Dataset Information

Factors associated with potentially serious incidental findings and with serious final diagnoses on multi-modal imaging in the UK Biobank Imaging Study: A prospective cohort study.

ABSTRACT:

Background

Feedback of potentially serious incidental findings (PSIFs) to imaging research participants generates clinical assessment in most cases. Understanding the factors associated with increased risks of PSIFs and of serious final diagnoses may influence individuals' decisions to participate in imaging research and will inform the design of PSIFs protocols for future research studies. We aimed to determine whether, and to what extent, socio-demographic, lifestyle, other health-related factors and PSIFs protocol are associated with detection of both a PSIF and a final diagnosis of serious disease.

Methods and findings

Our cohort consisted of all UK Biobank participants who underwent imaging up to December 2015 (n = 7334, median age 63, 51.9% women). Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry images from the first 1000 participants were reviewed systematically by radiologists for PSIFs. Thereafter, radiographers flagged concerning images for radiologists' review. We classified final diagnoses as serious or not using data from participant surveys and clinical correspondence from GPs up to six months following imaging (either participant or GP correspondence, or both, were available for 93% of participants with PSIFs). We used binomial logistic regression models to investigate associations between age, sex, ethnicity, socio-economic deprivation, private healthcare use, alcohol intake, diet, physical activity, smoking, body mass index and morbidity, with both PSIFs and serious final diagnoses. Systematic radiologist review generated 13 times more PSIFs than radiographer flagging (179/1000 [17.9%] versus 104/6334 [1.6%]; age- and sex-adjusted OR 13.3 [95% confidence interval (CI) 10.3-17.1] p<0.001) and proportionally fewer serious final diagnoses (21/179 [11.7%]; 33/104 [31.7%]). Risks of both PSIFs and of serious final diagnoses increased with age (sex-adjusted ORs [95% CI] for oldest [67-79 years] versus youngest [44-58 years] participants for PSIFs and serious final diagnoses respectively: 1.59 [1.07-2.38] and 2.79 [0.86 to 9.0] for systematic radiologist review; 1.88 [1.14-3.09] and 2.99 [1.09-8.19] for radiographer flagging). No other factor was significantly associated with either PSIFs or serious final diagnoses. Our study is the largest so far to investigate the factors associated with PSIFs and serious final diagnoses, but despite this, we still may have missed some associations due to sparsity of these outcomes within our cohort and small numbers within some exposure categories.

Conclusion

Risks of PSIFs and serious final diagnosis are substantially influenced by PSIFs protocol and to a lesser extent by age. As only 1/5 PSIFs represent serious disease, evidence-based PSIFs protocols are paramount to minimise over-investigation of healthy research participants and diversion of limited health services away from patients in need.

SUBMITTER: Gibson LM

PROVIDER: S-EPMC6576786 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Factors associated with potentially serious incidental findings and with serious final diagnoses on multi-modal imaging in the UK Biobank Imaging Study: A prospective cohort study.

Gibson Lorna M LM Nolan John J Littlejohns Thomas J TJ Mathieu Edouard E Garratt Steve S Doherty Nicola N Petersen Steffen S Harvey Nicholas C W NCW Sellors Jonathan J Allen Naomi E NE Wardlaw Joanna M JM Jackson Caroline A CA Sudlow Cathie L M CLM

PloS one 20190617 6

<h4>Background</h4>Feedback of potentially serious incidental findings (PSIFs) to imaging research participants generates clinical assessment in most cases. Understanding the factors associated with increased risks of PSIFs and of serious final diagnoses may influence individuals' decisions to participate in imaging research and will inform the design of PSIFs protocols for future research studies. We aimed to determine whether, and to what extent, socio-demographic, lifestyle, other health-rela ...[more]

PMID: 31206530

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Project description:Background: There are limited data on the impact of feedback of incidental findings (IFs) from research imaging. We evaluated the impact of UK Biobank's protocol for handling potentially serious IFs in a multi-modal imaging study of 100,000 participants (radiographer 'flagging' with radiologist confirmation of potentially serious IFs) compared with systematic radiologist review of all images. Methods: Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry scans from the first 1000 imaged UK Biobank participants were independently assessed for potentially serious IFs using both protocols. We surveyed participants with potentially serious IFs and their GPs up to six months after imaging to determine subsequent clinical assessments, final diagnoses, emotional, financial and work or activity impacts. Results: Compared to systematic radiologist review, radiographer flagging resulted in substantially fewer participants with potentially serious IFs (179/1000 [17.9%] versus 18/1000 [1.8%]) and a higher proportion with serious final diagnoses (21/179 [11.7%] versus 5/18 [27.8%]). Radiographer flagging missed 16/21 serious final diagnoses (i.e., false negatives), while systematic radiologist review generated large numbers of non-serious final diagnoses (158/179) (i.e., false positives). Almost all (90%) participants had further clinical assessment (including invasive procedures in similar numbers with serious and non-serious final diagnoses [11 and 12 respectively]), with additional impact on emotional wellbeing (16.9%), finances (8.9%), and work or activities (5.6%). Conclusions: Compared with systematic radiologist review, radiographer flagging missed some serious diagnoses, but avoided adverse impacts for many participants with non-serious diagnoses. While systematic radiologist review may benefit some participants, UK Biobank's responsibility to avoid both unnecessary harm to larger numbers of participants and burdening of publicly-funded health services suggests that radiographer flagging is a justifiable approach in the UK Biobank imaging study. The potential scale of non-serious final diagnoses raises questions relating to handling IFs in other settings, such as commercial and public health screening.

Project description:ObjectivesTo determine prevalence and types of potentially serious incidental findings on magnetic resonance imaging (MRI) in apparently asymptomatic adults, describe factors associated with potentially serious incidental findings, and summarise information on follow-up and final diagnoses.DesignSystematic review and meta-analyses.Data sourcesCitation searches of relevant articles and authors' files in Medline and Embase (from inception to 25 April 2017).Review methodsEligible studies included prevalence and types of incidental findings detected among apparently asymptomatic adults undergoing MRI of the brain, thorax, abdomen, or brain and body. Data on study population and methods, prevalence and types of incidental findings, and final diagnoses were extracted. Pooled prevalence was estimated by random effects meta-analysis, and heterogeneity by τ2 statistics.Main outcome measuresPrevalence of potentially serious incidental findings on MRI of the brain, thorax, abdomen, and brain and body.ResultsOf 5905 retrieved studies, 32 (0.5%) met the inclusion criteria (n=27 643 participants). Pooled prevalence of potentially serious incidental findings was 3.9% (95% confidence interval 0.4% to 27.1%) on brain and body MRI, 1.4% (1.0% to 2.1%) on brain MRI, 1.3% (0.2% to 8.1%) on thoracic MRI, and 1.9% (0.3% to 12.0%) on abdominal MRI. Pooled prevalence rose after including incidental findings of uncertain potential seriousness (12.8% (3.9% to 34.3%), 1.7% (1.1% to 2.6%), 3.0% (0.8% to 11.3%), and 4.5% (1.5% to 12.9%), respectively). There was generally substantial heterogeneity among included studies. About half the potentially serious incidental findings were suspected malignancies (brain, 0.6% (95% confidence interval 0.4% to 0.9%); thorax, 0.6% (0.1% to 3.1%); abdomen, 1.3% (0.2% to 9.3%); brain and body, 2.3% (0.3% to 15.4%)). There were few informative data on potential sources of between-study variation or factors associated with potentially serious incidental findings. Limited data suggested that relatively few potentially serious incidental findings had serious final diagnoses (48/234, 20.5%).ConclusionsA substantial proportion of apparently asymptomatic adults will have potentially serious incidental findings on MRI, but little is known of their health consequences. Systematic, long term follow-up studies are needed to better inform on these consequences and the implications for policies on feedback of potentially serious incidental findings.Systematic review registrationProspero CRD42016029472.

Project description:The UK Biobank has made general practitioner (GP) data (censoring date 2016-2017) available for approximately 45% of the cohort, whilst hospital inpatient and death registry (referred to as "HES/Death") data are available cohort-wide through 2018-2022 depending on whether the data comes from England, Wales or Scotland. We assessed the importance of case ascertainment via different data sources in UKB for three diseases that are usually first diagnosed in primary care: Parkinson's disease (PD), type 2 diabetes (T2D), and all-cause dementia. Including GP data at least doubled the number of incident cases in the subset of the cohort with primary care data (e.g. from 619 to 1390 for dementia). Among the 786 dementia cases that were only captured in the GP data before the GP censoring date, only 421 (54%) were subsequently recorded in HES. Therefore, estimates of the absolute incidence or risk-stratified incidence are misleadingly low when based only on the HES/Death data. For incident cases present in both HES/Death and GP data during the full follow-up period (i.e. until the HES censoring date), the median time difference between an incident diagnosis of dementia being recorded in GP and HES/Death was 2.25 years (i.e. recorded 2.25 years earlier in the GP records). Similar lag periods were also observed for PD (median 2.31 years earlier) and T2D (median 2.82 years earlier). For participants with an incident GP diagnosis, only 65.6% of dementia cases, 69.0% of PD cases, and 58.5% of T2D cases had their diagnosis recorded in HES/Death within 7 years since GP diagnosis. The effect estimates (hazard ratios, HR) of established risk factors for the three health outcomes mostly remain in the same direction and with a similar strength of association when cases are ascertained either using HES only or further adding GP data. The confidence intervals of the HR became narrower when adding GP data, due to the increased statistical power from the additional cases. In conclusion, it is desirable to extend both the coverage and follow-up period of GP data to allow researchers to maximise case ascertainment of chronic health conditions in the UK.

Project description:BackgroundAdverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all-cause mortality using data from UK Biobank.MethodsThere were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat-tissue free muscle volume and muscle fat infiltration (MFI) using AMRA® Researcher (AMRA Medical, Linköping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z-score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z-score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex-specific)], and (iv) adverse MC (low muscle volume z-score and high MFI). Association of MC groups with mortality was investigated using Cox proportional-hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index).ResultsMuscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m2 ]. Three hundred twenty-eight deaths were recorded during a follow-up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81-4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all-cause mortality [1.58 (1.13-2.21), P = 0.007, and 2.02 (1.51-2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28-2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P < 0.001 and P = 0.020) while the association with only low muscle volume was attenuated to non-significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42-2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47-2.53), P < 0.001] and smoking [1.71 (1.02-2.84), P = 0.040]. Low hand grip strength was borderline non-significant [1.34 (0.96-1.88), P = 0.090].ConclusionsAdverse MC was a strong and independent predictor of all-cause mortality. Sarcopenia guidelines can be strengthened by including cut-offs for myosteatosis enabling detection of adverse MC.

Project description:PurposeThe retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.ParticipantsUK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to dateUK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plansThe collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Project description:BackgroundSleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.Methods and findingsIn this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.ConclusionsIn this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.

Dataset Information

Factors associated with potentially serious incidental findings and with serious final diagnoses on multi-modal imaging in the UK Biobank Imaging Study: A prospective cohort study.

Background

Methods and findings

Conclusion

Publications

Factors associated with potentially serious incidental findings and with serious final diagnoses on multi-modal imaging in the UK Biobank Imaging Study: A prospective cohort study.

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