scholarly journals Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial

2018 ◽  
Vol 42 (3) ◽  
pp. 613-623 ◽  
Author(s):  
Lara A. Ray ◽  
ReJoyce Green ◽  
Daniel J.O. Roche ◽  
Spencer Bujarski ◽  
Emily E. Hartwell ◽  
...  
2019 ◽  
Vol 12 ◽  
pp. 117954411989085 ◽  
Author(s):  
Ena Sharma ◽  
Brian Pedersen ◽  
Robert Terkeltaub

Objective: The interleukin-1 (IL-1) receptor antagonist anakinra is an effective, off-label option in acute gout flares, when conventional therapy options are narrowed. We performed a retrospective, randomized, case-controlled study to gain clinical insight on baseline factors for gout patients most likely to receive anakinra, and ultimate mortality of those who received anakinra. Methods: Of 1451 gout patients seen between January 2003 and January 2015 in a Veterans Affairs (VA) rheumatology group practice, under stringent managed care principles, 13 (100% male), who received anakinra at least once for flares, were compared with 1:4 age- and sex-matched gout controls. Each patient’s first rheumatology encounter was studied by factor analysis for variables associated with later anakinra. Results: At baseline, patients that received anakinra had higher urate burden (palpable tophi [10/13] vs controls [16/52], P = .003), serum urate ([10.6 mg/dL] vs controls [7.6 mg/dL], P < .0001), and East Asian descent ([7/13] vs [16/52], P = .041). The anakinra group had higher ultimate all-cause mortality ([6/13] vs controls [7/52], relative risk [RR] = 3.43, 95% confidence interval [CI] = 1.39-8.48, P = .0076). Factor analysis showed baseline visit palpable tophus and statin use to be most strongly associated with later anakinra use. Increased mortality of anakinra users, as per a factorial analysis, was linked more strongly to comorbidities than to anakinra. Conclusions: At baseline rheumatology gout encounter, higher urate, palpable tophi, statin prescription, and East Asian descent were associated with later anakinra use for flares. Mortality was more closely associated to the presence of comorbidities at baseline rheumatology visit than to anakinra prescription.


2016 ◽  
Vol 23 (1) ◽  
Author(s):  
Stacy L. McAllister ◽  
Katherine Sun ◽  
Eric R. Gross

Tumor Biology ◽  
2015 ◽  
Vol 37 (5) ◽  
pp. 6379-6387 ◽  
Author(s):  
Joy Shi ◽  
Anne Grundy ◽  
Harriet Richardson ◽  
Igor Burstyn ◽  
Johanna M. Schuetz ◽  
...  

Author(s):  
Lihong Chen ◽  
Zhuo Zhao ◽  
Zhen Wang ◽  
Ying Zhou ◽  
Xin Zhou ◽  
...  

AbstractResident physician training is associated with a substantial increase in depression in the United States, with rates increasing from about 4% before internship to 35% at least once during the first year of residency1.Here, we sought to assess whether the rate of depression among residents in China are similar to their US counterparts and identify the common and differential predictors of depression in the two training systems. We assessed 1006 residents across three cohorts (2016-2019) at 16 affiliated hospitals of Shanghai Jiao Tong University and Peking Union Medical College. In parallel, we assessed three cohorts of 7028 residents at 100+ US institutions.At the Chinese institutions, similarly, the proportion of participants who met depression criteria increased from 9% prior to residency to 35% at least once during the first year of residency (P<0.0001), an increase similar in magnitude to residents during internship in US institutions. Among factors assessed before residency, prior history of depression and depressive symptom score at baseline were common factors associated with depression during residency in both China and the US. In contrast, neuroticism and early family environment were strongly associated with depression risk in the US but not in China. Young age was a predictor of depression in China but not in the US sample. Among residency training factors, long duty hours and reduced sleep duration emerged as predictors of depression in both China and the US.To gain insight into whether differences in personal predictors between the residents in China compared to the US residents were driven more by differences between cohorts, or by training system differences, we compared US residents of East Asian descent to other US and Chinese residents. We found that for most predictors (age, Neuroticism, early family environment), US residents of East Asian descent were more similar to other US residents than to the residents training in China.Overall, the magnitude of depression increase and work-related drivers of depression were similar between China and the US, suggesting a need for system reforms, and that the types of effective reforms may be similar across the two systems.


2019 ◽  
Vol 23 (6) ◽  
pp. 595-601 ◽  
Author(s):  
Marisa Grace Ponzo ◽  
Monica Miliszewski ◽  
Mark G. Kirchhof ◽  
Paul A. Keown ◽  
Jan P. Dutz

Background and objective East Asians exposed to the urate-lowering drug allopurinol have a predilection for severe cutaneous drug reactions such as drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Screening is recommended in patients of East Asian descent for the presence of HLA-B*58:01 prior to allopurinol initiation to avoid these complications. Utilization rates of the HLA-B*58:01 predictive screening test within the Greater Vancouver area, which has a population composed of 40.1% people of East Asian descent, are unknown. Measures We identified cases of DRESS or SJS/TEN due to allopurinol using the Vancouver General Hospital dermatology consult service database. We next compared the frequency in which the HLA-B*58:01 screening test was ordered since 2012 to the estimated frequency of new prescriptions for allopurinol prescribed for the management of gout among the East Asians. Results We report 5 cases of East Asian patients exposed to allopurinol for management of gout between 2012 and 2016, who developed DRESS (4 patients) or SJS/TEN (1 patient). All were of HLA-B*58:01 genotype, representing preventable cases. The HLA-B*58:01 test was ordered 6 times in 2012, whereas the estimated number of new cases of allopurinol-prescribed gout among patients of East Asian descent during that time period was 13. For 2012, testing was ordered for only 46% of at-risk patients. Conclusion We continue to observe cases of severe cutaneous drug reactions among high-risk individuals due to allopurinol exposure. The HLA-B*58:01 screening test for allopurinol hypersensitivity is underutilized in our geographic area.


2014 ◽  
Vol 231 (19) ◽  
pp. 3843-3853 ◽  
Author(s):  
Lara A. Ray ◽  
Kelly E. Courtney ◽  
Dara G. Ghahremani ◽  
Karen Miotto ◽  
Arthur Brody ◽  
...  

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