Publications

OBJECTIVE

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE.

METHODS

Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS.

RESULTS

The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036).

CONCLUSION

These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk.

Asthma disproportionally affects different ethnic/racial groups, with Puerto Ricans and African Americans suffering the highest asthma prevalence and morbidity, Mexicans the lowest, and non-Hispanic whites in between. Genome-wide association studies of asthma have found both shared and race/ethnic-specific genetic risks factors for asthma. However, the majority of genetic asthma research is performed in populations of European descent, which limits the benefits of genetic research to European populations. It is important to biomedical and clinical research to include more diverse and underrepresented populations. The rich genetic diversity of all populations can be leveraged to scientific advantage. For example, admixture mapping provides a more powerful approach than traditional genome-wide allelic association studies in discovering genetic associations for complex diseases. By being more inclusive we can achieve a better understanding of the genetics of asthma, address health disparities, and ensure that scientific advances will benefit populations worldwide.

OBJECTIVES

To determine whether cumulative symptom burden predicts hospitalization or emergency department (ED) visits in a cohort of older adults.

DESIGN

Prospective, observational study with a baseline in-home assessment of symptom burden.

SETTING

Central Alabama.

PARTICIPANTS

Nine hundred eighty community-dwelling adults aged 65 and older (mean 75.3 ± 6.7) recruited from a random sample of Medicare beneficiaries stratified according to sex, race, and urban/rural residence.

MEASUREMENTS

Symptom burden score (range 0-10). One point was given for each symptom reported: shortness of breath, tiredness or fatigue, problems with balance or dizziness, leg weakness, poor appetite, pain, stiffness, constipation, anxiety, and loss of interest in activities. Dependent variables were hospitalizations and ED visits, assessed every 6 months during the 8.5-year follow-up period. Using Cox proportional hazards models, time from the baseline in-home assessment to the first hospitalization and first hospitalization or ED visit was determined.

RESULTS

During the 8.5-year follow-up period, 545 (55.6%) participants were hospitalized or had an ED visit. Participants with greater symptom burden had higher risk of hospitalization (hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.05-1.14) and hospitalization or ED visit (HR = 1.10, 95% CI = 1.06-1.14) than those with lower scores. Participants living in rural areas had significantly lower risk of hospitalization (HR = 0.83, 95% CI = 0.69-0.99) and hospitalization or ED visit (HR = 0.80, 95% CI = 0.70-0.95) than individuals in urban areas, independent of symptom burden and comorbidity.

CONCLUSION

Greater symptom burden was associated with higher risk of hospitalization and ED visits in community-dwelling older adults. Healthcare providers treating older adults should consider symptom burden to be an additional risk factor for subsequent hospital utilization.

OBJECTIVE

We sought to understand how neuromuscular clinicians respond to the ethical challenges that arise in caring for children with life-limiting neuromuscular diseases.

METHODS

We conducted a national survey of interdisciplinary professionals who care for children with Duchenne Muscular Dystrophy and Spinal Muscular Atrophy Type-1 to document their knowledge, attitudes, beliefs and reported practices with regard to prominent ethical challenges, and their suggestions for ethics interventions that would assist them in improving clinical practice.

RESULTS

157 participants completed paper or electronic surveys for an overall participation rate of 24%. A significant minority of respondents were either unaware of or chose not to adopt relevant ethical guidelines, and reported experiencing crises of conscience in the care of their patients. In response to 8 ethical dilemmas, there was variability in how often respondents encountered them, their comfort in addressing them, and their reported practices, including only 24% who have requested ethics consultation.

CONCLUSION

Training of interdisciplinary clinicians is needed to improve their adoption of relevant ethical guidelines, cultivate greater awareness of diverse attitudes regarding the ethical permissibility of different treatment options and the utility of ethics consultation, and foster greater confidence and competence in responding to ethical challenges that arise in pediatric neuromuscular practice.

We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an "innate" phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4(+) CD44(lo) NK1.1(-) cells) and Stage 2 (CD4(+) CD44(hi) NK1.1(-) cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the "Th2-prone" phenotype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.