Objective To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main measures of interest Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.

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.

Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.

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ImportanceThe long-term effects of COVID-19 on the incidence of vascular diseases are unclear.ObjectiveTo quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease.DesignCohort study based on population-wide linked electronic health records, with follow up from January 1st to December 7th 2020.Setting and participantsAdults registered with an NHS general practice in England or Wales and alive on January 1st 2020.ExposuresTime since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis.Main outcomes and measuresPrimary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications.ResultsAmong 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses.Conclusions and RelevanceHigh rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID_19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.Key pointsQuestionIs COVID-19 associated with higher long-term incidence of vascular diseases?FindingsIn this cohort study of 48 million adults in England and Wales, COVID-19 was associated with higher incidence, that declined with time since diagnosis, of both arterial thromboses [week 1: adjusted HR [aHR] 21.7 (95% CI 21.0-22.4) weeks 27-49: aHR 1.34 (1.21-1.48)] and venous thromboembolism [week 1: aHR 33.2 (31.3-35.2), weeks 27–49 1.80 (1.50-2.17)]. aHRs were higher, for longer, after hospitalised than non-hospitalised COVID-19. The estimated excess number of arterial thromboses and venous thromboembolisms was 10,500.MeaningAvoidance of COVID-19 infection through vaccination, and use of secondary preventive agents after infection in high-risk patients, may reduce post-COVID-19 acute vascular diseases.

IMPORTANCE Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be associated with intolerance of uncertainty and compulsive behaviors; however, little is known about the mechanisms underlying learning and decision-making in youths with OCD because research into this population has been limited. OBJECTIVE To investigate cognitive mechanisms associated with decision-making in youths withOCD by using executive functioning tasks and computational modeling. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK. MAIN OUTCOMES AND MEASURES Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed. RESULTS In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, −1.31 to −0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, −2.17 to −1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, −0.29; 95% HDI, −0.39 to −0.18), reinforcement sensitivity (MD, −4.91; 95% HDI, −9.38 to −1.12), and stickiness (MD, −0.35; 95% HDI, −0.57 to −0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for (continued) Key Points Questio...

Importance: Thromboses after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. Objective: Quantify associations of vaccination with ChAdOx1-S and BNT162b2 with major arterial, venous and thrombocytopenic events. Design: Cohort study based on linked electronic health records, with follow up from December 8th, 2020, to March 18th, 2021. Setting and participants: Adults registered with an NHS general practice in England and alive on December 8th, 2020. Exposures: First dose of vaccination with ChAdOx1-S and BNT162b2. Main Outcomes and Measures: Incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination with ChAdOx1-S or BNT162b2 vaccine. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors. Results: Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with pre-vaccination rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.9-1.05) and 0.58 (0.53-0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74-0.88) and 0.57 (0.53-0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33-3.88 and 1.71, 1.35-2.16 respectively), but not after BNT162b2 (0.59, 0.24-1.45 and 1.00, 0.75-1.34) compared with pre-vaccination. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9-3 per million, varying by age and sex. Conclusions and Relevance: Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years are small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.

Background Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. Methods and findings In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. Conclusions In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.