Faculty Bibliography

Introduction: Our study assesses the incidence of TB, serious bacterial infection (SBI) and lymphoma in rheumatoid arthritis (RA) patients who received anti-TNF therapy and non-biologic treatment in Taiwan, as limited data exists. Methods: National Health Insurance Research Database data (1999-2009, covering 99.9% of the Taiwan population) were analyzed.1 Eligible patients (>18 years) were required to have: >2 recorded RA diagnostic codes (ICD-9 "714.0x"), a catastrophic illness card and had received traditional Disease Modifying Anti-Rheumatic Drugs (tDMARDs) or biologic DMARDs (bDMARDs). Patients with prior TB/SBI/lymphoma were excluded. Propensity scoring matched patients received tDMARDs and bDMARDs 2:1, adjusting for age, gender, disease severity, and co-morbidities. Incidence rates (IR) of TB, SBI and lymphoma were defined: (number of events/total patient exposure years); ratios (IRRs) were calculated across therapies. Results: Of 34 947 eligible patients (mean age 60.6 years, 79% female, mean RA duration 7.6 years), the bDMARDs group had higher incidence of TB, SBI and lymphoma than the tDMARDs only group (Table). Within the bDMARDs group 3109 patients (77.1%) were treated solely with ETN and 865 patients (21.4%) solely with ADA. Patients receiving ADA had higher rates of TB, SBI and lymphoma, which also occurred earlier, than those receiving ETN. All stated differences were statistically significant, except bMARDs versus tMARDs SBI and ADA versus ETN lymphoma incidence (Table). Conclusions: bDMARDs increase the risk of TB, SBI and lymphoma, risks to differing extents: risk was lower with ETN than ADA. (Table Presented)

To use optical coherence tomography (OCT) and contrast letter acuity to characterize vision loss in Friedreich ataxia (FRDA). High- and low-contrast letter acuity and neurological measures were assessed in 507 patients with FRDA. In addition, OCT was performed on 63 FRDA patients to evaluate retinal nerve fiber layer (RNFL) and macular thickness. Both OCT and acuity measures were analyzed in relation to genetic severity, neurologic function, and other disease features. High- and low-contrast letter acuity was significantly predicted by age and GAA repeat length, and highly correlated with neurological outcomes. When tested by OCT, 52.7 % of eyes (n = 110) had RNFL thickness values below the fifth percentile for age-matched controls. RNFL thickness was significantly lowest for those with worse scores on the Friedreich ataxia rating scale (FARS), worse performance measure composite Z 2 scores, and lower scores for high- and low-contrast acuity. In linear regression analysis, GAA repeat length and age independently predicted RNFL thickness. In a subcohort of participants, 21 % of eyes from adult subjects (n = 29 eyes) had macular thickness values below the first percentile for age-matched controls, suggesting that macular abnormalities can also be present in FRDA. Low-contrast acuity and RNFL thickness capture visual and neurologic function in FRDA, and reflect genetic severity and disease progression independently. This suggests that such measures are useful markers of neurologic progression in FRDA.

Colorectal cancer (CRC) can be effectively prevented via screening colonoscopy, yet adherence rates remain low among Latinos. Interventions targeting individual and cultural barriers to screening are needed. We developed an educational brochure to target these barriers faced by a diverse Latino population. The objective was to evaluate the responses of the target population to the culturally and theoretically informed brochure through community member focus groups. Facilitators conducted six focus groups, stratified by gender, language, and prior colonoscopy experience. Topics included: brochure content and layout, cancer knowledge, and CRC screening determinants. Focus groups documented community members' responses to the brochure's overall message and its informational and visual components. Changes to wording, visual aids, and content were suggested to make the brochure culturally more acceptable. Results indicated relevance of the theoretically and culturally guided approach to the development of the brochure leading to refinement of its content and design.

Anomalies of the membranous portion of the interventricular septum include perimembranous ventricular septal defect and/or membranous septal aneurysm (MSA). In congenitally corrected transposition of the great arteries (L-TGA in sinus solitus), the combination of ventricular inversion and arterial transposition creates a unique anatomic substrate that fosters subpulmonic left ventricular outflow tract obstruction by an MSA. The combination of an L-TGA with subpulmonic obstruction by an MSA is referred to as the windsock syndrome. We report a case of windsock syndrome in a 25-year-old man which is to our knowledge the first three-dimensional echocardiographic description of this congenital entity.

Staphylococcus aureus is a well-recognized, clinically important cause of nosocomial infections, and as such, a vaccine to prevent S. aureus infections would be an important achievement. A Phase IIB/III study of V710, a vaccine containing iron-regulated surface determinant B (IsdB), demonstrated significant sero-conversion rates in cardiovascular surgery patients following a single pre-surgery immunization. However, the vaccine was not efficacious in preventing bacteremia or deep sternal wound infection post-surgery, thus raising the possibility that IsdB might not be available for immune recognition during infection. The purpose of the work described herein was to evaluate and quantify the naturally occurring anti-IsdB levels at baseline and over time during infection, to understand whether IsdB is expressed during a S. aureus infection in hospitalized non-vaccinated patients. We evaluated baseline and follow-up titers in 3 populations: (1) healthy subjects, (2) hospitalized patients with non-S. aureus infections, and (3) hospitalized patients with S. aureus infections. Baseline anti-IsdB levels generally overlapped between the 3 groups, but were highly variable within each group. In healthy subjects, baseline and follow-up levels were highly correlated (Spearman's rho = 0.93), and the geometric mean fold-rise (GMFR) in anti-IsdB levels between study entry and last value was 0.9-fold (95% confidence interval (CI): 0.8 to 1.0 ; p = 0.09), showing no trend over time. The convalescent GMFR in anti-IsdB levels from baseline was 1.7-fold (95% CI: 1.3 to 2.2, p = 0.0008) during S. aureus infection, significantly different from the 1.0-fold GMFR (95% CI: 0.9-1.2, p = 0.60) in non-S. aureus infection, p = 0.005. Additionally, S. aureus isolates (51) obtained from the hospitalized patient group expressed the IsdB protein in vitro. Collectively, these data suggest that IsdB expression levels rise substantially following infection with S. aureus, but not with other pathogens, and IsdB is likely well-conserved across S. aureus strains.

BACKGROUND:As the Veterans Health Administration (VHA) reorganizes providers into the patient-centered medical home, questions remain whether this model of care can demonstrate improved patient outcomes and cost savings. OBJECTIVE:We measured adoption of medical home features by VHA primary care clinics prior to widespread implementation of the patient-centered medical home and examined if they were associated with lower risk and costs of potentially avoidable hospitalizations. DESIGN/METHODS:Secondary patient data was linked to clinic administrative and survey data. Patient and clinic factors in the baseline year (FY2009) were used to predict patient outcomes in the follow-up year. PARTICIPANTS/METHODS:2,853,030 patients from 814 VHA primary care clinics MAIN MEASURES/METHODS:Patient outcomes were measured by hospitalizations for an ambulatory care sensitive condition (ACSC) and their costs and identified through diagnosis and procedure codes from inpatient records. Clinic adoption of medical home features was obtained from the American College of Physicians Medical Home Builder®. KEY RESULTS/RESULTS:The overall mean home builder score in the study clinics was 88 (SD = 13) or 69%. In adjusted analyses an increase of 10 points in the medical home adoption score in a clinic decreased the odds of an ACSC hospitalization for patients by 3% (P = 0.032). By component, higher access and scheduling (P = 0.004) and care coordination and transitions (P = 0.020) component scores were related to lower risk of an ACSC hospitalization, and higher population management was related to higher risk (P = 0.023). Total medical home features was not related to ACSC hospitalization costs among patients with at least one (P = 0.074). CONCLUSION/CONCLUSIONS:Greater adoption of medical home features by VHA primary care clinics was found to be significantly associated with lower risk of avoidable hospitalizations with access and scheduling and care coordination/transitions in care as key factors.

Classically derived estimates of heritability from twin models have been plagued by the possibility of genetic-environmental covariance. Survey questions that attempt to measure directly the extent to which more genetically similar kin (such as monozygotic twins) also share more similar environmental conditions represent poor attempts to gauge a complex underlying phenomenon of GE-covariance. The present study exploits a natural experiment to address this issue: Self-misperception of twin zygosity in the National Longitudinal Survey of Adolescent Health (Add Health). Such twins were reared under one "environmental regime of similarity" while genetically belonging to another group, reversing the typical GE-covariance and allowing bounded estimates of heritability for a range of outcomes. In addition, we examine twins who were initially misclassified by survey assignment--a stricter standard--in three datasets: Add Health, the Minnesota Twin Family Study and the Child and Adolescent Twin Study in Sweden. Results are similar across approaches and datasets and largely support the validity of the equal environments assumption.