Person:

Walcott, Brian

Background: Increasingly studies have identified socioeconomic factors adversely affecting healthcare outcomes for a multitude of diseases. To date, however, there has not been a study correlating socioeconomic details from nationwide databases on the prevalence of advanced coronary artery disease. We seek to identify whether socioeconomic factors contribute to advanced coronary artery disease prevalence in the United States. Methods and Findings: State specific prevalence data was queried form the United States Nationwide Inpatient Sample for 2009. Patients undergoing percutaneous coronary angioplasty and coronary artery bypass graft were identified as principal procedures. Non-cardiac related procedures, lung lobectomy and hip replacement (partial and total) were identified and used as control groups. Information regarding prevalence was then merged with data from the Behavioral Risk Factor Surveillance System, the largest, on-going telephone health survey system tracking health conditions and risk behaviors in the United States. Pearson's correlation coefficient was calculated for individual socioeconomic variables including employment status, level of education, and household income. Household income and education level were inversely correlated with the prevalence of percutaneous coronary angioplasty (−0.717; −0.787) and coronary artery bypass graft surgery (−0.541; −0.618). This phenomenon was not seen in the non-cardiac procedure control groups. In multiple linear regression analysis, socioeconomic factors were significant predictors of coronary artery bypass graft and percutaneous transluminal coronary angioplasty (p<0.001 and p = 0.005, respectively). Conclusions: Socioeconomic status is related to the prevalence of advanced coronary artery disease as measured by the prevalence of percutaneous coronary angioplasty and coronary artery bypass graft surgery.

Background: Medical studies are more likely to report favorable findings when a conflict of interest is declared. We aim to quantify and determine the effect of author disclosure of conflict of interest on scientific reporting. Methods: Abstracts from an international spine research meeting (North American Spine Society 2010) were selected that specifically evaluated a device, biologic, or proprietary procedure. They were then made anonymous to reviewers. An item of interest was established in each of the abstracts in order to standardize evaluation. Next, three blinded reviewers independently rated the abstracts as favorable, neutral, or unfavorable with regard to the item of interest. Additionally, the blinded reviewers attempted to predict whether a related disclosure was made. The meeting disclosure index was used to tabulate the minimum US dollar value attributable to disclosures. Results: Of the 344 total abstracts, 76 met inclusion criteria. In 79%, a related conflict of interest was reported. The amount of the disclosure was incompletely reported in 30% of cases. Where available, it averaged a cumulative minimum of $219,634 USD per abstract. The results of the abstracts were judged to be favorable, neutral, and unfavorable in 63%, 32% and 5% of abstracts, respectively. There was no correlation between the presence of a related disclosure and the findings of the studies (p = 0.81), although interpretation of this is limited by a small sample size and an overall apparent bias to report favorable studies. Additionally, the blinded reviewers were unable to predict whether a related disclosure was made (p = 0.40). Conclusion: No association existed between the presence of a related disclosure and the results of the studies. While the actual compliance with reporting a potential conflict of interest is unable to be determined, the value amount related to the disclosures made was inadequately reported according to meeting guidelines.

Background: The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions. Methodology/Principal Findings: We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%. Conclusions/Significance: Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport—particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage.

Abnormal cerebral vasculature can be a manifestation of a vascular malformation or a neoplastic process. We report the case of a patient with angiography-negative subarachnoid hemorrhage (SAH) who re-presented 3 years later with a large intraparenchymal hemorrhage. Although imaging following the intraparenchymal hemorrhage was suggestive of arteriovenous malformation, the patient was ultimately found to have an extensive glioblastoma associated with abnormal tumor vasculature. The case emphasizes the need for magnetic resonance imaging to investigate angiography-negative SAH in suspicious cases to rule out occult etiologies, such as neoplasm. We also discuss diagnostic pitfalls when brain tumors are associated with hemorrhage and abnormal vasculature.

MRI is widely used in the assessment of acute ischemic stroke. In particular, it identifies the mismatch between hypoperfused and the permanently damaged tissue, the PWI-DWI mismatch volume. It is used to help triage patients into active or supportive treatment pathways. COMBAT Stroke is an automated software tool for estimating the mismatch volume and ratio based on MRI. Herein, we validate the decision made by the software with actual clinical decision rendered. Furthermore, we evaluate the association between treatment decisions (both automated and actual) and outcomes. COMBAT Stroke was used to determine PWI-DWI mismatch volume and ratio in 228 patients from two European multi-center stroke databases. We performed confusion matrix analysis to summarize the agreement between the automated selection and the clinical decision. Finally, we evaluated the clinical and imaging outcomes of the patients in the four entries of the confusion matrix (true positive, true negative, false negative, and false positive). About 186 of 228 patients with acute stroke underwent thrombolytic treatment, with the remaining 42 receiving supportive treatment only. Selection based on radiographic criteria using COMBAT Stroke classified 142 patients as potential candidates for thrombolytic treatment and 86 for supportive treatment; 60% sensitivity and 29% specificity. The patients deemed eligible for thrombolytic treatment by COMBAT Stroke demonstrated significantly higher rates of compromised tissue salvage, less neurological deficit, and were more likely to experience thrombus dissolving and reestablishment of normal blood flow at 24 h follow-up compared to those who were treated without substantial PWI-DWI mismatch. These results provide evidence that COMBAT Stroke, in addition to clinical assessment, may offer an optimal framework for a fast, efficient, and standardized clinical support tool to select patients for thrombolysis in acute ischemic stroke.

Cerebral arteriovenous malformations (AVMs) are vascular anomalies that carry a high risk of stroke and death. To test potential AVM therapies, a reverse genetics approach was used to model AVMs in zebrafish. Antisense morpholino oligonucleotides were used to knockdown activin receptor-like kinase I (alk1), which encodes a transforming growth factor (TGF)-beta family type I receptor implicated in a subset of human AVMs. Knockdown of alk1 caused a spectrum of morphologic, functional, and molecular defects that resemble those seen in humans with AVMs. It was found that losartan, an angiotensin II receptor antagonist, attenuated abnormal blood vessel morphology and systemic manifestations of high-output arteriovenous shunting in vivo. SMAD1 phosphorylation was significantly decreased in alk1 morphants compared with uninjected organisms (0.189±0.0201, 0.429±0.0164, P=0.0002). After treatment, morphant SMAD1 levels approached uninjected levels (0.326±0.0360, P=0.0355) and were significantly higher than those seen in the morphant-control group (P=0.0294). These data suggest that modulating the BMP signaling pathway with losartan, a drug in widespread clinical use in humans as an antihypertensive, may have the potential to be further evaluated as a therapeutic strategy for patients with AVMs.

The treatment of meningiomas is tailored to their histological grade. While World Health Organization (WHO) grade I lesions can be treated with either surgery or external beam radiation, WHO Grade II and III lesions often require a combination of the two modalities. For these high-grade lesions, conventional external beam radiation is delivered to either the residual tumor or the surgical resection margin. The optimal timing of radiation, either immediately following surgical resection or at the time of recurrence, is yet to be determined. Additionally, another method of radiation delivery, brachytherapy, can be administered locally at the time of surgery for recurrent lesions. Altogether, the complex nature of WHO grade II and III meningiomas requires careful treatment planning and delivery by a multidisciplinary team.

Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish (Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.

Neonatal intensive care has advanced rapidly in the last 40 years, with dramatic decreases in mortality and morbidity; however, for neonatal seizures, neither therapies nor outcomes have changed significantly. Basic and clinical studies indicate that seizures in neonates have long-term neurodevelopmental and psychiatric consequences, highlighting the need for novel pharmacotherapeutics. First-line treatments targeting GABAA receptors, like barbiturates and benzodiazepines, are limited in their efficacy and carry significant risks to the developing brain. Here, we review the use of current GABA agonist therapies for neonatal seizures and suggest other treatment strategies given recent developments in the understanding of disease pathogenesis. One promising avenue is the indirect manipulation of the GABAergic system, via the modulation of neuronal Cl− gradients, by targeting the cation-Cl− cotransporters (NKCC1 and KCC2) or their regulatory signaling molecules. This strategy might yield a novel class of more efficacious anti-epileptics with fewer side effects by specifically addressing disease pathophysiology. Moreover, this strategy may have ramifications for other adult seizure syndromes in which GABA receptor-mediated depolarizations play a pathogenic role, such as temporal lobe epilepsy.

Object: Resolution of syringomyelia is common following hindbrain decompression for Chiari malformation, yet little is known about the kinetics governing this process. The authors sought to establish the volumetric rate of syringomyelia resolution. Methods: A retrospective cohort of patients undergoing hindbrain decompression for a Chiari malformation Type I with preoperative cervical or thoracic syringomyelia was identified. Patients were included in the study if they had at least 3 neuroimaging studies that detailed the entirety of their preoperative syringomyelia over a minimum of 6 months postoperatively. The authors reconstructed the MR images in 3 dimensions and calculated the volume of the syringomyelia. They plotted the syringomyelia volume over time and constructed regression models using the method of least squares. The Akaike information criterion and Bayesian information criterion were used to calculate the relative goodness of fit. The coefficients of determination R2 (unadjusted and adjusted) were calculated to describe the proportion of variability in each individual data set accounted for by the statistical model. Results: Two patients were identified as meeting inclusion criteria. Plots of the least-squares best fit were identified as 4.01459e−0.0180804x and 13.2556e−0.00615859x. Decay of the syringomyelia followed an exponential model in both patients (R2 = 0.989582 and 0.948864). Conclusions: Three-dimensional analysis of syringomyelia resolution over time enables the kinetics to be estimated. This technique is yet to be validated in a large cohort. Because syringomyelia is the final common pathway for a number of different pathological processes, it is possible that this exponential only applies to syringomyelia related to treatment of Chiari malformation Type I.