Retrospective checking of compliance with practice guidelines for acute stroke care: a novel experiment using openEHR’s Guideline Definition Language

BACKGROUND: Providing scalable clinical decision support (CDS) across institutions that use different electronic health record (EHR) systems has been a challenge for medical informatics researchers. The lack of commonly shared EHR models and terminology bindings has been recognised as a major barrier to sharing CDS content among different organisations. The openEHR Guideline Definition Language (GDL) expresses CDS content based on openEHR archetypes and can support any clinical terminologies or natural languages. Our aim was to explore in an experimental setting the practicability of GDL and its underlying archetype formalism. A further aim was to report on the artefacts produced by this new technological approach in this particular experiment. We modelled and automatically executed compliance checking rules from clinical practice guidelines for acute stroke care. METHODS: We extracted rules from the European clinical practice guidelines as well as from treatment contraindications for acute stroke care and represented them using GDL. Then we executed the rules retrospectively on 49 mock patient cases to check the cases’ compliance with the guidelines, and manually validated the execution results. We used openEHR archetypes, GDL rules, the openEHR reference information model, reference terminologies and the Data Archetype Definition Language. We utilised the open-sourced GDL Editor for authoring GDL rules, the international archetype repository for reusing archetypes, the open-sourced Ocean Archetype Editor for authoring or modifying archetypes and the CDS Workbench for executing GDL rules on patient data. RESULTS: We successfully represented clinical rules about 14 out of 19 contraindications for thrombolysis and other aspects of acute stroke care with 80 GDL rules. These rules are based on 14 reused international archetypes (one of which was modified), 2 newly created archetypes and 51 terminology bindings (to three terminologies). Our manual compliance checks for 49 mock patients were a complete match versus the automated compliance results. CONCLUSIONS: Shareable guideline knowledge for use in automated retrospective checking of guideline compliance may be achievable using GDL. Whether the same GDL rules can be used for at-the-point-of-care CDS remains unknown

Are you suffering from a large arterial occlusion? Please raise your arm!

Background and purpose: Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods: Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results: The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions: Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions

Recovery from focal brain ischemia induced by extradural compression in diabetic and non-diabetic rats

Cerebrovascular disease and head trauma are among the leading causes of death and disability. In addition to severe motor disturbances, ischemia resulting from stroke or traumatic brain injury (TBI) can cause mild to severe cognitive deficits. One-third of all patients with stroke show hyperglycemia upon hospital admission, and the majority of these are diabetic. The combination of diabetes and stroke was reported to worsen recovery. In agreement with clinical evidence, larger infarct sizes and neurodegeneration were observed in rats following hyperglycemic brain ischemia. The Goto-Kakizaki (GK) rat is a non-insulin-dependent, spontaneously diabetic animal and, to our knowledge, few studies of recovery from focal brain ischemia were performed in this rat strain. In our laboratory, we have developed a model of experimental brain injury in the Sprague-Dawley rat produced by transient, short-lasting (30 min) unilateral extradural compression (EC) of the right sensorimotor cortex. EC produces neurological manifestations (contralateral fore- and hind-limb paresis) and selective neuronal death in the cortex, hippocampus and thalamus, resembling clinical cortical stroke. The aims of the present thesis were to (1) characterize motor and cognitive deficits in both non-diabetic Wistar and diabetic GK rats following EC, (2) to study compression induced-neurodegeneration and potential correlations with the behavioural findings in non-diabetic Wistar and diabetic GK rats, (3) to compare glucose levels and cerebral blood flow (CBF) upon EC and reperfusion in both strains and (4) to investigate strain differences in the expression of several antioxidant and heme-degrading enzymes. Recovery of motor and cognitive functions following EC were assessed with the lever-press task (LPT) and locomotor activity (LMA) monitoring in a novel environment, in parallel with the beam walking and the rotarod. Neurodegeneration induced by EC was concomitantly characterized in several brain regions by using Fluoro-Jade (FJ) as a marker of neurodegeneration and GFAP as marker of reactive astrocytosis at 2, 5, 7, 10 and 14 days in Wistar rats and at 2, 7 and 14 days in GK rats. Cortical CBF upon EC and during reperfusion was measured with Laser-Doppler flowmetry. At 48 h post-EC, mRNA expression of heme-degrading enzymes (HO-1, HO-2), biliverdin reductase (BVR), superoxide dismutases (SOD-1, SOD-2), inflammatory and proapoptotic markers (iNOS, TNFalpha, Bax) were compared between strains with real time RT-PCR. HO-1 expression at 48 h post-EC was studied using double-fluorescence immunohistochemistry for neurons (Fluorescent Nissl staining), astrocytes (GFAP) and microglia (OX-42). Locomotor and exploratory activities of compressed Wistar rats were reduced, in parallel with hemiparesis, detected on the beam walking and on the rotarod on day 1. The LMA parameters normalized on day 2, whereas a phase of increased locomotor activity coupled with deficient habituation to the environment was observed on day 3. Importantly, the deficient habituation was no longer attributable to the motor impairments. The learning of the LPT was delayed in naive-to-task Wistar rats up to 10 days after EC. Fluoro-Jade/GFAP staining demonstrated a consistent pattern of cortical, striatal and thalamic degeneration but revealed variable degrees of degeneration in hippocampal areas. The improvement in LPT performance of naïve-compressed rats was followed by a reduction of damage in cortical associative areas. Additional lesion-effects from damaged hippocampii may have overlapped in a minority of subjects, while the subcortical lesions provoked by EC were unlikely to explain the behavioural findings. GK but not control Wistar rats showed a pronounced hyperglycemic response upon EC, a lower degree of cortical CBF recovery during reperfusion, impaired behavioural habituation to a novel environment on the first five days post-ischemia, impaired learning of a LPT two weeks after EC and a higher degree of neurodegeneration labelled by FJ in the cortex, hippocampus and thalamus at virtually all time-points post-ischemia. Under basal conditions, GK rats exhibited higher mRNA expression of heme degrading, antioxidant and pro-inflammatory genes such as HO-1, iNOS and TNFalpha under basal conditions. At 48 h post-ischemia, HO- 1 was one of the main upregulated genes in the ipsilateral cortex of both diabetic and non-diabetic rats. HO-1 secretion was localized in peri-lesional astrocytes and few microglial cells. Previous experience with the task and familiarity with the environment appear to accelerate recovery from brain ischemia and may initiate compensatory mechanisms at early stages of recovery, with emphasis on the associative cortical areas. The GK rat consistently showed aggravated hyperglycemia, worsened cortical reperfusion and longer-lasting impairments of motor and cognitive functions encouraging further brain injury studies in this rat strain. Counteracting oxidative stress caused by heme degradation and neuroinflammation following normo- and hyperglycemic brain ischemia may thus provide an effective therapy for focal brain ischemia due to a potentially extended therapeutic window

Intima-Media Thickness and Pulsatility Index of Common Carotid Arteries in Acute Ischaemic Stroke Patients with Diabetes Mellitus

Ultrasonographic parameters such as the common carotid artery (CCA) pulsatility index (PI) and CCA intima-media thickness (IMT) have been associated with an increased mortality and risk of recurrent stroke, respectively. We hypothesized that these ultrasonographic parameters may be useful for monitoring diabetic patients after an acute stroke. We analysed retrospective data of consecutive acute ischaemic stroke patients from the ASTRAL registry who underwent pre-cerebral ultrasonographic evaluation within 7 days of symptom onset. We compared clinical, demographic, radiological and ultrasonographic parameters in diabetic versus non-diabetic patients (univariable and multivariable analyses) and the association of these parameters with CCA PI and CCA IMT. We analysed 1507 carotid duplex ultrasound examinations from patients with a median age of 74 years. Cardiovascular co-morbidities, including hypertension, hypercholesterolemia, obstructive sleep apnoea syndrome, higher body-mass index (BMI) and peripheral artery disease, were associated with diabetes mellitus (DM). Diabetics were more often under antiplatelet therapy and had atrial fibrillation at admission. Diabetic patients showed an increased CCA PI and IMT in line with more atherosclerotic changes on acute CTA compared to non-diabetic patients. Taking IMT as the dependent variable in a second analysis, DM, higher age, hypertension, smoking and CCA PI were associated with higher IMT. Taking CCA PI as the dependent variable in a third analysis, DM, higher age and higher NIHSS at admission were associated with higher CCA PI values. Increased IMT was also associated with higher PI. We show that CCA PI and IMT are higher in diabetic patients in the first week after an initial stroke

Applying openEHR\u2019s Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study

Abstract Background Interoperability standards intend to standardise health information, clinical practice guidelines intend to standardise care procedures, and patient data registries are vital for monitoring quality of care and for clinical research. This study combines all three: it uses interoperability specifications to model guideline knowledge and applies the result to registry data. Methods We applied the openEHR Guideline Definition Language (GDL) to data from 18,400 European patients in the Safe Implementation of Treatments in Stroke (SITS) registry to retrospectively check their compliance with European recommendations for acute stroke treatment. Results Comparing compliance rates obtained with GDL to those obtained by conventional statistical data analysis yielded a complete match, suggesting that GDL technology is reliable for guideline compliance checking. Conclusions The successful application of a standard guideline formalism to a large patient registry dataset is an important step toward widespread implementation of computer-interpretable guidelines in clinical practice and registry-based research. Application of the methodology gave important results on the evolution of stroke care in Europe, important both for quality of care monitoring and clinical research

Isolation, molecular characterization and geoprocessing of enteropathogenic, enterotoxigenic, and Shiga toxin-producing Escherichia coli in drinking water sources from southeast Brazil.

In Brazil, safe drinking water is not widely available, and consequently waterborne diseases are still associated with high morbidity and mortality rates. Among waterborne bacteria, diarrheagenic Escherichia coli (DEC) should be highlighted. This study targeted the evaluation of enteropathogenic (EPEC), enterotoxigenic (ETEC), and shiga toxin-producing (STEC)/ enterohemorrhagic Escherichia coli in drinking water in Southeast Brazil and the georeferencing of generated data. A total of 1185 water samples were studied. Among them 7.8% and 4.1% gave positive results for total and fecal coliforms, respectively. By employing PCR, a total of 12 diarrheagenic E. coli (DEC) isolates (6 ETEC, 4 STEC, and 2 EPEC) from eight water samples (4, 2, and 2 positives for STEC, ETEC, and EPEC, respectively) were detected including samples collected in schools and a healthcare facility where particularly susceptible hosts are found. Data generated were submitted to georeferencing. A positive correlation (r 2 = 0.9) between DEC detection and the rainy period was observed. The presence of DEC in drinking water samples in the studied municipalities highlights the relevance of controlling the sources of human and animal fecal pollution, as well as the management of municipal wastewater sources in order to reduce potential risks to human health. Searching for DEC and georeferencing DEC positive sites may subsidize the proposal of corrective and preventive actions by environmental surveillance agencies