bmjpaedsopen.bmj.com€¦ · confidential: for review only 23 table 1. hospital characteristics...

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on March 22, 2021 by guest. P

rotected by copyright.http://bm

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Confidential: For Review OnlyDiversity in the Emergency care for febrile children in

Europe.

Journal: BMJ Paediatrics Open

Manuscript ID bmjpo-2019-000456

Article Type: Original article

Date Submitted by the Author: 06-Feb-2019

Complete List of Authors: Borensztajn, Dorine; Erasmus MC-Sophia Childrens Hospital, Department of PediatricsYeung, Shunmay; LSHTM, 15-17 Tavistock Place, London, WC1H 9SH, Department of Global HealthHagedoorn, Nienke; Erasmus MC Sophia, Department of PediatricsBalode, Anda; Rīgas Stradiņa universitāte, Children clinical university hospital, Department of Pediatricsvon Both, Ulrich; University Children\'s Hospital at Dr. von Haunersches Kinderspital, LMU MunichCarrol, Enitan; University of Liverpool, Institute of Infection and Global Health ; Alder Hey Children's NHS Foundation TrustDewez, Juan ; London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population HealthEleftheriou, Irini; National and Kapodistrian University of Athens, Second Department of Paediatrics, P. and A. Kyriakou Children’s HospitalEmonts, Marieke; Great North Children’s Hospital, Paediatric Immunology, Infectious Diseases & Allergy, Newcastle upon Tyne Hospitals NHS Foundation Trust; Institute of Cellular Medicine, Newcastle Universityvan der Flier, Michiel; Amalia Children's Hospital, Pediatric Infectious Diseases and Immunologyde Groot, Ronald; Amalia Children's Hospital, Radboudumc., Pediatric Infectious Diseases and ImmunologyHerberg, Jethro; Imperial College London, PaediatricsKohlmaier, Benno; Medical University of Graz, Department of General PaediatricsLim, Emma; Great North Children's HospitalMaconochie, Ian; Imperial College Hospital NHS Healthcare Trust, Paediatric Emergency DepartmentMartinón-Torres, Federico; Hospital Clinico Universitario de Santiago, PediatricsNijman, ruud; Imperial College Hospital NHS Healthcare Trust, Paediatric Emergency Department Pokorn, Marko; University Medical Centre Ljubljana, Department of Infectious DiseasesStrle, Franc; University Medical Centre Ljubljana, Department of Infectious DiseasesTsolia, Maria; "P&A Kyriakou" Childrens Hospital, Department of Paediatric Infectious Diseases, University of Athens

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bmjpo: first published as 10.1136/bm

jpo-2019-000456 on 27 June 2019. Dow

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Confidential: For Review OnlyWendelin, Gerald; Medical University of Graz, Department of General PaediatricsZavadska, Dace; Rīgas Stradiņa universitāte, Children clinical university hospital, Department of PediatricsZenz, Werner; Medical University of Graz, Department of General PaediatricsLevin, Michael; Imperial College Hospital NHS Healthcare Trust, Section of PaediatricsMoll, Henriette; Erasmus MC-Sophia Childrens Hospital, Department of Pediatrics

Keywords: Infectious Diseases, Accident & Emergency

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1

Title: Diversity in the Emergency care for febrile children in Europe.

Dorine M. Borensztajn1, MD, Shunmay Yeung2, MBBS, PhD, Nienke N. Hagedoorn1, MD, Anda

Balode3, MD, Ulrich von Both4,5, MD, Enitan D Carrol6,7, MD, PhD, Juan Emmanuel Dewez2,

MD, Irini Eleftheriou8, MD, Marieke Emonts9,10, MD, PhD, Michiel van der Flier11, MD, PhD,

Ronald de Groot11, MD, PhD, Jethro Herberg12, MD, PhD, Benno Kohlmaier13, MD, Emma Lim9,

MD, Ian Maconochie12, MD, PHD, Federico Martinon-Torres14, MD, PhD, Ruud Nijman12, MD,

PHD, Marko Pokorn15, MD, PhD, Franc Strle15, MD, PhD, Maria Tsolia8, MD, PhD, Gerald

Wendelin13, MD, Dace Zavadska3, MD, PhD, Werner Zenz13, MD, Michael Levin12, MD, PhD,

Henriette A. Moll1, MD, PhD.

On behalf of the PERFORM consortium (appendix 1).

Author affiliations:

1. Erasmus MC-Sophia Children’s Hospital, Department of General Paediatrics,

Rotterdam, the Netherlands.

2. London School of Hygiene and Tropical Medicine, Faculty of Infectious and Tropical

Disease, London, United Kingdom.

3. Rīgas Stradiņa universitāte, Children clinical university hospital, Department of

Pediatrics, Riga, Latvia

4. Division of Paediatric Infectious Diseases, Dr. von Hauner Children's Hospital, University

Hospital, Ludwig-Maximilians-University (LMU), München, Germany.

5. German Centre for Infection Research, DZIF, Munich site, Germany

6. University of Liverpool, Institute of Infection and Global Health Liverpool, United

Kingdom.

7. Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom

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8. National and Kapodistrian University of Athens, Second Department of Paediatrics, P.

and A. Kyriakou Children’s Hospital, Athens, Greece.

9. Great North Children’s Hospital, Paediatric Immunology, Infectious Diseases & Allergy,

Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United

Kingdom.

10. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United

Kingdom

11. Pediatric Infectious Diseases and Immunology, Amalia Children's Hospital, and Section

Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for

Molecular Life Sciences and Radboud Center for Infectious Diseases, Radboudumc,

Nijmegen, the Netherlands

12. Imperial College, Section of Paediatrics, London, United Kingdom and Paediatric

Emergency Department Imperial College Healthcare NHS trust

13. Medical University of Graz, Department of General Paediatrics, Graz, Austria.

14. Hospital Clínico Universitario de Santiago de Compostela, Genetics, Vaccines, Infections

and Pediatrics Research group (GENVIP), Santiago de Compostela, Spain.

15. University Medical Centre Ljubljana, Department of Infectious Diseases, Ljubljana,

Slovenia.

Corresponding author:

Dorine Borensztajn

Department of General Paediatrics, Erasmus MC – Sophia Children’s Hospital

P.O. Box 2060, 3000 CB, Rotterdam, the Netherlands

Telephone: +31 10 703 61 96

E-mail: [email protected]

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Word count: 2500

Author contribution

Conceptualization: DB, SY, IM, FM, JH, EDC, ME, MT, RG, MF, WZ, FS, MP, DZ, UB, ML, HMFunding: SY, IM, FM, JH, EDC, ME, MT, RG, MF, WZ, FS, MP, DZ, UB, ML, HMData curation: DB, NH, SY, IM, FM, JH, EDC, ME, MT, RG, MF, WZ, FS, MP, DZ, UB, ML, HM, RN, JD, EL, IE, BK, GW, ABFormal analysis: DB, HMInvestigation: DB, NH, SY, IM, FM, JH, EDC, ME, MT, RG, MF, WZ, FS, MP, DZ, UB, ML, HM, RN, JD, EL, IE, BK, GW, ABProject administration: HMSupervision: HMWriting – original draft: DBWriting – review & editing: DB, NH, SY, JD, IM, FM, JH, EDC, ME, MT, RG, MF, WZ, BK, FS, MP, DZ, UB, ML, HM

Abbreviations

CRP = C-reactive protein

ED = Emergency Department

EHR = Electronic Health Records

MOFICHE = Management and Outcome of Fever in children in Europe

MTS = Manchester Triage System

PERFORM = Personalised Risk assessment in Febrile illness to Optimise Real-life Management

PICU = Paediatric Intensive Care Unit

POCT = Point-of-care tests

RTI = Respiratory Tract Infections

UTI = Urinary Tract Infections

WHO = World Health Organization

Funding:

This project has received funding from the European Union’s Horizon 2020 research and

innovation programme under grant agreement No. 668303

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The Research was supported by the National Institute for Health Research Biomedical

Research Centre based at Imperial College (JH, ML) and at Newcastle Hospitals NHS

Foundation Trust and Newcastle University (EL, ME). The views expressed are those of the

author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Competing interest: the authors declare they have no potential conflicts of interest to disclose.

Abstract

Objective: To provide an overview of care in Emergency Departments (EDs) across Europe, in

order to interpret observational data and implement interventions regarding the management of

febrile children.

Design and setting: An electronic questionnaire was sent to the principal investigators of an

ongoing study (PERFORM) in 11 European hospitals in eight countries.

Outcome measures: The questionnaire covered indicators in three domains: local ED quality

(supervision, guideline availability, paper versus electronic health records); organisation of

health care (primary care, immunisation) and local factors influencing or reflecting resource use

(availability of point-of-care tests (POCT), admission rates).

Results:

Reported admission rates ranged from 4-51%. 55% of supervising ED physicians were general

paediatricians and the rest were general or paediatric emergency physicians. The supervising

physician was present on-site in all settings during office hours and in 45% of settings out-of-

office hours.

Guidelines for fever and sepsis were available in all settings, however, the type of guideline that

was used differed. Primary care was available in all settings during office hours and in 73%

during out-of-office hours. There were differences in routine immunisations as well as in

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additional immunisations that were offered; immunisation rates varied between and within

countries.

Conclusion: Differences in local, regional and national aspects of care exist in the management

of febrile children across Europe. This variability has to be considered when trying to interpret

differences in the use of diagnostic tools, antibiotics and admission rates. Any future

implementation of interventions diagnostic tests will need to be aware of this European diversity.

Introduction

The emergency department (ED) is the setting where reliable care has to be provided for

acutely ill patients.1 Children represent a large part of the ED workload, with nearly 40 visits per

100 population.2 General as well as paediatric visits have increased during the last years.2,3

Factors that contribute to this increase are lack of access to 24/7 primary care, lack of paediatric

training among primary care physicians4 and parent’s preferences to go directly to the ED.5

Fever is one of the most frequent reasons for paediatric ED consultation.2 Although often self-

limiting, infection still remains a common cause of death in children.6 Delayed recognition of

potential life-threatening infections may have disastrous implications7 while overtreatment can

be invasive, costly and can lead to increasing antibiotic resistance.8 Caring for this broad

spectrum of patients remains an ongoing challenge and several studies have shown large

practice pattern variation in the care for febrile children.9

The organisation of healthcare varies between countries as well as hospitals. For example,

healthcare for children can be delivered by general practitioners, primary care paediatricians,

general or paediatric EDs.4

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It has been suggested that variation in healthcare organisation accounts for part of the

differences in paediatric mortality in Europe.4 For example, death rates from illnesses that rely

on first-access services such as primary care—e.g. pneumonia, are higher in the UK and

Belgium than in Germany and Denmark.4

Our aim was to provide an overview of the delivery of care for febrile children at European EDs,

which can aid the interpretation of observational studies and the implementation of future

interventions.

Methods

Participating hospitals and questionnaire development

This study is embedded in the MOFICHE study (Management and Outcome of Fever in children

in Europe) which is part of the EU funded PERFORM Project (Personalised Risk assessment in

Febrile illness to Optimise Real-life Management), GA:668303, www.perform2020.eu.

MOFICHE collects information regarding patient characteristics, resource use (diagnostic tests,

antibiotic prescription and hospitalisation) and outcome in febrile children.

An electronic questionnaire (appendix 2) was sent by e-mail to the Principal Investigator of each

participating centre.

The questionnaire was based on the article by Mintegi et al. on organisation of Paediatric

Emergency Care10 and was further developed by the MOFICHE research team, consisting of a

team of experts with a background in paediatrics, epidemiology, paediatric emergency care,

paediatric infectious diseases and health economics. We gathered information on factors

influencing case mix as well as resource use.

We focused on local ED quality indicators, regional systems of care and local factors influencing

resource use based on Medford-Davis et al., classification of value-based emergency care.1

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There were no patients involved in the study.

The questionnaire was created with Google forms. Questions consisted of multiple-choice or

multiple-option questions, 5-point Likert-scale questions and open questions.

All analyses were descriptive and performed with SPSS software, version 21 (SPSS, IBM

Corporation, Armonk, NY).

Quality of care

In the quality of care domain, we included availability and type of triage system, guideline

availability, ICU admission criteria, guidelines on maximum time spent in the ED, supervision

and availability of electronic health records (EHR).

Four types of supervision were distinguished:11

Direct Supervision, the supervising physician is present on site with the junior doctor and

patient;

Indirect Supervision (I) the supervising physician is within the hospital and is immediately

available for direct supervision;

Indirect Supervision (II), the supervising physician is not present within the hospital, but is

immediately available by telephone and available for direct supervision within 20-30 minutes;

Oversight, the supervising physician is available for feedback after care is delivered;

Out-of-office hours were defined as evenings, nights, weekends and public holidays.

Regarding EHR we asked for the electronic availability of history, physical examination, vital

signs, diagnostic tests, treatment and disposition.

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Regional aspects of care

In the regional aspects domain, we studied the organisation of primary care. We focused on the

type of clinician providing primary care, out-of-office hours availability and ED self-referral rates.

Information concerning routine immunisation was taken from the website of the European

Centre for Disease Prevention and Control12

We used 2016 World Health Organization (WHO) data to outline immunisation rates.13

Resource use

In the resource use domain, we studied admission rates and availability of point-of-care tests

(POCT). Admission rates were based on annual admission rates of 2016.

Results

General ED characteristics

All 11 hospitals participating in the MOFICHE study filled in the electronic questionnaire. Nine

were university hospitals, three were large district general hospitals; seven had a dedicated

Paediatric ED (Table 1). All hospitals had an on-site paediatric intensive care unit (PICU). Nine

settings served mixed inner-city/rural populations and in 10 settings the population was from a

mixed socio-economic status.

Quality of care

The Manchester Triage System (MTS) was used in 8 settings. The other settings used a local or

national triage system.

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During office hours, in six settings the senior clinician responsible for the care of febrile children

was a general paediatrician. In the other settings care could also be delivered by a paediatric

emergency physician or an emergency physician.

During office hours, three settings used direct supervision, while eight used type I indirect

supervision. During out-of-office hours most settings used type II indirect supervision. Oversight

was not used in any setting.

In four settings all febrile children were discussed with a supervisor; this number was lower

during out-of-office-hours (figure 1).

We studied the availability of guidelines for common infections: fever, respiratory tract infections

(RTI), urinary tract infections (UTI) and sepsis.14 All settings had guidelines available for fever

and sepsis. Ten settings had guidelines available for RTI and UTI. For fever, three settings used

the NICE guideline, while eight settings used a local or a national guideline. For sepsis, five

settings used the NICE guideline.

Invasive ventilation was a reason for ICU admission in all settings, inotrope use in 91% and

non-invasive ventilation in 82%. High-flow oxygen or continuous anti-epileptic drugs required

ICU admission in five settings and continuous cardiorespiratory monitoring in four (appendix 3).

Six hospitals had guidelines regarding the time a child could stay in the ED, after which they

should be admitted or discharged. This varied between three and 24 hours.

In four settings all items were available electronically and in one setting all items were registered

on paper; all other settings used a combination of paper and EHR (appendix 4). Eight settings

had patient data (e.g. vital signs) available electronically, 10 had diagnostic tests available

electronically.

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Regional systems of care

In six settings, primary care was provided by general practitioners, while in two settings this was

offered by primary care paediatricians. In the other settings, primary care could be delivered by

either type of physician. Primary care was available during out-of-office hours in eight settings.

Overall, self-referral rate was high (table 1).

Immunisation to DTaP/IPV/MMR, Hib and PCV was part of routine care in all areas.

Meningococcal immunisation was part of routine care in six countries. Subtypes of PCV and

meningococcal serotype vaccines in use differed. Other routine immunisations that varied are

outlined in table 2. In some regions, additional immunisation was offered to specific groups,

such as influenza in children with comorbidity or BCG to high-risk infants.12 In Slovenia and

Latvia several immunisations are mandatory (table 2).

Figure 2 shows the 2016 WHO immunisation data in the participating countries.13 Overall,

immunisation rates are estimated to be over 90-95%, however, in several countries regional

data show large differences in immunisation rates. Actual immunisation rates can be lower in

specific regions, specific age groups, for specific immunisations and for booster

immunisations,15 therefore, the shown WHO data might be an overestimation of actual

immunisation rates.

Resource use

Paediatric admission rates ranged from 4% to 51% (table 1).

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Glucose POCT was available in all settings. Blood gas and urinalysis were available as a POCT

in nine settings and C-reactive protein (CRP) POCT in six. Nasopharyngeal aspirate tests were

available in six settings and a streptococcal antigen test in five.

Discussion

We found several differences between the participating EDs regarding the care for febrile

children in all three domains: quality indicators, regional aspects of care and resource use.

Based on previous literature, we will discuss which of these factors are likely to influence

outcome measures such as resource use (table 3).

Factors influencing resource use directly

We found variability in physician specialty and supervision; both have been previously found to

influence resource use.16 For example, supervised ED visits-as opposed to consultant-alone-

have been linked to higher resource use and longer ED stay.17

In our study we asked whether guidelines were available but did not assess actual use or

adherence. Guideline adherence can improve the quality of care18 and has been shown to

reduce resource use and lead to more appropriate antibiotic use without adversely affecting

outcomes.19 However, despite guideline availability, there is considerable practice pattern

variation, as guideline availability does not automatically lead to adherence.19

In around half of the EDs a CRP POCT was available. POCT provide results quickly and

therefore can reduce time to treatment initiation and ED length of stay.20 CRP has shown to be

of value in ruling in or out bacterial infections.21 A Cochrane review concluded that the use of a

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CRP POCT could reduce antibiotic prescription in adults;22 however, this was not confirmed in a

paediatric primary care population.23 In their discussion, the authors emphasize that performing

a CRP POCT in all children with fever will not reduce antibiotic use, as it can lead to false

positive values.23 Which children will benefit most from a CRP POCT and how this will affect

resource use still has to be evaluated.

There were marked differences in electronic health care records (EHR) availability in our study.

Use of EHR can increase efficiency in ordering diagnostic tests, reduce errors, improve

overview, reduce duplicate testing and admissions and improve information exchange between

healthcare providers.24,25

From a researcher’s perspective, it’s important to recognise that paper-based records can be

incomplete and lack standardisation. Conducting research in settings using EHR potentially

offers benefits and new opportunities,26 although aspects such as accuracy, completeness,

standardisation, comparability and anonymity need to be addressed.25,26

Triage aims to prioritize patients who need immediate care from those who can safely wait, in

order to improve outcomes.27 Most settings used the MTS, but local systems were common as

well. Research has shown that the performance of MTS is ‘moderate to good’ in children,

however, its performance is lower in young children and children with comorbidities, who are at

risk for under-triage (i.e. they are assigned a lower priority level than they should).28 To our

knowledge, most local systems have not been thoroughly validated in children.

The impact of triage on resource use is not straightforward. As expected, a higher triage

category is linked to higher resource use.29 There is some evidence that “down-triaging” of non-

ill appearing children to a lower category can reduce resource use without increasing adverse

outcomes.30 On the other hand, as under-triage can cause treatment delay, it has been

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hypothesized that under-triage can increase resource use31 and improved triage can lead to

more appropriate resource use.32 However, it’s possible that triage influences resource use and

use of different triage systems can explain practice pattern variation. More research is needed

on this topic to understand this exact relationship.

Six hospitals had local guidelines on how long a child could stay in the ED. In the UK, it is a

national target that 95% of all ED patients should be discharged or admitted within 4 hours.3

Limiting ED stay can have a large impact on children and their families. It has been shown to

decrease crowding, mortality and to improve patient satisfaction.33 However, it has also been

suggested that the introduction of the 4-hour target has increased (short-duration) admission

rates, but consistent data is lacking.3 This leads to the discussion of a possible role of short-stay

units, as these can potentially reduce ED length of stay as well as admissions.34

We found marked variation in ICU admission criteria. This can influence general admissions as

well as ICU admissions. ICU admissions are frequently used as an outcome measure for

disease severity, it is important to realise this can be influenced by other factors than disease

severity alone.

Factors influencing resource use indirectly through case-mix

Even though primary care was available in all settings, not all settings offered out-of-office

primary care. Furthermore, the self-referral rate at the ED was high in many settings, suggesting

that other factors than merely primary care availability influence self-referral. A high rate of self-

referred patients can lead to a higher proportion of non-urgent patients who can delay resources

being given to those who need it more urgently.35

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In their systematic review, Kraaijvanger et al. identified several reasons for self-referral, such as

patient expectations and accessibility to primary care.5

In some settings urgent primary care has been made available at the same site as the ED, and

this has been shown to reduce self-referral rates, especially of low-urgent patients.5

Although there were large similarities in immunisations, there were also differences. This could

explain some of the variation in the population and subsequent resource use between EDs.36

For example, the introduction of the rotavirus immunisation has led to a large reduction of ED

visits and admissions for children with gastroenteritis.37

While the introduction of immunisations has led to a great reduction of invasive diseases,36 the

presented data show that low immunisation rates still occur in Europe. Low immunisation rates

can lead to increased susceptibility by a direct effect as well as indirect effect by decreasing

herd immunity.38

In two recent European studies, the burden of life-threatening infections in children, including

PICU admission for sepsis, was found to be largely due to vaccine-preventable meningococcal

and pneumococcal infections.39,40

Strengths and limitations

The strengths of our study include the comprehensive collaboration of researchers who are part

of a large EU consortium, using a standardised protocol. To our knowledge, this is the first study

comparing healthcare for febrile children at European EDs.

The main limitation is the proportional representation as in most countries only one or two

hospitals contributed to this study, so results can reflect differences between hospitals as well

as between countries.

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However, all participating hospitals were either a university or a large district general hospital.

The standard of care in these hospitals is high and therefore diversity might represent practice

variability between countries.

This study gives an overview of setting related factors that may influence resource use,

however, this is not exhaustive.

Conclusion

Our study shows differences in the emergency care for febrile children across Europe.

Resource use such as diagnostic tests, antibiotic prescription and admission rates can be

influenced by differences in the organisation of healthcare.

Our study provides an overview of setting related factors that need to be considered when

interpreting results of observational studies. As new interventions are developed, these factors

need to be considered to model their potential impact, to accurately plan clinical trials and to

conduct health economic analyses.

More in-depth research is needed to study the factors described above some of which will be

covered In the MOFICHE study, in more detail.

Studying these differences can be used as a starting point to improve paediatric emergency

care across Europe.4

What is already known

Fever is one of the most frequent reasons for paediatric ED consultation.

Differences in outcome of paediatric infectious diseases still exist in Europe and have been linked to differences in organisation of healthcare.

What this study adds

Our study shows marked differences regarding the organisation of emergency care for

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febrile children across Europe.

Differences in the organisation of healthcare can influence resource use such as

diagnostic tests, antibiotic prescription rates and admission rates.

Our study provides an overview of setting-related factors that can influence resource use

and thus need to be considered when interpreting results of observational studies.

References

1. Medford-Davis L, Marcozzi D, Agrawal S, Carr BG, Carrier E. Value-Based approaches for

emergency care in a new era. Ann Emerg Med 2017, Jun;69(6):675-83.

2. Rasooly IR, Mullins PM, Alpern ER, Pines JM. US emergency department use by children,

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29. Gravel J, Gouin S, Goldman RD, Osmond MH, Fitzpatrick E, Boutis K, et al. The canadian

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37. Burnett E, Jonesteller CL, Tate JE, Yen C, Parashar UD. Global impact of rotavirus

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38. Metcalf CJ, Ferrari M, Graham AL, Grenfell BT. Understanding herd immunity. Trends

Immunol 2015, Dec;36(12):753-5.

39. Boeddha NP, Schlapbach LJ, Driessen GJ, Herberg JA, Rivero-Calle I, Cebey-López M, et

al. Mortality and morbidity in community-acquired sepsis in european pediatric intensive care

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disease study (EUCLIDS). Crit Care 2018, May 31;22(1):143.

40. Martinón-Torres F, Salas A, Rivero-Calle I, Cebey-López M, Pardo-Seco J, Herberg JA, et

al. Life-threatening infections in children in europe (the EUCLIDS project): A prospective cohort

study. Lancet Child Adolesc Health 2018, Jun;2(6):404-14.

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Table 1. Hospital characteristics

Hospital Paediatric upper age limit(yrs)

Population rural/ inner city

Type Paediatric ED visits(n)

Primary care during out-of-office hours

Self-referral

Paediatric or mixed paediatric - adult ED

Triagesystem

Admission rate

AT, MUG1 17 mixed University 25.000-30.000

No 50-75% Paediatric MTS 12%

DE, LMU2 18 mixed Large district general hospital

10.000-25.000

Yes 50-75% Paediatric MTS 10%

GR, NKUA3

16 Inner city University >30.000 No 50-75% Paediatric local/national

15%

LV, RSU4 18 mixed Large district general hospital

>30.000 No 20-50% Paediatric MTS 12%

NL, EMC6 18 mixed University 30.000 Yes 50-75% Paediatric MTS 15%

1. Medical University of Graz, Department of General Paediatrics, Graz, Austria.2. Dr. von Hauner Children's Hospital, university hospital, Ludwig-Maximilians-University (LMU), Munich, Germany.3. National and Kapodistrian University of Athens, Second Department of Paediatrics, P. and A. Kyriakou Children’s

Hospital, Athens, Greece.4. Rīgas Stradiņa universitāte, Children clinical university hospital, Department of Pediatrics, Riga, Latvia.5. Erasmus MC-Sophia Children’s Hospital, Department of General Paediatrics, Rotterdam, the Netherlands.6. Amalia Children's Hospital, Radboudumc, Nijmegen, the Netherlands.7. University Medical Centre Ljubljana, Department of Infectious Diseases, Ljubljana, Slovenia. 8. Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.9. Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom.10. Imperial College of Science, Technology and Medicine, Section of Paediatrics, London, United Kingdom.11. Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United

Kingdom.

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Table 2. Routine immunisation in the 8 participating countries.12

DTAP/IPV/MMR/HIB PCV Men Hep-A Hep-B RV Varicella Influenza BCG TBE

Austria + +10 + ACWY - + + - - - -

Germany + +13 + C - + + + - - -

Greece + +13+ C, ACWY + + + + - - -

Latvia ++ ++ 10 - - ++ ++ ++ + ++ +-

Netherlands, the + +10 + C - + - - - - -

Slovenia ++ +10 - - ++ - - - - -

Spain + +13 + C - + - + - - -

United Kingdom + +13+ B,C, ACWY - + + - + +- -

+ routine immunisation (all children)

+-specific regions only

++ mandatory immunisation

- not part of the routine immunisation program

DTaP: diphtheria, tetanus and acellular pertussis vaccine. IPV: inactivated polio vaccine. MMR: measles, mumps, rubella vaccine. Hib: Haemophilus influenzae type b vaccine. PCV: pneumococcal conjugate vaccine. Men: meningococcal vaccine. Hep-A: hepatitis A vaccineHep-B: hepatitis B vaccine. RV: rotavirus vaccine. BCG: Bacillus Calmette-Guérin vaccine. TBE: tick-borne encephalitis vaccine

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Table 3: Factors that can potentially influence resource use, based on previous literature

Diagnostic tests

Antibiotic prescription rates

Admission rates

Triage + - +

Supervision and physician specialty + + +

Guideline implementation + + +

Electronic health records + - -

Criteria for ICU admission - - +

Time spent in the ED - - +

Primary care and pre-hospital services

+ + +

Immunisation + + +

Point-of-care tests + +* +

+Possible influence+ Influence not clear - No influence expected* in adults

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Figure 1. Supervision type and frequency: office hours versus out-of-office hours.

Attached separately

- Direct Supervision – the supervising physician is physically present on site with the resident and patient.

- Indirect Supervision: (I) with direct supervision immediately available – the supervising physician is physically within the hospital and is immediately available to provide Direct Supervision.

- Indirect Supervision: (II) with direct supervision available – the supervising physician is not physically present within the hospital or other sites of patient care, but is immediately available by means of telephonic and/or electronic modalities, and is available to provide Direct Supervision in person within 20-30 minutes at all times.

- Oversight – the supervising physician is available to provide review of procedures/encounters with feedback provided after care is delivered.

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Figure 2. Immunisation rates.13

Attached separately

*Slovenia PCV rate not included in graphic. PCV immunisation rate not available for Austria and Spain.

DTaP: percentage of surviving infants who received the 3rd dose of diphtheria and tetanus toxoid with pertussis containing vaccine. MCV: percentage of surviving infants who received the 1st dose of measles containing vaccine. In countries where the national schedule recommends the 1st dose of MCV at 12 months or later based on the epidemiology of disease in the country, coverage estimates reflect the percentage of children who received the 1st dose of MCV as recommended.HIB: percentage of surviving infants who received the 3rd dose of Haemophilus influenzae type b containing vaccine.PCV: percentage of surviving infants who received the 3rd dose of pneumococcal conjugate vaccine. In countries where the national schedule recommends two doses during infancy and a booster dose at 12 months or later based on the epidemiology of disease in the country, coverage estimates may reflect the percentage of surviving infants who received two doses of PCV prior to the 1st birthday.

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Appendix 1: Perform consortium (separate document)

Appendix 2: Questionnaire (separate document)

Appendix 3. Criteria for ICU admission (separate document)

Appendix 4. Availability of electronic health records (separate document)

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PERFORM consortium author list. SERGAS Partner (Spain) Principal Investigators Federico Martinón-Torres1 Antonio Salas1,2 GENVIP RESEARCH GROUP (in alphabetical order): Fernando Álvez González1, Cristina Balo Vázquez1, Ruth Barral-Arca1,2, Miriam Cebey-López1, Ana Cotovad Bellas1, María José Curras-Tuala1,2, Natalia García1, Luisa García Vicente1, Alberto Gómez-Carballa1,2, Jose Gómez Rial1, Pilar Leboráns Iglesias1, Federico Martinón-Torres1, Nazareth Martinón-Torres1, José María Martinón Sánchez1, Beatriz Morillo Gutiérrez1, Belén Mosquera Pérez1, Jacobo Pardo-Seco1,2, Sara Pischedda1,2, Irene Rivero Calle1, Carmen Rodríguez-Tenreiro1, Cristina Rodriguez-Tenreiro Rodríguez1, Lorenzo Redondo-Collazo1, Elena Sánchez-Mira1, Antonio Salas1,2, Sonia Serén Fernández1, María del Sol Porto Silva1, Ana Vega1,3. 1 Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain. 2 Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain 3 Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), and Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain PERFORM SPANISH CLINICAL NETWORK: Pablo Rojo1, J.Ruiz Contreras1, Alba Palacios1. 1 Hospital Universitario 12 de Octubre; Madrid, Spain. RSU Partner (Latvia) Principal Investigator Dace Zavadska1,2 Other RSU group authors (in alphabetical order): Anda Balode1,2, Arta Bārzdiņa1,2, Dārta Deksne1,2, Dace Gardovska1,2, Dagne Grāvele2, Ilze Grope1,2, Ieva Nokalna1,2, Jana Pavāre1,2, Zanda Pučuka1,2, Katrīna Selecka1,2, Aleksandra Sidorova1,2, Dace Svile2, Urzula Nora Urbāne1,2. 1 Riga Stradins university, Riga, Latvia. 2 Children Clinical University Hospital, Riga, Latvia. Medical Research Council Unit The Gambia (MRCG) Partner Principal Investigator Dr Akram Zaman

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Investigator/Research Fellow Dr Fatou Secka Additional Investigators Kalifa Bojang Suzanne Anderson Anna Roca Effua Ussuf Isatou Sarr Momodou Saidykhan Saffiatou Darboe Samba Ceesay Umberto D’allesandro

ERASMUS MC-Sophia Children’s Hospital Principal Investigator Henriëtte A. Moll¹ Research group Dorine M. Borensztajn¹, Nienke N. Hagedoorn¹, Leontien M.H. Roos¹, Clementien L. Vermont² ¹ Erasmus MC-Sophia Children’s Hospital, Department of General Paediatrics, Rotterdam, the Netherlands ² Erasmus MC-Sophia Children’s Hospital, Department of Paediatric Infectious Diseases & Immunology, Rotterdam, the Netherlands

Swiss Pediatric Sepsis Study

Steering Committee:

Luregn J Schlapbach, MD, FCICM 1,2,3,4

, Philipp Agyeman, MD 1, Christoph Aebi, MD

1, Christoph

Berger, MD 1

Luregn J Schlapbach, MD, FCICM 1,2,3,4

, Philipp Agyeman, MD 1, Christoph Aebi, MD

1, Eric

Giannoni, MD 5,6

, Martin Stocker, MD 7, Klara M Posfay-Barbe, MD

8, Ulrich Heininger, MD

9, Sara

Bernhard-Stirnemann, MD 10

, Anita Niederer-Loher, MD 11

, Christian Kahlert, MD 11

, Paul Hasters, MD

12, Christa Relly, MD

13, Walter Baer, MD

14, Christoph Berger, MD

13 for the Swiss Pediatric

Sepsis Study

1. Faculty of Medicine, The University of Queensland, Brisbane, Australia

2. Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland

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3. Paediatric Critical Care Research Group, Mater Research Institute, University of Queensland, Brisbane, Australia

4. Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Children’s Health Queensland, Brisbane, Australia

5. Service of Neonatology, Lausanne University Hospital, Lausanne, Switzerland

6. Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland

7. Department of Pediatrics, Children’s Hospital Lucerne, Lucerne, Switzerland

8. Pediatric Infectious Diseases Unit, Children’s Hospital of Geneva, University Hospitals of Geneva, Geneva, Switzerland

9. Infectious Diseases and Vaccinology, University of Basel Children’s Hospital, Basel, Switzerland

10. Children’s Hospital Aarau, Aarau, Switzerland

11 Division of Infectious Diseases and Hospital Epidemiology, Children’s Hospital of Eastern Switzerland St. Gallen, St. Gallen, Switzerland

12. Department of Neonatology, University Hospital Zurich, Zurich, Switzerland

13. Division of Infectious Diseases and Hospital Epidemiology, and Children’s Research Center, University Children’s Hospital Zurich, Switzerland

14. Children’s Hospital Chur, Chur, Switzerland

Medical University Graz Partner

Principal Investigator

Werner Zenz1

Co-Investigators/Steering committee (in alphabetical order):

Alexander Binder1, Daniela S. Klobassa1, Benno Kohlmaier1, Manfred Sagmeister1, Nina A. Schweintzger1, Vendula Svendova1

Clinical recruitment partners (in alphabetical order):

Hinrich Baumgart2, Astrid Ceolotto1, Angelika Doder3, Ernst Eber4, Siegfried Gallistl1, Harald Haidl1, Siegfried Rödl5, Holger Till2, Gerald Wendelin6

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1Department of General Paediatrics, Medical University Graz, Austria

2Department of Paediatric and Adolescence Surgery, Medical University Graz, Austria

3Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Austria

4Department of Pulmonology, Medical University Graz, Austria

5Paediatric Intensive Care Unit, Medical University Graz, Austria

6University Clinic of Paediatrics and Adolescent Medicine Graz, Austria

Liverpool Partner

Principal Investigators

Enitan Carrol1,2

Stéphane Paulus 1,2

Research Group (in alphabetical order):

Elizabeth Cocklin, Rebecca Jennings3, Joanne Johnston3, Simon Leigh1, Karen Newall3,

1 Department of Clinical Infection, Microbiology and Immunology, University of Liverpool Institute of Infection and Global Health , Liverpool, England

2 Alder Hey Children’s Hospital, Department of Infectious Diseases, Eaton Road, Liverpool, L12 2AP

3 Alder Hey Children’s Hospital, Clinical Research Business Unit, Eaton Road, Liverpool, L12 2AP

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11/01/2019, 14)49Information about hospital and healthcare organisation

Page 1 of 17https://docs.google.com/forms/d/1eJTRn5HjgLRrfBJUuU6SC5EucFZeXp0AShOaMtU9oE0/printform

Information about hospital and healthcareorganisation

1. Email address *

2. Hospital, name and countryMark only one oval.

SMH, Londen, UK

LIV, Liverpool, UK

UNEW, Newcastle, UK

EMC, Rotterdam, the Netherlands

NKUA, Athens, Greece

SERGAS, Santiago de Compostela, Spain

RUMC, Nijmegen, the Netherlands

MUG, Graz, Austria

RSU, Riga, Latvia

LMU, München, Germany

UKCL, Ljubljana, Slovenia

3. What is the upper age limit in years at your ED defined as paediatric?Mark only one oval.

16

18

Other:

4. Catchment areaNumber of pediatric inhabitants

5. Patient population in your settingMark only one oval.

Inner city

Rural

Mixed

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6. Socioeconomic status of the population in the adherence areaMark only one oval.

Generally high

Generally low

Mixture of high and low SES

Other:

7. Type of hospitalMark only one oval.

Academic

Teaching

Non-teaching

8. Does your setting offer tertiary paediatric services (e.g. specialist consultants)?Mark only one oval.

Yes

No

9. Please specify

10. Number of paediatric emergency visitsannually

11. Number or percent of hospital admissionsannually from the paediatric emergencydepartment

12. Total number of inpatient beds forpaediatric patients (medical and surgicalcombined) at your hospital

13. Is there a paediatric ICU at your hospital?Mark only one oval.

Yes

No

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14. Type of triage system usedMark only one oval.

MTS

CTCS

ESI

None

Local system

Other:

15. Is the emergency department in your hospital mixed adult and pediatric ED or an EDwith pediatric patients only?Mark only one oval.

Mixed

Paediatric only

16. Comments

Physicians and referrals

17. During office hours the first medical person assessing a febrile child visiting the ED isa residentMark only one oval.

1 2 3 4 5

never always

18. During office hours a febrile child is reviewed by or discussed with a senior doctorMark only one oval.

1 2 3 4 5

never always

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19. During office hours what is the background of the person in charge of a febrile childvisiting the ED?Check all that apply.

Paediatrician

Emergency physician

Pediatric emergency physician

Other:

20. During office hours a supervising specialist is available forMark only one oval.

Direct Supervision – the supervising physician is physically present onsite with theresident and patient.

Indirect Supervision: (I) with direct supervision immediately available – the supervisingphysician is physically within the hospital and is immediately available to provide DirectSupervision.

Indirect Supervision: (II) with direct supervision available – the supervising physician isnot physically present within the hospital or other sites of patient care, but is immediatelyavailable by means of telephonic and/or electronic modalities, and is available to provideDirect Supervision in person within 20-30 minutes at all times.

Oversight – the supervising physician is available to provide review ofprocedures/encounters with feedback provided after care is delivered.

21. During out-of-office hours (evenings, nights, weekends) the first medical personassessing a febrile child visiting the ED is a residentMark only one oval.

1 2 3 4 5

never always

22. During out-of-office hours a febrile child is reviewed by or discussed with a seniordoctorMark only one oval.

1 2 3 4 5

never always

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23. During out-of-office hours what is the background of the person in charge of a febrilechild visiting the ED?Check all that apply.

Paediatrician ...%

Emergency physician ...%

Pediatric emergency physician ...%

Other:

24. During out-of-office hours a supervising specialist is available for:Mark only one oval.

Direct Supervision – the supervising physician is physically present onsite with theresident and patient.

Indirect Supervision: (I) with direct supervision immediately available – the supervisingphysician is physically within the hospital and is immediately available to provide DirectSupervision.

Indirect Supervision: (II) with direct supervision available – the supervising physician isnot physically present within the hospital or other sites of patient care, but is immediatelyavailable by means of telephonic and/or electronic modalities, and is available to provideDirect Supervision in person within 20-30 minutes at all times.

Oversight – the supervising physician is available to provide review ofprocedures/encounters with feedback provided after care is delivered.

25. Comments

Primary care and emergency services

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26. Which of the following pre-hospital emergency services are available in your catchmentareaMultiple answers possibleCheck all that apply.

Telephone consultation service (e.g. 111 in the UK)

General practitioners

Primary care paediatricians

Out-of-office GP / primary care service

Urgent care centres (usually run by nurse practitioners or non-paediatric doctors)

None

Other:

27. What is approximately the percent of self-referrals visiting the ED?Mark only one oval.

< 5%

5 - 10%

10 - 20%

20 - 50%

50 - 75%

> 75%

28. The majority of children visiting the ED has a primary care physicianMark only one oval.

Yes

No

29. The primary care physician most often is a:Mark only one oval.

1 2 3 4 5

General practitioner Primary care paediatrician

30. Primary care physicians deliver acute primary care during office hours in theadherence area of your EDMark only one oval.

Yes

No

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31. Primary care physicians deliver acute primary care during out-of-office hours in theadherence area of your EDMark only one oval.

Yes

No

32. Patients officially need a referral from their primary care physician to attend the EDMark only one oval.

Yes

No

33. Comments

Implementation of delidelines and immunization

34. Which paediatric guidelines are implemented at your hospitalMark only one oval per row.

NICE National Local None

Children with feverRespiratory tract infectionsUrinary tract infectionsSepsis/meningitis

35. National immunization coverage %

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36. Which vaccines are part of the standard national immunization schedule that isprovided to all children?Check all that apply.

Diptheria, Pertussis, Tetanus, Polio

Measles, mumps & rubella (MMR)

S.Pneumoniae / pneumococcal (PCV) (please specify in next question)

Haemophilus influenzae type B (HIB)

N. Meningococcus (please specify in next question)

Hepatitis A

Hepatitis B

Rotavirus

Influenza

Tuberculosis (TBC)

Tick-borne encephalitis (TBE)

Varicella

Other:

37. Which pneumococcal immunization is part of the standard immunization schedule?Check all that apply.

13 subtypes

23 subtypes

10 subtypes

Other:

38. Which meningococcal immunization is part of the standard immunization schedule?Check all that apply.

Men B

Men C

Men ACWY

Other:

39. Comments

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Specialists

40. Is there a paediatric haematology / oncology department at this hospital?Mark only one oval.

Yes

No

41. How many patients with haematologicalmalignancies are diagnosed on a yearlybases?

42. How many patients with haematologicalmalignancies are in treatment on a yearlybasis?

43. How many episodes of febrile neutropeniaare seen on an annual basis?

44. Is there a paediatric rheumatology department at this hospital?Mark only one oval.

Yes

No

45. How many patients are seen withautoinflammatory diseases on an annualbasis?

46. How many patients are on biologicals on anannual basis?

47. Comments

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48. Is there a paediatric stem cell transplant unit at this hospital?Mark only one oval.

Yes Skip to question 48.

No Skip to question 54.

Skip to question 54.

Stem cell patients

49. How many patients are being transplantedwith a stem cell transplant on a yearlybasis?

50. How many are haematology oncology?

51. How many are primaryimmunodeficiencies?

52. How many are other (e.g. autoimmune)?

53. How many episodes of suspected infectionin stem cell patients are seen on an annualbasis?

54. Comments

Quality control variables - General characteristics

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55. Are all patients at your ED registered?Mark only one oval.

Yes

No, please specify below

56. Please specify

57. Do some patients go to the ICU directly without being seen at the ED?Mark only one oval.

Yes

No

58. If yes, please specify how often this happens and which patients go directly to ICU

59. Who usually performs the initial triage?Mark only one oval.

Triage nurse

General nurse

Nurse practitioner / physician assistant

Physician

Student

Other:

60. Can vital signs be estimated as normal instead of measured (for example in a wellappearing child)?Mark only one oval.

Yes

No

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61. Comments

Data registration

62. How are the following items registered?Mark only one oval per row.

Paper chart Electronic chart

History and physical examinationVital signsDiagnostic tests (e.g. labs,imaging)Treatment (e.g. oxygen,medication)Immediate life saving interventions(e.g. intubation)Working and final diagnosisPatient progress (admission,follow-up)

63. Are diagnostic tests recorded in the chart during the ED stay?Mark only one oval.

Yes, automatically

Yes, manually during the ED visit

No, manually after the ED visit

No, not at all

Other:

64. Are diagnostic tests recorded in the chart complete?Mark only one oval.

Yes

No

Other:

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65. Is treatment (e.g. oxygen, antibiotics), recorded in the chart during the ED stay?Mark only one oval.

Yes, automatically



No, not at all

Other:

66. Is treatment that is recorded in the chart complete?Mark only one oval.

Yes

No

Other:

67. Are immediate life saving interventions (e.g. intubation), recorded in the chart duringthe ED stay?Mark only one oval.

Yes, automatically



No, not at all

Other:

68. Are immediate life saving interventions that are recorded in the chart complete?Mark only one oval.

Yes

No

Other:

69. Are patient outcome and follow-up recorded in the chart during the ED stay?Mark only one oval.

Yes, automatically



No, not at all

Other:

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70. Is patient outcome and follow-up that is recorded in the chart complete?Mark only one oval.

Yes

No

Other:

71. Comments

Diagnostics (e.g. labs, imaging)

72. Is temperature measured routinely in all febrile childrenMark only one oval.

Yes

No

Other:

73. How is the temperature measured in general?Mark only one oval.

Oral

Rectal

Tympanic (ear)

Axillary

Temporal (forehead)

Other:

74. Who usually takes finger prick / finger stick blood samples (e.g. for blood sugar)?Mark only one oval.

Nurse

Nurse practitioner / physician assistant

Physician

Phlebotomi

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