692 55 Irritant Contact Dermatitis 56 Unspecified Contact Dermatitis 57 58 Exfoliative Dermatitis 695.89 59 Dermatitis due to Substances Taken Internally 693 60 Lichen Simplex Chronicus and Prurigo 698.2, 698.3
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1 2 Pruritus 698.0, 698.1, 698.8, 3
698.9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Other Dermatitis 692.9, 705.81, 690.8, 6 696.5 7 8 Papulosquamous Disorders 696.0 - 696.4, 696.8, 9 694.3, 697.0, 697.1, 10 697.8, 057.8, 709.8 11 12 Confidential: For Review Only 13 14 15 16 Other Erythematosus Conditions 695.0, 695.89, 695.9 17 18 19 Sunburn 692.71, 692.76, 692.77 20 21 22 Other Acute Skin Changes due to Ultraviolet Radiation 692.72, 692.82, 692.75, 23 692.79 24 25 26 27 Vitiligo 709.01 28 29 Atrophic Disorders of the Skin 701.0, 701.3, 701.8, 30 701.9, 709.2 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Lupus Erythematosus 695.4 37 38 Antipsoriasics 39 40 Salicylates for Dermatological Use 41 Corticosteroids Moderately Potent Other 42 43 Combinations 44 Corticosteroids Potent Other Combinations 45 on September 25, 2021 by guest. Protected copyright. 46 Corticosteroids (Group IV) Clobetasol 47 Clobetasol and Antibiotics 48 Antifungals (implies corticosteroid (group IV) use for 49 50 vaginal fungal infection) 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Disease/Disorder 7 8 Atopic Dermatitis and Related Conditions 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Disease/Disorder 20 Atopic dermatitis and related conditions Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 21 22 Diaper or Napkin Rash Added this exclusion since L20 doesn't include diaper rash but 691 does 23 24 Agents for Dermatitis: Tacrolimus, Pimecrolimus Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 25 26 27 28 29 30 Corticosteroids for Topical Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 31 32 33 Corticosteroids, very potent (group IV) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 34 35 Corticosteroids, weak (group I) Original ATC codes were mapped to Canadian http://bmjpaedsopen.bmj.com/ Drug Identification Numbers (DIN) on the last tab 36 37 38 39 Corticosteroids, moderately potent (group II) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 40 41 Corticosteroids, potent (group III) Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 Atopic dermatitis and related conditions Removed L308C "Winter Feet" since not in Canadian ICD-10-CA codes 50 51 Seborrheic dermatitis 52 Diaper or Napkin Rash 53 54 Contact dermatitis and other eczema 55 56 57 58 Other Specified Erythematous Conditions 59 Dermatitis due to Substances Taken Internally 60 Prurigo & Lichenification
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1 2 Pruritus ani, Pruritus of genitalia, Pruritic 3
conditions NEC & Pruritic disorder NOS bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Dermatitis NOS, Dyshidrosis, Erythmtsquamous Removed 'except Winter Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 6 derm NEC & Pityriasis NEC & NOS 7 8 Psoriatic arthropathy, Other psoriasis, 9 Parapsoriasis, Pityriasis rosea, Pityriasis rubra 10 pilaris, Psorias related dis NEC, Impetigo 11 12 herpetiformis,Confidential: Lichen planus, Lichen nitidus, ForLichen Review Only 13 NEC, Viral exanthemata NEC & Skin disorders NEC 14 15 16 Toxic erythema, Erythematous cond NEC & 17 Erythematous cond NOS 18 19 Sunburn, 2nd degree sunburn & 3rd degree 20 sunburn 21 22 Acute dermatitis due to solar radiation, Dermatitis 23 due to other radiation, Disseminated superficial 24 actinic porokeratosis (DSAP) & Other dermatitis 25 26 due to solar radiation 27 Vitiligo 28 29 Circumscribe scleroderma, Striae atrophicae, Other 30 specified hypertrophic and atrophic conditions of 31 skin, Unspecified hypertrophic and atrophic 32 33 conditions of skin & Scar conditions and fibrosis of 34 skin 35 http://bmjpaedsopen.bmj.com/ 36 Lupus Erythematosus 37 38 Antipsoriasics Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 39 40 Salicylates for Dermatological Use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 41 Corticosteroids Moderately Potent Other Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 Combinations 44 Corticosteroids Potent Other Combinations Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 45 on September 25, 2021 by guest. Protected copyright. 46 Corticosteroids (Group IV) Clobetasol Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 47 Clobetasol and Antibiotics Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 48 Antifungals (implies corticosteroid (group IV) use Original ATC codes were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 49 50 for vaginal fungal infection) 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Removed L308C "Winter20 Feet" since not in Canadian ICD-10-CA codes 21 Added this exclusion22 since L20 doesn't include diaper rash but 691 does 23 Original ATC codes24 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 25 26 27 28 29 Original ATC codes30 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 31 32 Original ATC codes33 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 34 Original ATC codes35 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab http://bmjpaedsopen.bmj.com/ 36 37 38 Original ATC codes39 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 40 Original ATC codes41 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 Removed L308C "Winter49 Feet" since not in Canadian ICD-10-CA codes 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from Removed 'except Winter5 Feet' L308C "Winter Feet" since not in Canadian ICD-10-CA codes 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Original ATC codes38 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 39 Original ATC codes40 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes41 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 42 43 Original ATC codes44 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 45 on September 25, 2021 by guest. Protected copyright. Original ATC codes46 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes47 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab Original ATC codes48 were mapped to Canadian Drug Identification Numbers (DIN) on the last tab 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Original Algorithm: Walsh et al, 2013 3
Uses ICD-9 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Algorithm Original ICD Code Disease/Disorder 7 8 In an inpatient or 995.0 Other Anaphylactic Shock 9 emergency 10 department 11 12 encounter (i.e.Confidential: DAD For Review Only 13 or NACRS) either: 14 15 999.4 Anaphylactic Shock due to Serum 16 17 995.6 Anaphylactic Shock due to Adverse Food Reaction 18 19 20 21 22 23 24 25 26 27 28 29 30 31 OR in an outpatient 995.0 Other Anaphylactic Shock 32 encounter (i.e. OHIP) 33 either: 34 35 999.4 Anaphylactic Shock due to Serum http://bmjpaedsopen.bmj.com/ 36 37 995.6 Anaphylactic Shock due to Adverse Food Reaction 38 39 40 41 42 43 44 45 AND at least one of: 519.11 Bronchospasm on September 25, 2021 by guest. Protected copyright. 46 786.1 Stridor 47 48 458.9 Hypotension 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 Mapped ICD/CCI Code Disease/Disorder 7 8 T78.2 Anaphylactic Shock, Unspecified 9 10 11 12 Confidential: For Review Only 13 14 15 T80.5 Anaphylactic Shock due to Serum 16 17 T78.0 Anaphylactic Shock due to Adverse Food 18 Reaction 19 20 21 22 23 24 T886 Anaphylactic shock due to adverse effect of 25 correct drug or medicament properly 26 administered 27 28 29 30 31 T78.2 Anaphylactic Shock, Unspecified 32 33 34 35 T80.5 Anaphylactic Shock due to Serum http://bmjpaedsopen.bmj.com/ 36 37 T78.0 Anaphylactic Shock due to Adverse Food 38 39 Reaction 40 41 T88.6 Anaphylactic shock due to adverse effect of 42 correct drug or medicament properly 43 administered 44 45 J98.01 Acute Bronchospasm on September 25, 2021 by guest. Protected copyright. 46 R06.1 Stridor 47 48 I95.9 Hypotension, Unspecified 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 Added this code due to high prevalence food-induced anaphylaxis among young 18 children. First-author of original paper said that they didn't include the code 19 since they were mostly interested in anaphylaxis due to medications, but that 20 21 the addition of this code was a good approach if food-induced anaphylaxis was 22 important to our study. 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Same comment as above 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 The three intervention codes in the original algorithm (epinephrine, injection of 50 diphenhydramine, and CPR) did not have analogous OHIP fee codes. As such, we 51 52 could not include these in our algorithm. 53 54 55 56 57 58 59 60
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1 2 Mapped using the WHO ATC/DDD Index 2020 (https://www.whocc.no/atc_ddd_index/) and the ICES DRUGLIST excel 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 Original Name Original ATC Code Drug 6 For Rhinitis Algorithm 7 Inhaled R01AD01 – R01AD60 Beclomethasone 8 9 Corticosteroids for 10 Rhinitis 11 12 Confidential: For Review Only 13 14 15 16 17 Prednisolone + combinations 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Dexamethasone + 38 combinations 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 Flunisolide 51 Budesonide 52 53 54 55 56 57 58 59 60
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1 2 Betamethasone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 tixocortol + combinations 24 25 Fluticasone 26 27 28 29 30 Mometasone 31 32 33 34 Triamcinolone http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 fluticasone furoate + 49 50 combinations 51 52 53 54 55 56 57 ciclesonide 58 59 60
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1 2 hydrocortisone, combinations 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Antihistamines for R06A Bromazine 37 Systemic Use 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Diphenhydramine + 3
combinations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Clemastine + combinations 37 Chlorphenoxamine + 38 39 combinations 40 Diphenylpyraline + 41 combinations 42 43 44
Carbinoxamine on September 25, 2021 by guest. Protected copyright. 45 46 Doxylamine + combinations 47 48 49 50 51 52 53 54 55 56 Trimethobenzamide 57 58 59 60
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1 2 Brompheniramine + 3
combinations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 Dexchlorpheniramine + 11 12 Confidential: Forcombinations Review Only 13 Dimetindene 14 15 Chlorphenamine + 16 combinations 17 Pheniramine 18 19 Dexbrompheniramine + 20 combinations 21 22 Talastine 23 Mepyramine 24 25 Histapyrrodine + combinations 26 27 Chloropyramine + 28 29 combinations 30 Tripelennamine 31 32 Methapyrilene 33 Thonzylamine 34 Alimemazine http://bmjpaedsopen.bmj.com/ 35 36 Promethazine + combinations 37 38 39 40 41 42 43 Thiethylperazine 44
Methdilazine on September 25, 2021 by guest. Protected copyright. 45 46 Hydroxyethylpromethazine + 47 combinations 48 Thiazinam 49 50 Mequitazine 51 Oxomemazine 52 53 Isothipendyl 54 Buclizine + combinations 55 Cyclizine + combinations 56 57 Chlorcyclizine 58 Meclizine + combinations 59 60 Oxatomide
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1 2 Cetirizine 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Levocetirizine 9 Bamipine 10 Cyproheptadine 11 12 Confidential: ForThenalidine Review + combinations Only 13 Phenindamine 14 15 Antazoline 16 Triprolidine 17 Pyrrobutamine + combinations 18 19 20 Astemizole 21 22 Terfenadine 23 24 25 Loratadine 26 27 Mebhydrolin 28 29 Deptropine 30 Ketotifen 31 32 33 Acrivastine 34 Azelastine http://bmjpaedsopen.bmj.com/ 35 36 Tritoqualine 37 Ebastine 38 39 Pimethixene 40 Epinastine 41 Mizolastine 42 43 Fexofenadine 44
Desloratadine on September 25, 2021 by guest. Protected copyright. 45 46 Rupatadine 47 Bilastine 48 Quifenadine 49 50 Sequifenadine 51 52 53 54 55 56 57 58 59 60
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1 2 Specific Immune V01A Allergen extracts and 3
Therapy, Allergen preparations bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Substract Therapy 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 Medication for S01GX Cromoglicic acid + 37 Allergic combinations 38 Conjunctivitis 39 40 Levocabastine 41 Spaglumic acid 42 43 Nedocromil 44
Lodoxamide on September 25, 2021 by guest. Protected copyright. 45 46 Emedastine 47 Azelastine 48 49 Ketotifen 50 51 Olopatadine 52 53 Epinastine 54 Alcaftadine 55 56 57 For dermatitis algorithm 58 59 60
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1 2 Agents for D11AH Tacrolimus 3
Dermatitis: bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Tacrolimus, 6 Pimecrolimus 7 8 Pimecrolimus 9 Cromoglicic acid 10 Alitretinoin 11 12 Confidential: ForDupilumab Review Only 13 Crisaborole 14 15 Corticosteroids for D07 Methylprednisolone 16 Topical Use 17 18 19 20 21 22 Hydrocortisone 23 24 25 26 27 28 29 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 Prednisolone 49 50 51 52 53 54 55 56 57 58 59 60 Clobetasone
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1 2 Hydrocortisone butyrate 3
Flumetasone bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Fluocortin 6 Fluperolone 7 8 Fluorometholone 9 Fluprednidene 10 Desonide 11 12 Confidential: For Review Only 13 Triamcinolone 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Alclometasone 28 29 Hydrocortisone buteprate 30 Dexamethasone 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 Clocortolone 41 Betamethasone 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Fluclorolone 3
Desoximetasone bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 Fluocinolone acetonide 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 Fluocortolone 20 Diflucortolone 21 22 Fludroxycortide 23 Fluocinonide 24 25 26 27 28 29 Budesonide 30 31 32 33 Diflorasone 34 Amcinonide http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Halometasone 40 Mometasone 41 42 43 44
Methylprednisolone on September 25, 2021 by guest. Protected copyright. 45 aceponate 46 47 Beclomethasone 48 49 50 51 52 53 54 55 56 57 Hydrocortisone aceponate 58 59 60
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1 2 Fluticasone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Prednicarbate 9 Difluprednate 10 Ulobetasol 11 12 Confidential: ForClobetasol Review Only 13 14 15 16 17 18 19 Halcinonide 20 21 22 Prednisolone and antiseptics 23 Hydrocortisone and antiseptics 24 25 26 Flumetasone and antiseptics 27 Desonide and antiseptics 28 29 Triamcinolone and antiseptics 30 31 32 Hydrocortisone butyrate and 33 antiseptics 34 Betamethasone and http://bmjpaedsopen.bmj.com/ 35 36 antiseptics 37 38 39 Fluocinolone acetonide and 40 antiseptics 41 Fluocortolone and antiseptics 42 43 Diflucortolone and antiseptics 44 45 on September 25, 2021 by guest. Protected copyright. 46 Hydrocortisone and antibiotics 47 48 49 50 51 52 53 54 Methylprednisolone and 55 antibiotics 56 57 Prednisolone and antibiotics 58 59 60
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1 2 Triamcinolone and antibiotics 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 Fluprednidene and antibiotics 9 Fluorometholone and 10 antibiotics 11 12 Confidential: ForDexamethasone Review and Only 13 antibiotics 14 15 Flumetasone and antibiotics 16 Betamethasone and antibiotics 17 18 19 Fluocinolone acetonide and 20 antibiotics 21 22 Fludroxycortide and antibiotics 23 24 25 Beclometasone and antibiotics 26 27 Fluocinonide and antibiotics 28 29 Fluocortolone and antibiotics 30 Clobetasol and antibiotics 31 32 Corticosteroids, D07AD Clobetasol 33 very potent (group 34
IV) http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Halcinonide 40 41 Corticosteroids, D07AA Methylprednisolone 42 43 weak (group I) 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Hydrocortisone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Prednisolone 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 Corticosteroids, D07AB Clobetasone 42 43 moderately potent 44 (group II) 45 on September 25, 2021 by guest. Protected copyright. 46 Hydrocortisone butyrate 47 Flumetasone 48 Fluocortin 49 50 Fluperolone 51 Fluorometholone 52 53 Fluprednidene 54 Desonide 55 56 57 58 59 60
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1 2 Triamcinolone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Alclometasone 17 Hydrocortisone buteprate 18 19 Dexamethasone 20 21 22 23 24 25 26 27 28 29 Clocortolone 30 Corticosteroids, D07AC Betamethasone 31 potent (group III) 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 Fluclorolone 52 53 Desoximetasone 54 55 56 57 58 59 60
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1 2 Fluocinolone acetonide 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 Fluocortolone 16 Diflucortolone 17 Fludroxycortide 18 19 Fluocinonide 20 21 22 23 24 25 Budesonide 26 27 28 29 Diflorasone 30 Amcinonide 31 32 33 34 Halometasone http://bmjpaedsopen.bmj.com/ 35 36 Mometasone 37 38 39 40 Methylprednisolone 41 aceponate 42 43 Beclomethasone 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 Hydrocortisone aceponate 54 Fluticasone 55 56 57 58 59 60 Prednicarbate Difluprednate
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1 2 Ulobetasol 3
Antipsoriasics D05 Tars bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 Dithranol + combinations 24 25 Trioxysalen 26 Methoxsalen 27 28 29 Fumaric acid 30 Calcipotriol 31 32 Calcitriol 33 34 Tacalcitol http://bmjpaedsopen.bmj.com/ 35 36 Tazarotene 37 Calcipotriol + combinations 38 39 Methoxsalen 40 41 Bergapten 42 43 Etretinate 44
Acitretin on September 25, 2021 by guest. Protected copyright. 45 46 Fumaric acid derivatives + 47 combinations 48 Salicylates for D02AF Salicylic acid preparations 49 50 Dermatological Use 51 52 53 54 55 Corticosteroids D07XB Flumetasone 56 57 Moderately Potent 58 Other 59 Combinations 60
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1 2 Triamcinolone 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Fluprednidene 17 Fluorometholone 18 19 Dexamethasone 20 21 22 23 24 25 26 27 28 29 Corticosteroids D07XC Betamethasone 30 Potent Other 31 Combinations 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 40 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 47 48 49 50 Desoximetasone 51 52 53 Mometasone 54 55 56 57 Diflucortolone 58 Fluocortolone 59 60
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1 2 Corticosteroids D07AD01 Clobetasol 3
(Group IV) bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 Clobetasol 6 7 8 9 Antifungals (implies D01 Nystatin 10 corticosteroid 11 12 (group IV) useConfidential: for For Review Only 13 vaginal fungal 14 infection) 15 16 17 18 19 Natamycin 20 Hachimycin 21 22 Pecilocin 23 Mepartricin 24 25 Pyrrolnitrin 26 Griseofulvin 27 28 29 Clotrimazole 30 31 32 33 34 35 http://bmjpaedsopen.bmj.com/ 36 37 38 39 Miconazole 40 41 42 43 44
Econazole on September 25, 2021 by guest. Protected copyright. 45 46 Chlormidazole 47 Isoconazole 48 Tiabendazole 49 50 Tioconazole 51 Ketoconazole 52 53 Sulconazole 54 Bifonazole 55 Oxiconazole 56 57 Fenticonazole 58 Omoconazole 59 60 Sertaconazole
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1 2 Fluconazole 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: ForFlutrimazole Review Only 13 Eberconazole 14 15 Luliconazole 16 Efinaconazole 17 Imidazoles/triazoles in 18 19 combination with 20 corticosteroids 21 22 Miconazole + combinations 23 24 25 26 27 Bifonazole + combinations 28 29 Bromochlorosalicylanilide 30 Methylrosaniline 31 32 Tribromometacresol 33 Undecylenic acid + 34
combinations http://bmjpaedsopen.bmj.com/ 35 36 37 38 39 Polynoxylin 40 2-(4-chlorphenoxy)-ethanol 41 Chlorphenesin 42 43 Ticlatone 44
Sulbentine on September 25, 2021 by guest. Protected copyright. 45 46 Ethyl hydroxybenzoate 47 Haloprogin 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 Salicylic acid 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Selenium sulfide 28 29 30 Ciclopirox 31 32 33 Terbinafine 34 35 http://bmjpaedsopen.bmj.com/ 36 37 Amorolfine 38 39 Dimazole 40 Tolnaftate 41 42 43 44 45 on September 25, 2021 by guest. Protected copyright. 46 Tolciclate + combinations 47 Flucytosine 48 Naftifine 49 50 Butenafine 51 Tavaborole 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 70 of 88
1 Mapped using the WHO ATC/DDD Index 2020 (https://www.whocc.no/atc_ddd_index/)2 and the ICES DRUGLIST excel 3 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 DIN 6 7 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 8 9 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 10 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 11 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 12 Confidential: For Review Only 13 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 14 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 15 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 16 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 17 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00194875 02241299 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 18 00030739 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 19 99100392 00237663 00237698 00806994 00807001 01934546 01944819 20 00828920 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 21 02245407 02245408 00895962 00194867 00806935 00030791 00030643 00030651 00030678 22 00036137 01962736 01962744 01962752 01962760 02063697 02063700 02063719 02063727 23 24 02230210 02230211 02231893 02231894 02231895 02232748 02232750 02241229 02367947 25 02367955 02367963 02367971 00194859 00021679 00031003 00178926 00210692 00544817 26 00993610 00813680 00028118 00093602 00250376 00252492 00278912 00299405 00300373 27 28 00301175 00622931 00700401 00727466 00764639 00801186 00809152 00894958 00896144 29 00898732 00901397 00908266 00961264 01916181 01916203 02023768 99100258 99100485 30 99100550 99113742 00042617 00042625 00042633 00045632 00177024 00307246 00395145 31 32 00630640 00806617 00807788 00807982 00810894 00903124 02023784 02023814 00281735 33 00281743 00526452 00526460 00756164 00756172 00907626 02133296 02133318 00218812 34
00281824 00527998 00760056 00808199 00843741 00903477 02133342 00544833 01924400 http://bmjpaedsopen.bmj.com/ 35 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 36 37 0022965299101412 00778907 00003603 00016217 00007668 00379689 00010197 00778915 00021687 02252716 00021695 00000698 00093629 00016462 00153710 00016470 00156876 38 0002250000178934 0002251900210188 0004256000232092 0004257900232378 0026902600252417 0028547100271373 0029509400271381 0034910000280852 0035430900312770 39 0048915800508586 0050105000550957 0050106900589194 0050113100598194 0050441600607517 0052528600610623 0072414900868426 0073288500868434 0073289300868442 40 41 0073983900901425 0090306200999108 0090421706623833 0190883909857797 0193096609857798 0194689709857799 0196406899100988 0196407000154008 0196496800023833 42 01964976 02016575 02237044 02237045 02237046 02239534 02240684 02240685 02240687 43 02250055 02260298 02260301 02261081 02279363 02311267 02363445 09850236 09852883 44 45 19649760 66901352 99503007 00140449 00173592 00173606 00228052 01987712 01987720 on September 25, 2021 by guest. Protected copyright. 46 02224623 02224631 02247920 00285110 00626597 00140732 00042668 00042676 00358177 47 02023806 02023849 00229679 00308455 00617199 00874582 00800767 00213624 00732907 48 49 00627763 00741752 00250325 00496219 00598542 00643122 00664200 00664227 00716715 50 0075186300421456 0078390000588997 0078526100790486 0091174200878790 0091174501927187 0091174602162687 0194704402230306 0197754702239288 0199502202240956 51 0202386500634530 0220426600634549 0220427400636460 0221297800814091 0237884300817228 0238567800851752 0238568600851760 0238774300852074 0241288800904059 52 0241289600911730 0001626800969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 53 54 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 55 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 56 49636460 49851752 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 71 of 88 BMJ Paediatrics Open
1 2 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 3 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 6 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 7 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 8 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 9 10 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 11 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 12 02217856 02217864Confidential: 02217872 02217880 For66899798 Review 00012181 00036366 Only 00176834 00212385 13 14 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 15 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 16 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 17 18 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 19 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 20 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 21 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 22 23 0060911000887439 00887455 x 00887471 00888494 00888672 00889024 00889490 00889504 00895873 24 0244656100895881 0244658800897728 02048043 00897833 02089912 00897841 0209001500897949 0217469300899550 0217470700904937 0217471500908355 0217472300908363 25 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 26 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 27 0221361302100193 0221362102106264 0221364802214350 0221365602357844 0221366402357852 0221367202357860 0221368002357879 0221369902366924 0223724402449773 28 0223724566887323 0223724666907960 0223724795000467 0224175299113736 0224364699900015 02244291 02244292 02244293 02248307 29 30 0080090202294745 0081364802296071 0085173602298589 0085174402336405 0087109502453738 0223846502460513 0224302102467895 0224302202467909 0224359502467917 31 0224359677700002 0224476777700003 02244768 02244769 02248130 02264749 02266385 02270862 02367157 32 33 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 34
. 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 000146 http://bmjpaedsopen.bmj.com/ 35 36 13 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 000295 37 64 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 003851 38 82 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 004725 39 81 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 005352 40 41 49 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 007169 42 87 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 008877 43 73 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 008884 44 45 51 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 008951 on September 25, 2021 by guest. Protected copyright. 46 48 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 019133 47 28 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 021940 48 02432889 02446561 02446588 02474522 02408872 02444186 02048043 02089912 02090015 49 31 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 022365 50 6902174693 02368676 02174707 02417510 02174715 02437635 02174723 09857128 02174731 66887889 02174738 00014834 02174758 00014842 02174766 00499846 02174774 0071699 51 502213581 00903208 02213583 01977555 02213591 02194120 02213605 02194147 02213613 66494240 02213621 00297151 02213648 00903175 02213656 02194155 02213664 0247063 52 202213672 02213680 02213699 02237244 02237245 02237246 02237247 02241752 02243646 53 54 02244291 02244292 02244293 02248307 02294745 02296071 02298589 02336405 02453738 55 02460513 02467895 02467909 02467917 77700002 77700003 02240835 02240836 02240837 56 02245125 02245126 02245127 02474611 02474638 02474646 02494507 02494515 02494523 None found. 57 02495597 02495600 02495619 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 72 of 88
1 2 02242485 00068772 00068780 00243124 00243132 00520322 00666246 00701904 00091820 3 00662461 00086096 00426350 00568074 00806099 00900737 01937979 00578533 00578541 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00856711 00768069 00155977 00156175 00163511 00163538 00438669 00704555 00704563 6 00750670 00763543 00837350 01980572 01980580 02240035 00074489 00074497 00074500 7 00074527 00193410 00193429 00245399 00338605 00774489 00807079 00807087 00807095 8 00807109 00811467 00091448 00215686 00216828 00521205 00521213 00521221 00449768 9 10 00456403 00203378 00445045 00476439 00229679 00387592 00448710 00530085 00530093 11 00807656 00807664 02226383 02226391 02247882 00173614 00173615 00173622 00807621 12 00813060 01988549Confidential: 01988573 02223252 For02223260 Review 02242527 02242528 Only 02247322 00534838 13 14 00534846 02463512 02238578 00209465 00003719 00003727 00006351 00016527 00021083 15 00021091 00024805 00030910 00030929 00093637 00093645 00133426 00151475 00157880 16 00177571 00192562 00192570 00192589 00192597 00192600 00193275 00193283 00193291 17 18 00193305 00195294 00216895 00216909 00228079 00228087 00230316 00245410 00245429 19 00265780 00275581 00298301 00298328 00303887 00303895 00338591 00341606 00341614 20 00461903 00461911 00477680 00479098 00482293 00482919 00502197 00502198 00502200 21 00502201 00513253 00513261 00513288 00521124 00521132 00551945 00551953 00562319 22 23 00562327 00564281 00567485 00595799 00595802 00641154 00661856 00716855 00728829 24 00728837 00740330 00748811 00748889 00756679 00763470 00804533 00824435 00862770 25 00862789 00880671 00887153 00887161 00887552 00887838 00888087 00889237 00889245 26 27 00889547 00894664 00896098 00900036 00900044 00903183 00903296 00904104 00905577 28 00907065 00907073 00960535 00967564 00967572 00968951 00990137 00990253 00990841 29 00990842 00999122 00999423 00999474 01925172 01931083 01940120 02060345 02086034 30 31 02112736 02187132 02243691 02243847 02244959 02412926 02469421 06260095 07196839 32 09857120 10502200 49513288 66123379 66123732 66123756 66896071 66903124 66903132 33 66903159 66903167 66903175 66903213 80021085 80021087 80021088 80026974 80037486 34 80052230 80057189 80057193 80061697 80061702 80061712 80061805 80064671 80066164 http://bmjpaedsopen.bmj.com/ 35 36 80066165None found. 80066167 80066168 80066699 80071959 80073687 80076663 80076664 80078409 37 80079355 88903167 90090250 99100725 99100726 99100727 99101368 00990313 00216941 38 00216968 00216976 00801666 00145718 00390748 00390798 00068667 00068675 00191282 39 40 00243140 00243159 00281816 00530611 00626600 00666211 00694401 00813559 00912828 41 01912828 02025736 02230386 00158046 00158178 00443298 00770957 01954210 00192678 42 00241067 00364134 00681989 00681997 00733083 00895911 02010720 80061502 80073645 43 44 80073689 00000671 00016276 00020818 00020826 00024775 00024783 00026581 00031054 45 00283231 00283258 00313319 00314242 00332151 00406708 00407836 00436275 00458155 on September 25, 2021 by guest. Protected copyright. 46 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00579335 00611301 47 48 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00752398 00811009 49 00888486 00889954 00895385 00897876 00897930 00906689 01932381 01980661 02044137 50 02099179 02099187 02131447 02176408 02239384 02242930 80056706 80057178 00063312 51 00063313 00576514 00194883 00194891 00194913 00194921 00194948 00194956 00806897 52 53 00807346 00363014 00203505 00203513 00395765 00427497 00476226 00476242 00505781 54 00811513 02234466 02240851 02242797 02247692 00503134 00560022 66894419 80061501 55 00203483 00319848 00395757 00461717 00476277 00476285 00505773 00511781 00607789 56 57 00811505 00894761 00897434 00898325 00363847 00385700 00404411 00607797 00885738 58 02128446 02179547 02209764 02210517 02236399 02240112 02242798 02247691 02387239 59 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 00338656 60 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 02242984 02242985 66888338 66895075 00622249 02240658 00090808 00090824 00355038 02404044 https://mc.manuscriptcentral.com/bmjpo 00429090 00807478 02038242 02224542 00062251 00062278 02062251 Page 73 of 88 BMJ Paediatrics Open
1 2 02246449 02246450 02358689 02289407 00022756 00022757 00022764 00022918 00023191 3 00023205 00130974 00155276 00271411 00304387 00337404 00337412 00370517 00421197 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00439118 00443441 00450839 00479764 00487791 00489867 00504653 00509345 00554294 6 00556726 00583332 00596612 00610755 00622796 00622818 00728152 00728160 00728162 7 00754889 00757683 00757691 00792705 00804193 00804401 00811432 00833266 00843482 8 00843490 00878200 00878634 00880043 00960314 01900005 01907034 01933434 01933442 9 10 01933450 01934414 01944290 01944347 01946986 01949454 01957996 01959395 01991086 11 01994247 01997025 02017849 02019671 02019698 02019701 02019728 02019736 02019744 12 02061287 02061597Confidential: 02087588 02097575 For02097583 Review 02141728 02141736 Only 02146142 02153165 13 14 02164574 02171279 02176483 02176580 02176883 02210657 02219298 02219336 02229492 15 02229958 02229959 02229960 02230398 02230485 02237169 02237788 02237789 02238644 16 02239029 02239030 02239138 02239548 02241167 02241734 02244203 02245778 02246936 17 18 02247037 02247560 02247659 02247762 02248858 02248859 02249529 02251817 02254425 19 02254433 02257548 02257556 02258250 02258994 02261286 02263882 02270900 02284170 20 02292734 02297701 02297728 02298503 02304244 02304252 02306352 02309629 02309742 21 02311232 02311240 02311771 02312352 02312360 02318849 02320789 02321076 02321270 22 23 02323346 02328895 02348608 02354578 02361256 02365685 02367939 02368374 02369567 24 02369656 02373300 02376202 02383268 02396599 02401932 02404869 02409224 02409240 25 02409259 02410214 02411415 02419769 02427427 02431181 02431203 02431599 02432129 26 27 02434385 02436884 02436930 02445182 02446170 02447827 02447835 02453711 02456303 28 02464683 02465108 02470144 02474867 02478242 02478757 02479710 02483122 02490943 29 02491850 02492318 02492326 09850791 09850805 66999121 80757683 88907502 99100522 30 31 99101300 99101367 02369672 00633917 00258350 00270695 00362611 00454494 02401193 32 02410583 02430770 02226626 02230939 00173568 00173576 02444593 02278170 02280612 33 02294354 02323915 00466069 00568473 01944789 02280868 02280876 02301717 02376148 34 02376156 02429721 02478072 02484838 02424630 02355841 22123333 00286710 02246391 http://bmjpaedsopen.bmj.com/ 35 36 0003597102278693 0216767000349046 02279150 00458570 02291371 01925946 0230566600728500 0241605001906577 02362643 02368528 02384175 37 0000649102387697 01979124 x 02383357 02385244 02469960 02469944 02238183 02359944 02385619 38 02356457 02273934 02275961 02276232 02319195 02322099 02326884 02409178 02413280 39 40 0049274402420929 0052498002420937 00230200 02423200 00425125 02432498 0046205502462265 0046207102487233 0041265102487276 00242977 02487322 00425133 02488574 41 0042514102490498 0046707302046784 0013326402203424 0044902402215241 0044903202215861 0046206302229367 0046203902230424 0046204702237483 0052205802237707 42 02239514 02240560 02241043 02241995 02242691 02245017 02248700 02250993 02255472 43 00091626 00091634 00091642 00425168 00214027 00425117 01940783 00763527 00091847 44 0014581502256576 00581771 02258633 00299596 02261014 00299561 02263874 00299588 02294370 02422964 02298171 02437953 02303833 00145963 02305305 00213543 02322269
None found. on September 25, 2021 by guest. Protected copyright. 45 02365766 02366797 02368196 02404974 02438348 00156345 00469122 00503215 00806781 0013415500218227 00545449 00550477 00749052 02048183 02230769 02244662 02485443 00507407 46 00156337 00361909 00420026 00464686 00535230 00659142 00690074 00792160 02190575 47 00713465 01946994 00435619 00134104 00460850 00373850 00481394 00609129 00806331 02244010 02245019 02245592 02486903 01905635 02005395 02242999 00156264 00361887 48 02304503 02406187 02413248 02383365 00566829 02047667 02409542 02410737 01982532 49 00361888 00370975 00710822 00766380 00156086 00156094 00156108 00358452 00358460 01996215 02198924 02248371 02272792 02291339 02293927 02374277 02378655 02380315 50 00462683 00538493 00609188 00730556 01945874 01945882 01962507 01962515 02241462 02438305 02449188 02492857 02494027 02276879 02291444 02458462 02481928 02482401 51 02246696 02310783 00889865 00156116 52 02483351 02492865 02493322 00237760 00758558 01900501 02050684 02148315 02218836 53 02239041 02239061 02241706 02248905 02254913 02254921 02258285 02258625 02258927 54 55 02260271 02262320 02272369 02273071 02293242 02298414 02307014 02335239 02426315 00012769 00013102 00115568 56 02427923 02472864 02472872 02368536 02427958 02273810 02380307 02437201 02459876 57 02240302 02245016 02380404 02385260 02383608 02388537 02246847 02253267 02255014 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 74 of 88
1 2 02241814 02241813 00295450 00295469 02245301 01900559 01934724 02243945 00026395 3 00026484 00172227 00172235 00172537 01932535 01932543 01932551 01933582 02052482 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02229557 00493082 01934716 02244079 00172545 00656828 01934694 02244078 02215314 6 00172529 00533963 00810711 00933620 01933574 01933620 02243969 02245076 02266466 7 02266474 02267446 02267454 02315483 02315491 02328658 02468204 00172650 01934708 8 02244080 01933590 00172383 00172391 00172405 00933647 01932608 01933604 01933647 9 02012146 02024616 02243980 02245075 02266180 02266199 02267411 02267438 02277239 10 00028142 00028207 00176893 00225533 02273330 11 02307316 02315475 02468212 00588229 01933639 02043947 02125714 02198916 00342718 12 00589292 00589306Confidential: 01934686 For Review Only 13 None found. 14 15 None found. 16 17 None found. 18 19 00298433 00616869 00411892 00471348 00746304 00808059 00808253 00810577 00905755 20 02154285 21 22 None found. 23 None found. 24 25 None found. 26 27 None found. 28 29 30 00005703 00074306 00488461 00584096 00623504 00659673 02239338 31 32 None found. 33 None found. 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 00164291 00385948 01937561 02162199 00164267 00385964 01937545 02162180 00209449 37 00209457 00232920 00236276 00450561 00450588 00518336 00518344 02043459 02043467 38 02225654 02225662 00164283 00385956 00811211 01937588 02162172 00164186 01927736 39 40 00164259 00385972 00811203 01937553 02162164 00025380 00025402 00025046 00025429 41 00025712 00025739 00164038 00164046 00213896 00236764 00248754 00567434 00575178 42 00575186 00583979 00627607 00911311 01927566 01937685 01937693 01937707 01937715 00027324 00027367 00027510 43 01937723 02068591 02162156 02162202 02162210 02162229 02162237 99101319 99101320 44
00003158 00003514 on September 25, 2021 by guest. Protected copyright. 45 99101340 46 None found. 47 48 None found. 49 50 None found. 51 None found. 52 53 None found. 54 None found. 55 00068586 00318809 00985562 00318795 00004448 00318817 56 57 None found. 58 00901069 00024724 00216151 00220442 02368838 22123148 66903076 90220442 00158127 59 00221850 60 None found.
https://mc.manuscriptcentral.com/bmjpo Page 75 of 88 BMJ Paediatrics Open
1 2 01900978 02315963 02427192 00900986 00980986 01900986 02145782 02145790 02223546 3 02223554 02231603 02238337 02240265 02240266 02240910 02241912 02241913 02295059 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02295067 02315947 02315955 02316609 02318873 02318881 02318903 02344572 02355868 6 02358352 02363844 02364689 02368064 02375087 02375095 02408732 02427133 02427141 7 None02432722 found. 02450526 02451751 02451778 02453363 02466171 02467577 02486954 02491125 8 41900986 9 None found. 10 00009989 00010073 00016314 00016454 00757713 02245667 02245668 02332248 09850775 11 12 None09991029 found.Confidential: For Review Only 13 None found. 14 15 00005436 x 16 00004812 00235768 17 None found. 18 19 20 00610070 00610089 02182912 02184656 02239669 21 22 00590908 00614394 00641774 00786624 00870927 00881694 00893528 00893536 00893552 23 01905058 01913395 02034433 02034441 02103575 02103621 02103648 02130882 02130890 24 25 00782696 02019973 02237734 02241523 02242957 02243880 02244691 02244692 02251795 26 02280159 02284669 02366444 02375990 02379481 02390388 02404494 02418959 27 None found. 28 29 None found. 30 02172585 02230799 00577308 00600784 02176084 02218305 02221330 02230730 02231679 31 02231680 02242324 02279223 02400871 02489651 99400864 32 33 None found. 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 None found. 37 None found. 38 39 None found. 40 None found. 41 None found. 42 43 02231462 02231463 02237296 02237633 02242818 02242819 44
02243919 02247192 02247193 02298155 02338424 02408740 on September 25, 2021 by guest. Protected copyright. 45 46 02456451 02456478 47 02454130 x 48 None found. 49 50 None found. 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 76 of 88
1 2 00006144 00061379 00061387 00061395 00061409 00061441 00099902 00286273 00286281 3 00499625 00499633 00499641 00499668 00499676 00504572 00514713 00541427 00541435 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00541443 00541451 00541478 00583448 00602752 00602760 00602779 00602787 00602795 6 00602809 00603384 00605263 00605298 00605301 00605328 00614424 00662283 00705300 7 00800227 00861081 00861111 00861138 00861162 00861170 00861189 00861219 00861227 8 00861251 00861286 00861308 00861316 00861332 00861359 00861367 00861375 00861405 9 10 00886831 00886912 00886920 00888540 00888559 00888613 00888648 00888656 00888796 11 00888818 00888826 00888834 00888842 00888850 00888877 00888885 00888893 00888915 12 00888958 00889601Confidential: 00889628 00889636 For00889644 Review 00889709 00889717 Only 00889725 00889733 13 14 00889741 00889768 00889776 00889784 00889792 00889814 00889822 00889849 00889857 15 00894346 00894354 00894362 00894524 00894583 00895245 00895296 00895334 00895423 16 00895431 00895458 00895466 00896853 00896934 00896942 00896950 00897752 00897817 17 18 00898422 00898430 00898449 00898465 00898473 00898481 00898503 00898511 00898538 19 00898546 00898589 00898597 00898619 00899828 00899836 00899844 00899852 00899895 20 00899968 00900702 00900818 00906115 00906271 00907529 00907545 00908614 00911496 21 00967483 00967823 00969702 00990303 00998885 00999900 01948873 01959123 01959131 22 23 01959133 01959157 01959158 01959166 01959182 02217104 02223961 02226219 02226251 24 02226286 02226294 02226928 02226944 02230863 02238472 02238473 02238485 02238497 25 02241328 02242672 02242713 02242714 02242715 02242716 02242717 02247755 02247756 26 27 02247757 02325470 02325543 09850724 11135717 14048555 66861073 66889210 66889695 28 66889830 66894699 66895318 66895326 66969680 66969699 66969818 95000650 99000350 29 99000407 99000415 99000423 99000431 99000458 99000466 99003651 99003678 99003686 30 31 99003694 99003708 99003716 99003724 99003732 99003740 99003759 99003767 99003775 32 99003791 99003805 99003813 99003821 99003848 99003856 99003864 99003872 99003880 33 99003899 99003902 99003910 99003929 99003937 99003945 99003953 99003961 99003988 34 99003996 99004003 99004097 99004100 99100018 99100062 99100225 99100226 99100227 http://bmjpaedsopen.bmj.com/ 35 36 None99100228 found. 99100229 99100230 99100267 99100268 99100269 99100270 99100278 99100279 37 99100280 99100281 99100282 99100284 99100625 99101105 99101106 99101107 99101108 38 99101109 99101110 99101111 99101112 99101113 99101114 99101115 99101117 99101118 39 40 0194513099101119 0202001799101120 0212336399101121 0213162599101122 99101123 99101124 99101125 00350245 00966134 41 None00999652 found. 00999938 00999981 09999938 11044212 99100026 02230860 99100021 02220075 42 01948903 01948911 02239410 02217082 02223953 02223988 02231321 02231322 02369737 43 00766038 02230543 02229636 02230446 02241407 44 01959174 02223996 02231325 02270919 02223937 02223945 02231323 02231324 02369745
00893560 x on September 25, 2021 by guest. Protected copyright. 45 01948938 01948946 01948881 01948997 01949004 02242666 00504564 02221314 00286303 46 0029997902237355 00522457 x 00662275 02372428 02238486 02242674 02238501 02242676 00155233 47 None found. 48 02230864 99100017 01948970 01948989 00299987 00522465 02372444 00648122 00648922 49 0046498802172585 0224132702230799 0224775400577308 9900054700600784 0223848902176084 0224267002218305 0221745702221330 0223529902230730 0213607402231679 50 0221746502231680 0223849302242324 0223849402279223 0224266802400871 0223850002489651 0194895499400864 01948962 02220091 02220105 51 9900460702233143 9910001602305054 9910026602358913 0223086202362171 0060527102402823 0222008302403986 0222011302404095 9900459302420171 02247753 02422727 52 53 None0224775802458411 found. 9910006102458551 99100063 99100064 99100065 99100066 99100067 99100068 99100070 54 None99100072 found. 99100073 99100074 99100075 99100076 99100077 99100078 99100079 99100080 55 99100082 99101141 99101142 99101143 99101144 99101145 99101146 99101147 99101148 56 57 99101149 99101150 99101151 99101153 99101155 00888023 02423723 02242669 02432889 58 02451778 02467577 02240953 02242675 02447231 02463644 02239030 02245778 02247659 59 02248858 02249529 02258250 02258994 02263882 02270900 02284170 02292734 02297728 60 02309629 02311771 02312352 02318849 02361256 02368374 02396599 02409259 02410214 02411415 02431181 02431203 02431599 02434385 02436884 02436930 02447827 02447835 02453711 02456303 02470144 02230865 02381885 02381893 02404494 02418959 02242665 https://mc.manuscriptcentral.com/bmjpo 02242673 02160501 02447304 02238502 02242677 02325500 02238498 02242664 02242667 Page 77 of 88 BMJ Paediatrics Open
1 2 00903944 00950645 00950653 00960039 00960632 00960634 02175983 02175991 02176009 3
02243144 02244148 02244149 02296462 02296470 02296489 02331667 02416816 02416824 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 02416832 02454068 02456095 02456109 02485877 02485885 02485893 09851984 09852069 6 09852662 09854786 66123987 66124086 66990973 99108093 99109293 7 8 02247238 x 9 None found. 10 02240328 02337630 02337649 02477432 02477440 11 12 02470365 02492504Confidential: For Review Only 13 02476991 x 14 15 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 16 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 17 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 18 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 19 20 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 21 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 22 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 23 00093637 00093645 00133426 00151475 00157880 00177571 00192562 00192570 00192589 24 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 25 26 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 27 00303887 00303895 00338591 00341606 00341614 00461903 00461911 00477680 00479098 28 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 29 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 30 31 00595802 00641154 00661856 00716855 00728829 00728837 00740330 00748811 00748889 32 00756679 00763470 00804533 00824435 00862770 00862789 00880671 00887153 00887161 33 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 34 35 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 00967564 http://bmjpaedsopen.bmj.com/ 36 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 37 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 38 39 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 40 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 41 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 42 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 43 44 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 45 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 on September 25, 2021 by guest. Protected copyright. 46 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 47 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 48 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 49 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 50 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 51 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 52 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 53 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 54 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 55 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 56 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 02242984 02242985 66888338 66895075 57 00278912 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 58 59 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 60 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 0075616400456543 0075617200456551 0090762600889938 0213329600889946 0213331800894591 00544833 02214415 01924400 02214423 01954237 02148498 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 78 of 88
1 2 None found. 3
00005134 00005789 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 None found. 6 None found. 7 8 00259454 00432814 00707511 00897469 02238568 00756784 9 None found. 10 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 11 12 00889563 02048639Confidential: 02115514 02115522 For02154862 Review 02154870 02229315 Only 02229323 02348489 13 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 14 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 15 16 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 17 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 18 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 19 20 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 21 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 22 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 23 24 00888702 00888729 00889288 00889296 00889458 00889466 00893463 00895121 00895148 25 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 26 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 27 02070855 02070871 28 02194058 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 29 02368676None found. 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 30 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 31 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 32 33 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 34 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 http://bmjpaedsopen.bmj.com/ 35 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 36 37 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 38 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 39 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 40 01977547None found. 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 41 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 42 02387743 02412888 02412896 00016268 43 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00028096 44 02237835 00274410 00335347 00351431 00887366 00908568 00323071 00344923 00417246 on September 25, 2021 by guest. Protected copyright. 45 00629367 00688622 00769614 00804991 00805009 00808187 00809187 00811769 00849650 46 00849669 00862975 00886688 00887390 00887404 00895679 00895768 00899291 00899305 47 48 00899313 00899364 00908215 00908223 00908231 00908258 00908487 00960942 00961051 49 00961442 00961450 01927914 01942050 01942069 01942077 01942085 01942093 01942107 50 02048132 02048140 02048159 02122030 02122049 02122057 02122065 02122073 02122081 51 52 02217821 02217848 02217856 02217864 02217872 02217880 66899798 00012181 00036366 53 00176834 00212385 02060876 02060884 02063190 00900516 99100521 00011916 00011924 54 00011932 00011940 00012378 00012386 00027898 00027899 00027901 00027902 00027944 55 56 00028355 00028363 00028364 00110647 00110655 00110663 00432571 00444537 00444545 57 00444561 00458139 00458147 00472603 00472611 00472638 00472646 00509698 00509701 58 00535400 00535419 00535427 00535435 00584800 00653209 00653217 00716618 00716626 59 60 00716634 00716642 00716650 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 00887439 00887455 00887471 00888494 00888672 00889024
00889490 00889504 00895873 https://mc.manuscriptcentral.com/bmjpo 00895881 00897728 00897833 00897841 00897949 00899550 00904937 00908355 00908363 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 66887323 66907960 95000467 99113736 99900015 Page 79 of 88 BMJ Paediatrics Open
1 2 None found. 3
00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 6 0003022866889318 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 7 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 8 9 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 10 00464627 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 11 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 12 Confidential: For Review Only 13 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 14 00806951 00862347 00862355 00862371 00862398 00873292 00886998 00887005 00887013 15 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 16 17 00889083 00889261 00889474 00889482 00894303 00894311 00894338 00894451 00894478 18 00895105 00895113 00897868 00897884 00897892 00897906 00899976 02129078 02162504 19 02162512None found. 02162520 02162539 02162547 02163470 02163489 02242738 02300559 02306980 20 6603023600527818 6689425700587818 9071679000587826 9910087800587834 9910087900777818 9910088300811017 00811025 00811033 00896012 21 22 None00896020 found. 00896047 00896055 02070995 23 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 24 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 25 26 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 27 00908282 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 28 02187663 02187671 02236996 02236997 02240269 22369960 66887102 66887129 66887137 29 00634530 00634549 00636460 00814091 00817228 00851752 00851760 00852074 00904059 30 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 31 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 32 33 0048179302483874 0048180709857675 0088937709857676 0088938509857677 0088940709857679 09857680 09857681 09857682 09991294 34 49636460 49851752
00443824 00559237 00571016 00575046 00591629 00810029 00810037 00888311 00889032 http://bmjpaedsopen.bmj.com/ 35 36 00894621 00894656 02052881 02154838 02170175 02192268 02192276 02192284 02219719 37 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 38 None02242542 found. 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 39 02257416 02370557 66894648 40 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 41 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 42 43 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 44
None found. on September 25, 2021 by guest. Protected copyright. 45 46 47 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 48 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 49 50 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 51 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 52 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 53 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 54 55 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 56 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 57 02241299None found. 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 58 59 99100392 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 80 of 88
1 2 02446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 3 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 6 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 7 0205975402294745 0222751702296071 0223064202298589 02336405 02453738 02460513 02467895 02467909 02467917 8 77700002 77700003 9 02415534 x 10 None found. 11 12 02216213 00234408Confidential: 00359718 00359726 For00479012 Review 00878707 00878723 Only 00881678 00887242 13 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 14 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 15 16 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 17 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 18 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 19 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 02475162 02489619 02490706 66888389 66895083 20 02010283 02010291 02010305 02011921 02200945 66887803 66887811 21 22 None found. 23 00063312 00063313 00449768 00456403 00091448 00215686 00216828 00521205 00521213 24 00521221 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 25 26 00074454 00806870 00806889 27 None found. 28 29 00128031 00128058 30 31 32 None found. 33 34 00271012 00575194 00611174 00813087 00417254 00417262 00811521 00811548 00586692 http://bmjpaedsopen.bmj.com/ 35 36 00586706 00614270 00682217 02244999 00177016 00813036 00813052 02244766 02238818 37 02238819 02247446 02244126 02457393 02319012 02474883 00177017 00232352 00807052 38 39 None found. 40 41 None found. 42 43 02028719 x 44 45 on September 25, 2021 by guest. Protected copyright. 46 02238578 00445045 00155977 00429090 00807478 02038242 02224542 02242485 00243124 47 00243132 00520322 00666246 00701904 00156175 00163511 00163538 00438669 00704555 48 00704563 00750670 00763543 00837350 01980572 01980580 00476439 00145718 00390748 49 00390798 00068667 00191282 00243140 00243159 00666211 00694401 00813559 00912828 50 51 01912828 02025736 02230386 00194883 00194891 00194913 00194921 00194948 00194956 52 00806897 00807346 00622249 00068772 00068780 00091820 00203378 00534838 00534846 53 00203378 00534838 00534846 00990313 00216941 00216968 00216976 00801666 00068675 54 00195057 00806919 00806927 00252395 00194867 00806935 00194859 00260428 00880787 00281816 00530611 00158046 00158178 00443298 00192678 00241067 00885738 00828947 55 00194875 56 57 00813680 00195057 00806919 00806927 00194867 00806935 00194859 00177121 00042617 58 00042625 00042633 00045632 00177024 00307246 00395145 00630640 00806617 00807788 59 00807982 00810894 00903124 02023784 02023814 00218812 00281824 00527998 00760056 60 00808199 00843741 00903477 02133342 00194875
https://mc.manuscriptcentral.com/bmjpo Page 81 of 88 BMJ Paediatrics Open
1 2 00128066 00128031 00128058 00184659 00184667 00199850 00245259 00245267 00382620 3 00433527 00464554 00464562 00464589 00492760 00501107 00562173 00562181 00717002 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00717029 00774659 00774667 00806846 00806854 00806862 00808083 00808091 00808105 6 00808113 00808555 00810959 00810975 00811440 00811459 00960101 01999826 01999834 7 01999842 01999850 00960128 00903365 00960497 66960500 00192627 00128090 00128112 8 None found. 9 00395153 x 10 11 12 00778907 00778915Confidential: 00173592 00173606 For00228052 Review 01987712 01987720 Only 02224623 02224631 13 02247920 00626597 00140732 00042668 00042676 00358177 02023806 02023849 14 15 None found. 16 02474883 x 17 18 19 00189499 x 20 21 22 None found. 23 24 25 None found. 26 27 00492442 00808393 00808407 07090343 28 29 None found. 30 None found. 31 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 32 33 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 34 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 http://bmjpaedsopen.bmj.com/ 35 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 36 37 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 38 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 00326941 00403075 00404179 00404187 00774179 00886696 00886726 00888273 00888281 39 02475162 02489619 02490706 66888389 66895083 40 02010283 02010291 02010305 02011921 02200945 66887803 66887811 41 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 42 43 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 44 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 on September 25, 2021 by guest. Protected copyright. 45 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 46 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 47 48 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 49 50 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 82 of 88
1 2 00003719 00003727 00006351 00016527 00021083 00021091 00024805 00030910 00030929 3 00093637 00093645 00133426 00151475 00157880 00177571 00192562 00192570 00192589 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00192597 00192600 00193275 00193283 00193291 00193305 00195294 00216895 00216909 6 00228079 00228087 00230316 00245410 00245429 00265780 00275581 00298301 00298328 7 00303887 00303895 00338591 00341606 00341614 00461903 00461911 00477680 00479098 8 00482293 00482919 00502197 00502198 00502200 00502201 00513253 00513261 00513288 9 10 00521124 00521132 00551945 00551953 00562319 00562327 00564281 00567485 00595799 11 00595802 00641154 00661856 00716855 00728829 00728837 00740330 00748811 00748889 12 00756679 00763470Confidential: 00804533 00824435 For00862770 Review 00862789 00880671 Only 00887153 00887161 13 14 00887552 00887838 00888087 00889237 00889245 00889547 00894664 00896098 00900036 15 00900044 00903183 00903296 00904104 00905577 00907065 00907073 00960535 00967564 16 00967572 00968951 00990137 00990253 00990841 00990842 00999122 00999423 00999474 17 18 01925172 01931083 01940120 02060345 02086034 02112736 02187132 02243691 02243847 19 02244959 02412926 02469421 06260095 07196839 09857120 10502200 49513288 66123379 20 66123732 66123756 66896071 66903124 66903132 66903159 66903167 66903175 66903213 21 80021085 80021087 80021088 80026974 80037486 80052230 80057189 80057193 80061697 22 23 80061702 80061712 80061805 80064671 80066164 80066165 80066167 80066168 80066699 24 80071959 80073687 80076663 80076664 80078409 80079355 88903167 90090250 99100725 25 99100726 99100727 99101368 00000671 00016276 00020818 00020826 00024775 00024783 26 27 00026581 00031054 00283231 00283258 00313319 00314242 00332151 00406708 00407836 28 00436275 00458155 00477699 00482277 00482285 00482307 00509620 00509639 00539538 00030961 00030988 00030989 00036129 00194573 00194980 00358711 66888095 00030739 29 00579335 00611301 00666467 00704458 00716685 00716693 00716820 00716839 00749834 30 00030740 00030759 00030767 00031062 00386847 00696617 00770759 00828912 00828920 00752398 00811009 00888486 00889954 00895385 00897876 00897930 00906689 01932381 31 00903205 00903213 00903531 01934325 01934333 01934341 02245400 02245406 02245407 32 01980661 02044137 02099179 02099187 02131447 02176408 02239384 02242930 80056706 02245408 00030791 00030643 00030651 00030678 00036137 01962736 01962744 01962752 33 80057178 00888206 00888214 00888222 00888230 00030600 00030619 00030627 00030635 34 01962760 02063697 02063700 02063719 02063727 02230210 02230211 02231893 02231894 00338656 00338664 00338672 00338680 00872520 00872539 00878618 00878626 02497530 http://bmjpaedsopen.bmj.com/ 35 02231895 02232748 02232750 02241229 02367947 02367955 02367963 02367971 00021679 02497549 00423165 00590800 00811491 00908592 00910124 00910132 01910124 01910132 36 00031003 00178926 00210692 00544817 00993610 00028118 00093602 00250376 00252492 37 02242984 02242985 66888338 66895075 38 00278912 00299405 00300373 00301175 00622931 00700401 00727466 00764639 00801186 39 00809152 00894958 00896144 00898732 00901397 00908266 00961264 01916181 01916203 40 02023768 99100258 99100485 99100550 99113742 00281735 00281743 00526452 00526460 41 00456543 00456551 00889938 00889946 00894591 02214415 02214423 42 00756164 00756172 00907626 02133296 02133318 00544833 01924400 01954237 02148498 43 02152541 02213079 02230619 02244395 02245532 02245858 99100839 99101412 44 45 on September 25, 2021 by guest. Protected copyright. 46 None found. 47 00005134 00005789 48 None found. 49 50 None found. 51 00259454 00432814 00707511 00897469 02238568 00756784 52 53 None found. 54 00210153 00410179 00521248 00521264 00559113 00886793 00887544 00887563 00889555 55 00889563 02048639 02115514 02115522 02154862 02154870 02229315 02229323 02348489 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 83 of 88 BMJ Paediatrics Open
1 2 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 3 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 6 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 7 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 8 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 9 10 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 11 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 12 00888702 00888729Confidential: 00889288 00889296 For00889458 Review 00889466 00893463 Only 00895121 00895148 13 14 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 15 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 16 0219405802070855 0219406602070871 02194074 02213834 02219271 02229540 02229550 02236568 02236569 17 None found. 18 02368676 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 19 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 20 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 21 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 22 23 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 24 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 25 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 26 27 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 28 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 29 01977547None found. 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 30 0238774300012173 0241288800012211 0241289600028185 0001626800726486 00779822 00804541 00907820 00907839 00990333 31 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 32 33 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 34 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 http://bmjpaedsopen.bmj.com/ 35 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 36 37 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 38 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 39 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 40 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 41 42 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 43 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 44
00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 on September 25, 2021 by guest. Protected copyright. 45 46 00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 47 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 48 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 49 50 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 51 None00887439 found. 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 52 0042027100895881 0048645000897728 0075254100897833 0079717000897841 0088665300897949 0090809600899550 0096107800904937 0198752600908355 0198784400908363 53 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 54 01990942 01995065 02221896 02221918 02221926 02221934 02239068 02239069 02241887 55 6688931802100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 56 66887323 66907960 95000467 99113736 99900015 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 84 of 88
1 2 00030228 00030229 00030230 00030236 00030237 00030238 00030244 00030260 00030392 3 00030393 00030394 00030406 00030407 00030408 00030414 00030415 00030416 00030422 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00030423 00030424 00130228 00189480 00385220 00385239 00424927 00424935 00428094 6 00464627 00470724 00472654 00472662 00472670 00472689 00488941 00488968 00501018 7 00501026 00509647 00509655 00530956 00532630 00535281 00535303 00535311 00535338 8 00562238 00562246 00716782 00716790 00716804 00716812 00776998 00777064 00777072 9 10 00806951 00862347 00862355 00862371 00862398 00873292 00886998 00887005 00887013 11 00887021 00887048 00887072 00887951 00887978 00888303 00888699 00888710 00889075 12 00889083 00889261Confidential: 00889474 00889482 For00894303 Review 00894311 00894338 Only 00894451 00894478 13 14 00895105 00895113 00897868 00897884 00897892 00897906 00899976 02129078 02162504 15 02162512None found. 02162520 02162539 02162547 02163470 02163489 02242738 02300559 02306980 16 6603023600527818 6689425700587818 9071679000587826 9910087800587834 9910087900777818 9910088300811017 00811025 00811033 00896012 17 None00896020 found. 00896047 00896055 02070995 18 19 00036099 00274437 00274445 00274453 00281913 00424943 00589896 00598933 00716863 20 00728365 00777080 00777102 00816132 00887145 00887668 00894273 00894281 00894613 21 00894753 00895687 00897698 00897701 00897914 00897922 00903360 00907227 00908274 22 23 00908282 00946970 00946972 01929607 02161923 02161966 02161974 02163152 02187655 24 0063453002187663 0063454902187671 0063646002236996 0081409102236997 0081722802240269 0085175222369960 0085176066887102 0085207466887129 0090405966887137 25 26 00911730 00969112 00999717 01974432 01978918 01978926 02035324 02052431 02229099 27 02229293 02230648 02231922 02231923 02241003 02241031 02455889 02465949 02465957 28 02483874 09857675 09857676 09857677 09857679 09857680 09857681 09857682 09991294 29 00481793 00481807 00889377 00889385 00889407 30 0044382449636460 0055923749851752 00571016 00575046 00591629 00810029 00810037 00888311 00889032 31 00894621 00894656 02052881 02154838 02170175 02192268 02192276 02192284 02219719 32 33 02230956 02237847 02238428 02238755 02240621 02240757 02240782 02242508 02242532 34 02242542 02243073 02246714 02247096 02247097 02247098 02247852 02248123 02248726 None found. http://bmjpaedsopen.bmj.com/ 35 02257416 02370557 66894648 36 00800902 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 37 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 38 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 39 40 None found. 41 42 43 00002712 00003697 00234243 00270466 00334243 00359688 00374407 00422053 00545325 44 00545333 00638617 00768707 00774407 00812951 00828521 00828548 00872318 00872326 on September 25, 2021 by guest. Protected copyright. 45 00872329 00872334 00872342 00880868 00887188 00887196 00887218 00887226 00887234 46 47 00893633 00894443 00895369 00895377 00897353 00899135 00901041 00901342 00903654 48 00905771 00908320 00908347 00923242 00923935 00969400 00973025 00986445 01923242 49 01923249 01923935 01927957 01927965 01927973 01949993 01950002 02079976 02079984 50 51 02089599 02089602 02089610 02172712 02213702 02213710 02213729 02215039 02215047 52 02215055 02216531 02228300 02229998 02237258 02237379 02238577 02238796 02239211 53 02241299None found. 02242029 02242030 09857672 09857673 09857674 09991292 66899127 99000393 54 9910039202446561 02446588 02048043 02089912 02090015 02174693 02174707 02174715 02174723 55 02174731 02174738 02174758 02174766 02174774 02213581 02213583 02213591 02213605 56 57 02213613 02213621 02213648 02213656 02213664 02213672 02213680 02213699 02237244 58 02237245 02237246 02237247 02241752 02243646 02244291 02244292 02244293 02248307 59 0205975402294745 0222751702296071 0223064202298589 02336405 02453738 02460513 02467895 02467909 02467917 60 77700002 77700003 02415534 x
https://mc.manuscriptcentral.com/bmjpo Page 85 of 88 BMJ Paediatrics Open
1 2 None found. 3
02241506 00023237 00035815 00085871 00086126 00090948 00208132 00238252 00241075 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 4 5 00245631 00246948 00251372 00276456 00280747 00342769 00343447 00358494 00358495 6 00423203 00426415 00426423 00509310 00517879 00530492 00539063 00577359 00579963 7 00621137 00623237 00632295 00632309 00644994 00645001 00710962 00776415 00810363 8 9 00811157 00811165 00812978 00860964 00864706 00875279 00894516 00897302 00897361 10 00899712 00900974 00903450 00905321 00908169 00972339 00982407 00999972 01908855 11 01918087 01918974 01918982 01918990 01921983 01937642 01937650 01981021 01981293 12 Confidential: For Review Only 02143941 02184672 02184680 02220350 02220393 02238310 02238311 02238642 02240151 13 14 02240152 02240645 02241910 02245737 02246735 02246736 02246802 02246974 02293978 15 02307146 02392046 02403854 02439085 02439093 02448963 02458837 66899704 66901032 16 66903256 88901121 00090905 00249866 00329231 00344508 00419133 00489271 00501832 17 18 00505765 00632260 00632279 00770428 00810401 00810428 00067229 00157562 00234206 19 00167800 00167819 00351881 00625280 00810886 00899704 02023075 00961043 01931121 20 02230134 00659703 00773492 00288640 00784753 01931237 01931245 01932446 01942379 21 22 02285703 02285711 02432366 02432439 00509302 00090891 00632244 01936980 02106299 23 None00800694 found. 00866601 00550434 00812226 00379727 00594792 00628042 00807133 00811076 24 0033117100812889 0196638302240942 01981307 02403862 00344494 00509906 00510335 00560448 00744298 25 00748269 00894508 00181757 00208205 00232890 00362204 00444448 00525383 01909118 26 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 27 0190747601981315 0194637402030462 0240623302403846 0985224700266493 0985290500332801 0999112500373222 2212304300506966 4900726900652326 9910069900740314 28 9910091601909185 0009091399100917 0009100699100918 00579955 00579971 00234141 00907308 29 None found. 30 01971633 x 31 32 02338572 00481815 00481823 00824291 00891738 00891746 02245686 02245687 02399334 33 02399342 02431637 02431645 02485710 02485729 02495899 02495902 34 None found. http://bmjpaedsopen.bmj.com/ 35 36 02230784 02230785 02243894 02243895 37 None found. 38 00007269 00007285 00252654 00642236 00646236 00646237 00698059 00903424 00960551 39 40 01907476 01946374 02406233 09852247 09852905 09991125 22123043 49007269 99100699 41 None99100916 found. 99100917 99100918 42 43 00616400 00616419 66123914 44
02070847 02070863 02080863 02466074 02466082 02468840 02468859 on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 48 00054232 00475238 00505757 00509914 00666106 00666108 00666114 00744263 00744271 49 50 00748277 00774232 00775238 00808202 00811306 00813346 02016447 02227274 02231520 51 02238910 02241695 02243936 02243937 02243938 02245006 02248196 02248197 66903051 52 80027681 00961043 01931121 02230134 00181757 00208205 00232890 00362204 00444448 53 54 00525383 01909118 01981315 02030462 02403846 00266493 00234141 00907308 00075973 00203297 00208175 00208183 00232882 00355607 00428752 00506974 00534854 00739316 55 00005134 00005789 56 00807958 00810312 00810320 00810991 00972584 01909096 01988239 00180076 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 86 of 88
1 2 00014893 00015016 00015024 00029475 02194082 02194090 02194139 00502022 00014613 3 00014621 00014648 00029106 00029114 00029130 00029270 00029300 00029505 00029564 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00029572 00074250 00127914 00192546 00192627 00282448 00282456 00282464 00385182 6 00385204 00405590 00460761 00464600 00464619 00472557 00472565 00472573 00472581 7 00488976 00488984 00494240 00501034 00501042 00502928 00509663 00509671 00535249 8 00535257 00535265 00535273 00562491 00562505 00716952 00716960 00716979 00716987 9 10 00769983 00887684 00887692 00887706 00887722 00887730 00887749 00887757 00887773 11 00887781 00887870 00887935 00887943 00888028 00888036 00888044 00888443 00888451 12 00888702 00888729Confidential: 00889288 00889296 For00889458 Review 00889466 00893463 Only 00895121 00895148 13 14 00897957 00897965 00897973 00897981 00913328 00969206 00977653 00990876 01913328 15 01926314 01964054 01977563 01999761 01999788 01999796 01999818 01999869 02194031 16 02194058None found. 02194066 02194074 02213834 02219271 02229540 02229550 02236568 02236569 17 00259454 00432814 00707511 00897469 02238568 00756784 18 02368676 02417510 02437635 09857128 66887889 00014834 00014842 00499846 00716995 19 0090320800000698 0197755500016462 0219412000016470 0219414700022500 6649424000022519 0029715100042560 0090317500042579 0219415500269026 0247063200285471 20 00295094 00349100 00354309 00489158 00501050 00501069 00501131 00504416 00525286 21 00724149 00732885 00732893 00739839 00903062 00904217 01908839 01930966 01946897 22 23 01964068 01964070 01964968 01964976 02016575 02237044 02237045 02237046 02239534 24 02240684 02240685 02240687 02250055 02260298 02260301 02261081 02279363 02311267 25 02363445 09850236 09852883 19649760 66901352 99503007 00308455 00617199 00874582 26 27 00213624 00732907 00627763 00741752 00250325 00496219 00598542 00643122 00664200 28 00664227 00716715 00751863 00783900 00785261 00911742 00911745 00911746 01947044 00012173 00012211 00028185 00726486 00779822 00804541 00907820 00907839 00990333 29 01977547 01995022 02023865 02204266 02204274 02212978 02378843 02385678 02385686 30 00999157 01925350 01944436 01944444 02048116 02048124 02060868 99100868 00274410 02387743 02412888 02412896 00016268 31 00335347 00351431 00887366 00908568 00323071 00344923 00417246 00629367 00688622 32 33 00769614 00804991 00805009 00808187 00809187 00811769 00849650 00849669 00862975 34 00886688 00887390 00887404 00895679 00895768 00899291 00899305 00899313 00899364 http://bmjpaedsopen.bmj.com/ 35 00908215 00908223 00908231 00908258 00908487 00960942 00961051 00961442 00961450 36 01927914 01942050 01942069 01942077 01942085 01942093 01942107 02048132 02048140 37 38 02048159 02122030 02122049 02122057 02122065 02122073 02122081 02217821 02217848 39 02217856 02217864 02217872 02217880 66899798 00012181 00036366 00176834 00212385 40 02060876 02060884 02063190 00900516 00011916 00011924 00011932 00011940 00012378 41 42 00012386 00027898 00027899 00027901 00027902 00027944 00028355 00028363 00028364 43 00110647 00110655 00110663 00432571 00444537 00444545 00444561 00458139 00458147 44
00472603 00472611 00472638 00472646 00509698 00509701 00535400 00535419 00535427 on September 25, 2021 by guest. Protected copyright. 45 46 00535435 00584800 00653209 00653217 00716618 00716626 00716634 00716642 00716650 47 00750050 00807222 00807230 00811939 00811947 00843822 00843830 00848360 00848387 48 00887269 00887277 00887285 00887293 00887307 00887315 00887331 00887382 00887412 49 00887439 00887455 00887471 00888494 00888672 00889024 00889490 00889504 00895873 50 00420271 00486450 00752541 00797170 00886653 00908096 00961078 01987526 01987844 51 0199094200895881 0199506500897728 0222189600897833 0222191800897841 0222192600897949 0222193400899550 0223906800904937 0223906900908355 0224188700908363 52 00908398 00908401 00980773 01929534 01940112 02089629 02100169 02100177 02100185 0080090266889318 00813648 00851736 00851744 00871095 02238465 02243021 02243022 02243595 53 02100193 02106264 02214350 02357844 02357852 02357860 02357879 02366924 02449773 54 02243596 02244767 02244768 02244769 02248130 02264749 02266385 02270862 02367157 66887323 66907960 95000467 99113736 99900015 55 02403587 02405601 02438690 02449811 02455870 02475863 09857431 49871095 90851744 56 57 00527818 00587818 00587826 00587834 00777818 00811017 00811025 00811033 00896012 58 None00896020 found. 00896047 00896055 02070995 59 60
https://mc.manuscriptcentral.com/bmjpo Page 87 of 88 BMJ Paediatrics Open
1 2 02216213 00234408 00359718 00359726 00479012 00878707 00878723 00881678 00887242 3 00887250 00888397 00910272 00961345 00961361 00961388 00961396 00961418 00964093 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00999564 00999843 01910272 01910280 01910299 02024187 02026767 02084465 02084473 6 02093162 02126192 02213265 02213273 02213281 02230071 02230072 02230073 02232191 7 02232193 02232195 02232548 02237272 02240267 02240268 02245522 02245523 02245524 8 02256371 02256398 02299739 02309521 02309548 02344408 02352001 02352028 02352036 9 00014850 00014974 00029319 00029416 00248169 00248170 00270113 00282219 00779121 02475162 02489619 02490706 66888389 66895083 10 00785709 00792667 00894834 00894893 00895210 00898953 00903212 00904479 00984671 11 12 02125145 02194198Confidential: 02194201 02229852 For02238544 Review 02433443 09850457 Only 09857764 40079266 13 49248169 66898929 66907472 66988170 00015067 00029092 00029491 00029556 00270091 14 00278793 00288195 00288209 00288217 00295973 00382639 00422592 00444383 00449792 15 00449806 00480819 00510297 00522864 00716871 00716898 00716901 00811084 00870552 16 17 00870560 00882607 00885126 00888761 00908053 00912972 00929092 00985074 00999954 18 00999958 02004674 02194163 02194171 02194228 02194236 02195704 09852921 09857765 19 09857767None found. 50237469 66908061 99113755 99900006 00464597 00811091 00885096 20 None found. 21 22 None found. 23 None found. 24 25 None found. 26 00012246 00012254 00012262 00028266 00028274 00028282 00513229 00513237 00901061 27 02100266 02100274 02100282 09991069 99100253 28 29 00903037 00903061 00001403 00139035 00325465 00325473 00353833 00420301 00513903 30 00513904 00513911 00513938 00513946 00516805 00516806 00516813 00516821 00516848 31 00567388 00576492 00629243 00731307 00731707 00759457 00810045 00810967 00812366 32 33 00812374 00812382 00874043 00874051 00874078 00895571 00895598 00896845 00898112 34 00899046 00899054 00899399 00901412 00903184 00904279 00908045 00908495 02029480 http://bmjpaedsopen.bmj.com/ 35 02029499 02029502 02029510 02126818 02126826 02130203 02130211 02130238 02130254 36 02130262 02130920 02131633 02131641 02131668 02131676 02150667 02150832 02150840 37 02150859 02150867 02150875 02150883 02150891 02150905 02150921 02150948 02180723 38 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 39 02229378 02229379 02229380 02230447 02230509 02232395 02236746 02239432 02240847 00685917 00771035 00771036 00807605 00807613 00895237 00895628 00900958 00980617 40 02264099 02264102 02311720 02462397 02490927 49812382 66894788 66999474 99113693 41 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 99113695 42 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 43 44 02231533 02239600 02239601 02244005 02245546 66894796 92085852 95003840 95023947
00452114 00561002 00895997 02010267 02011948 on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 None found. 48 None found. 49 50 00657395 00791725 02095009 02095017 02095025 02171902 02171910 02217406 02218283 51 0096734302218291 0063383602241700 00788813 00903341 02122197 02231061 02237235 02237882 00703974 52 00803588 02182920 02245662 02292661 53 None found. 54 None found. 55 02230452 02230453 56 57 None found. 58 None found. 59 60 None found.
https://mc.manuscriptcentral.com/bmjpo BMJ Paediatrics Open Page 88 of 88
1 2 00891800 00891819 00891827 00891835 00891900 00901418 02024152 02091216 02091372 3 02091380 02141442 02236978 02236979 02236980 02237370 02237371 02237372 02241895 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 02243645 02245292 02245293 02245294 02245643 02245644 02245697 02246108 02246109 6 02246620 02246942 02247749 02247922 02248443 02248731 02249294 02249308 02249316 7 02255510 02261472 02271516 02273632 02273640 02273659 02281260 02281279 02282348 8 02282453 02287242 02287250 02287269 02294036 02294044 02301938 02301946 02301954 9 10 02309432 02310686 02310694 02311690 02312686 02312694 02323419 02336162 02339560 11 02340038 02340046 02340798 02340801 02340828 02352133 02357496 02378302 02388448 12 02428792None found. 02432471Confidential: 02433702 02462168 For22123126 Review 22123127 99101272 Only 13 None found. 14 15 None found. 16 02413388 x 17 00611174 00813087 02244766 18 19 20 21 22 00321035 00321036 00321037 00326968 00387193 00471534 00497797 00504203 00530999 23 00685917 00771035 00771036 00807605 00807613 00895237 00895628 00900958 00980617 24 00980625 00990779 01996401 02084295 02084309 02085852 02126249 02126257 02126567 25 26 02126605 02134837 02171775 02194368 02219476 02230303 02230304 02230305 02231106 27 None02231533 found. 02239600 02239601 02244005 02245546 66894796 92085852 95003840 95023947 28 02382628 29 None found. 30 None found. 31 32 None found. 33 00240664 00829315 02222736 02239048 02243662 80041595 80041596 80043930 00240656 34
00030163 00030201 00373443 00373478 00376906 00519898 00595926 00829145 00829153 http://bmjpaedsopen.bmj.com/ 35 00829307 00864137 00864145 02021838 02021846 02021862 02021900 02021919 02154552 36 37 80041594 00373451 00829285 02021803 00228796 00374598 00484334 00501840 00146013 38 00522074 00145661 00145831 00213497 00464651 39 None found. 40 None found. 41 00253065 00253073 02089637 02091496 42 43 None found. 44
None found. on September 25, 2021 by guest. Protected copyright. 45 46 None found. 47 00291021 00291048 00800953 01910094 01910108 48 49 50 51 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo Page 89 of 88 BMJ Paediatrics Open
1 2 00187542 00438294 00636347 00685186 00740292 00764361 00766216 00766240 00805300 3 00807583 00896063 00900796 00967548 00967556 00968978 00990141 00990244 00999036 4 bmjpo: first published as 10.1136/bmjpo-2020-000893 on 5 January 2021. Downloaded from 5 00999081 01908553 01908561 01914847 01915185 01930575 01939513 01939521 01947451 6 01947494 01978861 01999540 02015358 02025868 02044412 02044471 02047403 02069725 7 02074257 02074265 02139073 02139081 02147076 02147114 02156172 02163055 02199009 8 02199017 02221349 02222442 02227266 02230960 02230961 02230963 02231101 02231619 9 10 02236775 02236983 02237796 02238309 02238314 02238418 02238573 02238815 02238816 11 02239079 02240447 02240758 02240763 02240902 02240903 02241153 02241420 02243321 12 02243578 02243590Confidential: 02243615 02243939 For02244191 Review 02244449 02245611 Only 02245763 02245873 13 14 02245984 02246380 02246604 02246681 02246710 02246712 02247218 02248036 02248585 15 02248586 02248587 02248711 66898848 66900788 66900818 66900893 66901164 80002908 16 80005358 80006363 80007324 00054232 00475238 00505757 00509914 00666106 00666108 17 18 00666114 00744263 00744271 00748277 00774232 00775238 00808202 00811306 00813346 19 02016447 02227274 02231520 02238910 02241695 02243936 02243937 02243938 02245006 20 02248196 02248197 66903051 80027681 00764310 02211203 02231218 02243011 02245989 21 02247262 00075914 00075957 00273104 00281891 00555967 00652342 00652350 02149044 22 23 02149052 02240107 00792020 00794759 02032945 00230081 00465976 00903371 01915177 24 02047764 02230957 02230959 02241590 80005624 80008630 80011794 80073326 66908029 25 00307580 00307904 00355828 00355895 00413356 00413372 00454893 00505978 00609501 26 00614246 00625353 00690333 00740276 00754951 00813044 00815861 00837733 00889598 27 00243000 00353809 00418293 00443581 00457086 00457094 00483788 00483796 00594601 28 00895059 00895067 00895075 00895083 00895091 00899372 00906018 00987034 01909029 00709069 00808466 00811181 01950487 01951653 02242871 02245007 29 01909037 01909134 01911384 01914456 01915258 01918729 01929429 01939645 01948156 30 0196787800001516 0197433502250535 0197772502349086 0198146302353288 0202291502410346 0203555302413574 0205028500593362 0205029300811688 0206049300836281 31 00895741 01987569 01989626 02221802 02221810 02247228 02298953 49593362 32 02123045 02223821 02229957 02229990 02230131 02230132 02230691 02231570 02237019 33 0223905502242735 0223929902254727 0224032202320134 0224112902352818 0224146502353121 0224162102357070 0224173802385279 0224333202299275 0224405409991323 34 0224485000903384 0224544502031108 8006321602031116 0090305602239893 0099908202240345 02240346 02240807 02242503 02247530 http://bmjpaedsopen.bmj.com/ 35 02262177 02262924 02286580 02294273 02297973 02320126 02341190 02343452 02352796 36 37 None02363836 found. 02372762 02031094 02238703 02239876 02241815 02241816 02248845 02332612 38 39 None found. 40 00027936 00027960 00028088 00415782 00458163 00549185 00576026 00576034 00576042 41 00576050 00576057 00596361 00614211 00614238 00658731 00716928 00810584 00810592 42 01918826 01919245 01942263 01942573 01942581 02029081 02078341 02220733 02226707 43 44 02239066 02239497 02240064 02243064 02243663 02244939 02295873 02311801 02319276 45 on September 25, 2021 by guest. Protected copyright. None02319314 found. 02375397 02378248 02380765 02396785 02401584 02413760 02417715 02431718 46 02434113 02475324 02476703 02480166 47 00990256 66123998 00384895 66128023 66124323 48 02011255 02011263 49 50 02231063 02238762 02244312 51 None found. 52 53 54 55 56 57 58 59 60
https://mc.manuscriptcentral.com/bmjpo