Traditional Chinese medicine in the treatment of patients with hyperuricemia: A randomized placebo-controlled double-blinded clinical trial.

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.

Risk of primary Sjogren's Syndrome following human papillomavirus infections: a nationwide population-based cohort study.

Introduction: Viral infection is an exogeneous factor for primary Sjogren's syndrome (pSS). This study investigated the association between human papillomavirus (HPV) infections and pSS through a nationwide population based cohort study. Methods: Patients with HPV infections between January, 1999 and December, 2013 were included. The incidence of new-onset pSS in patients with HPV infections and non-HPV controls were derived. The multiple Cox regression model derived the risk of pSS in patients with HPV infections. Subgroup analysis and sensitivity analysis were performed to validate the association. Results: During a follow-up period of 12 years, the adjusted hazard ratio (aHR) of pSS in patients with HPV infections was significantly higher than that in non-HPV controls (aHR=1.64, 95% CI=1.47-1.83, P<0.001). The risk of pSS increased with age and the risk increased by 2.64-fold (95% CI= 2.37-2.93) for those older than 45 years. The significant association between HPV infections and the risk of pSS persisted in the sensitivity analysis restricted in HPV infections that lasted over 12 months (aHR=1.63, 95%CI=1.45-1.83, P<0.0001). Subgroup analyses revealed that both male (aHR=1.83, 95%CI=1.47-2.28, P<0.0001) and female (aHR=1.58, 95%CI=1.40-1.79, P<0.0001) patients with HPV infections and HPV-infected patients aged between 16 and 45 years (aHR=1.60, 95%CI=1.34-1.91, P<0.0001) and over 45 years (aHR=1.67, 95%CI=1.46-1.91, P<0.0001) were associated with a significantly greater risk of pSS. Conclusion: Patients with HPV infections presented with a significantly higher risk of pSS, regardless of age and sex.

Traditional Chinese Medicine in Patients With Primary Sjogren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease mainly characterized by dryness, fatigue, and pain. Current therapies for SS in Western medicine are limited. The purpose of this clinical study was to explore the efficacy and safety of using a traditional Chinese medicine (TCM) formula on patients with primary SS. Methods: We performed a 12-week, randomized, double-blinded, placebo-controlled clinical trial at Chung Shan Medical University Hospital. We included 42 patients with SS between the ages of 20 and 80 years who met the classification criteria of the American and European Consensus Group (AECG). Patients who had other severe systemic manifestations or diseases were excluded from this trial. After screening, patients were randomly assigned to the TCM treatment group or placebo group (ratio of 2:1). We treated the TCM group with 6 g of Gan-Lu-Yin granules after breakfast and 6 g of Jia-Wei-Xiao-Yao-San combined with 1 g of Suan-Zao-Ren-Tang and 1 g of Ye-Jiao-Teng every night after dinner. Patients in the control group were treated with a placebo with the same appearance and flavor but only one-tenth the dosage of that received by the treatment group. The European League Against Rheumatism Sjogren's Syndrome Patient-Reported Index (ESSPRI) was used as the primary endpoint at week 12. Secondary endpoints were the Sjogren's Syndrome Disease Activity Index (SSDAI), physician global assessment (PGA), visual analogue scale (VAS), Multidimensional Fatigue Inventory, Medical Outcomes Survey Short Form-36, and the Pittsburgh Sleep Quality Score (PSQI). Adverse events were also recorded. Results: Of the 42 randomized patients, 28 patients were assigned to the TCM treatment group and 14 patients were assigned to the controlled group. During the study period, 5 patients withdrew from the TCM group and 7 withdrew from the control group. At week 12, the ESSPRI scores of both groups had improved. The ESSPRI score of the treatment group decreased by 0.62 (95% CI P = 0.557) and that of the placebo group decreased by 0.91 (P = 0.557). However, no significant difference was observed between the two groups. Sleep duration in the PSQI was -0.61, which exhibited an improvement of more than the -0.21 compared with the placebo group (P = 0.914). Conclusion: At week 12, the ESSPRI scores did not reveal that the use of the TCM formula was efficacious for treating patients with Sjogren's syndrome. However, the PSQI scores indicated that this formula could prolong patient sleep duration. We also found that this formula could decrease the blood pressure of patients.

Relationship between Helicobacter pylori infection and psoriasis: a nationwide population-based longitudinal cohort study.

BACKGROUND: In the current literature, studies assessing the role of Helicobacter pylori (HP) infection in psoriasis have reported conflicting data. Therefore, we investigated the association between HP infection and psoriasis using a nationwide population-based longitudinal cohort study. METHODS: We identified 41,539 patients with HP infection and 83,078 matched controls between 2000 and 2013 from the Longitudinal Health Insurance Research Database of the National Health Insurance Research Database in Taiwan. Propensity score analysis was used to match age, sex, comorbidities, and medical visits at a ratio of 1:2. Multiple Cox regression analysis was used to estimate the adjusted hazard ratio of psoriasis. Furthermore, sensitivity tests and a stratified analysis were conducted. RESULTS: The incidence rates of psoriasis did not differ significantly between the HP and control cohorts (4.58 vs 4.20 per 100,000 person-months, crude relative risk: 1.092, 95% confidence interval: 0.917-1.302). After multivariate adjustment, no significant difference in psoriasis risk was observed in patients with HP infection (adjusted hazard ratio: 1.081, 95% confidence interval: 0.907-1.288). Risk of psoriasis was significantly higher in men and the elderly, and in those with diabetes, hyperlipidemia, chronic obstructive pulmonary disease, or tuberculosis. Stratified analysis also confirmed that HP infection was not correlated with an increased risk of psoriasis based on follow-up duration, sex, and age. CONCLUSION: This retrospective population-based longitudinal cohort study, conducted in Taiwan, found no association between HP infection and risk of psoriasis. Further research may be warranted.

Effect of early eradication therapy on systemic lupus erythematosus risk in patients with Helicobacter pylori infection: a nationwide population-based cohort study.

BACKGROUND: This study aimed to investigate whether early eradication therapy influences systemic lupus erythematosus (SLE) risk in patients with Helicobacter pylori (HP) infection. METHODS: We identified 41,653 patients with HP infection in Taiwan from 2000 to 2013. The patient population was divided into early (within three months) and late (after three months) eradication cohorts. age, sex, co-morbidities and medical visits were matched at a 1:1 ratio. Multiple Cox regression, sensitivity analysis and stratified analysis were used to estimate SLE adjusted hazard ratios (aHR). RESULTS: The relative risk of SLE was 0.75 (95% confidence interval 0.43-1.31) in the early eradication cohort. After multivariate adjustment, the SLE risk was non-significantly lower in the early eradication cohort than in the late eradication cohort (aHR = 0.74, 95% CI 0.42-1.29). Stratified analysis revealed that early eradication could significantly reduce SLE risk during the three-year follow-up period (aHR = 0.16, 95% CI 0.05-0.53, p for interaction = 0.0013). Compared to eradication within three months of diagnosis, eradication within 3-36 months and >36 months corresponded with SLE aHRs of 4.78 (95% CI 1.19-19.20) and 7.66 (95% CI 2.17-27.05), respectively, when the follow-up period was less than three years. CONCLUSION: Early HP eradication could significantly reduce SLE risk, especially in the first three-year follow-up.

Methotrexate at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with rheumatoid arthritis: a nationwide population-based cohort study.

BACKGROUND: We investigated whether taking methotrexate (MTX) is associated with a lower risk of new-onset cancers in patients with rheumatoid arthritis (RA). METHODS: We conducted a 12-year retrospective cohort study from a population-based National Health Insurance Research Database in Taiwan. A total of 21,699 patients with newly diagnosed RA were enrolled during 2000-2009. The overall cancer rate was compared between 10,352 new users of MTX and 11,347 non-users. We used the WHO Defined Daily Dose (DDD) as a tool to assess drug exposure. Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of disease after controlling for demographics and other comorbidities. RESULTS: After adjusting for age, sex, cancer-related comorbidities, and RA-combined medication, the HR of cancer risk was 0.87 (95% CI = 0.74-1.02) for the MTX user group compared with the MTX non-user group. The cumulative incidence of cancer in the MTX non-user group was significantly higher than that of the MTX user group (log-rank test p < 0.001). In the low accumulative dose group [cumulative dose <1125 mg, cumulative defined daily dose (cDDD) <450], the HR of cancer risk for MTX users was 1.20 (95% CI = 1.01-1.42) compared with the MTX-non-user group. However, the adjusted HR of cancer risk was reduced to 0.66 (95% CI = 0.49-0.87) in MTX middle-dose users (cumulative dose 1125-2250 mg, cDDD: 450-899) and 0.33 (95% CI = 0.23-0.48) for the MTX high-dose group (cumulative dose ⩾2250 mg, cDDD ⩾900), respectively (p for trend < 0.0001). CONCLUSION: MTX at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with RA.

Impact of mycoplasma pneumonia infection on urticaria: A nationwide, population-based retrospective cohort study in Taiwan.

Mycoplasma pneumonia (MP) infection might be pathogenically closely related to urticaria. This study is a nationwide population-based cohort study from 1997 to 2013, which investigated the association between MP infection and urticaria in Taiwan. A total of 1,175 patients were included for the study group, and 2,350 for the control group. Multivariate Cox regression analysis was performed to estimate the adjusted hazard ratio (aHR) for urticaria. Result showed that 254 patients with new-onset urticaria were involved in the study group and 465 incident cases in the control group. The incidence rates (per 100,000 person-months) of urticaria were 37.2 and 32.5 in the study and control groups, respectively. The relative risk is 1.1 (95% CI = 1.0-1.3) indicating no significant correlation between MP and urticaria. The multivariate analysis revealed that the risk of urticaria with MP infection (aHR = 1.1, P = 0.1058) had no statistically significance difference compared to the control group. However, the risk of urticaria in MP-infected patients aged between 20 and 59 years old was found to have increased (aHR = 1.6, 95% CI = 1.1-2.2) prior to a diagnosis.

Risk of dementia among patients with Sjogren's syndrome: A nationwide population-based cohort study in Taiwan.

OBJECTIVE: Autoimmunity may play a role in early-stage dementia. The association between Sjogren's syndrome (SS) and dementia remains unknown. This study was conducted to provide epidemiologic evidence for this relationship. METHODS: This 12-year, nationwide, population-based, retrospective cohort study analyzed the risk of dementia in the SS cohort. We also investigated the incidence of dementia among patients with SS by using data from the Longitudinal Health Insurance Database 2000, maintained by the Taiwan National Health Research Institutes. To balance the prevalence of characteristics in the cohorts, we used the propensity score to match selected comorbidities in the two cohorts. We also analyzed the association between SS and dementia among patients with different potential risks by using a Cox proportional hazard model. RESULTS: According to the analysis of data obtained from follow-up conducted during 2000-2012, the incidence of dementia in the SS cohort was 1.21-fold that in the control cohort (95% confidence interval [CI] = 1.02-1.45, p < 0.05). In the group older than 65years, the incidence of dementia was significantly high (adjusted hazard ratio [aHR] = 5.30, 95% CI = 4.26-6.60, p < 0.01). After adjustment for comorbidities, including Parkinson's disease (aHR = 2.98, 95% CI = 1.80-4.94), insomnia (aHR = 1.45, 95% CI = 1.14-1.85), and hypertension (aHR = 1.43, 95% CI = 1.19-1.71), the association between SS and dementia was still significant. CONCLUSION: This 13-year, nationwide, population-based retrospective cohort study revealed patients with SS to have a higher risk of dementia.

Increased Risk of Systemic Lupus Erythematosus in Patients With Helicobacter pylori Infection: A Nationwide Population-Based Cohort Study.

Helicobacter pylori (HP) infection is associated with systemic lupus erythematosus (SLE), but the related results have been controversial. Therefore, this study investigated the association between HP infection and SLE by using a nationwide longitudinal population-based cohort. We identified 41,651 patients with HP infection and 83,302 matched controls between 2000 and 2013 from the Longitudinal Health Insurance Research Database of the National Taiwan Insurance Research Database. Age, gender, comorbidities, and medical visits were matched at a 1:2 ratio by using propensity score analysis. The adjusted hazard ratio (aHR) of SLE was calculated by multiple Cox regression. Furthermore, sensitivity test and stratified analysis were performed. The SLE incidence rate was 1.17 [95% confidence interval (CI): 0.89-1.54] per 100,000 person-months in the HP cohort, and the hazard ratio was 1.63 (95% CI: 1.12-2.37) in comparison with the propensity score-matched control cohort. After multivariate adjustment, patients with HP infection had a significantly high overall aHR (1.58; 95% CI: 1.08-2.30) of SLE. Stratified analysis revealed the aHR of 8.23 (95% CI: 1.77-38.32) in patients <30 years old, and the p for interaction between age and HP infection was 0.039. For age-sex subgroup analysis, the highest aHR was 12.74 (95% CI: 1.55-104.59) in young (aged <30 years) female patients with HP infection. HP infection is associated with a 1.63-fold increased SLE risk, particularly with female patients aged <30 years. Future research is required to elucidate the underlying mechanism of this association.

Impact of chronic urticaria on systemic lupus erythematosus: A nationwide population-based study in Taiwan.

Chronic urticaria (CU) may be closely pathogenically related to systemic lupus erythematosus (SLE). This study aims to investigate the association between CU and SLE patients in Taiwan. A nationwide population-based cohort study from 1997 to 2013 was conducted. Investigated subjects were selected from the Taiwan National Health Insurance Research Database using the International Classification of Disease, Ninth Revision code. Participants consisted of 13 845 subjects newly diagnosed with CU from 2003 to 2013. We estimated the incidence risk of SLE among patients with CU by time-to-event analysis. Patients with CU were more likely to be female, and had a significant difference in urbanization and length of hospital stays (P < 0.0001). The incidence rates of SLE for the CU and control groups were 3.55 and 1.68, respectively. The crude hazard ratio of SLE among subjects with CU was 2.113 compared with the non-urticarial control group. After adjusting the demographic, length of hospital stay and comorbidity, the adjusted hazard ratio (aHR) of SLE was still significantly higher in the CU group (aHR = 2.113) compared with the control group. The use of non-steroidal anti-inflammatory drugs or corticosteroids may decrease the risk of SLE in patients with CU (P = 0.0216 and 0.0120, respectively). In conclusion, CU is associated with a higher risk of incidental SLE in this population-based, nationwide, cohort study. Inflammation and immune dysregulation are considered two potential mechanisms. Clinically, patients with urticaria should be carefully evaluated for risk of future SLE.

Patients with urticaria are at a higher risk of anaphylaxis: A nationwide population-based retrospective cohort study in Taiwan.

The clinical features of urticaria and anaphylaxis are similar, and they share common causal immune-mediated pathways. We aimed to investigate the risk of anaphylaxis among patients with urticaria. A 12-year population-based retrospective cohort study was conducted. Investigated subjects were identified from the Taiwan National Health Insurance Research Database by the International Classification of Disease, Ninth Revision, Clinical Modification. We included 126 031 subjects with newly diagnosed urticaria and 252 062 matched controls between 2000 and 2013. Risk of anaphylaxis among patients with urticaria was calculated by calculating adjusted hazards ratios (HR) after matching for confounding comorbidities. Urticaria was more common in women than it was in men (58% vs 42%), with a peak onset age of 20-40 years. The number of comorbidities including asthma, allergic rhinitis, herpes zoster, hepatitis B and C, rheumatoid arthritis and gout were higher in patients with urticaria than that in age- and sex-matched controls. The crude HR for anaphylaxis among urticaria subjects was 2.883 (95% confidence interval [CI], 2.787-2.982; P < 0.001). After adjustment for potential confounders which have been proposed to increase the risk of anaphylaxis, patients with urticaria were found to be at a significantly high risk of anaphylaxis with an adjusted HR of 2.529 (95% CI, 2.442-2.619; P < 0.001). We conclude that the incidence rate of anaphylaxis is significantly high in patients with urticaria in Taiwan.

Increased risk of coronary heart disease among patients with primary Sjögren's syndrome: a nationwide population-based cohort study.

To investigate the association between primary Sjögren's syndrome (pSS) and coronary heart disease (CHD), and the influence of medications for pSS patients on risk of CHD. The authors identified 4175 patients with a new diagnosis of pSS between 2002 and 2013 from the National Health Insurance Research database. The control-to-case ratio was 4:1. The risk and cumulative incidences of CHD were calculated. The adjusted hazard ratio (HR) of CHD for pSS patients was 1.17 (1.03-1.34) after adjusting for age, sex, comorbidities, and medications. The cumulative incidence for CHD in the pSS group was significantly higher than that in the control group (log-rank p < 0.0001). The risk of CHD in pSS patients was increased with age by 4% per year, and 45- to 59-year-olds were at the highest risk (HR = 1.464, 1.195-1.794). The application of corticosteroids (HR = 1.45, 1.07-1.97) as well as NSAIDs (HR = 1.31, 1.05-1.65) both increased the risk of CHD among pSS patients. pSS is associated with an increased risk of subsequent CHD in Taiwan. Primary Sjögren's syndrome might be an independent risk factor for CHD. Use of corticosteroids and NSAIDs in the treatment of pSS patients increased the risk of developing CHD.