Recent Publications by CFE Educators

Globally, hepatitis C virus (HCV), the cause of one of the most common infectious diseases, infects approximately 4 million to 5 million Americans with approximately half of infected individuals undiagnosed. Some workplaces screen employees for HCV exposure and other bloodborne pathogens (BBP) after needlestick injuries, but it is not well known whether employers screen employees for HCV without an occupational exposure. New guidelines from the Centers for Disease Control and Prevention (CDC) recommend that all individuals born between 1945 and 1965 should be screened for HCV regardless of risk; this provides an opportunity at the worksite for HCV outreach to employees, dependents, and retirees. To understand this recommendation, the management of HCV in the age of direct-acting antivirals (DAAs) should be reviewed. Now that new DAA treatment can cure HCV, occupational health nurses should identify potential HCV-positive individuals at the worksite via HCV education, screening, testing, and, if positive, linking to specialists for treatment.

In the original publication [1] two author names were missing the middle names. The corrected versions can be found in this Erratum.

BACKGROUND

Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent.

METHODS

Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling.

RESULTS

Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS.

CONCLUSIONS

Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures.

BACKGROUND

In patient-based studies, biomarker data are often subject to left censoring due to the detection limits, or to incomplete sample or data collection. In the context of longitudinal regression analysis, inappropriate handling of these issues could lead to biased parameter estimates. We developed a specific multiple imputation (MI) strategy based on weighted censored quantile regression (CQR) that not only accounts for censoring, but also missing data at early visits when longitudinal biomarker data are modeled as a covariate.

METHODS

We assessed through simulation studies the performances of developed imputation approach by considering various scenarios of covariance structures of longitudinal data and levels of censoring. We also illustrated the application of the proposed method to the Prospective Study of Outcomes in Ankylosing spondylitis (AS) (PSOAS) data to address the issues of censored or missing C-reactive protein (CRP) level at early visits for a group of patients.

RESULTS

Our findings from simulation studies indicated that the proposed method performs better than other MI methods by having a higher relative efficiency. We also found that our approach is not sensitive to the choice of covariance structure as compared to other methods that assume normality of biomarker data. The analysis results of PSOAS data from the imputed CRP levels based on our method suggested that higher CRP is significantly associated with radiographic damage, while those from other methods did not result in a significant association.

CONCLUSION

The MI based on weighted CQR offers a more valid statistical approach to evaluate a biomarker of disease in the presence of both issues with censoring and missing data in early visits.

BACKGROUND

Electronic medical records (EMR) data are increasingly used in research, but no studies have yet evaluated similarity between EMR and research-quality data and between characteristics of an EMR multiple sclerosis (MS) population and known natural MS history.

OBJECTIVES

To (1) identify MS patients in an EMR system and extract clinical data, (2) compare EMR-extracted data with gold-standard research data, and (3) compare EMR MS population characteristics to expected MS natural history.

METHODS

Algorithms were implemented to identify MS patients from the University of California San Francisco EMR, de-identify the data and extract clinical variables. EMR-extracted data were compared to research cohort data in a subset of patients.

RESULTS

We identified 4142 MS patients via search of the EMR and extracted their clinical data with good accuracy. EMR and research values showed good concordance for Expanded Disability Status Scale (EDSS), timed-25-foot walk, and subtype. We replicated several expected MS epidemiological features from MS natural history including higher EDSS for progressive versus relapsing-remitting patients and for male versus female patients and increased EDSS with age at examination and disease duration.

CONCLUSION

Large real-world cohorts algorithmically extracted from the EMR can expand opportunities for MS clinical research.

BACKGROUND AND OBJECTIVES

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.

METHODS

We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).

RESULTS

Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P  0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.

CONCLUSIONS

Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.

BACKGROUND/OBJECTIVES

Childhood-onset psoriasis is a common skin disorder that has recently received increasing attention, particularly because of its significant medical, social, financial, and psychological burdens and its associated comorbidities. With limited data available and lack of standardized management guidelines for pediatric psoriasis, an expert panel desired to provide an updated critical overview and practical guidance for management of the affected population.

METHODS

A panel of pediatric dermatologists with extensive experience in pediatric psoriasis defined and prioritized a core set of topics, performed an English-language literature review, prepared critical evaluations and presentations of topic areas, and carried out a consensus meeting and follow-up consensus manuscript.

RESULTS

The summation of evolving perspectives in pediatric psoriasis includes epidemiology and natural history of the disease, precipitating factors and comorbidities, quality of life and burden of disease, clinical features and disease presentation, differential diagnosis, pathogenesis and treatment, including topical, photo, and systemic therapies.

CONCLUSION

Pediatric psoriasis is an important immune-mediated inflammatory skin disease with potential for significant impact on affected individuals and their caregivers. Current state-of-the-art care is based primarily on experience and expert consensus, but pediatric data are accumulating and therapeutic options are rapidly evolving.

OBJECTIVES

Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use.

STUDY DESIGN

This is a retrospective review and projected cost savings analysis.

METHODS

Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670.

RESULTS

A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually.

CONCLUSIONS

Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness.

OBJECTIVE

To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes).

APPROACH AND RESULTS

AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; =0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (β=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; 0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (β=0.33; 95% confidence interval, 0.15-0.52; 0.001).

CONCLUSIONS

Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to 70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden.