Subtle excess in lifetime cancer risk related to CT scanning in Spanish young people

Background: CT scan is a life-saving medical diagnostic tool, entailing higher levels of ionising radiation exposure than conventional radiography, which may result in an increase in cancer risk, particularly in children. Information about the use and potential health effects of CT scan imaging among young people in Spain is scarce. Objective: This paper aims to estimate the number of radiation-related cancer cases which can be expected due to the use of CT scanning in Spanish children and young adults in a single year (2013). Methods: The 2013 distribution of number and types of CT scans performed in young people was obtained for Catalonia and extrapolated to the whole Spain. Organ doses were estimated based on the technical characteristics of 17,406 CT examinations extracted from radiology records. Age and sex-specific data on cancer incidence and life tables were obtained for the Spanish population. Age and sex-specific risk models developed by the Committee on Health Risks of Exposure to Low Levels of Ionizing Radiations (BEIR VII) and Berrington de Gonzalez were used, together, with the dose estimates to derive the lifetime attributable risks of cancer in Spain due to one year of CT scanning and project the number of future cancer cases to be expected. Results: In 2013, 105,802 CT scans were estimated to have been performed in people younger than age 21. It was estimated that a total of 168.6 cancer cases (95% CrI: 30.1-421.1) will arise over life due to the ionising radiation exposure received during these CTs. Lifetime attributable risks per 100,000 exposed patients were highest for breast and lung cancer. The largest proportion of CTs was to the head and neck and hence the highest numbers of projected cancer cases were of thyroid and oral cavity/pharynx. Conclusions: Despite the undeniable medical effectiveness of CT scans, this risk assessment suggests a small excess in cancer cases which underlines the need for justification and optimisation in paediatric scanning. Given the intrinsic uncertainties of these risk projection exercises, care should be taken when interpreting the predicted risks

CT scan exposure in Spanish children and young adults by socioeconomic status: Cross-sectional analysis of cohort data

Recent publications reported that children in disadvantaged areas undergo more CT scanning than others. The present study is aimed to assess the potential differences in CT imaging by socioeconomic status (SES) in Spanish young scanned subjects and if such differences vary with different indicators or different time point SES measurements. The associations between CT scanning and SES, and between the CT scan rate per patient and SES were investigated in the Spanish EPI-CT subcohort. Various SES indicators were studied to determine whether particular SES dimensions were more closely related to the probability of undergoing one or multiple CTs. Comparisons were made with indices based on 2001 and 2011 censuses. We found evidence of socio-economic variation among young people, mainly related to autonomous communities of residence. A slightly higher rate of scans per patient of multiple body parts in the less affluent categories was observed, possibly reflecting a higher rate of accidents and violence in these groups. The number of CT scans per patient was higher both in the most affluent and the most deprived categories and somewhat lower in the intermediate groups. This relation varied with the SES indicator used, with lower CT scans per patients in categories of high unemployment and temporary work, but not depending on categories of unskilled work or illiteracy. The relationship between these indicators and number of CTs in 2011 was different than that seen with the 2001 census, with the number of CTs increasing with higher unemployment. Overall we observed some differences in the SES distribution of scanned patients by Autonomous Community in Spain. There was, however, no major differences in the frequency of CT scans per patient by SES overall, based on the 2001 census. The use of different indicators and of SES data collected at different time points led to different relations between SES and frequency of CT scans, outlining the difficulty of adequately capturing the social and economic dimensions which may affect health and health service utilisation

Trends and patterns in the use of computed tomography in children and young adults in Catalonia — results from the EPI-CT study

Background Although there are undeniable diagnostic benefits of CT scanning, its increasing use in paediatric radiology has become a topic of concern regarding patient radioprotection. Objective To assess the rate of CT scanning in Catalonia, Spain, among patients younger than 21 years old at the scan time. Materials and methods This is a sub-study of a larger international cohort study (EPI-CT, the International pediatric CT scan study). Data were retrieved from the radiological information systems (RIS) of eight hospitals in Catalonia since the implementation of digital registration (between 1991 and 2010) until 2013. Results The absolute number of CT scans annually increased 4.5% between 1991 and 2013, which was less accentuated when RIS was implemented in most hospitals. Because the population attending the hospitals also increased, however, the rate of scanned patients changed little (8.3 to 9.4 per 1,000 population). The proportions of patients with more than one CT and more than three CTs showed a 1.51- and 2.7-fold increase, respectively, over the 23 years. Conclusion Gradual increases in numbers of examinations and scanned patients were observed in Catalonia, potentially explained by new CT scanning indications and increases in the availability of scanners, the number of scans per patient and the size of the attended population.Supported in part by the Seventh Framework Programme from the European Community (Grant agreement no: 269912) and the Consejo de Seguridad Nuclear

Gestational phthalate exposure and lung function during childhood: A prospective population-based study

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV1 at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (-0.02 (-0.04, 0)) and FEV1 z-scores (-0.02 (-0.04,-0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV1 at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV1, especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure.The INMA study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1) , and from Spain: Instituto de Salud Carlos III and Ministry of Health (Red INMA G03/176; CB06/02/0041; PI041436, PI081151, PI06/0867, PS09/00090, PI13/02187; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI12/01890, PI13/1944, PI13/2032, PI14/00891, PI14/1687, PI17/01194, and PI17/00663; MV16/00015; predoctoral grant PFIS - FI14/00099, pre-doctoral grant PFIS FIS-FSE: 17/00260, FIS19/1338, MV16/00015, Miguel Servet-FEDER: CP11/0178, and Miguel Servet-FSE: MS13/00054, MSII16/00051, and MS16/00128) , CIBERESP; Department of Health of the Basque Government (2005111093 and 2009111069) ; the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001) ; and the Generalitat de Catalunya-CIRIT (1999SGR 00241) . ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX 2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program

Validity of prognostic models of critical COVID-19 is variable. A systematic review with external validation

Objectives: To identify prognostic models which estimate the risk of critical COVID-19 in hospitalized patients and to assess their validation properties. Study design and setting: We conducted a systematic review in Medline (up to January 2021) of studies developing or updating a model that estimated the risk of critical COVID-19, defined as death, admission to intensive care unit, and/or use of mechanical ventilation during admission. Models were validated in two datasets with different backgrounds (HM [private Spanish hospital network], n = 1,753, and ICS [public Catalan health system], n = 1,104), by assessing discrimination (area under the curve [AUC]) and calibration (plots). Results: We validated 18 prognostic models. Discrimination was good in nine of them (AUCs ≥ 80%) and higher in those predicting mortality (AUCs 65%-87%) than those predicting intensive care unit admission or a composite outcome (AUCs 53%-78%). Calibration was poor in all models providing outcome's probabilities and good in four models providing a point-based score. These four models used mortality as outcome and included age, oxygen saturation, and C-reactive protein among their predictors. Conclusion: The validity of models predicting critical COVID-19 by using only routinely collected predictors is variable. Four models showed good discrimination and calibration when externally validated and are recommended for their use

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

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol

Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration: ISRCTN12051706

CT scans in children and young adults and cancer risk: the Spanish EPI-CT cohort

The present thesis introduces the EPI-CT cohort study; a European collaborative effort aimed at quantifying the health risks of computed tomography (CT scan) radiation exposure during childhood and assesses the main epidemiological factors that could bias the risk estimates in similar studies. It confirms an increase in the CT scan usage among patients younger than 21 years in Catalonia during the period 1991-2013. Of importance is that, the results obtained within the Spanish branch of the EPI-CT study do not suggest that the number of CT scans per person differ among the socioeconomic spectrum. This thesis also includes a health risk assessment of the 2013 Spanish CT imaging practice in young population, which projects 0.2% additional cancer cases (over the spontaneously arising cancer cases) to occur in the expected lifespan of the CT scan exposed individuals. A very initial analysis quantifying the association between the cumulative organ-doses and leukaemia and brain cancer mortality is included, suggesting a dose-related increase in the risk of brain tumours and leukaemia mortality.Aquesta tesi presenta l'estudi de cohort EPI-CT; un estudi Europeu adreçat a la quantificació dels riscos per a la salut associats a l'exposició a la radiació de la tomografia computaritzada (TC) durant la infància i avalua els principals factors epidemiològics que podrien esbiaixar les estimacions de risc en estudis similars. Aquesta tesi confirma un augment en l'ús de la TC en pacients menors de 21 anys a Catalunya durant el període 1991-2013 i alhora, conclou que el nombre de TCs per persona no difereix segons el nivell socioeconòmic del pacient, suggerint un ús similar en tota la població. Aquesta tesi inclou també una avaluació del risc per a la salut de totes les TCs que es van dur a terme al 2013 en població jove a Espanya, i projecta un increment d’un 0,2% de càncers respecte als que s’esperen que ocorrin de forma espontànea entre la població exposada. S’inclou també una anàlisi molt inicial en la que s’observa una associació entre dosi a nivell d’òrgan i mortalitat per leucèmia i càncer de cervell

PI-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.This work was supported by the European Community's Seventh Framework Programme (FP7/2007–2013) (grant number 269912 - EPI-CT: Epidemiological study to quantify risks for paediatric computerised tomography and to optimise doses). The International Agency for Research in Cancer (IARC) received complementary funding from the Ministry of Health, Labour and Welfare of Japan (grant agreement number 2012-02-21-01). In France, complementary funding was obtained from the French national Institute of Cancer and from the Association 'La ligue contre le Cancer'. Complementary funding was received from the German Federal Ministry of Education and Research [grant number 02NUK016] for the German KICT study. In Spain, complementary funding was received from a the Consejo de Seguridad Nuclear and M Bosch de Basea was the recipient of a fellowship of the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) for a short stay abroad at Newcastle University. In The Netherlands Worlwide Cancer Research, formerly known as the Association for International Cancer Research, provided partial funding [Grant 12–1155]. The original United Kingdom cohort study was funded by the United Kingdom Department of Health and the United States National Cancer Institute and further funding for the study has been obtained from Cancer Research UK. In Norway, it was funded by the Norwegian Research Council through the EURATOM programme, project no. 209096/E40