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Objectives: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. Background: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. Methods: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. Results: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [3.1 to 34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [1.9 to 12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 (2.33 to 28.7), P = 0.0010). Conclusions: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

BackgroundCoded healthcare data may not capture all stroke cases and has limited accuracy for stroke subtypes. We sought to determine the incremental value of adding natural language processing (NLP) of free-text radiology reports to international classification of disease (ICD-10) codes to phenotype stroke, and stroke subtypes, in routinely collected healthcare datasets.MethodsWe linked participants in a community-based prospective cohort study, Generation Scotland, to clinical brain imaging reports (2008-2020) from five Scottish health boards. We used five combinations of NLP outputs and ICD-10 codes to define stroke phenotypes. With these phenotype models we measured the: stroke incidence standardised to a European Standardised Population; adjusted hazard ratio (aHR) of baseline hypertension for later stroke; and proportion of participants allocated stroke subtypes.ResultsOf 19,026 participants, over a mean follow-up of 10.2 years, 1938 had 3493 brain scans. Any stroke was identified in 534 participants: 319 with NLP alone, 59 with ICD-10 codes alone and 156 with both ICD-10 codes and an NLP report consistent with stroke. The stroke aHR for baseline hypertension was 1.47 (95%CI: 1.12-1.92) for NLP-defined stroke only; 1.57 (95%CI: 1.18-2.10) for ICD-10 defined stroke only; and 1.81 (95%CI: 1.20-2.72) for cases with ICD 10 stroke codes and NLP stroke phenotypes. The age-standardised incidence of stroke for these phenotype models was 1.35, 1.34, and 0.65 per 1000 person years, respectively. The proportion of strokes not subtyped was 26% (57/215) using only ICD-10, 9% (42/467) using only NLP, and 12% (65/534) using both NLP and ICD-10.ConclusionsAddition of NLP derived phenotypes to ICD-10 stroke codes identified approximately 2.5 times more stroke cases and greatly increased the proportion with subtyping. The phenotype model using ICD 10 stroke codes and NLP stroke phenotypes had the strongest association with baseline hypertension. This information is relevant to large cohort studies and clinical trials that use routine electronic health records for outcome ascertainment.

BackgroundBetter understanding of global variation in simple tests of cognition and function would aid the delivery and interpretation of multi-national studies of the prevention of dementia and functional decline.MethodsWe aim to describe the variation in simple measures of cognition and function by world region, study, recruitment centre or individual level factors. In six RCTs that measured cognition with the mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), and instrumental activities of daily living (IADL) with the Standardised Assessment of Everyday Global Activities (SAGEA), we estimated average scores by global region with multilevel mixed-effects models. We estimated the proportion of participants with cognitive or functional impairment with previously defined thresholds (MMSE≤24 or MoCA≤25, SAGEA≥7), and with a country-standardised z-score threshold of cognitive or functional score of ≤-1.ResultsIn 91,396 participants (mean age 66.6±7.8 years, 31% females) from seven world regions, all global regions differed significantly in estimated cognitive function (z-score differences 0.11–0.45, pConclusionsAccounting for country-level factors reduced large differences between world regions in estimates of cognitive impairment. Measures of IADL were less variable across world regions, and could be used to better estimate dementia incidence in large studies.Impact statementWe certify that this work is novel. After analysing data from a large cohort of participants with a history of cardiovascular disease or cardiovascular risk factors, who were recruited in six international randomised controlled trials (RCTs) we found that accounting for country-level factors reduced large differences between world regions in estimates of cognitive impairment, while measures of functional impairment were less variable across world regions.Key PointsCognitive and functional test scores in randomized controlled clinical trial cohorts vary widely across world regions.The difference in cognitive test performance was large in comparison to difference in measures of activities of daily living (ADLs). Accounting for country-level factors reduced the differences between world regions in estimates of cognitive impairment.Cognitive test measures were less variable and could be used to better estimate dementia incidence in international studies.Why this study matters?We found that cognitive and functional test scores in RCT cohorts varied widely across world regions. The difference in cognitive test performance was large in comparison to difference in measures of activities of daily living. The impact of differences on the performance of cognitive tests, which were developed in high-income countries, creates challenges for harmonized studies of cognitive decline prevention in different world regions. Future studies using the same test around the world could standardise cognitive score by country, and consider using in addition measures of instrumental and basic activities of daily living, where there is less variation across world regions.

Background: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. Methods: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. Results: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%–42%]); possible 26 out of 151 (17% [12%–24%]); and uncertain 9 out of 43, (20% [10%–36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%–53%]); migraine aura 4 out of 38 (11% [3%–25%]); non-TIA focal symptoms 16 out of 99 (16% [10%–25%]); and no focal features 1 out of 29 (3% [0%–18%]). After MRI, a further 14 (5% [95% CI, 3–8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3–62]; P Conclusions: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0–22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21–1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3–35.2) in week 1 to 1.80 (95% CI, 1.50–2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. Conclusions: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Function is an important outcome after stroke; traditional assessments may not capture functional deficits important to patients. We examined the validity of the Standard Assessment of Global Everyday Activities (SAGEA), a patient-reported outcome that assesses activities important to patients and for use in international clinical trials.The NAVIGATE-ESUS trial evaluated rivaroxaban compared to aspirin in preventing recurrent stroke in 7213 participants. The Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the SAGEA were collected at entry. Chi square tests were used to compare proportions and Spearman rank correlations were used to compare between measures. SAGEA was compared to the Modified Frailty Index (MFI) and the occurrence of infarct to examine criterion validity RESULTS: Participants were 67 years, 2/3 were male, and at baseline 30% had no disability and 58% had slight disability according to mRS scores. SAGEA was weakly correlated with the mRS (r=0.37), the NIHSS (r=0.29) and the MFI (r=0.30). Of the 2154 with an mRS score of 0, 61% reported difficulty on the SAGEA. The largest discrepancies between SAGEA and other measures were because of cognitive functional deficits detected by the SAGEA that were not identified on other assessments. A larger number of MRI identified infarcts (acute and covert) were associated with a higher SAGEA score (p=0.007).The SAGEA is a simple, globally applicable measure of cognitive and functional abilities that identifies issues that other commonly used assessments of disability and function do not capture.

Background Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding British Heart Foundation Data Science Centre, led by Health Data Research UK.

Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.The purpose of this study was to investigate whether thoracicIn a post hoc observational cohort study, we quantified thoracic aortic and coronaryAfter 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aorticIn patients with established cardiovascular disease, thoracic aortic

The effect of interventions on functional impairment is an important outcome in stroke prevention trials and should be considered as an adjunct to counting discrete events. In the NAVIGATE-ESUS trial, 7213 patients with recent embolic strokes of undetermined source were randomized to rivaroxaban (15 mg once daily) or aspirin (100 mg daily). After 11 months there was no effect on the prevention of recurrent stroke.To determine the effect of rivaroxaban compared to aspirin on functional and cognitive outcomes.Function and cognition were measured at baseline, 1 year, and study end using the Standard Assessment of Global Everyday Activities (SAGEA), a 15-item scale assessing cognitive, instrumental, and basic activities of daily living as well as mobility, and the Montreal Cognitive Assessment (MoCA). Changes in scores were calculated by subtracting either study end or 1-year scores from baseline, and differences in distributions were compared using the Mann-Whitney U test. SAGEA and MoCA scores were also correlated with recurrent stroke.Follow-up SAGEA scores were available in 6378 (88%) participants. There was no difference in change in function for those allocated to rivaroxaban compared to aspirin (Mann-Whitney U test, p = 0.8), with both distributions having a median (25p,75p) change of 0 (-2,1). Overall, more of those who experienced a recurrent stroke (n=247; mostly minor ischemic), reported functional difficulty at study end versus entry, compared with those who did not (51% versus 30%, chi-square test, p0.001), and this was consistent across global regions. There was no difference in the change in cognition by treatment group, nor were recurrent strokes associated with a change in cognition.Rivaroxaban, compared to aspirin, was not associated with changes in functional or cognitive status in patients with recent ESUS. The SAGEA scale detected changes in functional status associated with recurrent strokes in an international stroke population.

Background For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Discussion Final results of RESTART will be analysed and disseminated in 2019. Trial registration ISRCTN71907627 (www.isrctn.com/ISRCTN71907627). Prospectively registered on 25 April 2013.

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.

Background: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs modifies the risks of recurrent ICH, haemorrhagic events, vaso-occlusive events, or a composite of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, parallel group, open, assessor-blind, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH. Recruitment began on 22 May 2013 and ended on 31 May 2018. Follow-up ends on 30 November 2018. This update to the protocol describes the statistical analysis plan (version 1.6, finalised on 18 September 2018). Data lock is expected to occur on 11 January 2019, after which the un-blinded trial statistician will conduct the final analyses according to this statistical analysis plan. Discussion: Final results of RESTART will be analysed and disseminated in 2019. Trial registration: ISRCTN registry 71907627. Prospectively registered on 25 April 2013. Funding/sponsor: The trial is funded by a British Heart Foundation special project grant (SP/12/2/29422) and a travel fellowship (FS/13/72/30531). The trial sponsor is the Academic and Clinical Central Office for Research and Development (ACCORD), which is a partnership between the University of Edinburgh and NHS Lothian Health Board.

Background— Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Methods— Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Results— Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91; P =0.004). Conclusions— Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit.

Objectives To 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. Design Systematic review and meta-analyses. Data sources Citation searches of relevant articles and authors’ files in Medline and Embase (from inception to 25 April 2017). Review methods Eligible 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 measures Prevalence of potentially serious incidental findings on MRI of the brain, thorax, abdomen, and brain and body. Results Of 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%). Conclusions A 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 registration Prospero CRD42016029472.

Introduction: Dysphagia screening protocols have been recommended to identify patients at risk for aspiration. The American Heart Association convened an Evidence Review Committee to systematically review evidence for the effectiveness of dysphagia screening protocols to reduce the risk of pneumonia, death, or dependency after stroke. Methods: The Medline, Embase, and Cochrane databases were searched on November 1, 2016, to identify randomized controlled trials (RCTs) comparing dysphagia screening protocols or quality interventions to increased dysphagia screening rates, and reporting outcomes of pneumonia, death or dependency. Results: Three RCTs were identified. One RCT (n=1,126) found that a combined nursing quality improvement intervention targeting fever and glucose management as well as dysphagia screening reduced death and dependency (42% vs. 58%, p=0.002), but without reducing the pneumonia rate (2.1% vs. 2.7%, p=0.82). Another RCT (n=311) failed to find evidence that pneumonia rates were reduced by adding the cough reflex test to routine dysphagia screening (26% vs. 21%, p=0.38). A smaller RCT (n=162) randomly assigned 2 hospital wards to a stroke care pathway including dysphagia screening or regular care, and found that patients on the stroke care pathway were less likely to require intubation and mechanical ventilation (7.8% vs. 20%, p=0.03 after adjustment); however, the study was small and at risk for bias. Conclusions: There were insufficient RCT data to determine the effect of dysphagia screening protocols on reducing rates of pneumonia, death, or dependency after stroke. Additional trials are needed to compare the validity, feasibility, and clinical effectiveness of different screening methods for dysphagia.