Recent Publications by CFE Educators

BACKGROUND

This phase 2, randomized, active-controlled, 48-week study assessed the noninferiority of the human immunodeficiency virus (HIV) integrase inhibitor elvitegravir to comparator ritonavir-boosted protease inhibitor (CPI/r) in treatment-experienced subjects.

METHODS

Subjects had HIV RNA levels 1000 copies/mL and 1 protease resistance mutation. Subjects received nucleoside or nucleotide reverse-transcriptase inhibitors (NRTIs) with or without T-20 and either CPI/r or once-daily elvitegravir at a dose of 20 mg, 50 mg, or 125 mg (blinded to dose) with ritonavir. After week 8, the independent data monitoring committee stopped the elvitegravir 20 mg arm and allowed subjects in the elvitegravir 50 mg and 125 mg arms to add protease inhibitors. The primary end point was the time-weighted average change from baseline in HIV RNA level through week 24 (DAVG(24)).

RESULTS

A total of 278 subjects with a median of 11 protease and 3 thymidine analog mutations were randomized and treated. One-half of subjects received NRTIs without expected antiviral activity. Compared with the DAVG(24) for the CPI/r arm (-1.19 log(10) copies/mL), the elvitegravir 50 mg arm was noninferior (-1.44 log(10) copies/mL), and the elvitegravir 125 mg arm was superior (-1.66 log(10) copies/mL; P = .021). Efficacy was impacted by activity of background agents. There was no relationship between elvitegravir dosage and adverse events.

CONCLUSIONS

Elvitegravir was well-tolerated and produced rapid virologic suppression that was durable with active background therapy. Trial registration. ClinicalTrials.gov identifier number: NCT00298350.

BACKGROUND

Surgery is the mainstay of treatment for medullary thyroid cancer (MTC), with long-term patient outcomes associated with adequacy of resection. This study benchmarked national practice patterns against 2009 American Thyroid Association (ATA) guidelines for MTC regarding use of thyroidectomy, lymphadenectomy, radioactive iodine (RAI), and external-beam radiotherapy (EBRT).

METHODS

This is a cross-sectional, retrospective cohort study of MTC patients in the Surveillance, Epidemiology, and End Results Program database, 1973 to 2006. ATA recommendations 61 to 66 (extent of surgery), 85 (RAI), and 93 (EBRT) were analyzed. Outcome of interest was practice accordance with these recommendations. Predictors of accordance were determined and Kaplan-Meier survival analyses were performed.

RESULTS

A total of 2033 patients with MTC were identified. Fifty-nine percent were women; 78% were white. Forty-one percent of patients did not receive appropriate surgical therapy (recommendations 61 to 63). Most patients with distant metastatic disease had less aggressive surgery and more EBRT (P 0.001) (recommendations 64 to 66). Four percent of patients received inappropriate RAI (recommendation 85). Two hundred nine patients had gross incomplete resections, with 33% receiving postoperative EBRT (recommendation 93). Statistically significant predictors of receiving surgery discordant with ATA recommendations in multivariate analysis were patient age >65, female sex, earlier year of diagnosis (1988 to 1997), geographic region, intrathyroidal tumor extent, and tumor size of

CONCLUSIONS

Variation in practice patterns exist in the United States with regard to extent of surgery and lymphadenectomy for MTC. Dissemination of standardized guidelines is important to ensure optimal treatment with less variation in quality of care.

BACKGROUND

Guidelines for triaging patients for cardiac catheterization recommend a risk assessment and noninvasive testing. We determined patterns of noninvasive testing and the diagnostic yield of catheterization among patients with suspected coronary artery disease in a contemporary national sample.

METHODS

From January 2004 through April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, we identified patients without known coronary artery disease who were undergoing elective catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive coronary artery disease, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery or stenosis of 70% or more of the diameter of a major epicardial vessel.

RESULTS

A total of 398,978 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26.0% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive coronary artery disease. No coronary artery disease (defined as 20% stenosis in all vessels) was reported in 39.2% of the patients. Independent predictors of obstructive coronary artery disease included male sex (odds ratio, 2.70; 95% confidence interval [CI], 2.64 to 2.76), older age (odds ratio per 5-year increment, 1.29; 95% CI, 1.28 to 1.30), presence of insulin-dependent diabetes (odds ratio, 2.14; 95% CI, 2.07 to 2.21), and presence of dyslipidemia (odds ratio, 1.62; 95% CI, 1.57 to 1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive coronary artery disease than those who did not undergo any testing (41.0% vs. 35.0%; P0.001; adjusted odds ratio, 1.28; 95% CI, 1.19 to 1.37).

CONCLUSIONS

In this study, slightly more than one third of patients without known disease who underwent elective cardiac catheterization had obstructive coronary artery disease. Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice.

The purpose of this study is to investigate whether specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across different white matter tracts in the normal human brain, and whether the relative strengths of these putative microstructural correlations might reflect phylogenetic and functional similarities between tracts. We performed quantitative DTI fiber tracking on 44 healthy adult volunteers to obtain tract-based measures of mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) from four homologous pairs of neocortical association pathways (arcuate fasciculi, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate fasciculi bilaterally), a homologous pair of limbic association pathways (left and right dorsal cingulum bundles), and a homologous pair of cortical-subcortical projection pathways (left and right corticospinal tracts). From the resulting inter-tract correlation matrices, we show that there are statistically significant correlations of DTI parameters between tracts, and that there are statistically significant variations among these inter-tract correlations. Furthermore, we observe that many, but by no means all, of the strongest correlations are between homologous tracts in the left and right hemispheres. Even among homologous pairs of tracts, there are wide variations in the degree of coupling. Finally, we generate a data-driven hierarchical clustering of the fiber pathways based on pairwise FA correlations to demonstrate that the neocortical association pathways tend to group separately from the limbic pathways at trend-level statistical significance, and that the projection pathways of the left and right corticospinal tracts comprise the most distant outgroup with high confidence (p0.01). Hence, specific patterns of microstructural correlation exist between tracts and may reflect phylogenetic and functional similarities between tracts. The study of these microstructural relationships between white matter pathways might aid research on the genetic basis and on the behavioral effects of axonal connectivity, as well as provide a revealing new perspective with which to investigate neurological and psychiatric disorders.

The distribution of neuroglobin (Ngb) was investigated in the normal rat cochlea using immunohistochemistry and non-radioactive insitu hybridization. We also determined whether chronic, very mild CO exposure at 25ppm in air over the gestational and postnatal period alters the expression of Ngb. Pregnant rats were exposed chronically to CO from gestational days 5-20. Four groups were made as follows: prenatal exposure to CO only; prenatal exposure to CO followed by postnatal exposure from postnatal days (5) P5 to P20; rat pups were exposed to CO from P5 to P20; controls (air without CO). In normal adult rats and control group pups, Ngb was found in spiral ganglia neurons, fibrocytes of the spiral ligament, and supporting cells of the organ of Corti. Ngb was not present in the stria vascularis and the inner and outer hair cells. At P20 Ngb immunoreactivity and transcript expression decreased in spiral ganglia neurons and the spiral ligament in the prenatal and pre- and postnatal groups. This decrease was not observed in the postnatal group. Ngb-IR did not decrease in supporting cells in any CO group. Cytochrome-C immunoreactivity followed Ngb distribution in normal controls and CO treated groups. A decrease in Ngb in spiral ganglia neurons and rat spiral ligament, but not in supporting cells, following CO exposure supports the idea that chronic, mild exposure to CO may create a vulnerable cellular environment predisposed to adverse cochlear development.

Abacavir has been at the center of research and clinical interest in the last two years. The frequency of the associated abacavir hypersensitivity syndrome has decreased substantially since the introduction of routine testing for the HLA-B*5701 allele; the activity of the drug in HIV-infected persons with HIV RNA values more than 100,000 copies/mL has been questioned; the possible increased risk of myocardial infarction after recent exposure to abacavir has been debated; and the drug has been moved from the "recommended" category to the "alternative" category in several guidelines. Still, the drug remains a useful agent in combination with other drugs, including lamivudine, for the treatment of HIV infection. This review will focus on the pharmacokinetics, activity, side effects, and resistance profile of both abacavir and lamivudine, including a thorough review of all of the recent studies relevant to both drugs.

GOALS

This study describes the prevalence of adenomatous polyps at serial follow-up exams after a colonoscopy finding 1 to 2 small tubular adenomas.

STUDY

We conducted a retrospective cohort of patients with 1 to 2 small tubular adenomas on an initial colonoscopy who underwent at least 2 additional surveillance examinations. Our primary outcome was any or advanced adenomas on the third colonoscopy.

RESULTS

Eighty-eight patients met inclusion criteria. At the second and third colonoscopy, 31/88 (35.2%) patients and 26/88 (29.6%) patients had at least 1 adenoma, respectively. Among the 28 patients with 1 to 2 small tubular adenomas on colonoscopy no. 2, the prevalence of any adenomas on colonoscopy no. 3 was 39.3% [95% confidence interval (CI): 21.5%-59.4%]. Among the 56 patients without adenomas at colonoscopy no. 2, the prevalence of any and advanced adenomas on colonoscopy no. 3 was 25% (95% CI: 14.4%-38.4%), and 3.6% (95% CI: 0.4%-12.3%), respectively.

CONCLUSIONS

In patients with 1-2 small tubular adenomas on initial colonoscopy the prevalence of adenomas and advanced lesions on the third colonoscopy remains high even if no adenomas are found on the second colonoscopy.

Chyluria is a rare condition resulting from an abnormal connection between the lymphatic and urinary collecting system and is known to occur after partial nephrectomy. We report 2 cases of chyluria in patients after radiofrequency ablation of renal cell carcinoma diagnosed on surveillance computed tomography.