Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network

Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications

OBJECTIVES: DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of DISH in relation to thoracic aortic calcification (TAC) severity. METHODS: This cross-sectional study included 4703 patients from the Second Manifestation of ARTerial disease cohort, consisting of patients with cardiovascular events or risk factors for cardiovascular disease. Chest radiographs were scored for DISH using the Resnick criteria. Different severities of TAC were scored arbitrarily from no TAC to mild, moderate or severe TAC. Using multivariate logistic regression, the associations between DISH and TAC were analysed with adjustments for age, sex, BMI, diabetes, smoking status, non-high-density lipoprotein cholesterol, cholesterol lowering drug usage, renal function and blood pressure. RESULTS: A total of 442 patients (9.4%) had evidence of DISH and 1789 (38%) patients had TAC. The prevalence of DISH increased from 6.6% in the no TAC group to 10.8% in the mild, 14.3% in the moderate and 17.1% in the severe TAC group. After adjustments, DISH was significantly associated with the presence of TAC [odds ratio (OR) 1.46 [95% CI 1.17, 1.82)]. In multinomial analyses, DISH was associated with moderate TAC [OR 1.43 (95% CI 1.06, 1.93)] and severe TAC [OR 1.67 (95% CI 1.19, 2.36)]. CONCLUSIONS: Subjects with DISH have increased TACs, providing further evidence that patients with DISH have an increased burden of vascular calcifications

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSIONS: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality

Uniform data collection in routine clinical practice in cardiovascular patients for optimal care, quality control and research: The Utrecht Cardiovascular Cohort

Background: Cardiovascular disease remains the major contributor to morbidity and mortality. In routine care for patients with an elevated cardiovascular risk or with symptomatic cardiovascular disease information is mostly collected in an unstructured manner, making the data of limited use for structural feedback, quality control, learning and scientific research. / Objective: The Utrecht Cardiovascular Cohort (UCC) initiative aims to create an infrastructure for uniform registration of cardiovascular information in routine clinical practice for patients referred for cardiovascular care at the University Medical Center Utrecht, the Netherlands. This infrastructure will promote optimal care according to guidelines, continuous quality control in a learning healthcare system and creation of a research database. / Methods: The UCC comprises three parts. UCC-1 comprises enrolment of all eligible cardiovascular patients in whom the same information will be collected, based on the Dutch cardiovascular management guideline. A sample of UCC-1 will be invited for UCC-2. UCC-2 involves an enrichment through extensive clinical measurements with emphasis on heart failure, cerebral ischaemia, arterial aneurysms, diabetes mellitus and elevated blood pressure. UCC-3 comprises on-top studies, with in-depth measurements in smaller groups of participants typically based on dedicated project grants. All participants are followed up for morbidity and mortality through linkage with national registries. / Conclusion: In a multidisciplinary effort with physicians, patients and researchers the UCC sets a benchmark for a learning cardiovascular healthcare system. UCC offers an invaluable resource for future high quality care as well as for first-class research for investigators

OSIRISv1.2: A named entity recognition system for sequence variants of genes in biomedical literature

<p>Abstract</p> <p>Background</p> <p>Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required.</p> <p>Results</p> <p>Our group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes <url>http://ibi.imim.es/osirisform.html</url>. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, <url>http://ibi.imim.es/OSIRISv1.2.html</url>) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented.</p> <p>Conclusion</p> <p>OSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.</p

Cerebral aneurysm exclusion by CT angiography based on subarachnoid hemorrhage pattern: a retrospective study

<p>Abstract</p> <p>Background</p> <p>To identify patients with spontaneous subarachnoid hemorrhage for whom CT angiography alone can exclude ruptured aneurysms.</p> <p>Methods</p> <p>An observational retrospective review was carried out of all consecutive patients with non-traumatic subarachnoid hemorrhage who underwent both CT angiography and catheter angiography to exclude an aneurysm. CT angiography negative cases (no aneurysm) were classified according to their CT hemorrhage pattern as "aneurismal", "perimesencephalic" or as "no-hemorrhage."</p> <p>Results</p> <p>Two hundred and forty-one patients were included. A CT angiography aneurysm detection sensitivity and specificity of 96.4% and 96.0% were observed. All 35 cases of perimesencephalic or no-hemorrhage out of 78 CT angiography negatives also had negative angiography findings.</p> <p>Conclusions</p> <p>CT angiography is self-reliant to exclude ruptured aneurysms when either a perimesencephalic hemorrhage or no-hemorrhage pattern is identified on the CT within a week of symptom onset.</p

A computerised decision support system for cardiovascular risk management ‘live’ in the electronic health record environment: development, validation and implementation—the Utrecht Cardiovascular Cohort Initiative

PURPOSE: We set out to develop a real-time computerised decision support system (CDSS) embedded in the electronic health record (EHR) with information on risk factors, estimated risk, and guideline-based advice on treatment strategy in order to improve adherence to cardiovascular risk management (CVRM) guidelines with the ultimate aim of improving patient healthcare. METHODS: We defined a project plan including the scope and requirements, infrastructure and interface, data quality and study population, validation and evaluation of the CDSS. RESULTS: In collaboration with clinicians, data scientists, epidemiologists, ICT architects, and user experience and interface designers we developed a CDSS that provides ‘live’ information on CVRM within the environment of the EHR. The CDSS provides information on cardiovascular risk factors (age, sex, medical and family history, smoking, blood pressure, lipids, kidney function, and glucose intolerance measurements), estimated 10-year cardiovascular risk, guideline-compliant suggestions for both pharmacological and non-pharmacological treatment to optimise risk factors, and an estimate on the change in 10-year risk of cardiovascular disease if treatment goals are adhered to. Our pilot study identified a number of issues that needed to be addressed, such as missing data, rules and regulations, privacy, and patient participation. CONCLUSION: Development of a CDSS is complex and requires a multidisciplinary approach. We identified opportunities and challenges in our project developing a CDSS aimed at improving adherence to CVRM guidelines. The regulatory environment, including guidance on scientific evaluation, legislation, and privacy issues needs to evolve within this emerging field of eHealth

Multislice CT angiography in the selection of patients with ruptured intracranial aneurysms suitable for clipping or coiling

Introduction We sought to establish whether CT angiography (CTA) can be applied to the planning and performance of clipping or coiling in ruptured intracranial aneurysms without recourse to intraarterial digital subtraction angiography (IA-DSA). Methods Over the period April 2003 to January 2006 in all patients presenting with a subarachnoid haemorrhage CTA was performed primarily. If CTA demonstrated an aneurysm, coiling or clipping was undertaken. IA-DSA was limited to patients with negative or inconclusive CTA findings. We compared CTA images with findings at surgery or coiling in patients with positive CTA findings and in patients with negative and inconclusive findings in whom IA-DSA had been performed. Results In this study, 224 consecutive patients (mean age 52.7 years, 135 women) were included. In 133 patients (59%) CTA demonstrated an aneurysm, and CTA was followed directly by neurosurgical (n=55) or endovascular treatment (n=78). In 31 patients (14%) CTA findings were categorized as inconclusive, and in 60 (27%) CTA findings were negative. One patient received surgical treatment on the basis of false-positive CTA findings. In 17 patients in whom CTA findings were inconclusive, IA-DSA provided further diagnostic information required for correct patient selection for any therapy. Five ruptured aneurysms in patients with a nonperimesencephalic SAH were negative on CTA, and four of these were also false-negative on IA-DSA. On a patient basis the positive predictive value, negative predictive value, sensitivity, specificity and accuracy of CTA for symptomatic aneurysms were 99%, 90%, 96%, 98% and 96%, respectively. Conclusion CTA should be used as the first diagnostic modality in the selection of patients for surgical or endovascular treatment of ruptured intracranial aneurysms. If CTA renders inconclusive results, IA-DSA should be performed. With negative CTA results the complementary value of IA-DSA is marginal. IA-DSA is not needed in patients with negative CTA and classic perimesencephalic SAH. Repeat IA-DSA or CTA should still be performed in patients with a nonperimesencephalic SAH