Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record.

Large-scale DNA databanks linked to electronic medical record (EMR) systems have been proposed as an approach for rapidly generating large, diverse cohorts for discovery and replication of genotype-phenotype associations. However, the extent to which such resources are capable of delivering on this promise is unknown. We studied whether an EMR-linked DNA biorepository can be used to detect known genotype-phenotype associations for five diseases. Twenty-one SNPs previously implicated as common variants predisposing to atrial fibrillation, Crohn disease, multiple sclerosis, rheumatoid arthritis, or type 2 diabetes were successfully genotyped in 9483 samples accrued over 4 mo into BioVU, the Vanderbilt University Medical Center DNA biobank. Previously reported odds ratios (OR(PR)) ranged from 1.14 to 2.36. For each phenotype, natural language processing techniques and billing-code queries were used to identify cases (n = 70-698) and controls (n = 808-3818) from deidentified health records. Each of the 21 tests of association yielded point estimates in the expected direction. Previous genotype-phenotype associations were replicated (p < 0.05) in 8/14 cases when the OR(PR) was > 1.25, and in 0/7 with lower OR(PR). Statistically significant associations were detected in all analyses that were adequately powered. In each of the five diseases studied, at least one previously reported association was replicated. These data demonstrate that phenotypes representing clinical diagnoses can be extracted from EMR systems, and they support the use of DNA resources coupled to EMR systems as tools for rapid generation of large data sets required for replication of associations found in research cohorts and for discovery in genome science.

Recovery following propofol-associated brugada electrocardiogram.

Brugada syndrome is a genetic disorder associated with an increased risk of sudden cardiac death that has typical electrocardiographic (ECG) patterns. Recently, there have been reports of Brugada ECG patterns seen in critically ill patients who received propofol,(1) and this pattern was associated with a very high imminent mortality. We report a case in which a critically ill patient developed a Brugada ECG pattern following high-dose propofol infusion. Once the ECG pattern was recognized, the propofol was discontinued and the ECG pattern resolved, and the patient was discharged home with no arrhythmic sequelae.

Heart block and cardiac embolization of fractured inferior vena cava filter.

OBJECTIVE: A 66-year-old man underwent a placement of an inferior vena cava filter before a gastric surgery 9 years prior, presented to the emergency room with a complete atrioventricular block. Chest x-ray and transthoracic echocardiogram showed struts migrating to right ventricle with tricuspid regurgitation. Cardiothoracic surgery was consulted and declined an open surgical intervention due to the location of the embolized fragments and the patient's overall condition. It was also felt that the fragments had migrated chronically and were adhered to the cardiac structures. METHODS: The patient underwent a dual-chamber permanent pacemaker implantation. Post-implant fluoroscopy showed no displacement of the inferior vena cava filter struts due to the pacemaker leads indicating that the filter fracture had likely been a chronic process. RESULTS: This case highlights a rare combination of complications related to inferior vena cava filter fractures and the importance of assessing for such fractures in chronic placements. Inferior vena cava filter placement for a duration greater than 1 month can be associated with filter fractures and strut migration which may lead to, although rare, serious or fatal complications such as complete atrioventricular conduction system disruption and valvular damage including significant tricuspid regurgitation. CONCLUSIONS: Assessing for inferior vena cava filter fractures in chronic filter placement is important to avoid such complications. When possible, retrieval of the filter should be considered in all patients outside the acute setting in order to avoid filter-related complications. Filter retrieval rates remain low even when a retrievable filter is in place and the patient no longer has a contraindication to anticoagulation.

Use of diagnostic testing in the emergency department for patients presenting with non-traumatic abdominal pain.

The objective of the study was to measure the utilization and diagnostic value of tests used in the Emergency Department (ED) on patients with undifferentiated non-traumatic abdominal or flank pain. Specific goals were to measure how often these tests led to changes in diagnosis or disposition, which tests were most commonly used, and which tests providers considered most helpful. We conducted a pilot single-center, prospective descriptive study, enrolling all eligible adult patients who presented to our ED with non-traumatic abdominal or flank pain during defined hours of our intake period. Based on serial provider interviews pre- and post-testing, we measured the frequency of change of most likely diagnosis and disposition, which tests were performed, and the provider-perceived value of tests. We enrolled 124 subjects with a mean age of 44 years; 27% were admitted. Testing led to a change in most likely diagnosis in 37% of subjects, and in disposition in 41%. Frequency of diagnostic test use varied from a high of 93% for CBC to 6% for a blood or urine culture. Overall, 65% of patients had at least one imaging study performed, and 39% had an abdominal/pelvic computed tomography (CT) scan. Over all subjects, providers identified the most useful tests as the CT scan (31%) and urinalysis (17%). In conclusion, among ED patients who presented with non-traumatic abdominal or flank pain to one academic center, the pre-test most likely diagnosis and disposition were changed based on the ED evaluation in over one-third of subjects. Almost all received blood tests and two-thirds received one or more imaging studies. Based on providers' subjective opinions, the most valuable tests were the abdomino/pelvic CT scan and the urinalysis.

Management of ventricular tachycardia in patients with structural heart disease.

Patients with structural heart disease and ventricular tachycardia (VT) can be difficult to manage clinically. Many treatment options are available, but no single approach can be applied to every patient. This review aims to discuss the current options available for the management of this population. VT can be associated with cardiomyopathy of any etiology, both ischemic and nonischemic. Antiarrhythmic drugs have not been shown to decrease mortality in this patient population, but they can help reduce episodes. While the advent of the implantable cardioverter-defibrillator has revolutionized the treatment of VT, patients with recurrent shocks for VT have high morbidity and mortality. The development of catheter ablation over the past few decades has greatly aided the ability to control VT in these patients. The approach to patients with VT and structural heart disease is multifaceted. Often, a combination of therapeutic techniques is required to obtain the best result.

The accuracy and completeness of data collected by prospective and retrospective methods.

OBJECTIVES: To describe and test a model that compares the accuracy of data gathered prospectively versus retrospectively among adult emergency department patients admitted with chest pain. METHODS: The authors developed a model of information flow from subject to medical record to the clinical study case report form, based on a literature review. To test this model, a bidirectional (prospective and retrospective) study was conducted, enrolling all eligible adult patients who were admitted with a chief complaint of chest pain. The authors interviewed patients in the emergency department to determine their chest pain history and established a prospective database; this was considered the criterion standard. Then, patient medical records were reviewed to determine the accuracy and completeness of the information available through a retrospective medical record review. RESULTS: The model described applies the concepts of reliability and validity to information passed on by the study subject, the clinician, and the medical record abstractor. This study was comprised of 104 subjects, of which 63% were men and the median age was 63 years. Subjects were uncertain of responses for 0-8% of questions and responded differently upon reinterview for subsets of questions 0-30% of the time. The sensitivity of the medical record for risk factors for coronary artery disease was 0.77 to 0.93. Among the 88 subjects (85%) who indicated that their chest pain was substernal or left chest, the medical record described this location in 44%. Timing of the chest pain was the most difficult item to accurately capture from the medical record. CONCLUSIONS: Information obtained retrospectively from the abstraction of medical records is measurably less accurate than information obtained prospectively from research subjects. For certain items, more than half of the information is not available. This loss of information is related to the data types included in the study and by the assumptions that a researcher performing a retrospective study makes about implied versus explicitly stated responses. A model of information flow that incorporates the concepts of reliability and validity can be used to measure some of the loss of information that occurs at each step along the way from subject to clinician to medical record abstractor.

The relation among spinal geometry on MRI, paraspinal electromyographic abnormalities, and age in persons referred for electrodiagnostic testing of low back symptoms.

STUDY DESIGN: A retrospective EMG study with blinded radiologic measurement was conducted. OBJECTIVE: To determine the relation among spinal measurements on MRI, paraspinal denervation, and age in patients referred for electrodiagnostic and radiologic evaluation of low back pain. SUMMARY OF BACKGROUND DATA: Spinal pathology, including disc herniation and spinal stenosis, can cause denervation of the paraspinal muscles. Various mechanisms including direct compression, inflammation, vascular compromise, and mechanical stretch of the posterior primary ramus may play a role in denervation. The relation between the amount of denervation and the size of the spinal canal can assist in understanding the pathophysiology of back pain. Since paraspinal denervation may increase with age in asymptomatic persons, age is an important covariable. METHODS: At a university hospital, 44 patients referred to undergo both electrodiagnostic evaluation and MRI for low back pain were studied. The study investigated the relation among the following: 1) axial MRI spinal measurements (canal transverse diameter, anteroposterior diameter, and area; thecal sac anteroposterior diameter and area; and the radiologist's overall impression at each level) and denervation measurements in terms of scores on the MiniPM, a quantified needle electromyographic measure of paraspinal denervation; 2) various models of multilevel spinal compression (smallest, smallest two, and average spinal levels for each measurement) and MiniPM scores; and 3) MRI spinal canal measurements and age. RESULTS: Although individual MRI measurements and combinations of measurements did not relate to MiniPM scores, the radiologist's impression was significantly related. The "smallest two" levels measurement had the strongest relation (r = 0.400; P < 0.007). Age related to the MiniPM scores (P = 0.004) and radiologic impression (P = 0.031). A regression suggested that MiniPM was an independent predictor of age. CONCLUSIONS: The radiologist's overall impression is more accurate than axial image measurements in predicting paraspinal denervation. A combination score of the smallest two levels is the most accurate, perhaps relating to the vascular pathophysiology of stenosis. There is more denervation with increasing age in this symptomatic population.

Duration of symptoms and follow-up patterns of patients discharged from the emergency department after presenting with abdominal or flank pain.

BACKGROUND: Little is known about the duration of symptoms and follow-up patterns of patients seen in emergency departments for abdominal or flank pain. OBJECTIVE: We aimed to measure the duration of symptoms and follow-up rate of patients discharged home from the emergency department after presenting with non-traumatic abdominal or flank pain. METHODS: We conducted a single-centre, prospective descriptive study of adult patients who presented to our emergency department with non-traumatic abdominal or flank pain and were discharged from the emergency department. We gathered clinical data during the index emergency department visit and conducted telephone interviews of subjects 2-5 weeks later. RESULTS: We reached 63 of 90 subjects (70%). The median duration of pain was 3 days after the emergency department visit. During the follow-up period, only 41% had followed-up with their family physician or primary care provider, although an additional 21% had planned to. Persistence of symptoms was common in the 37% of subjects who did not follow-up. CONCLUSION: Of subjects discharged from the emergency department after visits for non-traumatic abdominal or flank pain, most improve within several days. Fewer than half follow-up with a family practitioner or a primary care provider. Emergency department revisits are uncommon and often for unrelated problems.