Publications

OBJECTIVE

To examine the effects of individual and local level socioeconomic status (SES) and health care access characteristics on the number of self-report physician visits for systemic lupus erythematosus (SLE).

METHODS

Data derived from 755 adult participants from the 2004 to 2007 Lupus Outcomes Study (LOS) resulted in a sample of 2,926 repeated-measures observations. The outcome measure was the number of physician visits in the prior 12 months. Information on disease activity and manifestations, demographics, health insurance, and specialty of the participants' main SLE physician was collected through yearly LOS interviews. Local area measures including neighborhood poverty, the number of subspecialists per capita, and hospital market areas were added from secondary data sources. We used a mixed model with repeated measures to estimate the number of physician visits for SLE by SES and health care access characteristics, as well as the extent of concentrated poverty and number of subspecialists per capita in the local community, and whether these relationships varied by specific hospital market area. Multivariate models were adjusted for demographic and health status covariates.

RESULTS

LOS respondents reported a mean +/- SD of 11.8 +/- 10.7 (range 0-52) physician visits for SLE. After adjustment, having less than a high school education, receiving care in a health maintenance organization, being treated by a generalist, and living in a community of concentrated poverty were associated with a significantly lower number of physician visits for SLE. These relationships varied by hospital market areas.

CONCLUSION

Beyond health status, the number of physician visits for SLE varies by SES, neighborhood poverty, and characteristics of the health care system.

OBJECTIVE

To determine the degree of discordance between patient and physician assessment of disease severity in a multiethnic cohort of adults with rheumatoid arthritis (RA), to explore predictors of discordance, and to examine the impact of discordance on the Disease Activity Score in 28 joints (DAS28).

METHODS

Adults with RA (n = 223) and their rheumatologists completed a visual analog scale (VAS) for global disease severity independently. Patient demographics, the 9-item Patient Health Questionnaire (PHQ-9) depression scale score, the Health Assessment Questionnaire score, and the DAS28 were also collected. Logistic regression analyses were used to identify predictors of positive discordance, defined as a patient rating minus physician rating of >25 mm on a 100-mm VAS (considered clinically relevant). DAS28 scores stratified by level of discordance were compared using a paired t-test.

RESULTS

Positive discordance was found in 30% of cases, with a mean +/- SD difference of 46 +/- 15. The strongest independent predictor of discordance was a 5-point increase in PHQ-9 score (adjusted odds ratio 1.61, 95% confidence interval 1.02-2.55). Higher swollen joint count and Cantonese/Mandarin language were associated with lower odds of discordance. DAS28 scores were most divergent among subjects with discordance.

CONCLUSION

Nearly one-third of RA patients differed from their physicians to a meaningful degree in assessment of global disease severity. Higher depressive symptoms were associated with discordance. Further investigation of the relationships between mood, disease activity, and discordance may guide interventions to improve care for adults with RA.

BACKGROUND

Short-acting inhaled beta2-agonists such as albuterol are used for bronchodilation and are the mainstay of asthma treatment worldwide. There is significant variation in bronchodilator responsiveness to albuterol not only between individuals but also across racial/ethnic groups. The beta2-adrenergic receptor (beta2AR) is the target for beta2-agonist drugs. The enzyme, S-nitrosoglutathione reductase (GSNOR), which regulates levels of the endogenous bronchodilator S-nitrosoglutathione, has been shown to modulate the response to beta2-agonists.

OBJECTIVE

We hypothesized that there are pharmacogenetic interactions between GSNOR and beta2AR gene variants that are associated with variable response to albuterol.

METHODS

We performed family-based analyses to test for association between GSNOR gene variants and asthma and related phenotypes in 609 Puerto Rican and Mexican families with asthma. In addition, we tested these individuals for pharmacogenetic interaction between GSNOR and beta2AR gene variants and responsiveness to albuterol using linear regression. Cell transfection experiments were performed to test the potential effect of the GSNOR gene variants.

RESULTS

Among Puerto Ricans, several GSNOR SNPs and a haplotype in the 3'UTR were significantly associated with increased risk for asthma and lower bronchodilator responsiveness (P=0.04-0.007). The GSNOR risk haplotype affects expression of GSNOR mRNA and protein, suggesting a gain of function. Furthermore, gene-gene interaction analysis provided evidence of pharmacogenetic interaction between GSNOR and beta2AR gene variants and the response to albuterol in Puerto Rican (P=0.03), Mexican (P=0.15) and combined Puerto Rican and Mexican asthmatics (P=0.003). Specifically, GSNOR+17059*beta2AR+46 genotype combinations (TG+GG*AG and TG+GG*GG) were associated with lower bronchodilator response.

CONCLUSION

Genotyping of GSNOR and beta2AR genes may be useful in identifying Latino individuals, who might benefit from adjuvant therapy for refractory asthma.

OBJECTIVE

To describe experiences of serious illness including concerns, preferences, and perspectives on improving end-of-life (EOL) care in underserved inpatients.

METHODS

Qualitative analysis of 1-hour interviews with inpatients at a public hospital whose physician "would not be surprised" by the patient's death or intensive care unit (ICU) admission within a year. Patients who were non-English speaking, lacked mental capacity, or had uncontrolled symptoms were excluded. A semistructured interview guide was developed and used for all interviews. We digitally recorded, transcribed, and conducted a thematic analysis of the interviews.

RESULTS

Twenty patients participated. Difficult events such as estrangement, homelessness, substance abuse, and imprisonment shaped patients' approaches to serious illness. This influence manifested in interpersonal relationships, conceptualizations of death and concerns about dying, and approaches to coping with EOL. Because patients lacked social support, providers played significant roles at EOL. Patients preferred honest communication with providers and sharing in medical decision-making. A prolonged dying process was feared more than sudden death. Concerns included pain, dying in the hospital, and feeling unwelcome in the hospital. Patients coped by advocating for their own care, engaging with religion/spirituality, and viewing illness as similar to past trauma. Participants suggested that providers listen to their concerns and requested accessible chaplaincy and home-based services.

CONCLUSIONS

Providers should consider that difficult life events influence underserved patients' approaches to dying. Attention to patients' specific preferences and palliative care in public hospitals and locations identified as home may improve care for patients who lack social support.

This paper describes a case of a hospice patient that a hospice and palliative care team struggled to palliate. We review a case of a 63-year-old man with anal squamous cell carcinoma who was transferred from an inpatient hospice unit to an intensive care setting in an ill-fated attempt to alleviate his pain and suffering. This paper also describes the frustration and desperation on the part of his medical and interdisciplinary team to provide him adequate relief. In retrospect, there were likely many system factors that may have contributed to this patient's ongoing suffering, including restrictions on the use of certain medications by location (i.e., hospice unit versus intensive care setting) as well as medication and ordering misunderstandings. Opiate neurotoxicity, existential and spiritual angst, and social isolation also contributed substantially to this patient's suffering. Furthermore, we describe not only the importance of exhausting all medical resources to relieve patients' pain and suffering, but also of learning to sit with patients in their suffering.

OBJECTIVE

To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility.

METHODS

We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with high-resolution computed tomography (N = 49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage and transbronchial biopsies.

RESULTS

The mean duration of employment at the facility was 18 years and the mean latency (from first possible exposure) to time of evaluation was 32 years. Five of the workers had CBD at the time of evaluation (based on histology or high-resolution computed tomography); three others had evidence of probable CBD.

CONCLUSIONS

These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

Alternative splicing is an important mechanism for increasing protein diversity. However, its functional effects are largely unknown. Here, we present our new software workflow composed of the open-source application AltAnalyze and the Cytoscape plugin DomainGraph. Both programs provide an intuitive and comprehensive end-to-end solution for the analysis and visualization of alternative splicing data from Affymetrix Exon and Gene Arrays at the level of proteins, domains, microRNA binding sites, molecular interactions and pathways. Our software tools include easy-to-use graphical user interfaces, rigorous statistical methods (FIRMA, MiDAS and DABG filtering) and do not require prior knowledge of exon array analysis or programming. They provide new methods for automatic interpretation and visualization of the effects of alternative exon inclusion on protein domain composition and microRNA binding sites. These data can be visualized together with affected pathways and gene or protein interaction networks, allowing a straightforward identification of potential biological effects due to alternative splicing at different levels of granularity. Our programs are available at http://www.altanalyze.org and http://www.domaingraph.de. These websites also include extensive documentation, tutorials and sample data.