Publications

BACKGROUND

Effective population management of patients with diabetes requires timely recognition. Current case-finding algorithms can accurately detect patients with diabetes, but lack real-time identification. We sought to develop and validate an automated, real-time diabetes case-finding algorithm to identify patients with diabetes at the earliest possible date.

METHODS

The source population included 160,872 unique patients from a large public hospital system between January 2009 and April 2011. A diabetes case-finding algorithm was iteratively derived using chart review and subsequently validated (n = 343) in a stratified random sample of patients, using data extracted from the electronic health records (EHR). A point-based algorithm using encounter diagnoses, clinical history, pharmacy data, and laboratory results was used to identify diabetes cases. The date when accumulated points reached a specified threshold equated to the diagnosis date. Physician chart review served as the gold standard.

RESULTS

The electronic model had a sensitivity of 97%, specificity of 90%, positive predictive value of 90%, and negative predictive value of 96% for the identification of patients with diabetes. The kappa score for agreement between the model and physician for the diagnosis date allowing for a 3-month delay was 0.97, where 78.4% of cases had exact agreement on the precise date.

CONCLUSIONS

A diabetes case-finding algorithm using data exclusively extracted from a comprehensive EHR can accurately identify patients with diabetes at the earliest possible date within a healthcare system. The real-time capability may enable proactive disease management.

AIM

To evaluate the influence of food habits, specifically adherence to the Mediterranean diet, on carotid intima-media thickness (CIMT) and the presence of plaques in HIV-infected patients taking antiretroviral therapy (ART) and non-HIV-infected participants and to determine if HIV infection contributes independently to subclinical atherosclerosis.

METHODS

We conducted a cross-sectional study of 110 HIV-infected patients on ART and 131 non-HIV-infected participants at the University Hospital for Infectious Diseases in Zagreb, Croatia, from 2009-2011. CIMT measurement and determination of carotid plaque presence was detected by ultrasound. Adherence to the Mediterranean diet was assessed by a 14-point food-item questionnaire. Subclinical atherosclerosis was defined by CIMT≥0.9 mm or ≥1 carotid plaque.

RESULTS

In HIV-infected patients, subclinical atherosclerosis was associated with older age (Plt;0.001; Mann-Whitney test), higher body mass index (P=0.051; Mann-Whitney test), hypertension (Plt;0.001; χ(2) test), and a lower Mediterranean diet score (P=0.035; Mann-Whitney test), and in non-HIV-infected participants with older age (P lt; 0.001; Mann-Whitney test) and hypertension (P=0.006; χ(2) test). Multivariate analysis showed that decreased adherence to the Mediterranean diet was associated with higher odds of subclinical atherosclerosis (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.10-4.72, P=0.027) as was current smoking (OR 2.86, 95% CI 1.28-6.40), hypertension (OR 3.04, 95% CI 1.41-6.57), and male sex (OR 2.35, 95% CI 0.97-5.70). There was a significant interaction of age and HIV status, suggesting that older HIV-infected patients had higher odds of subclinical atherosclerosis than controls (OR 3.28, 95% CI 1.24-8.71, P=0.017 at the age of 60 years).

CONCLUSION

We confirmed the association between lower adherence to the Mediterranean diet and increased risk of subclinical atherosclerosis and found that treated HIV infection was a risk factor for subclinical atherosclerosis in older individuals.

PURPOSE

Asian Americans have consistently reported poorer communication with physicians compared with non-Hispanic Whites (NHW). This qualitative study sought to elucidate the similarities and differences in communication with physicians between Chinese and NHW breast cancer survivors.

METHODS

Forty-four Chinese and 28 NHW women with early stage breast cancer (stage 0-IIa) from the Greater Bay Area Cancer Registry participated in focus group discussions or individual interviews. We oversampled Chinese women because little is known about their cancer care experiences. In both interview formats, questions explored patients' experiences and feelings when communicating with physicians about their diagnosis, treatment, and follow-up care.

RESULTS

Physician empathy at the time of diagnosis was important to both ethnic groups; however, during treatment and follow-up care, physicians' ability to treat cancer and alleviate physical symptoms was a higher priority. NHW and US-born Chinese survivors were more likely to assert their needs, whereas Chinese immigrants accepted physician advice even when it did not alleviate physical problems (e.g., pain). Patients viewed all physicians as the primary source for information about cancer care. Many Chinese immigrants sought additional information from primary care physicians and stressed optimal communication over language concordance.

CONCLUSIONS

Physician empathy and precise information were important for cancer patients. Cultural differences such as the Western emphasis on individual autonomy vs. Chinese emphasis on respect and hierarchy can be the basis for the varied approaches to physician communication we observed. Interventions based on cultural understanding can foster more effective communication between immigrant patients and physicians ultimately improving patient outcomes.

A key function of the skin is to provide a permeability barrier to restrict the movement of water, electrolytes, and other small molecules between the outside environment and the internal milieu. Following disruption of the permeability barrier, there is a rapid restoration of barrier function, and one of the key signals initiating this repair response is a decrease in the concentration of calcium in the outer epidermis. In this issue, Borkowski et al. present evidence showing that activation of Toll receptor 3 by double-stranded RNA may be another pathway for activation of permeability barrier repair. These results provide further evidence for a link between innate immunity and the permeability barrier.

PURPOSE OF REVIEW

Advances in human genetics and investigations in animal models of autoimmune disease have allowed insight into the basic mechanisms of immunologic tolerance. These advances allow us to understand the pathogenesis of type 1 diabetes and other autoimmune diseases as never before. Here, we discuss the tolerance mechanisms of the autoimmune polyendocrine syndromes and their relevance to type 1 diabetes.

RECENT FINDINGS

Defects in central tolerance with alteration of self-antigen expression levels in the thymus are a potent cause of autoimmunity. Peripheral tolerance defects that alter T-cell activation and signaling also play an important role in the pathogenesis of diabetes and other associated autoimmune disorders, with multiple modest defects working in concert to produce disease. Regulation of the immune response through the action of regulatory T cells is a potent mode of tolerance induction in autoimmunity that is important in type 1 diabetes.

SUMMARY

Rare syndromes of autoimmunity provide a valuable window into the breakdown of tolerance and identify multiple checkpoints that are critical for generation of autoimmunity. Understanding the application of these in type 1 diabetes will allow the development of future immunomodulatory therapies in the treatment and prevention of disease.

BACKGROUND

Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models.

OBJECTIVE

We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma.

METHODS

ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot.

RESULTS

Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4).

CONCLUSIONS AND CLINICAL RELEVANCE

ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.