University of Southern California
Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy
Redesigning Lives Globally
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Faculty

Cheryl Vigen PhD

Cheryl Vigen

Research Assistant Professor

Room: CHP 101J
Phone: (323) 442-2749
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Biography

Cheryl Vigen has served as a teaching and research assistant at the Keck School of Medicine of USC, and currently teaches biostatistics in the Department of Preventive Medicine. Dr. Vigen has been a research investigator on projects in such diverse areas as atherosclerosis, HIV, hematology, Alzheimer's Disease, cancer and ophthalmology. Within the Division, Dr. Vigen is currently working on the Pressure Ulcer Prevention in SCI (PUPS) research study and the USC Well Elderly Study, and is available to consult with other researchers regarding study design, data management and statistical analysis.

Education

Doctor of Philosophy (PhD) in Epidemiology
University of Southern California
2007

Master of Science (MS) in Biostatistics
University of Southern California
2003

Master of Science (MS) in Mathematics
University Illinois at Chicago
1979

Bachelor of Arts (BA) in Mathematics
University of California, San Diego
1977

Publications

Journal Articles

Kwan, M. L., John, E. M., Caan, B. J., Lee, V. S., Bernstein, L., Cheng, I., Gomez, S. L., Henderson, B. E., Keegan, T. H., Kurian, A. W., Lu, Y., Monroe, K. R., Roh, J. M., Shariff-Marco, S., Sposto, R., Vigen, C., & Wu, A. H. (2014). Obesity and mortality after breast cancer by race/ethnicity: The California Breast Cancer Survivorship Consortium. American Journal of Epidemiology, 179, 95-111. doi:10.1093/aje/kwt233. Link to full text Abstract →← Abstract 

We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI >18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI > 40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups.

Carlson, M., Jackson, J., Mandel, D., Blanchard, J., Holguin, J., Lai, M. Y., Marterella, A., Vigen, C., Gleason, S., Lam, C., Azen, S., & Clark, F. (2014). Predictors of retention among African American and Hispanic older adult research participants in the Well Elderly 2 randomized controlled trial. Journal of Applied Gerontology, 33, 357-382. doi:10.1177/0733464812471444. Link to full text Abstract →← Abstract 

The purpose of this study was to document predictors of long-term retention among minority participants in the Well Elderly 2 Study, a randomized controlled trial of a lifestyle intervention for community-dwelling older adults. The primary sample included 149 African American and 92 Hispanic men and women aged 60 to 95 years, recruited at senior activity centers and senior residences. Chi-square and logistic regression procedures were undertaken to examine study-based, psychosocial and health-related predictors of retention at 18 months following study entry. For both African Americans and Hispanics, intervention adherence was the strongest predictor. Retention was also related to high active coping and average (vs. high or low) levels of activity participation among African Americans and high social network strength among Hispanics. The results suggest that improved knowledge of the predictors of retention among minority elders can spawn new retention strategies that can be applied at individual, subgroup, and sample-wide levels.

Pyatak, E. A., Sequeira, P. A., Whittemore, R., Vigen, C. P., Peters, A. L., & Weigensberg, M. J. (2014). Challenges contributing to disrupted transition from paediatric to adult diabetes care in young adults with Type 1 diabetes. Diabetic Medicine, Advance online publication. doi:10.1111/dme.12485. Link to full text Abstract →← Abstract 

AIM: To examine challenges contributing to disruptions in care during the transition from paediatric to adult care among young adults with Type 1 diabetes who are primarily in ethnic minority groups and have low socio-economic status.
 
METHODS: Participants (n = 20) were newly enrolled patients in a transition clinic for young adults with Type 1 diabetes with a history of loss to medical follow-up. Participants completed qualitative semi-structured interviews detailing their transition experiences in addition to demographic, HbA1c and psychosocial measures. Descriptive statistics were completed for quantitative data, and narrative thematic analysis of interviews was used to identify common themes. A mixed-method analysis was used to identify the associations between stressors identified in interviews and clinical and psychosocial variables.
 
RESULTS: Three categories of challenges contributing to loss to follow-up were identified: psychosocial challenges, health provider and health system challenges and developmental challenges. Participants experienced a high degree of stressful life circumstances which were associated with higher HbA1c (r = 0.60, P = 0.005), longer duration of loss to follow-up (r = 0.51, P = 0.02), greater emergency department utilization (r = 0.45, P = 0.05), and lower life satisfaction (r = -0.62, P = 0.003).
 
CONCLUSIONS: A confluence of challenges, including stressful life circumstances, healthcare system barriers and the developmental trajectory of young adulthood, contributes to a high risk of loss to follow-up and poor health in this population of young adults with Type 1 diabetes. An integrated approach to transition addressing medical and psychosocial needs may facilitate improved follow-up and health outcomes in clinical settings.

Clark, F., Pyatak, E. A., Carlson, M., Blanche, E. I., Vigen, C., Hay, J., Mallinson, T., Blanchard, J., Unger, J. B., Garber, S. L., Diaz, J., Florindez, L. I., Atkins, M., Rubayi, S., & Azen, S. P. (2014). Implementing trials of complex interventions in community settings: The USC-Rancho Los Amigos Pressure Ulcer Prevention Study (PUPS). Clinical Trials, 11, 218-229. doi:10.1177/1740774514521904. Link to full text Abstract →← Abstract 

BACKGROUND: Randomized trials of complex, non-pharmacologic interventions implemented in home and community settings, such as the University of Southern California (USC)-Rancho Los Amigos National Rehabilitation Center (RLANRC) Pressure Ulcer Prevention Study (PUPS), present unique challenges with respect to (1) participant recruitment and retention, (2) intervention delivery and fidelity, (3) randomization and assessment, and (4) potential inadvertent treatment effects.
 
PURPOSE: We describe the methods employed to address the challenges confronted in implementing PUPS. In this randomized controlled trial, we are assessing the efficacy of a complex, preventive intervention in reducing the incidence of, and costs associated with, the development of medically serious pressure ulcers in people with spinal cord injury.
 
METHODS: Individuals with spinal cord injury recruited from RLANRC were assigned to either a 12-month preventive intervention group or a standard care control group. The primary outcome is the incidence of serious pressure ulcers with secondary endpoints including ulcer-related surgeries, medical treatment costs, and quality of life. These outcomes are assessed at 12 and 24 months after randomization. Additionally, we are studying the mediating mechanisms that account for intervention outcomes.
 
RESULTS: PUPS has been successfully implemented, including recruitment of the target sample size of 170 participants, assurance of the integrity of intervention protocol delivery with an average 90% treatment adherence rate, and enactment of the assessment plan. However, implementation has been replete with challenges. To meet recruitment goals, we instituted a five-pronged approach customized for an underserved, ethnically diverse population. In intervention delivery, we increased staff time to overcome economic and cultural barriers to retention and adherence. To ensure treatment fidelity and replicability, we monitored intervention protocol delivery in accordance with a rigorous plan. Finally, we have overcome unanticipated assessment and design concerns related to (1) determining pressure ulcer incidence/severity, (2) randomization imbalance, and (3) inadvertent potential control group contamination.
 
LIMITATIONS: We have addressed the most daunting challenges encountered in the recruitment, assessment, and intervention phases of PUPS. Some challenges and solutions may not apply to trials conducted in other settings.
 
CONCLUSIONS: Overcoming challenges has required a multifaceted approach incorporating individualization, flexibility, and persistence, as well as the ability to implement needed mid-course corrections.

Wu, A. H., Gomez, S. L., Vigen, C., Kwan, M. L., Keegan, T. H., Lu, Y., Shariff-Marco, S., Monroe, K. R., Kurian, A. W., Cheng, I., Caan, B. J., Lee, V. S., Roh, J. M., Sullivan-Halley, J., Henderson, B. E., Bernstein, L., John, E. M., & Sposto, R. (2013). The California Breast Cancer Survivorship Consortium (CBCSC): Prognostic factors associated with racial/ethnic differences in breast cancer survival. Cancer Causes & Control, 24, 1821-1836. doi:10.1007/s10552-013-0260-7. Link to full text Abstract →← Abstract 

Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95% CI 0.97-1.33) for African Americans, 0.84 (95% CI 0.70-1.00) for Latinas, and 0.60 (95% CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.

Wu, A. H., Lee, E., & Vigen, C. (2013). Soy isoflavones and breast cancer. American Society of Clinical Oncology Educational Book, 2013, 102-106. doi:10.1200/EdBook_AM.2013.33.102. Link to full text Abstract →← Abstract 

The soybean and its products have been a staple in the Asian diet for centuries. Although intake of soy remains low in most Western populations, the use of soy isoflavone supplements has become commonplace, and an increasing number of food products contain soy ingredients. This review will present an updated summary of the observational results on soy isoflavones and risk of breast cancer development and outcome in patients with breast cancer. Results from soy intervention studies that have specifically examined the effects of soy on breast cell proliferation in breast tissues will be discussed. We will conclude by highlighting gaps in our knowledge on soy and breast cancer and issues that need to be addressed in future studies.

Baydur, A., Vigen, C., & Chen, Z. (2012). Expiratory flow limitation in obstructive sleep apnea and COPD: A quantitative method to detect pattern differences using the negative expiratory pressure technique. Open Respiratory Medicine Journal, 6, 111-120. doi:10.2174/1874306401206010111. Link to full text Abstract →← Abstract 

BACKGROUND: Expiratory flow limitation (EFL), determined by the negative expiratory pressure (NEP) technique, can exhibit overlapping patterns in COPD, obstructive sleep apnea (OSA) and non-OSA obesity. We assessed the ability of a quantitative method to assess EFL to discriminate COPD from obese and OSA patients during NEP (-2 to -3 cm H(2)O) testing.
 
METHODS: EFL was quantified by measuring the area under the preceding control tidal breath (Vt) subtended by the NEP curve (%AUC). To quantify mean lost flow, the ratio of %AUC to percentage of control Vt over which EFL occurred (%EFL) (= %AUC/%EFL) was computed. Percent EFL, %AUC, and %AUC/%EFL was compared in 42 patients with COPD, 28 obese subjects without OSA, 50 with OSA (26 mild-moderate, 24 severe) and 19 control subjects, in seated and supine postures.
 
RESULTS: All patients exhibited %EFL values significantly higher than control subjects, corrected for age and gender (ANOVA). All but the COPD group exhibited higher %EFL while supine, but not %AUC or %AUC/%EFL. Amongst seated subjects, %EFL was highest in COPD, and amongst supine groups, it was greatest in OSA and COPD. %AUC/%EFL was significantly higher in mild-moderate OSA than in COPD only while seated. %AUC or %AUC/%EFL did not discriminate amongst other cohorts in either posture.
 
CONCLUSIONS: Computation of %EFL helps distinguish EFL in COPD, obese and OSA patients from those of control subjects. Computation of %AUC and %AUC/%EFL is useful in determining the magnitude of extrathoracic FL in individuals with obesity and OSA, but does not distinguish between cohorts.

Grimminger, P. P., Shi, M., Barrett, C., Lebwohl, D., Danenberg, K. D., Brabender, J., Vigen, C. L., Danenberg, P. V., Winder, T., & Lenz, H. J. (2012). TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials. The Pharmacogenomics Journal, 12, 404-411. doi:10.1038/tpj.2011.29. Link to full text Abstract →← Abstract 

To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases) or CONFIRM-2, mRNA was isolated of microdissected formalin-fixed paraffin-embedded samples and quantitated using TaqMan-based technology. Existing TS and ERCC-1 cutoff levels were tested for their prognostic value in first-line and second-line therapy. TS expression was associated with overall survival (OS) in first-line, but not second-line therapy. ERCC-1 was associated with OS in patients treated with first-line and second-line FOLFOX4. In first-line FOLFOX4, combination of high TS and/or high ERCC-1 was associated with shorter OS. A correlation was observed between ERCC-1 expression and benefit from PTK/ZK+FOLFOX4 treatment. TS and ERCC-1 expression is associated with clinical outcome in mCRC. Baseline TS and ERCC-1 levels may allow the selection of patients who benefit from FOLFOX4 chemotherapy.

Wu, A. H., Vigen, C., Razavi, P., Tseng, C. C., & Stancyzk, F. Z. (2012). Alcohol and breast cancer risk among Asian-American women in Los Angeles County. Breast Cancer Research: BCR, 14, R151. doi:10.1186/bcr3363. Link to full text Abstract →← Abstract 

INTRODUCTION: The role of alcohol and breast cancer risk in Asians has not been well studied. Recent studies suggest that even moderate alcohol intake may be associated with an increase in breast cancer risk, and this may be particularly relevant as alcohol intake is traditionally low among Asians.
 
METHODS: We investigated the association between lifetime alcohol intake (including frequency, quantity, duration, timing, and beverage type) and breast cancer in a population-based case-control study of 2,229 Asian Americans diagnosed with incident breast cancer and 2,002 matched control women in Los Angeles County. Additionally, we examined the relation between current alcohol intake and serum concentrations of sex-hormones and growth factors in a subset of postmenopausal control women.
 
RESULTS: Regular lifetime alcohol intake was significantly higher in US-born than non-US-born Asian Americans (P < 0.001) and almost twice as common in Japanese- than in Chinese- and Filipino-Americans (P < 0.001). Breast cancer risk increased with increasing alcohol intake among US-born Asian Americans; the odds ratios (ORs) per 5 grams per day and per 10 years of drinking were 1.21 (95% confidence interval (CI) 1.00 to 1.45) and 1.12 (95% CI, 0.98 to 1.28), respectively. Regular alcohol intake was a significant risk factor for Japanese-, but not for Chinese- and Filipino-Americans. Current consumers compared with nondrinkers showed lower concentrations of insulin-like growth factor binding protein 3 (P = 0.03) and nonsignificantly higher concentrations of estrone and androgens.
 
CONCLUSIONS: Regular lifetime alcohol intake is a significant breast cancer risk factor in US-born Asian Americans and Japanese Americans, emphasizing the importance of this modifiable lifestyle factor in traditionally low-risk populations.

McDonald, A. E., & Vigen, C. (2012). Reliability and validity of the McDonald Play Inventory. American Journal of Occupational Therapy, 66, e52-e60. doi:10.5014/ajot.2012.002493. Link to full text Abstract →← Abstract 

OBJECTIVE: This study examined the ability of a two-part self-report instrument, the McDonald Play Inventory, to reliably and validly measure the play activities and play styles of 7- to 11-yr-old children and to discriminate between the play of neurotypical children and children with known learning and developmental disabilities.
 
METHOD: A total of 124 children ages 7–11 recruited from a sample of convenience and a subsample of 17 parents participated in this study.
 
RESULTS: Reliability estimates yielded moderate correlations for internal consistency, total test intercorrelations, and test–retest reliability. Validity estimates were established for content and construct validity.
 
CONCLUSION: The results suggest that a self-report instrument yields reliable and valid measures of a child’s perceived play performance and discriminates between the play of children with and without disabilities.

Kim, J. S., Holtom, P., & Vigen, C. (2011). Reduction of catheter-related bloodstream infections through the use of a central venous line bundle: Epidemiologic and economic consequences. American Journal of Infection Control, 39, 640-646. doi:10.1016/j.ajic.2010.11.005. Link to full text Abstract →← Abstract 

BACKGROUND: Central venous lines (CVLs) are used extensively in intensive care units (ICUs) but can sometimes lead to catheter-related blood stream infections (CRBSIs). This study evaluated a "CVL bundle" to see whether the CRBSI rate would decrease, analyze any changes in the flora of CRBSIs, and project any decrease in health care costs.
 
METHODS: The CVL bundle was implemented on all patients admitted to the ICU starting January 2008. Data from CRBSI rates from 2006 and 2007 were pooled to compare the intervention. A Poisson analysis generated a relative risk reduction. Determination of costs were made by taking the excess length of stay multiplied by other costs (supplies, medications, cost of replacement of CVL) at our institution.
 
RESULTS: Overall infection rates decreased with an improvement in CRBSIs in all ICUs that participated. Although the proportion of gram-negative organisms did not change significantly, there was a decrease in the proportion of gram-positive infections (P = .05) and an increase in fungal infections (P = .04). The total excess cost per organism was determined by the following: total excess cost = excess length of stay + replacement of CVL + drug administration + antibiotic cost. The weighted excess cost took the total excess cost times a correction factor based on organism frequency. The total excess cost of any given CRBSI is approximately $32,254.
 
CONCLUSION: Preventing CRBSIs can improve patient care while reducing hospital stays, costs, and possible mortality. CVL bundles are fairly easy to perform with reproducible results.

Vigen, C. L., Mack, W. J., Keefe, R. S., Sano, M., Sultzer, D. L., Stroup, T. S., Dagerman, K. S., Hsiao, J. K., Lebowitz, B. D., Lyketsos, C. G., Tariot, P. N., Zheng, L., & Schneider, L. S. (2011). Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: Outcomes from CATIE-AD. American Journal of Psychiatry, 168, 831-839. doi:10.1176/appi.ajp.2011.08121844. Link to full text Abstract →← Abstract 

OBJECTIVE: The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD).
 
METHOD: CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks.
 
RESULTS: Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests.
 
CONCLUSIONS: In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.

Francis, B. A., Varma, R., Vigen, C., Lai, M. Y., Winarko, J., Nguyen, B., & Azen, S. (2011). Population and high-risk group screening for glaucoma: The Los Angeles Latino Eye Study. Investigative Ophthalmology & Visual Science, 52, 6257-6264. doi:10.1167/iovs.09-5126. Link to full text Abstract →← Abstract 

PURPOSE: To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups.
 
METHODS: The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening.
 
RESULTS: Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters-C/D, HVF, and IOP-substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92).
 
CONCLUSIONS: No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs.

Salama, H., Zekri, A. R., Zern, M., Bahnassy, A., Loutfy, S., Shalaby, S., Vigen, C., Burke, W., Mostafa, M., Medhat, E., Alfi, O., & Huttinger, E. (2010). Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transplantation, 19, 1475-1486. doi:10.3727/096368910X514314. Link to full text Abstract →← Abstract 

The only presently viable treatment for end-stage liver disease is whole organ transplantation. However, there are insufficient livers available. The aim of the present study is to provide autologous bone marrow-derived stem cells as a potential therapeutic for patients with end-stage cirrhosis. This is a retrospective chart review of autologous stem cell treatment in 48 patients, 36 with chronic end-stage hepatitis C-induced liver disease and 12 with end-stage autoimmune liver disease. For all patients, granulocyte colony-stimulating factor was administered to mobilize their hematopoietic stem cells. Following leukapheresis, CD34(+) stem cells were isolated, amplified, and partially differentiated in culture, then reinjected into each subject via their hepatic artery or portal vein. Treatment was generally well tolerated with the expected moderate but transient bone pain from G-CSF in less than half of the patients. Three patients had serious treatment-related complications, and only 20.8% of these end-stage liver disease patients died during 12 months of follow up. For all patients there was a statistically significant decrease in ascites. There was clinical and biochemical improvement in a large percentage of patients who received the transplantation. In the viral group, there were marked changes in albumin (p = 0.0003), bilirubin (p = 0.04), INR (p = 0.0003), and ALT levels (p = 0.02). In the autoimmune group, values also improved significantly for albumin (p = 0.001), bilirubin (p = 0.002), INR (p = .0005), and ALT levels (p = 0.003). These results suggest that autologous CD34(+) stem cell transplantation may be safely administered and appears to offer some therapeutic benefit to patients with both viral and autoimmune-induced end-stage liver disease.

Zheng, L., Mack, W. J., Dagerman, K. S., Hsiao, J. K., Lebowitz, B. D., Lyketsos, C. G., Stroup, T. S., Sultzer, D. L., Tariot, P. N., Vigen, C., & Schneider, L. S. (2010). Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: The CATIE-AD study. American Journal of Psychiatry, 166, 583-590. doi:10.1176/appi.ajp.2008.08081218. Link to full text Abstract →← Abstract 

OBJECTIVE: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects.
 
METHOD: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models.
 
RESULTS: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., > or = 7% of body weight) was seen among patients with antipsychotic use < or = 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and > 24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides.
 
CONCLUSION: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

Nowicki, M. J., Vigen, C., Mack, W. J., Seaberg, E., Landay, A., Anastos, K., Young, M., Minkoff, H., Greenblatt, R., & Levine, A. M. (2008). Association of cells with natural killer (NK) and NKT immunophenotype with incident cancers in HIV-infected women. AIDS Research and Human Retroviruses, 24, 163-168. doi:10.1089/aid.2007.0119. Link to full text Abstract →← Abstract 

Evidence indicates that immunosupression is associated with the development of certain cancers. The pathogenesis of HIV disease includes an alteration in innate immunity, mediated through NK and NKT cells. The evaluation of innate immune status in HIV patients prior to cancer diagnosis may identify the specific immunological events preceding the development of malignant disease. We evaluated the association between immunophenotypically defined NK, NKT, and CD8(+) cell percentages and incident malignancies in 1817 HIV(+) women in the Women's Interagency HIV Study (WIHS) who were followed for a median of 7.5 years. A total of 52 incident cancers of 20 different sites were identified. Compared to cancer-free women, cancer cases were older (p < 0.01), more likely to be anti-HCV(+) (p = 0.02), and had higher baseline median HIV RNA levels than controls. The CD8(+), NK, and NKT percents at baseline were not related to cancer risk. However, when time-dependent values for NKT cells were used, higher levels of NKT cells were associated with a reduced risk of cancer (adjusted hazard ratio = 0.67, 95% CI = 0.50, 0.89 per NKT percentage point). In addition to the loss of CD4(+) lymphocytes and an increased risk of opportunistic infections, HCV coinfected individuals may also experience alterations in innate immunity, including reduced NKT and NK cell number and possibly their function. In time-dependent analyses, increased numbers of NKT cells were associated with a reduced risk of cancer. HIV-induced innate immune dysfunction may contribute to the eventual emergence of cancer in the setting of existing coinfections and altered immunosurveillance.

Vigen, C., Hodis, H. N., Chandler, W. L., Lobo, R. A., & Mack, W. J. (2007). Postmenopausal oral estrogen therapy affects hemostatic factors, but does not account for reduction in the progression of subclinical atherosclerosis. Journal of Thrombosis and Haemostasis, 5, 1201-1208. doi:10.1111/j.1538-7836.2007.02547.x. Link to full text Abstract →← Abstract 

BACKGROUND: Hemostatic factors influenced by postmenopausal hormone therapy may contribute to atherosclerosis. The Estrogen in the Prevention of Atherosclerosis Trial (EPAT), a 2-year, randomized, double-blind, placebo-controlled trial, demonstrated reduced subclinical atherosclerosis progression measured by change in common carotid artery intima-media thickness (CIMT) with unopposed oral 17beta-estradiol.
 
OBJECTIVES: To assess the effect of postmenopausal hormone therapy on the levels of several hemostatic factors, and the relationship between these factors and the progression of subclinical atherosclerosis.
 
PATIENTS AND METHODS: We measured tissue plasminogen activator (t-PA) antigen, factor (F) VII, D-dimer and albumin longitudinally, and plasminogen activator inhibitor type 1 (PAI-1) and fibrinogen at trial-end, in 186 postmenopausal women.
 
RESULTS: Estradiol vs. placebo was associated with greater FVII and lower t-PA, albumin, PAI-1 and fibrinogen (all P < or = 0.001), with no estradiol effect on D-dimer (P = 0.42). Only mean on-trial t-PA was positively associated with the absolute level of CIMT on-trial (r = 0.29, P < 0.0001), but this was attenuated with age and body mass index adjustment. No longitudinally measured hemostatic factor was associated with CIMT progression. However, higher CIMT during the trial was significantly related to increases in t-PA.
 
CONCLUSIONS: These results confirm previous findings regarding estrogen's effect on hemostatic factors and show that albumin is negatively associated with estrogen therapy. These hemostatic factors did not account for the reduction of CIMT progression with 17beta-estradiol seen in EPAT. Atherosclerosis itself may affect levels of hemostatic factors (reverse causality), with subsequent involvement in atherosclerosis-associated thrombosis.

Anastos, K., Lu, D., Shi, Q., Tien, P. C., Kaplan, R. C., Hessol, N. A., Cole, S., Vigen, C., Cohen, M., Young, M., & Justman, J. (2007). Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens. Journal of Acquired Immune Deficiency Syndromes, 45, 34-42. doi:10.1097/QAI.0b013e318042d5fe. Link to full text Abstract →← Abstract 

BACKGROUND: The effects of HIV infection, highly active antiretroviral therapy (HAART), and specific antiretroviral agents on lipoproteins in women are not well described.
 
METHODS: In a cross-sectional substudy of the Women's Interagency HIV Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed multivariate analyses of associations among fasting lipoprotein levels, HIV infection, and HAART.
 
RESULTS: Untreated HIV-positive women had lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TGs) but not lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and were the most likely to have unfavorable HDL-C by National Cholesterol Education Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV-infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL, respectively; P < 0.001 for all). Lamivudine, didanosine, nevirapine, and efavirenz were independently associated with higher HDL-C (P < 0.001 for all). Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C (P < 0.01 for all). Stavudine, abacavir, and all ritonavir-containing regimens were associated with higher TGs (P < 0.05 for all), and tenofovir was associated with lower TGs (P = 0.009).
 
CONCLUSIONS: A dyslipidemic pattern was associated with HIV infection itself, was more severe in users of PI-containing HAART, but was not present in women taking non-PI HAART.

Andel, R., Vigen, C., Mack, W. J., Clark, L. J., & Gatz, M. (2006). The effect of education and occupational complexity on rate of cognitive decline in Alzheimer's patients. Journal of the International Neuropsychological Society, 12, 147-152. http://dx.doi.org/10.1017/S1355617706060206. Link to full text Abstract →← Abstract 

We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimer's disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset.

Levine, A. M., Vigen, C., Gravink, J., Mack, W., Watts, C. H., & Liebman, H. A. (2006). Progressive prothrombotic state in women with advancing HIV disease. Journal of Acquired Immune Deficiency Syndromes, 42, 572-577. doi:10.1097/01.qai.0000230320.78288.79. Link to full text Abstract →← Abstract 

BACKGROUND: HIV-infected patients are at increased risk for venous thrombotic events (VTEs). We sought to determine if advancing stages of HIV were associated with coagulation abnormalities that could predispose to VTE.
 
METHODS: Functional protein S, factor VIII activity, and lupus anticoagulant were assayed in 144 participants of the Women's Interagency HIV Study. Women with conditions associated with VTE (cancer, pregnancy, hormone use, acute infection, cancer, and autoimmune disease) were excluded. Subjects included 34 women with history of clinical AIDS, 11 with immunologic AIDS (CD4 count, <200 cells/dL), 49 with asymptomatic HIV, and 50 HIV-negative comparators.
 
RESULTS: We found progressive decreases in protein S, when comparing HIV-negative women (median, 76%) to women with asymptomatic HIV (median, 67%), immunologic AIDS (median, 62%), or clinical AIDS (median, 46%; P < 0.0001). Similarly, advancing HIV was associated with stepwise increases in factor VIII, from a median of 116% in HIV-negative women to 149% in those with asymptomatic HIV, 196% in those with immunologic AIDS, and 211% in those with clinical AIDS (P < 0.0001). No subject had lupus anticoagulant.
 
CONCLUSIONS: Advancing HIV is associated with progressive abnormalities of protein S and factor VIII; both of which are associated with increased risk for VTE, thus providing a biologic mechanism for the increased prevalence of VTE in HIV.

O'Connell, C. L., Boswell, W. D., Duddalwar, V., Caton, A., Mark, L. S., Vigen, C., & Liebman, H. A. (2006). Unsuspected pulmonary emboli in cancer patients: Clinical correlates and relevance. Journal of Clinical Oncology, 24, 4928-4932. doi:10.1200/JCO.2006.06.5870. Link to full text Abstract →← Abstract 

PURPOSE: Advances in computed tomography (CT) scanning have led to the detection of unsuspected pulmonary emboli (PE) on routine cancer staging scans. We hypothesized that these patients had signs or symptoms suggestive of PE that may have been overlooked by their health care providers.
 
PATIENTS AND METHODS: A retrospective chart review was performed on 59 patients found on routine cancer staging CT scans to have unsuspected PE. Information on patient demographics, malignancy characteristics, risk factors for venous thromboembolism (VTE), and symptoms was recorded. A retrospective case-control analysis was then performed using two age- and stage-matched control patients for each patient who had similar staging CT scans performed during the same period.
 
RESULTS: Fifty-two patients with unsuspected PE were identified. Forty-four percent had signs or symptoms commonly associated with PE; when fatigue was included, 75% were symptomatic. Ninety-two control patients were identified for 46 of the case patients. Patients with unsuspected PE were significantly more likely to have had a prior history of VTE (20% v 3%; P = .007). The patients with PE were significantly more likely than control patients to complain of fatigue (54% v 20%; P = .0002) and shortness of breath (22% v 8%; P = .02). There was no difference between the groups in administration of chemotherapy within 30 days, central venous catheter use, or erythropoietin therapy.
 
CONCLUSION: Seventy-five percent of patients found to have unsuspected PE on cancer staging CT scans were symptomatic. Fatigue and shortness of breath were significantly more common in patients with unsuspected PE than in control patients.

Vigen, C., Bernstein, L., & Wu, A. H. (2006). Occupational physical activity and risk of adenocarcinomas of the esophagus and stomach. International Journal of Cancer, 118, 1004-1009. doi:10.1002/ijc.21419. Link to full text Abstract →← Abstract 

Physical activity may have a role in many cancers, but little is known about its effect on esophageal and gastric adenocarcinoma risk. We investigated occupational physical activity and esophageal and gastric adenocarcinoma risk in a population-based, case-control study including 212 esophageal, 264 gastric cardia and 389 distal gastric cancer cases, and 1,330 controls in Los Angeles County. Lifetime occupational histories were obtained during in-person interviews, and total lifetime occupational activity (Total Activity Index) was calculated using US Census job codes classified as sedentary, or moderately or highly physically active. Average Annual Activity Index was a per-year Total Activity Index counterpart. Unconditional logistic regression was used to calculate odds ratios, 95% confidence intervals and trend tests adjusting for gender, race, age, birthplace, education, smoking, body mass index (BMI) and number of years worked. Esophageal adenocarcinoma risk tended to decrease with increasing Total Activity Index (OR = 0.67, 95% CI = 0.38,1.19 for highest versus lowest quartile), but neither gastric cardia nor distal gastric cancer was associated with the Total Activity Index. This inverse association held for esophageal adenocarcinoma (OR = 0.61, 95% CI = 0.38,0.99 for highest vs. lowest quartile) and modest associations were observed for gastric cardia (OR = 0.76, 95% CI = 0.49,1.18) and distal gastric cancer (OR = 0.77, 95% CI = 0.52,1.14) when based on Average Annual Activity Index before age 65 years. Analyses stratified by gender, race, age, BMI, education and years worked provided similar results. We found a modest protective effect of Total Activity Index on esophageal adenocarcinoma. Future studies with more complete information on occupational and recreational physical activity are needed to confirm and further investigate the suggested protective effect of physical activity on these tumor types.

Vigen, C., Hodis, H. N., Selzer, R. H., Mahrer, P. R., & Mack, W. J. (2005). Relation of progression of coronary artery atherosclerosis to risk of cardiovascular events (from the Monitored Atherosclerosis Regression Study). American Journal of Cardiology, 95, 1277-1282. http://dx.doi.org/10.1016/j.amjcard.2005.01.068. Link to full text Abstract →← Abstract 

We investigated whether change in coronary artery atherosclerosis as measured by quantitative coronary angiography is related to cardiovascular event risk. Although many studies have demonstrated the effectiveness of statins in decreasing atherosclerotic progression and cardiovascular event risk, a relation between coronary atherosclerotic progression and event risk has not been documented in clinical trials that have evaluated statin therapy. The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebo-controlled trial designed to test whether lovastatin would decrease coronary atherosclerotic progression as measured by quantitative coronary angiography. We followed 173 subjects in the MARS who had minimum luminal diameter and percent diameter stenosis measured at the beginning and end of a 2-year intervention. Postintervention follow-up events over a mean period of 9.4 years were reported by subjects and verified by medical records. Two-year percent stenosis and minimum luminal diameter changes were tested in relation to clinical event risk in multivariate Cox's regression models. Events ascertained were (1) coronary death and myocardial infarction, (2) coronary death, myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty, and (3) any cardiovascular event. Increased percent stenosis was associated with significantly increased hazard ratios (HRs) in all event categories (category 1 HR 1.55 per SD percent stenosis, p <0.01; category 2 HR 1.58, p <0.01; category 3 HR 1.47, p = 0.01). Conversely, event risks were decreased for subjects who had increased minimum luminal diameter (category 1 HR 0.79, p = 0.04) and were not associated with category 2 (HR 0.79, p = 0.12) or category 3 (HR 0.81, p = 0.17). These results indicate that quantitative coronary angiographic changes are associated with cardiovascular events and support the long-term benefit of early intervention to decrease atherosclerosis.