Rs10230207 genotype confers changes in HDAC9 and TWIST1, but not FERD3L in lymphoblasts from patients with intracranial aneurysm.

Intracranial aneurysms (IA) are weakened outpouchings of the arterial wall in the cerebrovasculature. Rupture of an IA often leads to devastating consequences. The early identification of IA patients is crucial for management of their condition. A genetic variant at rs10230207, located nearby the HDAC9, TWIST1, and FERD3L genes, is associated with IA. HDAC9 is a class IIa histone deacetylase that mediates vascular smooth muscle cell dysfunction. TWIST1 is a mechanosensitive transcription factor and its expression is reduced in unstable carotid atherosclerotic plaques. In this study, the expression of the HDAC9, TWIST1, and FERD3L genes was characterized and associated with the presence of the rs10230207 genetic variant. Allelic discrimination and gene expression analysis were performed using lymphoblasts from 85 population controls and 109 IA patients. Subjects that were heterozygous (GT) within rs10230207 were 4.32 times more likely to have an IA than those that were homozygous for the reference allele (GG; 95%CI 1.23 to 14.16). Subjects that were homozygous (TT) were 8.27 times more likely to have an IA than those that were GG (95%CI 2.45 to 27.85). While the presence of the risk allele was not associated with changes in FERD3L gene expression, the risk allele was associated with increased HDAC9 and decrease in TWIST1 mRNA expression. The significant inverse correlation between HDAC9 and TWIST1 gene expression suggests that changes in the expression of both of genes may contribute to the formation of IAs.

The Extended Treatment Window's Impact on Emergency Systems of Care for Acute Stroke.

The window for acute ischemic stroke treatment was previously limited to 4.5 hours for intravenous tissue plasminogen activator and to 6 hours for thrombectomy. Recent studies using advanced imaging selection expand this window for select patients up to 24 hours from last known well. These studies directly affect emergency stroke management, including prehospital triage and emergency department (ED) management of suspected stroke patients. This narrative review summarizes the data expanding the treatment window for ischemic stroke to 24 hours and discusses these implications on stroke systems of care. It analyzes the implications on prehospital protocols to identify and transfer large-vessel occlusion stroke patients, on issues of distributive justice, and on ED management to provide advanced imaging and access to thrombectomy centers. The creation of high-performing systems of care to manage acute ischemic stroke patients requires academic emergency physician leadership attentive to the rapidly changing science of stroke care.

Impact of an Expanded Hospital Recognition Program for Stroke Quality of Care.

BACKGROUND: In 2009, the Get With The Guidelines-Stroke (GWTG-Stroke) program offered additional recognition if hospitals performed well on certain stroke quality measures. We sought to determine whether quality of care for all hospitals participating in GWTG-Stroke improved with this expanded recognition program. METHODS AND RESULTS: We examined hospital-level performance on 6 quality of care (process) measures and 1 defect-free composite quality measure for stroke following expansion of the existing performance measure recognition program. Compliance with all measures improved following launch of the expanded program, and this rate increased significantly for all 9 measures. When evaluated as the relative rate of increase in use over time, process improvement slowed significantly (P<0.05) following launch of the program for 2 measures, and accelerated significantly for 1 measure. However, when evaluated as a gap in care, the decrease in the quality gap was greater following launch of the program for 5 of 6 (83%) measures. There was no evidence that other processes of stroke care suffered as the result of the increase in measures and expanded recognition program. CONCLUSIONS: While care for stroke continues to improve in this country, expanded hospital process performance recognition had mixed results in accelerating this improvement. However, the quality gap continues to shrink among those participating in provider performance programs.

Have clinicians adopted the use of brain MRI for patients with TIA and minor stroke?

BACKGROUND: Use of MRI with diffusion-weighted imaging (DWI) can identify infarcts in 30%-50% of patients with TIA. Previous guidelines have indicated that MRI-DWI is the preferred imaging modality for patients with TIA. We assessed the frequency of MRI utilization and predictors of MRI performance. METHODS: A review of TIA and minor stroke patients evaluated at Veterans Affairs hospitals was conducted with regard to medical history, use of diagnostic imaging within 2 days of presentation, and in-hospital care variables. Chart abstraction was performed in a subset of hospitals to assess clinical variables not available in the administrative data. RESULTS: A total of 7,889 patients with TIA/minor stroke were included. Overall, 6,694 patients (84.9%) had CT or MRI, with 3,396/6,694 (50.7%) having MRI. Variables that were associated with increased odds of CT performance were age >80 years, prior stroke, history of atrial fibrillation, heart failure, coronary artery disease, anxiety, and low hospital complexity, while blood pressure >140/90 mm Hg and high hospital complexity were associated with increased likelihood of MRI. Diplopia (87% had MRI, p = 0.03), neurologic consultation on the day of presentation (73% had MRI, p < 0.0001), and symptom duration of >6 hours (74% had MRI, p = 0.0009) were associated with MRI performance. CONCLUSIONS: Within a national health system, about 40% of patients with TIA/minor stroke had MRI performed within 2 days. Performance of MRI appeared to be influenced by several patient and facility-level variables, suggesting that there has been partial acceptance of the previous guideline that endorsed MRI for patients with TIA.

Quantitative validation of a general competency composite assessment evaluation.

OBJECTIVES: The authors sought to modify and validate a composite assessment evaluation process that assesses resident acquisition of the Accreditation Council for Graduate Medical Education (ACGME) general competencies (GCs). METHODS: This study critically analyzed the evaluation process used in a multicenter study (150 emergency medicine resident evaluations) to determine whether the procedure was psychometrically valid. For each GC, principal component analysis (PCA) was used to determine whether certain evaluation items could be eliminated, as well as to determine the magnitude of variability explained by up to three linear combinations or "principal components." The factor proportions (factor loadings) of various eigenvectors were measured to determine the degree of variability (determined by the square of the factor proportion) within a data or item set. The factor proportions essentially measure the length of the eigenvector as determined from a correlation matrix. RESULTS: The first three principal components are reported as factor proportion sum (% of total variability) as follows: patient care 0.91 (83%), medical knowledge 0.87 (76%), practice-based learning and improvement 0.90 (81%), interpersonal and communication skills 0.84 (71%), professionalism 0.74 (55%), and systems-based practice 0.80 (64%). PCA showed that evaluating certain traditional categories such as medical knowledge seemed to capture a single element, whereas professionalism appeared to measure a more complex, multidimensional phenomenon. CONCLUSIONS: By using a structured development process, the authors were able to create valid evaluation items for determining resident acquisition of the ACGME GCs.