Evaluation of radiological capacity and usage in paediatric TB diagnosis: A mixed-method protocol of a comparative study in Mozambique, South Africa and Spain.

INTRODUCTION: Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited. METHODS: A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum. DISCUSSION: As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management.

Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults.

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.

Pediatric computed tomography doses in Germany from 2016 to 2018 based on large-scale data collection.

PURPOSE: Accumulating evidence from epidemiological studies that pediatric computed tomography (CT) examinations can be associated with a small but non-zero excess risk for developing leukemia or brain tumor highlights the need to optimize doses of pediatric CT procedures. Mandatory dose reference levels (DRL) can support reduction of collective dose from CT imaging. Regular surveys of applied dose-related parameters are instrumental to decide when technological advances and optimized protocol design allow lower doses without sacrificing image quality. Our aim was to collect dosimetric data to support adapting current DRL to changing clinical practice. METHOD: Dosimetric data and technical scan parameters from common pediatric CT examinations were retrospectively collected directly from Picture Archiving and Communication Systems (PACS), Dose Management Systems (DMS), and Radiological Information Systems (RIS). RESULTS: We collected data from 17 institutions on 7746 CT series from the years 2016 to 2018 from examinations of the head, thorax, abdomen, cervical spine, temporal bone, paranasal sinuses and knee in patients below 18 years of age. Most of the age-stratified parameter distributions were lower than distributions from previously-analyzed data from before 2010. Most of the third quartiles were lower than German DRL at the time of the survey. CONCLUSIONS: Directly interfacing PACS, DMS, and RIS installations allows large-scale data collection but relies on high data-quality at the documentation stage. Data should be validated by expert knowledge or guided questionnaires. Observed clinical practice in pediatric CT imaging suggests lowering some DRL in Germany is reasonable.

Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study.

BACKGROUND: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer. METHODS: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination. FINDINGS: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded. INTERPRETATION: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible. FUNDING: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England.

Dose Estimation for the European Epidemiological Study on Pediatric Computed Tomography (EPI-CT).

Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies.

The HARMONIC project: study design for the assessment of radiation doses and associated cancer risks following cardiac fluoroscopy in childhood.

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac fluoroscopy component of HARMONIC. A pooled cohort of approximately 100 000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports. Uncertainties in dose estimates will be modelled using 2D Monte Carlo methods. The cohort will be followed up using national registries and insurance records to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development in this patient group) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.

Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands.

BACKGROUND: Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood. METHODS: For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries. Standardized incidence ratios were calculated using cancer incidence rates from the general Dutch population. Excess relative risks (ERRs) per 100 mGy organ dose were calculated with Poisson regression. All statistical tests were two-sided. RESULTS: Standardized incidence ratios were elevated for all cancer sites. Mean cumulative bone marrow doses were 9.5 mGy at the end of follow-up, and leukemia risk (excluding myelodysplastic syndrome) was not associated with cumulative bone marrow dose (44 cases). Cumulative brain dose was on average 38.5 mGy and was statistically significantly associated with risk for malignant and nonmalignant brain tumors combined (ERR/100 mGy: 0.86, 95% confidence interval = 0.20 to 2.22, P = .002, 84 cases). Excluding tuberous sclerosis complex patients did not substantially change the risk. CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. No association was observed for leukemia. Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.

Patient safety in external beam radiotherapy, results of the ACCIRAD project: Recommendations for radiotherapy institutions and national authorities on assessing risks and analysing adverse error-events and near misses.

The ACCIRAD project, commissioned by the European Commission (EC) to develop guidelines for risk analysis of accidental and unintended exposures in external beam radiotherapy (EBRT), was completed in the year 2014. In 2015, the "General guidelines on risk management in external beam radiotherapy" were published as EC report Radiation Protection (RP)-181. The present document is the third and final report of the findings from the ACCIRAD project. The main aim of this paper is to describe the key features of the risk management process and to provide general guidelines for radiotherapy departments and national authorities on risk assessment and analysis of adverse error-events and near misses. The recommendations provided here and in EC report RP-181 are aimed at promoting the harmonisation of risk management systems across Europe, improving patient safety, and enabling more reliable inter-country comparisons.

Individual radiation exposure from computed tomography: a survey of paediatric practice in French university hospitals, 2010-2013.

OBJECTIVES: To describe computed tomography (CT) scanning parameters, volume CT dose index (CTDIvol) and dose-length product (DLP) in paediatric practice and compare them to current diagnostic reference levels (DRLs). METHODS: The survey was conducted in radiology departments of six major university hospitals in France in 2010-2013. Data collection was automatised to extract and standardise information on scanning parameters from DICOM-header files. CTDIvol and DLP were estimated based on Monte Carlo transport simulation and computational reference phantoms. RESULTS: CTDIvol and DLP were derived for 4,300 studies, four age groups and 18 protocols. CTDIvol was lower in younger patients for non-head scans, but did not vary with age for routine head scans. Ratios of 95th to 5th percentile CTDIvol values were 2-4 for most body parts, but 5-7 for abdominal examinations and 4-14 for mediastinum CT with contrast, depending on age. The 75th percentile CTDIvol values were below the national DRLs for chest (all ages) and head and abdominal scans (≥10 years). CONCLUSION: The results suggest the need for a better optimisation of scanning parameters for routine head scans and infrequent protocols with patient age, enhanced standardisation of practices across departments and revision of current DRLs for children. KEY POINTS: • CTDIvol varied little with age for routine head scans. • CTDIvol was lowest in youngest children for chest or abdominal scans. • Individual and inter-department variability warrant enhanced standardisation of practices. • Recent surveys support the need for revised diagnostic reference levels. • More attention should be given to specific protocols (sinuses, neck, spine, mediastinum).

Patient safety in external beam radiotherapy, results of the ACCIRAD project: Current status of proactive risk assessment, reactive analysis of events, and reporting and learning systems in Europe.

PURPOSE: To describe the current status of implementation of European directives for risk management in radiotherapy and to assess variability in risk management in the following areas: 1) in-country regulatory framework; 2) proactive risk assessment; (3) reactive analysis of events; and (4) reporting and learning systems. MATERIAL AND METHODS: The original data were collected as part of the ACCIRAD project through two online surveys. RESULTS: Risk assessment criteria are closely associated with quality assurance programs. Only 9/32 responding countries (28%) with national regulations reported clear "requirements" for proactive risk assessment and/or reactive risk analysis, with wide variability in assessment methods. Reporting of adverse error events is mandatory in most (70%) but not all surveyed countries. CONCLUSIONS: Most European countries have taken steps to implement European directives designed to reduce the probability and magnitude of accidents in radiotherapy. Variability between countries is substantial in terms of legal frameworks, tools used to conduct proactive risk assessment and reactive analysis of events, and in the reporting and learning systems utilized. These findings underscore the need for greater harmonisation in common terminology, classification and reporting practices across Europe to improve patient safety and to enable more reliable inter-country comparisons.

Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates.

OBJECTIVE: To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . METHODS: National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. RESULTS: Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. CONCLUSIONS: The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. KEY POINTS: • Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. • Small children may have received doses 2-3 times higher compared with adults. • Different scanner models varied by a factor of 2-3 in dose to patients. • Different local scan parameter settings gave dose variations of a factor 2-3. • Modern CTs and age-adjusted protocols will give much lower paediatric doses.

EPI-CT: design, challenges and epidemiological methods of an international study on cancer risk after paediatric and young adult CT.

Computed tomography (CT) has great clinical utility and its usage has increased dramatically over the years. Concerns have been raised, however, about health impacts of ionising radiation exposure from CTs, particularly in children, who have a higher risk for some radiation induced diseases. Direct estimation of the health impact of these exposures is needed, but the conduct of epidemiological studies of paediatric CT populations poses a number of challenges which, if not addressed, could invalidate the results. The aim of the present paper is to review the main challenges of a study on the health impact of paediatric CTs and how the protocol of the European collaborative study EPI-CT, coordinated by the International Agency for Research on Cancer (IARC), is designed to address them. The study, based on a common protocol, is being conducted in Belgium, Denmark, France, Germany, the Netherlands, Norway, Spain, Sweden and the United Kingdom and it has recruited over one million patients suitable for long-term prospective follow-up. Cohort accrual relies on records of participating hospital radiology departments. Basic demographic information and technical data on the CT procedure needed to estimate organ doses are being abstracted and passive follow-up is being conducted by linkage to population-based cancer and mortality registries. The main issues which may affect the validity of study results include missing doses from other radiological procedures, missing CTs, confounding by CT indication and socioeconomic status and dose reconstruction. Sub-studies are underway to evaluate their potential impact. By focusing on the issues which challenge the validity of risk estimates from CT exposures, EPI-CT will be able to address limitations of previous CT studies, thus providing reliable estimates of risk of solid tumours and leukaemia from paediatric CT exposures and scientific bases for the optimisation of paediatric CT protocols and patient protection.

Patient safety in external beam radiotherapy - guidelines on risk assessment and analysis of adverse error-events and near misses: introducing the ACCIRAD project.

In 2011 the European Commission launched a tender to develop guidelines for risk analysis of accidental and unintended exposures in external beam radiotherapy. This tender was awarded to a consortium of 6 institutions, including the ESTRO, in late 2011. The project, denominated "ACCIRAD", recently finished the data collection phase. Data were collected by surveys administered in 38 European countries. Results indicate non-uniform implementation of event registration and classification, as well as incomplete or zero implementation of risk assessment and events analysis. Based on the survey results and analysis thereof, project leaders are currently drafting proposed guidelines entitled "Guidelines for patient safety in external beam radiotherapy - Guidelines on risk assessment and analysis of adverse-error events and near misses". The present article describes the aims and current status of the project, including results of the surveys.

Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study.

Computed tomography (CT) scans are indispensable in modern medicine; however, the spectacular rise in global use coupled with relatively high doses of ionizing radiation per examination have raised radiation protection concerns. Children are of particular concern because they are more sensitive to radiation-induced cancer compared with adults and have a long lifespan to express harmful effects which may offset clinical benefits of performing a scan. This paper describes the design and methodology of a nationwide study, the Dutch Pediatric CT Study, regarding risk of leukemia and brain tumors in children after radiation exposure from CT scans. It is a retrospective record-linkage cohort study with an expected number of 100,000 children who received at least one electronically archived CT scan covering the calendar period since the introduction of digital archiving until 2012. Information on all archived CT scans of these children will be obtained, including date of examination, scanned body part and radiologist's report, as well as the machine settings required for organ dose estimation. We will obtain cancer incidence by record linkage with external databases. In this article, we describe several approaches to the collection of data on archived CT scans, the estimation of radiation doses and the assessment of confounding. The proposed approaches provide useful strategies for data collection and confounder assessment for general retrospective record-linkage studies, particular those using hospital databases on radiological procedures for the assessment of exposure to ionizing or non-ionizing radiation.

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit.

OBJECTIVE: To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). METHODS: A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. RESULTS: Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. CONCLUSIONS: The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. KEY POINTS: • External support through clinical audit may optimise default parameters of routine CT. • Reduction of 75th percentiles used as reference diagnostic levels is 18-75 %. • The effect of this audit is sustainable over time. • Dose savings through optimisation can be added to those achievable through CT.

Assessing organ doses from paediatric CT scans--a novel approach for an epidemiology study (the EPI-CT study).

The increasing worldwide use of paediatric computed tomography (CT) has led to increasing concerns regarding the subsequent effects of exposure to radiation. In response to this concern, the international EPI-CT project was developed to study the risk of cancer in a large multi-country cohort. In radiation epidemiology, accurate estimates of organ-specific doses are essential. In EPI-CT, data collection is split into two time periods--before and after introduction of the Picture Archiving Communication System (PACS) introduced in the 1990s. Prior to PACS, only sparse information about scanner settings is available from radiology departments. Hence, a multi-level approach was developed to retrieve information from a questionnaire, surveys, scientific publications, and expert interviews. For the years after PACS was introduced, scanner settings will be extracted from Digital Imaging and Communications in Medicine (DICOM) headers, a protocol for storing medical imaging data. Radiation fields and X-ray interactions within the body will be simulated using phantoms of various ages and Monte-Carlo-based radiation transport calculations. Individual organ doses will be estimated for each child using an accepted calculation strategy, scanner settings, and the radiation transport calculations. Comprehensive analyses of missing and uncertain dosimetry data will be conducted to provide uncertainty distributions of doses.

Computed tomographies and cancer risk in children: a literature overview of CT practices, risk estimations and an epidemiologic cohort study proposal.

Radiation protection is a topic of great public concern and of many scientific investigations, because ionizing radiation is an established risk factor for leukaemia and many solid tumours. Exposure of the public to ionizing radiation includes exposure to background radiation, as well as medical and occupational exposures. A large fraction of the exposure from diagnostic procedures comes from medical imaging. Computed tomography (CT) is the major single contributor of diagnostic radiation exposure. An increase in the use of CTs has been reported over the last decades in many countries. Children have smaller bodies and lower shielding capacities, factors that affect the individual organ doses due to medical imaging. Several risk models have been applied to estimate the cancer burden caused by ionizing radiation from CT. All models predict higher risks for cancer among children exposed to CT as compared to adults. However, the cancer risk associated with CT has not been assessed directly in epidemiological studies. Here, plans are described to conduct an historical cohort study to investigate the cancer incidence in paediatric patients exposed to CT before the age of 15 in Germany. Patients will be recruited from radiology departments of several hospitals. Their individual exposure will be recorded, and time-dependent cumulative organ doses will be calculated. Follow-up for cancer incidence via the German Childhood Cancer Registry will allow computation of standardized incidence ratios using population-based incidence rates for childhood cancer. Dose-response modelling and analyses for subgroups of children based on the indication for and the result of the CT will be performed.