Publications

Toll-free telephone quitlines are successful alternatives to direct clinician contact. In 2004, the U.S. Department of Health and Human Services created a national quitline number, 1-800-QUIT-NOW. This enabled states without quitlines to establish them, giving free access to cessation services to every smoker in the U.S. It also created a new mechanism for national quitline marketing, employing simplified and streamlined approaches.

Colorectal cancer (CRC) screening rates are low among Latinos. To identify factors associated with CRC screening, we conducted a telephone survey of Latino primary care patients aged 50-79 years. Among 1,013 participants, 38% were up-to-date (UTD) with fecal occult blood test (FOBT); 66% were UTD with any CRC screening (FOBT, sigmoidoscopy, or colonoscopy). Individuals less than 65, females, those less acculturated, and patients of female physicians were more likely to be UTD with FOBT. CRC screening among Latinos is low. Younger patients, women, and patients of female physicians receive more screening.

Candida albicans is an opportunistic fungal pathogen of humans. Although a normal part of our gastrointestinal flora, C. albicans has the ability to colonize nearly every human tissue and organ, causing serious, invasive infections. In this chapter we describe current methodologies used in molecular genetic studies of this organism. These techniques include rapid sequential gene disruption, DNA transformation, RNA isolation, epitope tagging, and chromatin immunoprecipitation. The ease of these techniques, combined with the high-quality C. albicans genome sequences now available, have greatly facilitated research into this important pathogen. Candida albicans is a normal resident of the human gastrointestinal tract; it is also the most common fungal pathogen of humans, causing both mucosal and systemic infections, particularly in immune compromised patients. C. albicans and Saccharomyces cerevisiae last shared a common ancestor more than 900 million years ago; in terms of conserved coding sequences, the two species are approximately as divergent as fish and humans. Although C. albicans and S. cerevisiae share certain core features, they also exhibit many significant differences. This is not surprising as C. albicans has the ability to survive in nearly every niche of a mammalian host, a property not shared by S. cerevisiae. Research into C. albicans is important in its own right, particularly with regards to its ability to cause disease in humans; in addition, comparison with S. cerevisiae can reveal important insights into evolutionary processes. Many of the methodologies developed for use in S. cerevisiae have been adapted for C. albicans, and we describe some of the most common. Although alternative procedures are described in the literature, we have found those described below to be the most convenient. Because the C. albicans parasexual cycle is cumbersome to use in the laboratory, genetics in this organism has been based almost entirely on directed mutations. Because the organism is diploid, creating a deletion mutant requires two rounds of gene disruption. We describe a rapid method for creating sequential disruptions, one which can be scaled up to create large collections of C. albicans deletion mutants. We also describe a series of additional techniques including DNA transformation, mRNA isolation, epitope tagging, and chromatin immunoprecipitation (ChIP). The ease of these techniques, combined with the high-quality C. albicans genome sequences now available, has greatly increased the quality and pace of research into this important pathogen.

Community-acquired pneumonia remains the primary infectious cause of death in the United States. At current levels of antimicrobial resistance, conventional agents are at risk of becoming less effective, and the need for new agents is pressing. Cethromycin is a new ketolide antibiotic being investigated for use in respiratory tract infections. To review its pharmacology, in vitro susceptibilities, pharmacokinetics, efficacy, safety, and drug interactions, we conducted a MEDLINE search restricted to English-language articles citing cethromycin or ABT-773 (its original designation) from 1990-May 2009. Additional data sources were identified from the references of selected articles. All published trials and available poster data citing cethromycin were selected for review. In vitro, cethromycin displays more potent antibacterial effects than its predecessor telithromycin. Cethromycin exhibits potent inhibition of both gram-positive and gram-negative respiratory pathogens. A new drug application for cethromycin was submitted to the United States Food and Drug Administration in 2008 for the treatment of community-acquired pneumonia. Clinical trial data in the treatment of respiratory tract infections support cethromycin's efficacy. The limited safety data have not included any reports of hepatotoxicity. If cethromycin proves to be safe with regard to hepatotoxicity, it has great promise as an alternative to current standard therapy for community-acquired respiratory infections, especially pneumonia. Given current resistance levels, cethromycin could provide more reliable coverage against common respiratory pathogens than traditional agents in the beta-lactam and macrolide classes.

BACKGROUND

Psychological functioning is an important determinant of health outcomes in chronic lung disease. To better define the role of anxiety in chronic obstructive pulmonary disease (COPD), a study was conducted of the inter-relations between anxiety and COPD in a large cohort of subjects with COPD and a matched control group.

METHODS

Data were used from the FLOW (Function, Living, Outcomes, and Work) cohort of patients with COPD (n=1202) and matched controls without COPD (n=302). Anxiety was measured using the Anxiety subscale of the Hospital Anxiety and Depression Scale.

RESULTS

COPD was associated with a greater risk of anxiety in multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18). Among patients with COPD, anxiety was related to poorer health outcomes including worse submaximal exercise performance (less distance walked during the 6-min walk test: -66.3 feet for anxious vs non-anxious groups; 95% CI -127.3 to -5.36) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41). Subjects with COPD with anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90).

CONCLUSION

COPD is associated with a higher risk of anxiety. Once anxiety develops among patients with COPD, it is related to poorer health outcomes. Further research is needed to determine whether systematic screening and treatment of anxiety in COPD will improve health outcomes and prevent functional decline and disability.

PURPOSE

The purpose of this study was to delineate the effect of chronic obstructive pulmonary disease (COPD) on a broad range of valued life activities (VLAs) and make comparisons to effects of other airways conditions.

METHODS

We used cross-sectional data from a population-based, longitudinal study of US adults with airways disease. Data were collected by telephone interview. VLA disability was compared among 3 groups defined by reported physician diagnoses: COPD/emphysema, chronic bronchitis, and asthma. Multiple regression analyses were conducted to identify independent predictors of VLA disability.

RESULTS

About half of individuals with COPD were unable to perform at least 1 VLA; almost all reported at least 1 VLA affected. The impact among individuals with chronic bronchitis and asthma was less but still notable: 74%-84% reported at least 1 activity affected, and about 15% were unable to perform at least 1 activity. In general, obligatory activities were the least affected. Symptom measures and functional limitations were the strongest predictors of disability, independent of respiratory condition.

CONCLUSION

VLA disability is common among individuals with COPD. Obligatory activities are less affected than committed and discretionary activities. A focus on obligatory activities, as is common in disability studies, would miss a great deal of the impact of these conditions. Because individuals are often referred to pulmonary rehabilitation as a result of dissatisfaction with ability to perform daily activities, VLA disability may be an especially relevant outcome for rehabilitation.

OBJECTIVE

In recent years hydroxychloroquine (HCQ) has emerged as a key therapy in systemic lupus erythematosus (SLE). We determined the rates of HCQ use in a diverse, community-based cohort of patients with SLE and identified predictors of current HCQ use.

METHODS

Patients were participants in the University of California San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with confirmed SLE. We examined the prevalence of HCQ use per person-year and compared baseline characteristics of users and nonusers, including demographic, socioeconomic, clinical, and health system use variables. Multiple logistic regression with generalized estimating equations was used to evaluate predictors of HCQ use.

RESULTS

A total of 881 patients contributed 3,095 person-years of data over 4 interview cycles. The prevalence of HCQ use was 55 per 100 person-years and was constant throughout the observation period. In multivariate models, the odds of HCQ use were nearly doubled among patients receiving their SLE care from a rheumatologist compared with those identifying generalists or nephrologists as their primary sources of SLE care. In addition, patients with shorter disease duration were more likely to use HCQ, even after adjusting for age and other covariates.

CONCLUSION

In this community-based cohort of patients, HCQ use was suboptimal. Physician specialty and disease duration were the strongest predictors of HCQ use. Patients who are not using HCQ, those with longer disease duration, and those who see nonrheumatologists for their SLE care should be targeted for quality improvement.

OBJECTIVE

To describe characteristics of systemic lupus erythematosus (SLE) patients who are frequent users of the emergency department and to identify predictors of frequent emergency department use.

METHODS

Data for this study were derived from the University of California, San Francisco Lupus Outcomes Study, a large cohort of persons with SLE who undergo annual structured interviews. Participants were categorized into 1 of 3 levels of emergency department utilization: nonusers (no visits in the preceding year), occasional users, (1-2 visits), and frequent users (> or =3 visits). We compared characteristics of the 3 groups and determined predictors of frequent emergency department use (> or =3 visits) using multivariate logistic regression, adjusting for a variety of potential confounding covariates.

RESULTS

Of 807 study participants, 499 (62%) had no emergency department visits; 230 (28%) had occasional emergency department visits (1-2 visits); and 78 (10%) had frequent (> or =3 visits) emergency department visits. Frequent users were younger, less likely to be employed, and less likely to have completed college. They also had greater disease activity, worse general health status, and more depressive symptoms. Frequent emergency department users were more likely to have Medicaid as their principal insurance. In multivariate logistic regression, older age predicted a lower likelihood of frequent emergency department visits, whereas greater disease activity and having Medicaid insurance predicted a higher likelihood of frequent emergency department visits.

CONCLUSION

In persons with SLE, greater disease activity and Medicaid insurance are associated with more frequent emergency department use.