CLASSIC – Development of a CLinical tool to Aid identification of SeriouS Infections in Children in Primary Care; building on The LUCI Study

Cardiff University requires access to NHS England data for the purpose of the following research project:

The LUCI Study (The long-term follow-up of urinary tract infection (UTI) in childhood)

The following is a summary of the aims of the research project provided by Cardiff University:

Cardiff University have previously conducted two large studies of acutely ill children less than five years old in primary care:

> Epidemiology of Urinary Tract Infection (UTI) in Children with Acute Illness in Primary Care (EURICA) study: n=1003, Wales only [Funder: Welsh Office for Research and Development (WORD), now known as Health & Care Research Wales];

> Diagnosis of Urinary Tract infection in Young children (DUTY) study: n=7163, England and Wales [Co-led by Cardiff and Bristol Universities; Funder: National Institute for Health Research Health Technology Assessment – NIHR HTA). DUTY collected urine samples systematically from all ill children.

The LUCI study links data from these cohort studies with routine hospital admission data giving a rich dataset of detailed symptoms and signs, including urinalysis, of acutely ill children presenting to general practice linked with outcomes including hospital admission.

Current guidelines advise the prompt diagnosis of treatment of UTI in children because childhood UTI can lead to scarring of the kidneys which is believed to lead to long term complications such as high blood pressure, chronic kidney disease and kidney failure in some cases. However, UTI is difficult to diagnose in children as the symptoms are non-specific and similar to those found in many common childhood illnesses. Cardiff University have shown that as many as 80% of UTIs are missed in primary care. A urine sample is required to diagnose UTI but urine is infrequently sampled from ill children in primary care (in less than 2% of consultations). If urine is not sampled, a UTI cannot be diagnosed.

The evidence linking childhood UTI with long-term complications is weak and has been questioned. There is an urgent need to clarify the association between childhood UTI, renal scarring and long-term complications as the correct approach to urine sampling and diagnosis of UTI in children hinges on this association. The studies, on which much of the current practice is based, are generally conducted in secondary care, and children have usually only had urine sampled when the clinician suspects a UTI rather than urine systematically sampled in all ill children. Therefore, the findings from these studies are not necessarily applicable to the population of acutely ill children in primary care.

Not all children with UTI will have had their urine tested and therefore not all will have been diagnosed. In addition, not children diagnosed will have been seen in secondary care and not all will have had a scan to look for renal scarring. The LUCI Study aims to compare outcomes of UTI identified through systematic urine sampling with UTI identified through standard (clinician-led) urine sampling.

The DUTY & EURICA studies found UTI was present in 5.9% and 5.6% respectively in NHS laboratories in the two studies. Cardiff University followed up EURICA children for six months and a sample of DUTY children for three months.

The LUCI Study aims to compare the presenting features, initial management and short and medium-term outcomes of UTI identified through systematic urine sampling (using DUTY and EURICA children) with UTI identified through standard (clinician-led) urine sampling. Cardiff University will use routinely collected data to identify a group of children who had a UTI identified in childhood (before the age of five) who were not part of the DUTY or EURICA studies and therefore identified through standard sampling rather than systematic sampling. Cardiff University will also determine longer term outcomes (more than five years) for those with a UTI identified through standard practice aged less than five years old where the data is available.

For systematically sampled children (DUTY and EURICA participants), Cardiff University will analyse HES/NHS England data (for participants living in England) and Secure Anonymised Information Linkage (SAIL) data (for participants living in Wales). For Routinely sampled children (not a DUTY or EURICA participant): Cardiff University will use data from SAIL only. In the current study, it is proposed that routinely collected health data (GP, hospital, microbiology) will be used to follow DUTY and EURICA children up for 5 years to determine short (up to 1 year) and medium (1-5 years) term outcomes for UTI identified through systematic urine sampling. The outcomes of interest will include further UTI episodes, difficulties with passing urine (dysfunctional voiding syndromes), hospital admissions, any scans on the kidneys or bladder, kidney scarring, high blood pressure, vesicoureteric reflux (VUR; a condition in which urine flows backward from the bladder) and kidney failure.

Cardiff University would like to retain this Data to ensure reconstruction of the study analysis is possible if required, and to give the Cardiff University the opportunity to apply for further funding to continue to complete their analysis of the linked dataset which has been created through this project. This will include further exploration of features which predict serious illnesses (including UTI) and hospital admission.

No additional data will be requested from NHS England.

This Data Sharing Agreement (DSA) permits processing of the Data for the purpose of secure storage and back up.

This DSA does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this DSA.

Following publication of the study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with Cardiff University, contact via the publishing journal or an open letter. In such circumstances, Cardiff University may repeat the previously analyses undertaken to verify that the published results were accurate and may write a response to be issued directly to the challenger or published.

Cardiff University may not undertake different analyses to those undertaken during the original analysis.

This DSA does not permit any onward sharing of the Data.

This DSA permits the necessary processing of the Data for the purposes of permanently destroying, deleting or erasing the Data once it is no longer required for the purpose for which it was collected. Once destroyed/deleted or erased, Cardiff University must confirm destruction to NHS England.

If any further data processing is required in addition to the above purposes or if the data needs to be moved to a different location/organisation, Cardiff University must submit an Amendment request to NHS England before Data is accessed.

Data from the following NHS England Data will be retained:

· Hospital Episode Statistics

o Admitted Patient Care

o Accident & Emergency

o Outpatients

The level of the Data being retained will be:

· Pseudonymised

The data was minimised as follows:

> Limited to a study cohort identified by Cardiff University – the cohort consists of 8,148 acutely ill children recruited from UK primary care who had a UTI identified through systematic urine sampling. This cohort was originally recruited for the EURICA and DUTY studies.

> Limited to data between 2008/09 to 2016/17.

Cardiff University is the research sponsor and the Controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

There is public interest in this work being carried out, as it is expected to help GPs identify which children are at risk of serious illness and need hospital admission or further assessment.

The funding is provided by the Welsh Government through Health and Care Research Wales. The funding is specifically for the study described.

The funder(s) will have no ability to suppress or otherwise limit the publication of findings.

Swansea University is a processor acting under the instructions of Cardiff University. Swansea University’s role is limited to processing the NHS England data on Cardiff University’s behalf, within SAIL.

The expected outputs of the processing will be:

> A report of findings to the funder, Health and Care Research Wales [report submitted in September 2019].

> Submissions to peer reviewed journals. The main paper from the LUCI study was accepted and published online in October 2023 in the British Journal of General Practice (BJGP) Long-term consequences of urinary tract infection in Childhood (LUCI): Electronic population-based cohort study. One further paper is in draft format and it is hoped that this will be submitted for analysis by December 2023. A paper outlining the study protocol was published by the British Medical Journal (BMJ) open. The paper reporting on the assessment of acutely ill children sub-study, looking at the performance of the NICE Traffic light tool, has been published in the BJGP, and was the number one most read paper for 2022.

> Presentations at appropriate conferences - The National Society for Academic Care (SAPC) and the International General Practice Research on Infections (GRIN) Conferences will be targeted, which are attended by practicing clinicians as well as academics from the UK and Europe. Initial findings were presented at the SAPC, GRIN, and Administrative Data Research (ADR) conferences in 2019. A presentation at the International GRIN conference also occurred in September 2022. Results from the assessment of acutely ill children sub-study, looking at the performance of the NICE Traffic light tool were presented at the following conferences in 2021: RCGP annual conference (Oct 2021; winner of Best Research Poster and invited for an oral presentation), National SAPC conference (July 2021; winner Best Research Poster) and the GRIN conference (Sep 2021).

> Publication of a lay summary of the results on the University project website and the participant website, once the main paper has been published. Both websites will link to any publications and news items.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

> Journals

> Reports provided to the funder

> University project website and the participant website

> Conferences

Unfortunately, there were some delays in getting the NHS England and SAIL hospital data linked to study data into the SAIL Databank in such a way that it could be analysed. There were also other delays with the publication of the main paper due to Covid-19 lockdowns, researcher illness, and work on Covid-related research being prioritised. Due to these delays, some of the LUCI study work originally planned could not be completed, predominantly, the work which utilised the linked study and hospital (NHS England and SAIL) data. However, Cardiff University have been able to address some of this work through unfunded student projects, focusing on the outcomes of DUTY children and the assessment and management of ill children. One student sub-project described how good a commonly used clinical scoring system (NICE Traffic Light System) was at identifying which DUTY children were admitted to hospital with serious illness.

A paper describing this work was published in the British Journal of General Practice in March 2022, titled, ‘Accuracy of the NICE Traffic Light system for detecting serious illness in acutely unwell children presenting to general practice: a retrospective cohort study’.

Following this piece of work, Cardiff University has looked at two other scoring systems (Lq-SOFA and National PEWS) to see if they can accurately predict which DUTY children were at risk of serious illness and hospitalisation. The analysis for this has been completed and the paper is now being drafted. It is expected that this will be submitted in late 2023 and published in 2024.

The main message from the research is that if a child has a UTI when they are under 5 then they are more likely to get scars on their kidneys and this risk is higher the younger they are at first UTI and if they have multiple UTIs. However, in all children, kidney scarring is rare and diagnosed considerably less often than previously thought. Children with underlying risk factors are more at risk of developing UTIs, kidney scarring and long-term complications (such as high blood pressure and kidney failure) but for children without other conditions, childhood UTI does not seem to increase longer-term consequences up to 10 years later.

Benefits are expected to continue to arise as further outputs arise.

The LUCI Study (The long-term follow-up of urinary tract infection (UTI) in childhood) is funded by Welsh Government through Health and Care Research Wales. It aims to determine the short, medium and longer-term outcomes of urine infections (UTI) in childhood and to determine whether there is a difference between UTI that is identified through routine practice and UTI identified through systematic urine sampling (where all ill children have their urine sampled).

Current guidelines advise the prompt diagnosis of treatment of UTI in children because childhood UTI can lead to scarring of the kidneys which is believed to lead to long term complications such as high blood pressure, chronic kidney disease and kidney failure in some cases. However, UTI is difficult to diagnose in children as the symptoms are non-specific and similar to those found in many common childhood illnesses. Cardiff University have shown that as many as 80% of UTIs are missed in primary care. A urine sample is required to diagnose UTI but urine is infrequently sampled from ill children in primary care (in less than 2% of consultations). If urine is not sampled, a UTI cannot be diagnosed.

The evidence linking childhood UTI with long-term complications is weak and has been questioned. There is an urgent need to clarify the association between childhood UTI, renal scarring and long term complications as the correct approach to urine sampling and diagnosis of UTI in children hinges on this association. The studies, on which much of the current practice is based, are generally conducted in secondary care, and children have usually only had urine sampled when the clinician suspects a UTI rather than urine systematically sampled in all ill children. Therefore, the findings from these studies are not necessarily applicable to the population of acutely ill children in primary care.

Not all children with UTI will have had their urine tested and therefore not all will have been diagnosed. In addition, not all of the children diagnosed will have been seen in secondary care and not all will have had a scan to look for renal scarring.

Cardiff University have previously conducted two large studies of acutely ill children less than five years old in primary care

(EURICA study n=1003 Wales only [Funder: Welsh Office for Research and Development (WORD), now known as Health &

Care Research Wales]; DUTY study n=7163 England and Wales[Co-led by Cardiff and Bristol Universities; Funder: National Institute for Health Research Health Technology Assessment – NIHR HTA) and collected urine samples systematically from all ill children. The DUTY & EURICA studies found UTI was present in 5.9% and 5.6% respectively in NHS laboratories in the two studies. Cardiff University followed up EURICA children for six months and a sample of DUTY children for three months.

Systematically sampled (DUTY and EURICA children): Cardiff University will use HES/NHS Digital data (for participants living in England) and Secure Anonymised Information Linkage (SAIL) data (for participants living in Wales). Routinely sampled (NOT a participant in DUTY or EURICA): Cardiff University will use data from SAIL ONLY.

In the current study, it is proposed to use routinely collected health data (GP, hospital, microbiology) to follow DUTY and EURICA children up for 5 years to determine short (up to 1 year) and medium (1-5 years) term outcomes for UTI identified through systematic urine sampling. The outcomes of interest will include further UTI episodes, difficulties with passing urine (dysfunctional voiding syndromes), hospital admissions, any scans on the kidneys or bladder, kidney scarring, high blood pressure and kidney failure.

Cardiff University want to compare the presenting features, initial management and short and medium-term outcomes of

UTI identified through systematic urine sampling (using DUTY and EURICA children) with UTI identified through standard (clinician-led) urine sampling.

Cardiff University will use routinely collected data to identify a group of children who had a UTI identified in childhood (before the age of five) who were not part of the DUTY or EURICA studies and therefore identified through standard sampling rather than systematic sampling.

Cardiff University will compare this cohort of children with the DUTY and EURICA cohorts. Cardiff University will also determine longer term outcomes (more than five years) for those with a UTI identified through standard practice aged less than five years old where the data is available.

Cardiff University are relying on Article 6 (1) e. Task in the public interest. For special category data (i.e. medical records) Cardiff University rely on Article 9(2) j. This is publicly funded research which received panel review (including lay/public reviewers) who recognised the importance of this research when recommended to be funded. Cardiff University intend to determine longer-term outcomes for children who experience a urinary tract infection and to determine risks of adverse outcomes. Full details are described below. The data are now in a de-identified format and no further processing of identifiable data is planned. Cardiff University have carried out a detailed risk assessment for the project and no harms were identified for those individuals whose records have been linked to. At the time of data transfer, all participants were contacted to be made aware of the planned data transfer. Now that the data are anonymised and held securely in a data safe haven no further risks have been identified. Cardiff University are requesting this extension to allow us to complete Cardiff Universities analysis of this anonymised data and to continue to have access to the data should any queries arise following peer review and publication of Cardiff Universities research.

This study maximises the benefits of the previously funded DUTY and EURICA cohorts, representing over 8000 acutely ill children recruited from UK primary care. Significant resources were invested by funders, patients and staff to develop these cohorts. Access to HES data will allow the University to determine longer-term outcomes for these children and to determine risks of adverse outcomes. It will also pave the way for even longer-term follow-up of cohorts of children with UTI (diagnosed both systematically and non-systematically) which has been identified as a high research priority by NICE.

A group of 4 lay members have contributed to the development of the participant letter and the content and design of the website. Prior to the letters being sent out, one of the lay members talked through with the study team possible questions they might get from participants. The LUCI Study continue to involve this group in the research by updating them on progress.

The University of Bristol and the University of Oxford will not act as data processors or data controllers in respect of this application.

This study aims to clarify the association between childhood UTI, renal scarring and long-term complications and to determine whether systematic urine sampling improves outcomes for children with UTI.

In addition to the funders of the study, Health and Care Research Wales, which is part of the Welsh Government, the findings from this study will be of interest to clinicians, parents of children and groups reviewing and developing clinical guidelines (such as NICE) across the UK and Europe with similar patient populations and clinical practices. This study was awarded the grant on the strength of the application in terms of the clinical need and impact of the research, fit with Welsh Government priority areas and on the scientific merit of the study.

The results from this study were reported to the funder – Health and Care Research Wales at the end of the study (September 2019) who are reviewing the report with a view to making recommendations on the management of UTI infections in childhood, based on the findings in the report, prior to making it publicly available. The funders will not suppress the findings from the report before it is published - the requirement for review is to ensure their own Public Relations (PR) team is prepared for the publication of the report to the public domain. The early diagnosis and treatment of childhood UTI is key to preventing future health problems and is consistent with the Welsh Government's commitment of giving every child a healthy start.

A lay summary of the results will be made available on the University project website, the participant website they are sent via opt-out and both will link to any publications and news items. All DUTY and EURICA participants were contacted to inform them of the study and given them the option of opting out of the study. They were given the link to the participant website and informed that the website will be updated throughout the course of the study. Results will therefore be made available in lay terms on the website.

In addition to the policy (via report for funder) and public outputs (via website), there will also be academic outputs which are outlined below. The purpose of these academic outputs is to report the methods used in order to answer the research questions and the results and implications of the study findings. These will be presented both in writing and at conferences for the purpose of sharing knowledge, to aid other researchers using these methods, these data and these topic areas. Publishing in scientific journals will involve rigorous independent scientific peer review. This provides additional reassurance to the funder, the public and other researchers that the methods and results presented are of high quality.

The study plans the following academic publications:

A ‘protocol paper’ has been published by the BMJ open: Lugg-Widger FV, Angel L, Cannings-John R, et alLong-term

outcomes of urinary tract infection (UTI) in Childhood (LUCI): protocol for an electronic record-linked cohort studyBMJ Open 2019;9:e024210. doi: 10.1136/bmjopen-2018-024210

A paper on the results of the study will be submitted for publication to a UK clinical journal such as the BMJ or BJGP. This is planned for 2020. Proposed Title – Adverse outcomes following childhood urinary tract infection (UTI) and risk factors for renal scarring: Electronic cohort study. To note. This paper uses data made available from the SAIL Databank (and not NHS Digital provided data).

Cardiff University will target a high impact journal which will reach academics and clinicians across the UK and in other countries with the results of the long-term outcomes of childhood UTI.

Two further papers are also planned that will use data provided by NHS Digital (paper mentioned above does not incorporate those analyses). These analyses were delayed (due to problems unrelated to the NHS Digital data) which has impacted on the study team's timelines to deliver all planned project analyses in time for the first paper. These will be similarly targeted at a high impact journal.

The first will describe the longer-term outcomes following children with and without UTI who were systematically sampled in primary care (follow up of EURICA and DUTY studies). The second will look more closely at symptoms and signs in children which may predict poor outcomes. Once these analyses are complete, the study team will be in a position to communicate the findings with participants, as described above.

All access for analysis is to de-identified data; no identifiable data will be accessed. Published results will only contain aggregated data with small numbers suppressed in line with the HES analysis guide, indeed all outputs from the SAIL data safe haven will abide by the small number policy.

Results generated from the study have been presented at the following conferences in 2019:

- Society for Academic Primary Care (SAPC)

- General Practice Research on Infections (GRIN)

- Administrative Data Research (ADR) conference

This has communicated the findings of the results generated from the SAIL Databank data to primary care clinicians, primary care academics and policy (all attendees at the above conferences).

The main message from the research to date is that if a child has a UTI when they are under 5 then they are more likely to get scars on their kidneys and this risk is higher the younger they are at first UTI and if they have multiple UTIs. However, in all children, kidney scarring is rare and diagnosed considerably less often than previously thought. Children with other medical conditions are more at risk of developing UTIs, kidney scarring and long-term complications (such as high blood pressure and kidney failure) but for children without other conditions, childhood UTI does not seem to increase longer-term consequences up to 10 years later.

The LUCI Study (The long-term follow-up of urinary tract infection (UTI) in childhood) is funded by Welsh Government through Health and Care Research Wales. It aims to determine the short, medium and longer-term outcomes of urine infections (UTI) in childhood and to determine whether there is a difference between UTI that is identified through routine practice and UTI identified through systematic urine sampling (where all ill children have their urine sampled).

Current guidelines advise the prompt diagnosis of treatment of UTI in children because childhood UTI can lead to scarring of the kidneys which is believed to lead to long term complications such as high blood pressure, chronic kidney disease and kidney failure in some cases. However, UTI is difficult to diagnose in children as the symptoms are non-specific and similar to those found in many common childhood illnesses. Cardiff University have shown that as many as 80% of UTIs are missed in primary care. A urine sample is required to diagnose UTI but urine is infrequently sampled from ill children in primary care (in less than 2% of consultations). If urine is not sampled, a UTI cannot be diagnosed.

The evidence linking childhood UTI with long-term complications is weak and has been questioned. There is an urgent need to clarify the association between childhood UTI, renal scarring and long term complications as the correct approach to urine sampling and diagnosis of UTI in children hinges on this association. The studies, on which much of the current practice is based, are generally conducted in secondary care, and children have usually only had urine sampled when the clinician suspects a UTI rather than urine systematically sampled in all ill children. Therefore, the findings from these studies are not necessarily applicable to the population of acutely ill children in primary care.

Not all children with UTI will have had their urine tested and therefore not all will have been diagnosed. In addition, not all of the children diagnosed will have been seen in secondary care and not all will have had a scan to look for renal scarring. Cardiff University have previously conducted two large studies of acutely ill children less than five years old in primary care (EURICA study n=1003 Wales only [Funder: Welsh Office for Research and Development (WORD), now known as Health & Care Research Wales]; DUTY study n=7163 England and Wales[Co-led by Cardiff and Bristol Universities; Funder: National Institute for Health Research Health Technology Assessment – NIHR HTA) and collected urine samples systematically from all ill children. The DUTY & EURICA studies found UTI was present in 5.9% and 5.6% respectively in NHS laboratories in the two studies. Cardiff University followed up EURICA children for six months and a sample of DUTY children for three months.

Systematically sampled (DUTY and EURICA children): Cardiff University will use HES/NHS Digital data (for participants living in England) and Secure Anonymised Information Linkage (SAIL) data (for participants living in Wales). Routinely sampled (NOT a participant in DUTY or EURICA): Cardiff University will use data from SAIL ONLY.

In the current study, it is proposed to use routinely collected health data (GP, hospital, microbiology) to follow DUTY and EURICA children up for 5 years to determine short (up to 1 year) and medium (1-5 years) term outcomes for UTI identified through systematic urine sampling. The outcomes of interest will include further UTI episodes, difficulties with passing urine (dysfunctional voiding syndromes), hospital admissions, any scans on the kidneys or bladder, kidney scarring, high blood pressure and kidney failure.

Cardiff University want to compare the presenting features, initial management and short and medium-term outcomes of UTI identified through systematic urine sampling (using DUTY and EURICA children) with UTI identified through standard (clinician-led) urine sampling. Cardiff University will use routinely collected data to identify a group of children who had a UTI identified in childhood (before the age of five) who were not part of the DUTY or EURICA studies and therefore identified through standard sampling rather than systematic sampling. Cardiff University will compare this cohort of children with the DUTY and EURICA cohorts. Cardiff University will also determine longer term outcomes (more than five years) for those with a UTI identified through standard practice aged less than five years old where the data is available.

This study maximises the benefits of the previously funded DUTY and EURICA cohorts, representing over 8000 acutely ill children recruited from UK primary care. Significant resources were invested by funders, patients and staff to develop these cohorts. Access to HES data will allow the University to determine longer-term outcomes for these children and to determine risks of adverse outcomes. It will also pave the way for even longer-term follow-up of cohorts of children with UTI (diagnosed both systematically and non-systematically) which has been identified as a high research priority by NICE.

A group of 4 lay members have contributed to the development of the participant letter and the content and design of the website. Prior to the letters being sent out, one of the lay members talked through with the study team possible questions they might get from participants. The LUCI Study continue to involve this group in the research by updating them on progress.

The University of Bristol and the University of Oxford will not act as data processors or data controllers in respect of this application.

This study aims to clarify the association between childhood UTI, renal scarring and long-term complications and to determine whether systematic urine sampling improves outcomes for children with UTI.

In addition to the funders of the study, Health and Care Research Wales, which is part of the Welsh Government, the findings from this study will be of interest to clinicians, parents of children and groups reviewing and developing clinical guidelines (such as NICE) across the UK and Europe with similar patient populations and clinical practices. This study was awarded the grant on the strength of the application in terms of the clinical need and impact of the research, fit with Welsh Government priority areas and on the scientific merit of the study.

The results from this study will be reported to the funder – Health and Care Research Wales at the end of the study (September 2018) who will review the report with a view to making recommendations on the management of UTI infections in childhood, based on the findings in the report, prior to making it publicly available. The funders will not suppress the findings from the report before it is published - the requirement for review is to ensure their own Public Relations (PR) team is prepared for the publication of the report to the public domain. The early diagnosis and treatment of childhood UTI is key to preventing future health problems and is consistent with the Welsh Government's commitment of giving every child a healthy start.

A lay summary of the results will be made available on the University project website, the participant website they are sent via opt-out and both will link to any publications and news items. All DUTY and EURICA participants were contacted to inform them of the study and given them the option of opting out of the study. They were given the link to the participant website and informed that the website will be updated throughout the course of the study. Results will therefore be made available in lay terms on the website.

In addition to the policy (via report for funder) and public outputs (via website), there will also be academic outputs which are outlined below. The purpose of these academic outputs is to report the methods used in order to answer the research questions and the results and implications of the study findings. These will be presented both in writing and at conferences for the purpose of sharing knowledge, to aid other researchers using these methods, these data and these topic areas. Publishing in scientific journals will involve rigorous independent scientific peer review. This provides additional reassurance to the funder, the public and other researchers that the methods and results presented are of high quality.

The study plans the following academic publications:

A ‘protocol paper’ to be submitted for publication to BMJ open or BMC Family Practice. This is planned for Summer 2018. Proposed Title - The long-term follow-up of urinary tract infection (UTI) in childhood: A Protocol Paper. This will describe the aims, objectives and research design of the study. This exposes the Universities approach to the scrutiny of other academics, raises awareness of the work taking place and provides an indication about when to expect the results.

A paper on the main results of the study will be submitted for publication to a UK clinical journal such as the BMJ or BJGP. This is planned for early 2019. Proposed Title - The long-term follow-up of urinary tract infection (UTI) in childhood. Cardiff University will target a high impact journal which will reach academics and clinicians across the UK and in other countries with the results of the long-term outcomes of childhood UTI.

All access for analysis is to de-identified data; no identifiable data will be accessed. Published results will only contain aggregated data with small numbers suppressed in line with the HES analysis guide, indeed all outputs from the SAIL data safe haven will abide by the small number policy.

Cardiff University plan to present results at conferences in 2018-2019. This is likely to include the Society for Academic Primary Care National Conference (July 2019) and the General Practice Research on Infections International Meeting (October 2018). A paper on the main results of the study will be submitted for publication to a UK clinical journal such as the BMJ or BJGP. This is planned for 2019.

Yielded Benefits is not a requirement for new applications.