Faculty Bibliography

BACKGROUND:Chinese-Americans are a fast-growing immigrant group with worse rheumatic disease outcomes compared to Caucasians and frequent use of Traditional Chinese Medicine (TCM). Whether TCM use is associated with lower adherence to western rheumatic medications is unknown. METHODS:Chinese-Americans actively treated for a systemic rheumatic disease were recruited from two Chinatown clinics. Socio-demographic, TCM use, and clinical data were gathered. Self-reported health status was assessed using Patient-Reported Outcome Measurement Information System (PROMIS®) short forms. Adherence was stratified using the 8-item Morisky Medication Adherence Scale. Factors independently associated with high adherence were identified using multivariable logistic regression. RESULTS:Among 230 subjects, median age was 55 (range 20-97), 65% were female, 71% had ≤ high school education, 70% were on Medicaid, and 22% reported English fluency. The most common rheumatic diagnoses were rheumatoid arthritis (41%), systemic lupus erythematosus (17%), and seronegative spondyloarthropathies (15%). Half reported TCM use in the past year, and 28% reported high adherence to western rheumatic medications. In multivariable analysis, high adherence was associated with TCM use (OR 3.96, p<0.001), being married (OR 3.69, p=0.004), medication regimen complexity (OR 1.13, p=0.004), older age (OR 1.06, p<0.001), and was negatively associated with anxiety (OR 0.94, p=0.001). CONCLUSIONS:While adherence to western rheumatic medications was low in this cohort, interestingly, it was higher among TCM users compared to non-users. TCM use appears to represent a complementary rather than an alternate approach to disease management for these patients. Future studies should evaluate whether TCM use is associated with better disease outcomes. This article is protected by copyright. All rights reserved.

OBJECTIVE:Chinese-Americans are a fast growing immigrant group with more severe rheumatic disease manifestations than Caucasians and often a strong cultural preference for Traditional Chinese Medicine (TCM). We aimed to examine TCM use patterns and association with patientreported outcomes (PROs) among Chinese-American rheumatology patients. METHODS:Chinese-Americans actively treated for systemic rheumatic diseases were recruited from urban Chinatown rheumatology clinics. Data on sociodemographics, acculturation, clinical factors, and TCM use (11 modalities) were gathered. Self-reported health status was assessed using Patient-Reported Outcome Measurement Information System (PROMIS®) short forms. TCM users and non-users were compared. Factors independently associated with TCM use were identified using multivariable logistic regression. RESULTS:Among 230 participants, median age was 55 (range 20-97), 65% were female, 71% had ≤ high school education, 70% were on Medicaid, 47% lived in the US for ≥20 years, and 22% spoke English fluently. Half used TCM in the past year; these participants had worse selfreported anxiety, depression, fatigue, and ability to participate in social roles and activities compared with non-users. In multivariable analysis, TCM use was associated with belief in TCM, female gender, ≥20 years' US residency, reporting western medicine as ineffective, and shorter rheumatic disease duration. CONCLUSION/CONCLUSIONS:Among these Chinese-American rheumatology patients, TCM users had worse PROs in many physical and mental health domains. TCM use may be a proxy for unmet therapeutic needs. Asking about TCM use could help providers identify patients with suboptimal health-related quality of life who may benefit from targeted interventions.

Background/Purpose: Chinese-Americans are one of the fastest growing immigrant groups in the US. They often use Traditional Chinese Medicine (TCM), but whether that affects medication adherence is unknown. This question is important because data suggest that ethnic Chinese have more severe SLE and RA than Caucasians, and thus nonadherence could be especially problematic. This study evaluates whether TCM use is associated with nonadherence to western medicines prescribed for chronic rheumatic diseases among Chinese- American patients. Secondary aims are to explore differences in self-reported health status between TCM users and non-users. Methods: Recruitment was from a rheumatology clinic that serves a predominantly Chinese-American immigrant population. A bilingual Mandarin/English speaker evaluated TCM use, medication adherence, patient-reported outcomes from the Patient-Reported Outcomes Measurement Information System (PROMIS), and other patient-level factors, all administered with validated instruments available in English and Mandarin. Inclusion criteria included speaking Mandarin or English, prescription of > 1 medication by the rheumatologist, and being actively followed for a systemic rheumatic disease or OA of hands, knees, or hips. Those with only fibromyalgia, neck/back pain, or other soft tissue diseases were excluded. Adherence was analyzed as low, medium or high based on the 8-item Morisky Medication Adherence Scale. Results: Seventy-three enrolled, mean age 56y (range 22-97), 59% female, 77% Medicaid, and only 21% spoke English. Diagnoses included RA (37%), spondyloarthropathies (22%), SLE (15%), SS (7%), gout/pseudogout (7%), OA (3%), and other (9%). Forty-nine percent reported TCM use in the past year, most commonly massage (53%), acupuncture (47%), and herbs (44%). There was a trend for TCM use to be more common in SLE vs. RA (65% vs. 37%, p=0.5) and TCM users had a shorter disease duration (5.3 vs. 11.2 years, p=0.03). Overall, 70% reported nonadherence to rheumatic medication. In multivariate analysis adjusting for patient characteristics, TCM use was not associated with lower adherence (OR 0.34, 95% CI 0.09-1.26), while herb use was associated (OR 5.3, 95% CI 1.09-25.87). TCM users also had worse PROMIS scores in anxiety (mean T-score 52 vs. 46, p=0.01) and depression (mean T-score 52 vs. 46, p=0.007), and a trend for worse pain (mean T-score 58 vs. 56, p=0.2), fatigue (mean T-score 55 vs. 51, p=0.1), function (mean T-score 43 vs.47, p=0.1), and worse ability to participate in social roles and activities (mean T-score 55 vs.59, p=0.06). Conclusion: In this group of poorly integrated Chinese-American rheumatology patients, most were non-adherent with western medicines, but only herb use was associated with non-adherence. This could reflect two divergent beliefs towards TCM. In general TCM is complementary, but herb may be seen as an alternative to western medicine. In addition, TCM users had worse scores in several important self-reported health domains. This may indicate unmet needs, particularly in mental health. These associations should be explored longitudinally, including the association of TCM use and adherence on disease activity

Non-fibrillar soluble oligomeric forms of amyloid-beta peptide (oAbeta) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAbeta initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Abeta, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAbeta levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAbeta to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Abeta on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Abeta and tau pathology.

Movement of free cholesterol between the cellular compartment and acceptor is governed by cholesterol gradients that are determined by several enzymes and reverse cholesterol transport proteins. We have previously demonstrated that adenosine A(2A) receptors inhibit foam cell formation and stimulate production of cholesterol 27-hydroxylase (CYP27A1), an enzyme involved in the conversion of cholesterol to oxysterols. We therefore asked whether the effect of adenosine A(2A) receptors on foam cell formation in vitro is mediated by CYP27A1 or apoE, a carrier for cholesterol in the serum. We found that specific lentiviral siRNA infection markedly reduced apoE or 27-hydroxylase mRNA in THP-1 cells. Despite diminished apoE expression (p < 0.0002, interferon-gamma (IFNgamma) CGS vs. IFNgamma alone, n = 4), CGS-21680, an adenosine A(2A) receptor agonist, inhibits foam cell formation. In contrast, CGS-21680 had no effect on reducing foam cell formation in CYP27A1 KD cells (4 +/- 2%; p < 0.5113, inhibition vs. IFNgamma alone, n = 4). Previously, we reported the A(2A) agonist CGS-21680 increases apoAI-mediated cholesterol efflux nearly twofold in wild-type macrophages. Adenosine receptor activation had no effect on cholesterol efflux in CYP27A1 KD cells but reduced efflux in apoE KD cells. These results demonstrate that adenosine A(2A) receptor occupancy diminishes foam cell formation by increasing expression and function of CYP27A1

Methotrexate has been widely used for the treatment of rheumatoid arthritis (RA). The mechanisms of action of methotrexate are complex. Developed as a folic acid analogue, methotrexate inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Recently, many studies have focused on the adenosine-mediated antiinflammatory effects of methotrexate. Certain aspects of methotrexate toxicities are also attributed to adenosine release. A better understanding of the mechanisms of action and toxicities of methotrexate will direct clinicians in their treatment approach and toxicity monitoring. Toward that objective, the latest developments in the pharmacokinetics, mechanism of action, pharmacogenetics, and toxicity of methotrexate are herein discussed