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

Cheryl Vigen PhD

Cheryl Vigen

Associate Professor of Research

Room: CHP 101J
(323) 442-2749
.(JavaScript must be enabled to view this email address)

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 USC Chan 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
2007 | University of Southern California

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

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

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

Publications

Books

Clark, F. A., Blanchard, J., Sleight, A., Cogan, A., Eallonardo, L., Florindez, L., Gleason, S., Heymann, R., Hill, V., Holden, A., Jackson, J. M., Mandel, D. R., Murphy, M., Proffitt, R., Niemiec, S. S., Vigen, C., & Zemke, R. (2015). Lifestyle redesign: The intervention tested in the USC Well Elderly Studies (2nd ed.). Bethesda, MD: American Occupational Therapy Association. Full text Show abstractHide abstract

Reorganized, expanded, and updated, this new edition of the award-winning Lifestyle Redesign gives practical guidance in this preventative occupational therapy program for independent-living older adults. The work integrates the concept of the USC's landmark Well Elderly Studies, which determined that preventive occupational therapy greatly enhances the health and quality of life of independent-living older adults.
 
Twelve modules, including those on longevity, stress, home safety and navigating health care, illustrate how to incorporate the program into practice. Includes a flash drive with program handouts.

Journal Articles

Carlson, M., Vigen, C. L., Rubayi, S., Blanche, E. I., Blanchard, J., Atkins, M., Bates-Jensen, B., Garber, S. L., Pyatak, E. A., Diaz, J., Florindez, L. I., Hay, J. W., Mallinson, T., Unger, J. B., Azen, S. P., Scott, M., Cogan, A., & Clark, F. (2017). Lifestyle intervention for adults with spinal cord injury: Results of the USC-RLANRC Pressure Ulcer Prevention Study. Journal of Spinal Cord Medicine. Advance online publication. https://doi.org/10.1080/10790268.2017.1313931 Show abstractHide abstract

CONTEXT/OBJECTIVE: Medically serious pressure injuries (MSPrIs), a common complication of spinal cord injury (SCI), have devastating consequences on health and well-being and are extremely expensive to treat. We aimed to test the efficacy of a lifestyle-based intervention designed to reduce incidence of MSPrIs in adults with SCI.
 
DESIGN: A randomized controlled trial (RCT), and a separate study wing involving a nonrandomized standard care control group.
 
SETTING: Rancho Los Amigos National Rehabilitation Center, a large facility serving ethnically diverse, low income residents of Los Angeles County.
 
PARTICIPANTS: Adults with SCI, with history of one or more MSPrIs over the past 5 years: N=166 for RCT component, N=66 in nonrandomized control group.
 
INTERVENTIONS: The Pressure Ulcer Prevention Program, a 12-month lifestyle-based treatment administered by healthcare professionals, largely via in-home visits and phone contacts.
 
OUTCOME MEASURES: Blinded assessments of annualized MSPrI incidence rates at 12 and 24 months, based on: skin checks, quarterly phone interviews with participants, and review of medical charts and billing records. Secondary outcomes included number of surgeries and various quality-of-life measures.
 
RESULTS: Annualized MSPrI rates did not differ significantly between study groups. At 12 months, rates were .56 for intervention recipients, .48 for randomized controls, and .65 for nonrandomized controls. At follow-up, rates were .44 and .39 respectively for randomized intervention and control participants.
 
CONCLUSIONS: Evidence for intervention efficacy was inconclusive. The intractable nature of MSPrI threat in high-risk SCI populations, and lack of statistical power, may have contributed to this inability to detect an effect.
 
TRIAL REGISTRATION: ClinicalTrials.gov NCT01999816.

Pyatak, E. A., Sequeira, P. A., Vigen, C. L., Weigensberg, M. J., Wood, J. R., Montoya, L., Ruelas, V., & Peters, A. L. (2017). Clinical and psychosocial outcomes of a structured transition program among young adults with type 1 diabetes. Journal of Adolescent Health, 60, 212-218. https://doi.org/10.1016/j.jadohealth.2016.09.004 Show abstractHide abstract

PURPOSE: We identified and treated young adults with type 1 diabetes who had been lost to follow-up during their transfer from pediatric to adult care, comparing their clinical, psychosocial, and health care utilization outcomes to participants receiving continuous care (CC) throughout the transition to adult care.
 
METHODS: Individuals in their last year of pediatric care (CC group, n = 51) and individuals lost to follow-up in the transfer to adult care ("lapsed care" [LC] group, n = 24) were followed prospectively for 12 months. All participants were provided developmentally tailored diabetes education, case management, and clinical care through a structured transition program.
 
RESULTS: At baseline, LC participants reported lapses in care of 11.6 months. Compared with CC participants, they had higher hemoglobin A1C (A1C; p = .005), depressive symptoms (p = .05), incidence of severe hypoglycemia (p = .005), and emergency department visits (p = .004). At 12-month follow-up, CC and LC participants did not differ on the number of diabetes care visits (p = .23), severe hypoglycemia (no events), or emergency department visits (p = .22). Both groups' A1C improved during the study period (CC: p = .03; LC: p = .02). LC participants' depressive symptoms remained elevated (p = .10), and they reported a decline in life satisfaction (p = .007). There was greater loss to follow-up in the LC group (p = .04).
 
CONCLUSIONS: Our study suggests that, for young adults with a history of lapses in care, a structured transition program is effective in lowering A1C, reducing severe hypoglycemia and emergency department utilization, and improving uptake of routine diabetes care. Loss to follow-up and psychosocial concerns remain significant challenges in this population.

Juang, C., Knight, B. G., Carlson, M., Schepens Niemiec, S. L., Vigen, C., & Clark, F. (2017). Understanding the mechanisms of change in a lifestyle intervention for older adults. The Gerontologist. Advance online publication. https://doi.org/10.1093/geront/gnw152 Show abstractHide abstract

PURPOSE OF THE STUDY: This study investigated the mechanisms of change underlying an activity-based lifestyle intervention, an occupational therapy program aimed at promoting healthy habits, and routines in older adults. We examined two activity-relevant factors as potential mediators linking the intervention to reduced symptoms of depression: activity frequency and global perceptions of activity significance. Social connections and perceived control were assessed to understand how activity-related factors relate to reduced symptoms of depression.
 
DESIGN AND METHODS: The sample consisted of 460 multiethnic community-dwelling older adults aged 60-95 years. Participants were randomly assigned to a 6-month lifestyle redesign intervention (n = 232) or a no-treatment control (n = 228) condition. After the 6-month period, 360 individuals completed post-testing. Latent change score models were used to represent changes from baseline over the experimental interval. Structural equation models were applied to examine the indirect effects of the intervention on reduced depressive symptoms.
 
RESULTS: The results demonstrated significant indirect effects from intervention receipt to decreased depressive symptoms via increased activity frequency and activity significance. Higher activity frequency was linked to fewer depressive symptoms via heightened social connections, whereas increased activity significance was associated with fewer depressive symptoms via enhanced perceived control.
 
IMPLICATIONS: The results support basic principles of occupational therapy by highlighting important mediating roles of activity frequency and activity significance in reducing depressive symptoms. Understanding of these change mechanisms can help optimize activity-centered interventions to reduce depressive symptoms.

Pyatak, E. A., Carandang, K., Vigen, C., Blanchard, J., Sequeira, P. A., Wood, J. R., Spruijt-Metz, D., Whittemore, R., & Peters, A. L. (2017). Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) study: Methodology and baseline characteristics of a randomized controlled trial evaluating an occupation-based diabetes management intervention for young adults. Contemporary Clinical Trials, 54, 8-17. https://doi.org/10.1016/j.cct.2016.12.025 Show abstractHide abstract

OVERVIEW: This paper describes the study protocol used to evaluate the Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) intervention and reports on baseline characteristics of recruited participants. REAL Diabetes is an activity-based intervention designed to address the needs of young adults diagnosed with type 1 (T1D) or type 2 diabetes (T2D) from low socioeconomic status or racial/ethnic minority backgrounds. The REAL intervention incorporates tailored delivery of seven content modules addressing various dimensions of health and well-being as they relate to diabetes, delivered by a licensed occupational therapist.
 
METHODS: In this pilot randomized controlled trial, participants are assigned to the REAL Diabetes intervention or an attention control condition. The study's primary recruitment strategies included in-person recruitment at diabetes clinics, mass mailings to clinic patients, and social media advertising. Data collection includes baseline and 6-month assessments of primary outcomes, secondary outcomes, and hypothesized mediators of intervention effects, as well as ongoing process evaluation assessment to ensure study protocol adherence and intervention fidelity.
 
RESULTS: At baseline, participants (n=81) were 51% female, 78% Latino, and on average 22.6years old with an average HbA1c of 10.8%. A majority of participants (61.7%) demonstrated clinically significant diabetes distress and 27.2% reported symptoms consistent with major depressive disorder. Compared to participants with T1D, participants with T2D had lower diabetes-related self-efficacy and problem-solving skills. Compared to participants recruited at clinics, participants recruited through other strategies had greater diabetes knowledge but weaker medication adherence.
 
DISCUSSION: Participants in the REAL study demonstrate clinically significant medical and psychosocial needs.

Carandang, K., Pyatak, E. A., & Vigen, C. P. (2016). Systematic review of educational interventions for rheumatoid arthritis. American Journal of Occupational Therapy, 70, 7006290020p1-7006290020p12. https://doi.org/10.5014/ajot.2016.021386 Show abstractHide abstract

OBJECTIVE: In this study, we systematically reviewed the effectiveness of educational interventions falling within the scope of occupational therapy practice for people with rheumatoid arthritis (RA). These interventions included disease education, joint protection and energy conservation, psychosocial techniques, pain management, and a combination category.
 
METHOD: Two databases, MEDLINE and CINAHL, and select journals were searched for randomized controlled trials published between January 2002 and June 2015. Qualitative synthesis was used for between-study comparisons.
 
RESULTS: Twenty-two studies, with approximately 2,600 participants, were included. The interventions were found to have strong evidence for constructs that dealt with increasing coping with pain and fatigue as well as maintaining positive affect. There was limited or no evidence supporting the effectiveness of these interventions on most other measured constructs.
 
CONCLUSION: Interventions in which a combination of educational techniques is used may complement pharmacological therapies in the care of people with RA. Future research is needed to identify specific mechanisms of change.

Leland, N. E., Fogelberg, D., Sleight, A., Mallinson, T., Vigen, C., Blanchard, J., Carlson, M., & Clark, F. (2016). Napping and nighttime sleep: Findings from an occupation-based intervention. American Journal of Occupational Therapy, 70, 7004270010p1-7. https://doi.org/10.5014/ajot.2016.017657 Show abstractHide abstract

OBJECTIVE: To describe sleeping behaviors and trends over time among an ethnically diverse group of community-living older adults.
 
METHOD: A descriptive secondary data analysis of a subsample (n = 217) from the Lifestyle Redesign randomized controlled trial was done to explore baseline napping and sleeping patterns as well as 6-mo changes in these outcomes.
 
RESULTS: At baseline, the average time sleeping was 8.2 hr daily (standard deviation = 1.7). Among all participants, 29% reported daytime napping at baseline, of which 36% no longer napped at follow-up. Among participants who stopped napping, those who received an occupation-based intervention (n = 98) replaced napping time with nighttime sleep, and those not receiving an intervention (n = 119) experienced a net loss of total sleep (p < .05).
 
CONCLUSION: Among participants who stopped napping, the occupation-based intervention may be related to enhanced sleep. More research examining the role of occupation-based interventions in improving sleep is warranted.

Cogan, A. M., Blanchard, J., Garber, S. L., Vigen, C. L., Carlson, M., & Clark, F. A. (2016). Systematic review of behavioral and educational interventions to prevent pressure ulcers in adults with spinal cord injury. Clinical Rehabilitation. Advance online publication. Full text Show abstractHide abstract

OBJECTIVE: To investigate the efficacy of behavioral or educational interventions in preventing pressure ulcers in community-dwelling adults with spinal cord injury (SCI).
 
DATA SOURCES: Cochrane, Clinical Trials, PubMed, and Web of Science were searched in June 2016. The search combined related terms for pressure ulcers, spinal cord injury, and behavioral intervention. Each database was searched from its inception with no restrictions on year of publication.
 
REVIEW METHODS: Inclusion criteria required that articles were (a) published in a peer-reviewed journal in English, (b) evaluated a behavioral or educational intervention for pressure ulcer prevention, (c) included community-dwelling adult participants aged 18 years and older with SCI, (d) measured pressure ulcer occurrence, recurrence, or skin breakdown as an outcome, and (e) had a minimum of 10 participants. All study designs were considered. Two reviewers independently screened titles and abstracts. Extracted information included study design, sample size, description of the intervention and control condition, pressure ulcer outcome measures, and corresponding results.
 
RESULTS: The search strategy yielded 444 unique articles of which five met inclusion criteria. Three were randomized trials and two were quasi-experimental designs. A total of 513 participants were represented. The method of pressure ulcer or skin breakdown measurement varied widely among studies. Results on pressure ulcer outcomes were null in all studies. Considerable methodological problems with recruitment, intervention fidelity, and participant adherence were reported.
 
CONCLUSIONS: At present, there is no positive evidence to support the efficacy of behavioral or educational interventions in preventing pressure ulcer occurrence in adults with SCI.

Sequeira, P. A., Pyatak, E. A., Weigensberg, M. J., Vigen, C. P., Wood, J. R., Ruelas, V., Montoya, L., Cohen, M., Speer, H., Clark, S., & Peters, A. L. (2015). Let's Empower and Prepare (LEAP): Evaluation of a structured transition program for young adults with type 1 diabetes. Diabetes Care, 38, 1412-1419. https://doi.org/10.2337/dc14-2577 Show abstractHide abstract

OBJECTIVE: To evaluate the efficacy of a structured transition program compared with usual care in improving routine follow-up, clinical, and psychosocial outcomes among young adults with type 1 diabetes.
 
RESEARCH DESIGN AND METHODS: Eighty-one young adults in their last year of pediatric care were recruited from three clinics. Intervention group (IG) participants (n = 51) received a structured transition program incorporating tailored diabetes education, case management, group education classes, and access to a newly developed young adult diabetes clinic and transition website. Control group (CG) participants (n = 30) received usual care. The primary outcome was the number of routine clinic visits. Secondary outcomes included glycemic control, hypoglycemia, health-care use, and psychosocial well-being. Assessments were conducted at baseline, and 6 and 12 months.
 
RESULTS: Limitations in CG follow-up prevented direct comparisons of adult care visits; however, at the 12-month follow-up among IG participants discharged from pediatric care (n = 32), 78% had one or more adult visits. Among IG participants, the total number of clinic visits did not differ between those who transitioned and those who remained in pediatric care (3.0 ± 1.24 vs. 3.11 ± 0.94, P = 0.74). IG compared with CG participants had improved glycemic control (-0.40 ± 1.16% vs. 0.42 ± 1.51% [4.4 ± 12.7 mmol/mol vs. 4.6 ± 16.5 mmol/mol], P = 0.01), incidence of severe hypoglycemia (0.0% vs. 16%, P = 0.02), and global well-being (P = 0.02) at 12 months.
 
CONCLUSIONS: A structured transition program was successful in facilitating transition to adult care without a decrease in clinical follow-up. Compared with usual care, the transition program facilitated improvements in glycemic control, hypoglycemia, and psychosocial well-being.

Mallinson, T., Schepens Niemiec, S. L., Carlson, M., Leland, N., Vigen, C., Blanchard, J., & Clark, F. (2014). Development and validation of the activity significance personal evaluation (ASPEn) scale. Australian Occupational Therapy Journal, 61, 384-393. https://doi.org/10.1111/1440-1630.12155 Show abstractHide abstract

BACKGROUND/AIM: Engagement in desired occupations can promote health and wellbeing in older adults. Assessments of engagement often measure frequency, amount or importance of specific activities. This study aimed to develop a scale to measure older adults' evaluation of the extent to which their everyday activities are contributing to their health and wellness.
 
METHODS: Eighteen items, each scored with a seven-point rating scale, were initially developed by content experts, covering perceptions of how daily activities contribute to physical and mental health, as well as satisfaction and activity participation in the last six months. Rasch analysis methods were used to refine the scale using the pencil and paper responses of 460 community-living older adults.
 
RESULTS: Initial Rasch analysis indicated three unlabelled rating scale categories were seldom used, reducing measurement precision. Five items were conceptually different by misfit statistics and principal component analysis. Subsequently, those items were removed and the number of rating scale steps reduced to 4. The remaining 13-item, 4-step scale, termed the Activity Significance Personal Evaluation (ASPEn), formed a unidimensional hierarchy with good fit statistics and targeting. Person separation reliability (2.7) and internal consistency (.91) indicated the tool is appropriate for individual person measurement. Relative validity indicated equivalence between Rasch measures and total raw scores.
 
CONCLUSIONS: ASPEn is a brief, easily administered assessment of older adults' perception of the contribution of everyday activities to personal health and wellness. ASPEn may facilitate occupational therapy practice by enabling clinicians to assess change in meaning of an older adult's activity over time.

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, 31, 1615-1624. https://doi.org/10.1111/dme.12485 Show abstractHide 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.

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. https://doi.org/10.1177/0733464812471444 Show abstractHide 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.

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. https://doi.org/10.1177/1740774514521904 Show abstractHide 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.

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. https://doi.org/10.1093/aje/kwt233 Show abstractHide 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.

Wu, A. H., Lee, E., & Vigen, C. (2013). Soy isoflavones and breast cancer. American Society of Clinical Oncology Educational Book, 2013, 102-106. https://doi.org/10.1200/EdBook_AM.2013.33.102 Show abstractHide 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.

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. https://doi.org/10.1007/s10552-013-0260-7 Show abstractHide 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., 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. https://doi.org/10.1186/bcr3363 Show abstractHide 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.

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. https://doi.org/10.1038/tpj.2011.29 Show abstractHide 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.

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. https://doi.org/10.2174/1874306401206010111 Show abstractHide 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.

McDonald, A. E., & Vigen, C. (2012). Reliability and validity of the McDonald Play Inventory. American Journal of Occupational Therapy, 66, e52-e60. https://doi.org/10.5014/ajot.2012.002493 Show abstractHide 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. https://doi.org/10.1016/j.ajic.2010.11.005 Show abstractHide 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. https://doi.org/10.1176/appi.ajp.2011.08121844 Show abstractHide 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. https://doi.org/10.1167/iovs.09-5126 Show abstractHide 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.

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. https://doi.org/10.1176/appi.ajp.2008.08081218 Show abstractHide 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.

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. https://doi.org/10.3727/096368910X514314 Show abstractHide 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.

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. https://doi.org/10.1089/aid.2007.0119 Show abstractHide 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. https://doi.org/10.1111/j.1538-7836.2007.02547.x Show abstractHide 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. https://doi.org/10.1097/QAI.0b013e318042d5fe Show abstractHide 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.

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. https://doi.org/10.1200/JCO.2006.06.5870 Show abstractHide 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.

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. https://doi.org/10.1097/01.qai.0000230320.78288.79 Show abstractHide 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.

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. https://doi.org/10.1002/ijc.21419 Show abstractHide 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.

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. https://doi.org/10.1017/S1355617706060206 Show abstractHide 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.

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. https://doi.org/10.1016/j.amjcard.2005.01.068 Show abstractHide 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.