Publications by authors named "James Cheng-Chung Wei"

244 Publications

Absence of Association between Previous Infection and Subsequent Myasthenia Gravis: A Nationwide Population-Based Matched Cohort Study.

Int J Environ Res Public Health 2021 Jul 19;18(14). Epub 2021 Jul 19.

Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan.

() is not only one of the most common pathogenic bacteria for respiratory infection but also a trigger for many autoimmune diseases. Its infection process shared many similarities with the pathogenesis of myasthenia gravis (MG) at cellular and cytokine levels. Recent case reports demonstrated patients present with MG after infection. However, no epidemiological studies ever looked into the association between the two. Our study aimed to investigate the relationship between infection and subsequent development of MG. In this population-based retrospective cohort study, the risk of MG was analyzed in patients who were newly diagnosed with infection between 2000 and 2013. A total of 2428 patients were included and matched with the non- control cohort at a 1:4 ratio by age, sex, and index date. Cox proportional hazards regression analysis was applied to analyze the risk of MG development after adjusting for sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The incidence rates of MG in the non- and cohorts were 0.96 and 1.97 per 10,000 person-years, respectively. Another case-control study of patients with MG ( = 515) was conducted to analyze the impact of on MG occurrence as a sensitivity analysis. The analysis yielded consistent absence of a link between and MG. Although previous studies have reported that infection and MG may share associated immunologic pathways, we found no statistical significance between infection and subsequent development of MG in this study.
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http://dx.doi.org/10.3390/ijerph18147677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306290PMC
July 2021

Endometriosis and New-Onset Coronary Artery Disease in Taiwan: A Nationwide Population-Based Study.

Front Med (Lausanne) 2021 25;8:619664. Epub 2021 Jun 25.

Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.

Endometriosis (EM) with chronic inflammation may accelerate the progression of atherosclerosis. Currently, no large or randomized clinical studies have assessed the incidence of cardiovascular events in patients with endometriosis in Asia to investigate whether incident EM is associated with a higher risk of new-onset coronary artery disease (CAD). In this study of a nationwide cohort in Taiwan, we identified 13,988 patients with newly diagnosed EM from 1 January, 2000, through 31 December, 2012. EM and non-EM groups were matched by propensity score at a ratio of 1:1. Of a total 27,976 participants, 358 developed CAD. The incidence rate in the EM group was higher than that in the non-EM group (1.8 per 1,000 person-years vs. 1.3 per 1,000 person-years) during the follow-up period. The adjusted hazard ratio (aHR) of CAD for the EM group was 1.52 with a 95% confidence interval (1.23-1.87, < 0.001) after adjusting for demographic characteristics, comorbidities, surgical procedures, frequency of outpatient visits, and medications. Stratified analysis revealed that, among four age groups (20-39, 40-49, 50-54, and above 55 years), the 20-39 years sub-group was associated with a higher risk of CAD (aHR, 1.73; 95% CI, 1.16-2.59, = 0.008). Several sensitivity analyses were conducted for cross-validation, and it showed consistent positive findings. In conclusion, this cohort study revealed that patients with symptomatic EM in Taiwan were associated with increased risk of subsequent CAD than patients without medical records of EM. Further prospective studies are needed to confirm this causal relationship.
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http://dx.doi.org/10.3389/fmed.2021.619664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290915PMC
June 2021

Chinese herbal medicine might be associated with a lower rate of joint replacement in patients with osteoarthritis: A 12-year population-based matched cohort analysis.

J Ethnopharmacol 2021 Jul 17:114419. Epub 2021 Jul 17.

Institute of Medicine, Chung Shan Medical University, Taiwan; Department of Medicine, Chung Shan Medical University Hospital, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address:

Ethnopharmacological Relevance: To determine whether adjuvant Chinese herbal medicine (CHM) treatment is associated with the risk of joint replacement in osteoarthritis (OA) patients.

Materials And Methods: This retrospective study used a population-based national health insurance (NHI) database from 2000 to 2012 in Taiwan. A total of 125,023 newly diagnosed OA patients were selected from one million beneficiaries of longitudinal health insurance database. Based on applying ten selected frequently used CHM formulas for OA, patients were divided into CHM user and non-CHM user. One-CHM to four-non-CHM user were propensity score matched with age, gender, monthly income, urbanization, comorbidities, Nonsteroidal anti-inflammatory drugs (NSAIDs) and index year were adjusted to reduce selection bias and confounding. Cox regression model was used for comparing the hazard ratios (HR) for the risk of joint replacement and Kaplan-Meier curve for the proportion of joint replacement.

Results: OA patients who were female, younger (20-60 years), higher income and lived in urbanization location were found to preferred using CHM. Younger CHM users had a lower adjusted HR (0.63) of the risk of joint replacement (95% confidence interval (CI) = 0.42-0.94). Compared to non-CHM user, HR among CHM users (≥225 days annually) is 0.48 (95% CI = 0.31-0.76). The proportion of joint replacement in younger non-CHM user began to rise notably with time (log-rank test, p = 0.026). However, this benefit by CHM did not apply to older (over 60 years) OA patients.

Conclusion: This study suggested that adjuvant CHM might be associated with a lower rate of joint replacement in OA patients. CHM therapy might be considered in OA patients to reduce the need of joint replacement.
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http://dx.doi.org/10.1016/j.jep.2021.114419DOI Listing
July 2021

Association of the Risk of Primary Sjögren's Syndrome With Fibrocystic Breast Disease: A Nationwide, Population-Based Study.

Front Med (Lausanne) 2021 1;8:704593. Epub 2021 Jul 1.

Big Data Center, Chung Hsing University, Taichung, Taiwan.

Primary Sjögren's syndrome (pSS) is characterized by exocrine glandular inflammation; however, the association between preceding mammary-gland-inflammation-related diseases and newly diagnosed pSS remains unexplored. We used the 2003-2013 data retrieved from Taiwan's National Health Insurance Research Database (NHIRD) to conduct the present population-based study. We identified newly diagnosed pSS female patients during the 2001-2013 period, as well as age-matched (1:20) and propensity-score-matched (1:2) non-SS individuals (as controls). We explored the associations between pSS and a history of mastitis and fibrocystic breast disease by determining adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using a conditional logistical regression analysis after controlling for potential confounders. We identified 9,665 patients with pSS and 193,300 age-matched non-SS controls, as well as 9,155 SS cases and 18,310 propensity-score-matched non-SS controls. We found that fibrocystic breast disease (aOR, 1.75; 95% CI, 1.63-1.88) were independently associated with incident SS, whereas mastitis and childbirth-associated breast infections were not associated with incident SS. We also found positive associations between SS and previously reported SS-associated diseases, including cardiovascular diseases, thyroid diseases, pancreatitis, bronchiectasis, infectious diseases, osteoporosis, and ankylosing spondylitis. In the propensity-score-matched populations, the associations between pSS and fibrocystic breast disease (aOR, 1.74; 95% CI, 1.58-1.91) remained consistent. The present population-based study revealed a previously unexplored association between pSS and history of fibrocystic breast disease, and the finding highlights the need to survey pSS in patients with mammary-gland-inflammation-associated diseases.
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http://dx.doi.org/10.3389/fmed.2021.704593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280500PMC
July 2021

Hydroxychloroquine might reduce risk of incident endometriosis in patients with systemic lupus erythematosus: A retrospective population-based cohort study.

Lupus 2021 Jul 14:9612033211031009. Epub 2021 Jul 14.

Institute of Medicine, 34899Chung Shan Medical University, Chung Shan Medical University, Taichung, Taiwan.

Background: SLE, which is common in women, is commonly treated with HCQ, an anti-inflammation medication. Reproductive-age women with SLE are prone to be impacted by endometriosis. This study analyzes the relationship between HCQ and endometriosis patients with SLE in order to determine whether HCQ is effective for treating the latter.

Methods: This population-based, retrospective cohort study analyzed the SLE risk in a cohort of newly diagnosed SLE patients with endometriosis during 2000 through 2013. Controls were selected at a 1:2 ratio through age-matching using the greedy algorithm. The Cox proportional hazard model was used to analyze the association between HCQ use and endometriosis incidence. Four different Cox regression models were used. Lastly, sensitivity analysis with PSOW and IPW was implemented to evaluate the hazard ratio (HR) of endometriosis after exposure with HCQ.

Results: In the cohort where age and sex matched high and low HCQ dosage, the average follow-up time was about 1 year. The cohort's overall incidence rates of endometriosis were 44.54 and 90.03 per 100000 person-month for high and low dosage respectively. The high dose group's conditional hazard ratio (aHR) for incidental endometriosis was 0.482 (CI = 0.191 to 1.213). The incidence rate and Kaplan-Meir curves of endometriosis were consistent with the results for the cohort.

Conclusion: This study demonstrated that SLE patients continuously treated with HCQ have a lower risk of developing endometriosis. Clinically, HCQ can be beneficial for endometriosis patients with SLE.
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http://dx.doi.org/10.1177/09612033211031009DOI Listing
July 2021

Health Assessment Questionnaire at One Year Predicts All-Cause Mortality in Patients with Early Rheumatoid Arthritis.

Arthritis Rheumatol 2021 Jul 5. Epub 2021 Jul 5.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

With great interest, we read the article by Fatima et al [1], which concluded that higher HAQ and disease activity score at 1 year were significantly associated with all-cause mortality in patients with early rheumatoid arthritis (RA). We agree with the use of discrete multivariate analysis on the cohort dataset. However, we would like to propose some methodological issues of the study.
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http://dx.doi.org/10.1002/art.41916DOI Listing
July 2021

Non-Typhoidal and the Risk of Kawasaki Disease: A Nationwide Population-Based Cohort Study.

Front Immunol 2021 16;12:701409. Epub 2021 Jun 16.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Objective: The aim of this study was to investigate the relationship between non-typhoidal (NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan.

Methods: In this retrospective cohort study, we enrolled 69,116 patients under 18 years of age, with NTS from January 1, 2000, to December 31, 2013, using the population-based National Health Insurance Research Database of Taiwan. A comparison group without NTS was matched (at a 1:4 ratio) by propensity score. The two cohorts were followed from the initial diagnosis of NTS until the date of KD development or December 31, 2013. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for covariates. Also, we conducted sensitivity analyses to examine our findings.

Results: After adjusting for covariates, the risk of KD for the children with NTS was significantly higher than that of the comparison group (hazard ratio = 1.31; 95% confidence interval = 1.03-1.66; p < 0.01). Stratified analysis showed that the associated risk of the investigated outcome was significant in children aged ≤2 years (aHR= 1.31, 95% C.I. 1.02-1.69), in female patients (aHR= 1.46, 95% C.I. 1.03-2.08), and in those without allergic diseases.

Conclusions: NTS is associated with an increased risk of KD in Taiwanese children.
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http://dx.doi.org/10.3389/fimmu.2021.701409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252964PMC
June 2021

Increased risk of valvular heart disease in patients with ankylosing spondylitis: a nationwide population-based longitudinal cohort study.

Ther Adv Musculoskelet Dis 2021 18;13:1759720X211021676. Epub 2021 Jun 18.

Division of Cardiology, Department of Internal Medicine, Chung Shan Medical University Hospital and Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, 40201.

Aims: We aimed to evaluate the risk of valvular heart disease (VHD) among patients with ankylosing spondylitis (AS).

Methods: This was a population-based cohort study utilizing the Longitudinal Health Insurance Research Database of the National Health Insurance in Taiwan. Patients with and without coding of newly diagnosed AS from 1999 to 2013 were assigned to the AS and non-AS groups, respectively. Primary outcome was the incidental risk of VHD. Multiple Cox regression was used to estimate the adjusted hazard ratio of VHD. Subgroup analysis and sensitivity tests were also conducted.

Results: The AS group included 3780 patients, and 22,680 matched subjects without an AS diagnosis were identified as controls. The AS group had an increased risk of VHD compared with non-AS controls (adjusted hazard ratio: 1.63; 95% confidence interval: 1.43-1.86;  < 0.001). Subgroup analysis also revealed an increased risk of individual types of VHD, including aortic, mitral, and tricuspid valve disease. Patients in the AS group had a higher incidence of valve replacement surgery after the onset of VHD.

Conclusion: Patients with AS had a significant risk of VHD compared to non-AS controls in this population-based cohort study. Screening for VHD may be needed in caring patients with AS. We suggest that echocardiography may be performed when patients are diagnosed with AS.
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http://dx.doi.org/10.1177/1759720X211021676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216336PMC
June 2021

Increased Risk of Sjögren's Syndrome in Patients with Obsessive-Compulsive Disorder: A Nationwide Population-Based Cohort Study.

Int J Environ Res Public Health 2021 06 1;18(11). Epub 2021 Jun 1.

Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.

Obsessive-compulsive disorder (OCD) includes a wide range of symptoms and is often associated with comorbidities. Although psychiatric involvement may be an early manifestation of Sjögren's syndrome (SS), only a few studies have demonstrated the relationship between OCD and SS. This is a nationwide cohort study identifying the risk of SS in OCD patients. We studied a longitudinal health insurance database for the period from 1999 to 2013. The study group was OCD patients with at least three outpatient visits or one hospitalization. The comparison cohort was matched by age and sex, as well as comorbidities. We calculated the risk of Sjögren's syndrome using Cox proportional hazard regression models. We performed a propensity score match for confounders and effect modifiers between the two groups. The propensity score probability was estimated through logistic regression. Primary outcome was the incidental SS. A total of 1678 patients with OCD (49% women, mean age: 35.6 years) and 3356 controls were followed up, resulting in 13,077 and 25,856 person-years, respectively. The hazard ratio for developing SS was 3.31 (95% C.I.: 1.74-6.28) in patients with OCD, compared to those without OCD after adjusting for age, sex, and comorbidities. Furthermore, the risk of SS significantly increased over the 2-year follow-up period after OCD diagnosis. We concluded that risk of SS is significantly increased in patients with OCD compared to those without OCD. Clinically, Sjögren's symptoms in OCD patients should be regularly assessed.
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http://dx.doi.org/10.3390/ijerph18115936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199316PMC
June 2021

Incidence of dementia after dengue fever: Results of a longitudinal population-based study.

Int J Clin Pract 2021 Aug 28;75(8):e14318. Epub 2021 Jun 28.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Objective: To investigate the epidemiological relationship between dengue fever and the subsequent development of dementia.

Methods: Using nationwide Taiwan registries from the National Health Insurance Research (NHIRD), we identified adults aged over 40 years who received a dengue fever diagnosis from 1 January 2000 to 31 December 2012 and who did not have a history of dementia. We used a propensity score match (PSM) to balance the baseline characteristics between groups. All eligible adults were sorted into either the dengue group or non-dengue group at a ratio of 1:4, matching by age, sex, index years, income level, and relevant comorbidities. Using Cox regression with proportional hazards models, we estimated the risk of dementia. The study period started from 1 January 2000 to 31 December 2013. We conducted sensitivity analyses to cross-validate study results.

Results: With a median of 8.01 years of follow-up, patients in the dengue group were more at risk of developing dementia than the non-dengue group. The estimated cumulative incidence of dementia was 7.21% in the dengue group and 4.03% in the non-dengue group (adjusted hazard ratio (aHR), 1.71; 95% CI, 1.03 to 2.83). Sensitivity analyses yielded consistent findings. We excluded any stroke cases before the end of the study, and subgroup analysis by follow-up time showed that the dengue group has a significantly higher risk of new-onset dementia >6 years after the index date (aHR 3.24; 95% CI, 1.42 to 7.37). The P value for interaction was significant (<.0001).

Conclusions: This study demonstrated a significantly higher risk of dementia in patients with dengue fever in Taiwan than in those without dengue fever.
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http://dx.doi.org/10.1111/ijcp.14318DOI Listing
August 2021

Outcomes of second-line oral antidiabetic drugs in persons with young-onset type 2 diabetes.

Diabetes Res Clin Pract 2021 Jun 24;177:108928. Epub 2021 Jun 24.

Department of Medicine, National Yang-Ming University School of Medicine, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road, Beitou District, Taipei 11217, Taiwan. Electronic address:

Aim: People with young-onset diabetes (YOD) exhibit a higher risk of morbidity and mortality than those with late-onset diabetes. Few studies have explored the preferred management of diabetes in such patients. We compared the risks of hospitalization and mortality among people with YOD to whom second-line oral antidiabetic drugs (OADs) were administered.

Methods: 7257 people taking second-line OADs after initial metformin therapy were enrolled during 2009-2014. Using add-on sulfonylureas (SUs) as a reference, the multivariable Cox regression model was used to compare the hospitalization and mortality risks among 5 categories of second-line OADs: alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, SUs, and thiazolidinediones.

Results: After baseline characteristics, comorbidities, duration of diabetes, and drug use were controlled, the adjusted hazard ratios and 95% confidence interval for all-cause, cardiovascular, and non-infection hospitalization and all-cause mortality for metformin plus DPP-4 inhibitors were 0.62 (0.52-0.73), 0.49 (0.29-0.85), 0.64 (0.54-0.76), and 0.50 (0.27-0.92), respectively, when compared with the data for metformin plus SUs.

Conclusions: Among people with YOD, taking add-on DPP-4 inhibitors was associated with lower risks of all-cause hospitalization and mortality than taking add-on SUs. DPP-4 inhibitors thus seem to be a suitable second-line OAD for such patients.
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http://dx.doi.org/10.1016/j.diabres.2021.108928DOI Listing
June 2021

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

Ann Rheum Dis 2021 Apr 20. Epub 2021 Apr 20.

Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.

Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), and sacroiliac MRI.

Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for these values were 51.9% and 97.9%, respectively.

Conclusions: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.
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http://dx.doi.org/10.1136/annrheumdis-2020-219446DOI Listing
April 2021

Bidirectional association between systemic lupus erythematosus and macrophage activation syndrome: a nationwide population-based study.

Rheumatology (Oxford) 2021 Jun 19. Epub 2021 Jun 19.

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Objectives: To determine the bidirectional relationship between macrophage activation syndrome (MAS) and systemic lupus erythematosus (SLE).

Methods: Using the 1997-2013 Taiwan's National Health Insurance Research Database, we identified patients with newly diagnosed SLE from 2001 to 2013 from the whole beneficiaries and selected individuals without SLE from a one-million representative population. Propensity score (PS) matching was performed to balance incident SLE patients and individuals without SLE according to age, sex, comorbidities and medical utilization. The association between a history of MAS and SLE was studied using conditional logistic regression analysis shown as adjusted odds ratio (aOR). The risk of MAS associated with SLE was analyzed using Cox proportional regression analysis shown as hazard ratio (aHR), and we conducted a sensitivity analysis using various definitions of MAS.

Results: We finally included 10,481 SLE patients and 20,962 PS-matched (1:2) non-SLE individuals. The correlation between a history of MAS and SLE did not reach statistical significance after adjustment for potential confounders (aOR, 1.18; 95% confidence interval, 0.80-1.75) in the age/sex-matched populations. In the 1:2 PS-matched populations, the risk of MAS markedly increased in patients with SLE (aHR, 7.18; 95% confidence interval, 4.97-10.36). Other risk factors for MAS included female, age ≥ 65 years, low income, a history of inflammatory bowel disease, and MAS history.

Conclusion: This nationwide, population-based study revealed that a history of MAS was not significantly associated with SLE risk. However, the risk of MAS was markedly associated with SLE and history of MAS.
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http://dx.doi.org/10.1093/rheumatology/keab502DOI Listing
June 2021

The influence of constipation on asthma: A real-world, population-based cohort study.

Int J Clin Pract 2021 Jun 16:e14540. Epub 2021 Jun 16.

Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan.

Background: Among respiratory diseases, asthma is one of the most burdensome disorder worldwide. Growing evidence disclose gut dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microflora. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess the risk of asthma in constipated patients by a nationwide population-based cohort study.

Methods: We analysed 86 860 constipated patients and 86 860 individuals without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Analysis of propensity score was utilised to match age, gender, comorbidities and medications at a ratio of 1:1. Besides, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and stratified analysis were conducted.

Results: The incidence of asthma was 10.4 per 1000 person-years in the constipation group, which was higher than the rate of 5.7 per 1000 person-years observed in the non-constipation group. After adjustment for age, gender, urbanisation, comorbidities and medications, constipated patients had a 1.81-fold greater risk of asthma compared with those without constipation (adjusted hazard ratio [aHR]: 1.81, 95% CI: 1.74-1.88). In subgroup analyses, patients aged 20-39 years had a 2.01-fold highest risk of asthma in the constipation cohort (aHR: 2.01, 95% CI: 1.82-2.22). Besides, the severity of constipation is associated with an increased risk of asthma; the aHR was 1.92 (1.84-2.00), 2.07 (1.94-2.21) and 2.10 (1.96-2.25) for ≤ 30 days, 31-120 days and >120 days of laxatives prescription within 1 year after the index date, respectively (P < .001).

Conclusion: Constipation relates to a significantly increased risk of asthma. Physicians should be aware of the possibility of asthma in constipated people. Further research is warranted to investigate the possible pathological mechanisms of this association.
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http://dx.doi.org/10.1111/ijcp.14540DOI Listing
June 2021

Is insulin the preferred treatment in persons with type 2 diabetes and liver cirrhosis?

BMC Gastroenterol 2021 Jun 12;21(1):263. Epub 2021 Jun 12.

Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei, 11221, Taiwan.

Background: Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis.

Methods: From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan's National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes.

Results: The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18-1.45), 1.18 (1.05-1.34), 1.53 (1.35-1.72), 1.26 (1.42-1.86), 1.41 (1.23-1.62), and 3.33 (2.45-4.53), respectively.

Conclusions: This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.
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http://dx.doi.org/10.1186/s12876-021-01773-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199810PMC
June 2021

Type 2 diabetes and the risk of colorectal polyps: A retrospective nationwide population-based study.

Medicine (Baltimore) 2021 May;100(19):e25933

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Abstract: The incidence rates of type 2 diabetes mellitus (T2DM) and colorectal polyps have been increasing over the last decades. However, direct associations between T2DM and colorectal polyps have not been extensively reported. We will explore the relationship between T2DM and colorectal polyps.In the retrospective study, we classified DM and NonDM groups (control) from 993,516 people in Taiwan nationwide population insurance database from the period of 2000 to 2013. We collected data on income and comorbidities through the international classification of diseases, ninth revision-clinical modification (ICD-9-CM) codes.The T2DM group had a higher incidence rate of colorectal polyps (31.97%, 95% confidence interval [CI] = 30.97-33.28) than the control group (25.9%, 95% CI = 25.1-26.72), and the crude incidence ratio was 1.235 (95% CI = 1.174-1.300). In 13 years of follow-up (2000-2013), T2DM was linked to a significantly higher cumulative probability of colorectal polyps (log-rank test: P = .0001).Patients with T2DM had a 1.23-fold higher risk of new colorectal polyps than control patients in 13 years of follow-up. We explain the T2DM increases incidence for colorectal polyps in long term follow-up.
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http://dx.doi.org/10.1097/MD.0000000000025933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133214PMC
May 2021

The association between air pollution level and breast cancer risk in Taiwan.

Medicine (Baltimore) 2021 May;100(19):e25637

University of Southampton, England.

Abstract: Breast cancer has the highest incidence of cancer among women in Taiwan, and air pollutants have been documented to have multiple adverse effects on human health. There is no relevant data, there has been no research in Taiwan to discuss the relevance of air pollutants to breast cancer, and evidence is sparse and inconclusive.Air quality data used in this study was collected from the 78 air quality monitoring stations situated in 74 municipalities in Taiwan during 2000 to 2011. The daily measurements taken at each monitoring station represented the level of exposure for each participant residing in that zone. The air pollution concentration is partitioned based on the concentration level in Quartile. We calculate the annual average air pollutants concentration (CO, NO, NO2, PM2.5, THC, and CH4) and the long-term average exposure levels of these pollutants until diagnosis of breast cancer, ending the study period for each individual.Patients who were living in areas with the highest air pollutants concentration (Quartile 4) had the most people diagnosed with breast cancer (CO:1.47%, NO:1.41%, NO2:1.63%, PM2.5:0.91%, THC:1.53%, CH4:2.33%). The patients who were exposed to Quartile 1 level of CO, NO, and NO2 concentration were the oldest, and other patients who were exposed to Quartile 4 level of CO, NO, and NO2 concentration were living in the areas of highest urbanization. Participants exposed to Quartile 4 level concentrations of air pollutants were associated with highest hazards ratios for breast cancer incidences.Most participants who were exposed to the high concentration of air pollutants (CO, THC and CH4) had a significantly higher risk of breast cancer. If we can improve air pollution in the environment, we can reduce the incidence of breast cancer and save precious medical resources.
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http://dx.doi.org/10.1097/MD.0000000000025637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133213PMC
May 2021

Urate-lowering Therapy and Chronic Kidney Disease Development in Patients with Gout.

Int J Med Sci 2021 29;18(12):2599-2606. Epub 2021 Apr 29.

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Chronic kidney disease (CKD) has emerged as a global health concern. Many studies have identified an association between hyperuricemia and CKD, and some studies have revealed that urate-lowering therapy (ULT) can attenuate CKD progression. However, only a few studies have explored the role of ULT in the prevention of new onset CKD. To compare the risk of incident CKD between users and nonusers of ULT in patients with gout, we conducted a 13-year population-based retrospective cohort study. Overall incidence of CKD was compared between 7126 ULT users and 7126 matched ULT nonusers. The CKD incidence rate for both the users and nonusers of ULT was 1.7 per 100 person-years, after adjusting for sex, age, region of residence, comorbidities, and medications used. No significant difference in CKD risk (adjusted hazard ratio [aHR]: 0.97; 95% confidence interval [CI]: 0.88-1.07) was noted between the ULT users and nonusers. In the subgroup of patients with diabetes mellitus (DM) and without hypertension (HT), ULT tended to be associated with lower risk of incident CKD (aHR: 0.52; 0.95% CI: 0.28-0.97). Compared with the risk of new onset CKD in patients receiving xanthine oxidase inhibitors, those receiving uricosuric agents seemed to have a lower risk of developing CKD (aHR: 0.81, 95% CI: 0.67-0.99). This population-based cohort study indicated that ULT is not associated with lower risk of CKD development. However, in the subgroup of patients with DM and without HT, ULT is associated with significantly lower risk of incident CKD.
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http://dx.doi.org/10.7150/ijms.59698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176173PMC
April 2021

Association between Traditional Chinese medicine and a lower risk of dementia in patients with major depression: A case-control study.

J Ethnopharmacol 2021 Oct 3;278:114291. Epub 2021 Jun 3.

Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China; Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan, Republic of China; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan, Republic of China. Electronic address:

Ethnopharmacological Relevance: Major depression is an important risk factor for dementia. Traditional Chinese medicine (TCM) can alleviate the symptoms of major depression. However, it is unclear whether TCM decreases the risk of dementia in patients with major depression. Therefore, in this nationwide case-control study, we aimed to evaluate the association between TCM and the risk of dementia.

Materials And Methods: We included 31,981 major depression patients with dementia from the National Dementia Database as the case group, and 4391 major depression patients without dementia from a one-million random sample database as the control group. We matched age (plus or minus two years), sex, and year of depression diagnosis based on a 1:4 ratio.

Result: There were 11,724 and 2931 patients in the case and control groups, respectively. Based on a conditional logistic regression analysis, the TCM groups exhibited significantly lower odds ratios with a 95% confidence interval of 0.83 (0.74-0.91). TCM treatment for more than 90 days, dispersing Qi, and activating blood circulation resulted in lower dementia risk with the following odds ratios and 95% confidence intervals: 0.60 (0.56-0.68), 0.87 (0.74-1.08), and 0.66 (0.49-0.81).

Conclusion: The results suggest that TCM is associated with lower dementia risk in major depression patients.
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http://dx.doi.org/10.1016/j.jep.2021.114291DOI Listing
October 2021

Association Between Chinese Herbal Medicine Therapy and the Risk of Chronic Kidney Disease in Gout Patients.

Front Pharmacol 2021 17;12:661282. Epub 2021 May 17.

Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.

Chinese herbal medicine (CHM) has been nationally and globally used in treating gout for over a millennium. The potential relationship between the incidence of chronic kidney disease (CKD) in gout patients and CHM therapy is unclear. Thus, this study aimed to provide some evidence regarding the relationship between CHM therapy and the occurrence of CKD in gout patients. : We used data from the National Health Insurance Research database (NHIRD) in Taiwan. In this population-based nested case-control study, all participants were identified by International Classification of Diseases, Ninth Revision (ICD-9). Conditional logistic regression was used to calculate the odds ratio (OR) of the risk of CKD in gout patients treated with CHM therapy. : Data on 1718 gout patients with CKD and 1:1 matched 1718 gout patients without CKD were collected for analysis. The results showed that CHM therapy in gout patients did not increase the risk of developing CKD (adjusted OR = 1.01; 95% confidence interval [CI]: 0.86-1.18; > 0.05). Moreover, CHM therapy in gout patients for >365 days did not increase the incidence of CKD (adjusted OR = 1.30; 95% CI: 0.90-1.88; = 0.162). : Traditional CHM therapy does not increase the incidence of CKD in gout patients.
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http://dx.doi.org/10.3389/fphar.2021.661282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165605PMC
May 2021

Association between Appendicitis and Incident Systemic Sclerosis.

J Clin Med 2021 May 27;10(11). Epub 2021 May 27.

Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan.

This nationwide study aimed to investigate the association between newly diagnosed systemic sclerosis (SSc) and previous appendicitis history. A total of 1595 patients who were newly diagnosed with SSc were recruited as the SSc cases from the 2003 to 2012 claims data of the entire population in Taiwan. The other 15,950 individuals who had never been diagnosed with SSc during 2003 and 2012 were selected as the non-SSc controls to match the SSc cases. We defined that the index date as the first date of SSc diagnosis of SSc cases and the first date of ambulatory visit for any reason of non-SSc controls. Conditional logistic regression analysis was applied for the association between appendicitis and the risk of the incident SSc, tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs). Potential confounders, including the Charlson comorbidity index (CCI), a history of periodontal disease, salmonella infection, and intestinal infection, were controlled. We further designed sensitivity analyses by varying the definition of appendicitis according to the status of receiving primary appendectomy. The mean age was 51 years in the case and control groups. Females accounted for 77.5%. A total of 17 (1.1%) out of 1595 SSc cases and 81 (0.5%) out of 15,950 non-SSc controls had a history of appendicitis before the index date had a history of appendicitis. A significant association between appendicitis and the risk of SSc was confirmed (OR, 2.03; 95% CI, 1.14-3.60) after adjusting potential confounders. CCI ≥ 1 (OR, 8.48; 95% CI, 7.50-9.58) and periodontal disease (OR, 1.55; 95% CI, 1.39-1.74) were also significantly associated with the risk of SSc. The association between appendicitis and SSc risk remained robust using various definitions of appendicitis. Our study demonstrated appendicitis was associated with the incident SSc. CCI ≥ 1 and periodontal disease also contributed to the risk of developing SSc.
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http://dx.doi.org/10.3390/jcm10112337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199283PMC
May 2021

Periodontitis is associated with incidental valvular heart disease: A nationwide population-based cohort study.

J Clin Periodontol 2021 Aug 1;48(8):1085-1092. Epub 2021 Jun 1.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Aim: Periodontitis and valvular heart disease (VHD) are common diseases. Both diseases are related to chronic inflammation and share many common risk factors. Previous periodontal studies had focused mainly on atherosclerotic cardiovascular disease. This study aimed to determine whether periodontitis is associated with the development of VHD.

Materials And Methods: This was a retrospective nationwide cohort study using Taiwan's Longitudinal Health Insurance Database. Using ICD-9-CM coding, both the periodontitis and non-periodontitis groups were matched.

Results: There were 8483 cases and 4919 cases of VHD diagnosed in the periodontitis group and non-periodontitis group, respectively. The cumulative incidence of VHD was significantly higher in the periodontitis group (log-rank test, p < .001), with the incidence density of 6.44 (95% CI, 6.31-6.58) per 1000 person-years in the periodontitis group compared to 4.65 (95% CI, 4.52-4.78) in the non-periodontitis group. The relative risk for VHD was 1.39 (95% CI, 1.34-1.44). After multivariate analysis, periodontitis was independently associated with a risk for VHD (HR, 1.38; 95% CI, 1.33-1.42, p < .001). Intensive treatment of periodontitis significantly lowered the risk for VHD (HR, 0.68; 95% CI, 0.60-0.77, p < .001).

Conclusions: Periodontitis was significantly associated with the development of VHD. Treatment of periodontitis reduced the risk for VHD.
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http://dx.doi.org/10.1111/jcpe.13478DOI Listing
August 2021

Correspondence to 'Cardiovascular and Renal Morbidity in Takayasu Arteritis: A Population-Based Retrospective Cohort Study From the United Kingdom'.

Arthritis Rheumatol 2021 May 27. Epub 2021 May 27.

Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.

We read with great interest the paper by Goel et al about cardiovascular disease in Takayasu arteritis (TAK) (1). They conducted an open retrospective matched cohort study to estimate risk of comorbidities in TAK. They then find out that Cardiovascular morbidity was increased among patients with TAK. It had excellent study questions and very innovative ideas. However, a few matters need to be addressed.
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http://dx.doi.org/10.1002/art.41804DOI Listing
May 2021

Association of hydroxychloroquine and cardiac arrhythmia in patients with systemic lupus erythematosus: A population-based case control study.

PLoS One 2021 20;16(5):e0251918. Epub 2021 May 20.

Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Objectives: Hydroxychloroquine is widely used to treat certain viral and rheumatic diseases including systemic lupus erythematosus. Cardiac arrhythmia is an important safety issue with hydroxychloroquine. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with systemic lupus erythematosus.

Methods: This was a nested case-control study using data from the Longitudinal Health Insurance Database of Taiwan. A conditional logistic regression model was used to analyse differences in the risk of arrhythmia between systemic lupus erythematosus patients with and without hydroxychloroquine treatment after controlling for related variables.

Results: A total of 2499 patients with newly diagnosed systemic lupus erythematosus were identified (81% females), of whom 251 were enrolled in the new-onset arrhythmia group (mean age 50.4 years) and 251 in the non-arrhythmia group (mean age 49.1 years). There was no significantly increased risk of cardiac arrhythmia (adjusted odds ratio = 1.49, 95% confidence interval: 0.98-2.25) or ventricular arrhythmia (adjusted odds ratio = 1.02, 95% confidence interval: 0.19-5.41) between the patients with and without hydroxychloroquine treatment. In addition, there were no significant differences in the risk of arrhythmia between those receiving hydroxychloroquine treatment for <180 days or ≥180 days, with a drug adherence rate of <50% or ≥50%, and receiving a daily dose of <400 mg or ≥400 mg.

Conclusion: In patients with systemic lupus erythematosus, hydroxychloroquine treatment did not significantly increase the risk of cardiac arrhythmia or life-threatening ventricular arrhythmia regardless of the different hydroxychloroquine treatment duration, drug adherence rate, or daily dose.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251918PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136629PMC
May 2021

Risk of subsequent atrial fibrillation in patients with myasthenia gravis: A population-based cohort study.

Medicine (Baltimore) 2021 May;100(20):e26008

Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung.

Abstract: The purpose of this study was to explore the association between myasthenia gravis (MG) and the risk of atrial fibrillation (AF) in an Asian population. The risk was analyzed in a cohort of 5528 patients with history of MG and 5528 individuals without MG using a hospitalization claim dataset. Both groups were matched by age, sex, index year and baseline comorbidities as an original analysis. A Cox proportional hazard model was used to estimate the hazard ratio and 95% confidence interval of AF after adjusting for demographic and relevant clinical covariates. The adjusted hazard ratio of the MG group compared with that of the non-MG group was 1.03 (95% confidence interval, 0.76-1.38) for AF. A stratified analysis showed that compared with the propensity score matched non-MG group, there was no increased risk of developing AF based on age categories, gender, or comorbidities. Different time follow-up periods results showed no increased risk of AF compared with the non-MG group. Overall, in the Taiwanese cohort, MG is not associated with an increased risk of AF.
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http://dx.doi.org/10.1097/MD.0000000000026008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137031PMC
May 2021

Correspondence on 'Which factors are associated with bone marrow oedema suspicious of axial spondyloarthritis as detected by MRI in the sacroiliac joints and the spine in the general population?'

Ann Rheum Dis 2021 May 17. Epub 2021 May 17.

Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan

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http://dx.doi.org/10.1136/annrheumdis-2021-220567DOI Listing
May 2021

Lymphoma and Sjögren Syndrome: A Common Overlapping Syndrome?

J Rheumatol 2021 May 15. Epub 2021 May 15.

Taichung Veterans General Hospital, Taichung; Institute of Medicine, College of Medicine, National Yang Ming University, Taipei; Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung; Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Institute of Medicine, College of Medicine, Chung Shan Medical University, Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. The authors have no conflict of interest to disclose. Address correspondence Dr. J. Cheng-Chung Wei, Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan. Email:

We read with interest the research article entitled, "Bidirectional Relationship Between Primary Sjögren Syndrome and Non-Hodgkin Lymphoma: A Nationwide Population-based Study" by Wang, published in The authors conducted research revealing that primary Sjögren syndrome (SS) and non-Hodgkin lymphoma (NHL) are bidirectionally associated with each other.
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http://dx.doi.org/10.3899/jrheum.201537DOI Listing
May 2021

Associations of Chinese Herbal Medicine Usage with Risk of Dementia in Patients with Parkinson's Disease: A Population-Based, Nested Case-Control Study.

J Altern Complement Med 2021 Jul 12;27(7):606-612. Epub 2021 May 12.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Patients who have Parkinson's disease (PD) comorbid with dementia is common. With the prolonged life expectancy, dementia is gradually becoming prevalent and affects most patients' life qualities. However, the efficacy of current treatments in dementia of PD is limited. Previous studies indicated the potential roles of Chinese herbal medicine (CHM) in treating dementia, yet the correlation between CHM usage and risk of dementia in PD patients is unclear. This case-control study was nested within a National Health Insurance database of patients over 50 years with newly diagnosed PD from year 2000 to 2010. Among these PD patients, dementia and nondementia groups were discussed, respectively, in terms of the duration of taking CHM (≥90 vs. <90 days), age (50-64 vs. ≥65 years) and gender. The risk of dementia in patients with PD is lower in CHM users compared with non-CHM users, especially in those taking CHM for more than 90 days (adjusted odds ratio [aOR] 0.58; 95% confidence interval [95% CI] 0.39-0.87). The use of CHM was significantly related to the lower risk of dementia in the subgroups of patients with age ≥65 years for CHM usage <90 days (aOR 0.68; 95% CI 0.53-0.88), patients with age ≥65 years for CHM usage ≥90 days (aOR 0.63; 95% CI 0.42-0.94), female patients using CHM for ≥90 days (aOR 0.43; 95% CI 0.22-0.84), and male patients using CHM for <90 days (aOR 0.62; 95% CI 0.43-0.88). The authors demonstrated the association of CHM usage with lower risk of dementia in patients with PD, especially in women with the usage of CHM for more than 90 days. Since no arbitrary causal conclusions could be drawn from retrospective cohort studies, the finding in this study could be used to generate a hypothesis for a subsequent design of prospective longitudinal study.
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http://dx.doi.org/10.1089/acm.2020.0422DOI Listing
July 2021
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