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Herpes simplex virus (HSV) is an opportunistic infection antigen in solid organ transplant (SOT) recipients. However, this phenomenon has received limited attention from epidemiologists. Our study aims to determine the HSV infection risk in SOT recipients. This was a nationwide population-based cross-sectional study based on the National Health Insurance Research Database from 2002 to 2015. We used propensity score matching to avoid selection bias and analyzed the association between HSV infection and SOT recipients with multiple logistic regression analysis. At a 3-year follow-up, SOT recipients had a higher risk of developing HSV, with an adjusted odds ratio (aOR) of 3.28 (95% confidence interval (CI), 2.51–4.29). Moreover, at 6-month, 1-year, and 2-year follow-ups, SOT recipients also had an increased risk of HSV than general patients with aORs of 3.85 (95% CI, 2.29–6.49), 4.27 (95% CI, 2.86–6.36), and 3.73 (95% CI, 2.74–5.08), respectively. In the subgroup analysis, lung transplant recipients (aOR = 8.01; 95% CI, 2.39–26.88) exhibited a significantly higher chance of HSV among SOT recipients, followed by kidney transplant recipients (aOR = 3.33; 95% CI, 2.11–5.25) and liver transplant recipients (aOR = 3.15; 95% CI, 2.28–4.34). HSV can develop at any time after organ transplantation. SOT recipients had a higher risk of HSV infection than the general population at 6 months, 1 year, 2 years, and 3 years after transplantation, with the highest chance at 1 year after. In addition, the patients who underwent lung transplantion were at higher risk for HSV infection than liver or kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: In previous studies, it was reported that non-alcoholic fatty liver disease (NAFLD) incidence and prevalence increased in children with atopic dermatitis. Nevertheless, the actual association between the two diseases has not been fully proven in large-scale studies, and real-world evidence is missing. The objective of this nationwide, longitudinal cohort study was to evaluate the association between NAFLD and atopic dermatitis. Methods: The National Health Insurance Research Database in Taiwan was utilized in this study. Patients with records of NAFLD diagnosis were recruited as the experimental group, and patients having less than three outpatient visits or one inpatient visiting record due to NAFLD were excluded from the study design. Non-NAFLD controls were matched based on a 1:4 propensity score matching. Potential confounders including age, gender, comorbidity, and medical utilization status were considered as covariates. The risk of future atopic dermatitis would be evaluated based on multivariate Cox proportional hazard regression. Results: Compared with people without NAFLD, a decreased risk of atopic dermatitis in NALFD patients had been observed (aHR = 0.93, 95% CI 0.87-0.98). The trend was especially presented in young NAFLD patients. In patients younger than 40 years old, a 20% decreased risk of atopic dermatitis was reported (aHR = 0.80, 95% CI 0.70-0.92). Conclusion: People with NAFLD were not associated with an increased risk of atopic dermatitis. Conversely, a 0.93-fold risk was noted in NAFLD patients, compared with NAFLD-free controls. Future studies are warranted to evaluate further the mechanism regarding the interplay between the inflammatory mechanisms of NAFLD and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Cheng-Hao Huang,1,2 Mei-Chen Lin,3,4 I-Ching Chou,5,6 Ching-Liang Hsieh2,7,8 1Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung City, 40447, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan; 4College of Medicine, China Medical University, Taichung, 40402, Taiwan; 5School of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 6Division of Pediatric Neurology, China Medical University Children’s Hospital, Taichung City, 40447, Taiwan; 7Chinese Medicine Research Center, China Medical University, Taichung City, 40402, Taiwan; 8Graduate Institute of Acupuncture Science, China Medical University, Taichung City, 40402, TaiwanCorrespondence: Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366 ext. 3128, Fax +886-4-22037690, Email clhsieh@mail.cmuh.org.twBackground: Migraine is a recurrent headache disease that has been identified as a risk factor for subsequent dementia. The present study collected data from Taiwan’s National Health Insurance Research Database (NHIRD) to investigate the incidence of dementia in patients with migraine who did or did not concurrently receive acupuncture treatment.Methods: A 1:1 propensity score method was used to match an equal number of patients (N = 4813) in the acupuncture and nonacupuncture cohorts based on sex, age, migraine diagnosis year, index year, insurance amount, urbanization level, baseline comorbidities, and medication usage. We employed Cox proportional hazards models to evaluate the risk of dementia.Results: Patients with migraine who received acupuncture treatment were found to have a lower risk of dementia (adjusted hazard ratio [aHR] = 0.51, 95% CI = 0.40– 0.65) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the nonacupuncture cohort (Log rank test, p < 0.001). This propensity score–matched cohort study demonstrated an association between acupuncture treatment and dementia development in patients with migraine in Taiwan.Conclusion: The results suggest that acupuncture treatment significantly reduced the development of dementia in patients with migraine.Keywords: acupuncture, migraine, dementia, National Health Insurance Research Database, NHIRD, propensity score, cohort

Purpose: Individuals with bipolar disorder (BD) may have an increased risk of exposure to prescription opioids. However, it is still unknown whether such risk also occurs in their offspring. This study aimed to investigate the risk of exposure to prescription opioid use and related medical conditions in the offspring of parents with BD. Methods: This study used the Taiwan National Health Research Database and included offspring who had any parent with a diagnosis of BD. The matched-control cohort was randomly identified from the offspring of parents without any major psychiatric disorders (MPD). We identified data pertaining to opioid prescription and related medical conditions, namely pain disorder, malignancy, autoimmune disease, and arthropathy. The Poisson regression was used to estimate odds ratios and 95% confidence intervals. Results: In total, 11,935 offspring of parents with BD and 119,350 offspring of parents without any MPD were included. After controlling for demographics and mental disorders, offspring of parents with BD demonstrated higher rates of prescription opioid use than those of parents without MPD, especially the intravenous/intramuscular form of opioids and prescription in hospital settings. In addition, offspring of parents with BD had a higher odds of pain disorders than those of parents without MPD. Conclusion: Our study identifies a higher odd for developing pain disorders and exposure to prescription opioids among children of parents with BD. [ABSTRACT FROM AUTHOR]

James Cheng-Chung Wei,1– 3 Yi-Jung Chang,4 Yu-Hsun Wang,5 Chih-Jung Yeh6 1Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; 2Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 4Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; 5Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Public Health, Chung Shan Medical University, Taichung, TaiwanCorrespondence: Chih-Jung Yeh, Department of Public Health, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, South District, Taichung, 40201, Taiwan, Tel +886 4 24739595 #11794, Fax +886 4 24637389, Email alexyeh@csmu.edu.twBackground: Previous research has pointed to the relationship between psoriasis and the development of gout. However, most previous studies had either small sample sizes or short study durations. Therefore, in this nationwide cohort study, we investigated the effect of psoriasis on the risk of gout development.Methods: The study group included one million patients from Taiwan, whom we followed for 14 years. The participants were divided into two cohorts designated as psoriasis and non-psoriasis. A 1:4 propensity score matching test was used to compare age, sex, and index year between the two cohorts. Cox proportional hazard regression was used to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of gout. Sensitivity analyses were conducted to evaluate the HR for gout after the occurrence of psoriasis.Results: The incidence densities of gout in the psoriasis and non-psoriasis cohorts were 6.96 and 5.09 per 1000 person-years, respectively. After adjusting for age, sex, urbanization, comorbidities, and nonsteroidal anti-inflammatory drug (NSAID) use, the adjusted hazard ratio (aHR) with 95% CI for incidental gout in the psoriasis group was 1.38 (1.2– 1.6). Moreover, the aHR (95% CI) values for gout risk in patients with psoriasis using NSAIDs and those who did not were 1.21 (1.0– 1.47) and 1.65 (1.33– 2.05), respectively.Conclusion: This study demonstrated an association between psoriasis and risk of developing gout. Clinically, patients with psoriasis should be evaluated for incidental gout.Keywords: psoriasis, gout, epidemiology, corticosteroids, NHIRD, cohort

Kuan-Yu Chen,1 Ming-Cheng Huang,2,3 Cheng-Li Lin,4 Yu-Chen Lee,2,3,5 Mei-Yao Wu,2,6,&ast; Hung-Rong Yen2,3,7– 9,&ast; 1Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 3Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 4Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 5Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 6School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 7Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 8Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 9Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong YenGraduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22053366 ext. 3001Fax +886-4-22365141Email hungrongyen@mail.cmu.edu.twMei-Yao WuSchool of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22052121 ext. 4561Fax +886-4-22037690Email meiyaowu0919@gmail.comBackground: Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence.Methods: Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts.Results: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50– 0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer’s disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48– 0.71) and 0.51 (95% CI 0.39– 0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001).Conclusion: The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.Keywords: acupuncture, Alzheimer’s disease, depression, dementia, National Health Insurance Research Database, NHIRD, traditional Chinese medicine

Background and aimsStudies have demonstrated that the short-term use of metformin benefits liver function among patients with type 2 diabetes mellitus (T2DM). However, few studies have reported on the effects of long-term metformin treatment on liver function or liver histology. This study investigated the correlation between metformin use and the incidence of nonalcoholic fatty liver disease (NAFLD) among patients with T2DM.MethodsThis population-based study investigated the risk of NAFLD among patients with T2DM who received metformin treatment between 2001-2018. Metformin users and metformin nonusers were enrolled and matched to compare the risk of NAFLD.ResultsAfter 3 years, the patients who received

Aims: Individuals with substance use disorders (SUD) have higher risk of developing pain disorders. This study aimed to investigate the risk of major psychiatric disorders (MPD), SUD, and pain disorders among their offspring. Methods: This study used data from the Taiwan National Health Research Database. The case cohort included participants who had a parent diagnosed with SUD. The matched control cohort was offspring of parents without any SUD or major psychiatric disorder (MPD). Poisson regression was applied to estimate the risk of MPD, SUD, and pain disorder between case and control cohorts. Results: We recruited 13,840 cases and 138,400 matched controls. After adjusting for demographic characteristics and family history of psychiatric disorder, the offspring of parents with SUD had higher risk for bipolar disorder (reported as risk ratio with 95% confidence interval: 2.48, 1.79–3.43), depressive disorder (2.22, 1.94–2.52), SUD (2.53, 2.18–2.92), and alcohol use disorder (1.43, 1.16–1.76) than controls. With adjustments of demographic characteristics, individual MPD, and family history of psychiatric disorder, they also presented higher risk than controls for several pain disorders, including migraine (1.43, 1.15–1.78), fibromyalgia (1.21, 1.03–1.42), dorsopathies (1.20, 1.06–1.37), dysmenorrhea (1.16, 1.04–1.29), irritable bowel syndrome (1.26, 1.11–1.43), and dyspepsia (1.14, 1.02–1.27). Conclusions: Clinicians should be aware of the influence of parental SUD on the elevated risk for MPD, SUD, and pain disorders in their offspring. [ABSTRACT FROM AUTHOR]

Background: Whether or not patients with gastroesophageal reflux disease (GERD) have a higher risk of developing subsequent dementia remains unknown, and no observational evidence from population-based data is available. This study was to determine whether patients with GERD have a higher future risk of developing dementia. Methods: For the period 2000–2012, datasets from the Longitudinal Health Insurance Database (LHID, subset of National Health Insurance Research Database in Taiwan) were analyzed. Definition of GERD was based on ICD-9-CM codes 530.11 and 530.81 and prescriptions for PPIs. After matching gender, age, index year, and comorbidities, each GERD patient was matched with four control patients without GERD. Future risk of dementia was evaluated, and sensitivity analysis of subgroups was conducted to clarify the potential association. Results: In the present study, 13,570 patients were included in the GERD cohort and 54,280 patients were included in the control cohort. Patients with GERD showed higher risk developing dementia than control group, with an aHR of 1.34 (95% C.I., 1.07, 1.67). In GERD patients between above 70 years old, the risk of developing dementia was higher than that of the control groups (aHR = 1.34; 95% C.I., 1.01, 1.77). Conclusion: Patients with GERD showed higher incidence of dementia, and elder patients had the highest risk of developing dementia. Clinicians should be concern of the association between GERD and dementia and should develop strategies to prevent dementia while managing patients with GERD. [ABSTRACT FROM AUTHOR]

Objectives To determine the bidirectional relationship between macrophage activation syndrome (MAS) and SLE. Methods Using the 1997–2013 Taiwan National Health Insurance Research Database, we identified patients with newly diagnosed SLE from 2001 to 2013 and selected individuals without SLE from a 1 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 an adjusted odds ratio (aOR). The risk of MAS associated with SLE was analysed using Cox proportional regression analysis, shown as an adjusted hazard ratio (aHR), and we conducted a sensitivity analysis using various definitions of MAS. Results We 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% CI, 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% CI 4.97, 10.36)]. Other risk factors for MAS included female gender, age ≥65 years, low income, a history of inflammatory bowel disease and a history of MAS. 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 a history of MAS. [ABSTRACT FROM AUTHOR]

Background: Association between nonalcoholic fatty liver disease (NAFLD) and future psoriasis has not yet been confirmed, although the two diseases partially share a common pathogenesis pathway. Studies have revealed an association between psoriasis and subsequent NAFLD; however, these studies were limited to small sample sizes and a cross-sectional study design. Hence, the main objective of this population-based longitudinal cohort study was to evaluate the bidirectional association between psoriasis and NAFLD. Methods: Data were retrieved from Taiwan's National Health Insurance Research Database. Patients with new-onset NAFLD and psoriasis were respectively enrolled in two cohorts. For each comparison cohort, propensity-score-matched controls with no record of NAFLD or psoriasis were selected. An adjusted hazard ratio (aHR) was applied to evaluate subsequent risks. Results: The risk of patients with new-onset NAFLD developing psoriasis was statistically significant, with an HR of 1.07 (95% CI, 1.01–1.14). For younger patients with NAFLD, the risk of developing psoriasis was 1.3-fold higher. The risk of patients with new-onset psoriasis developing NAFLD in the future was 1.28-fold higher than that of patients without psoriasis (95% CI, 1.21–1.35), and patients in younger psoriasis subgroups below the age of 40 years were at a higher risk than those in older subgroups, with an aHR of 1.55 (95% CI, 1.40–1.71). Conclusion: Evidence supports a bidirectional association between NAFLD and psoriasis, especially in patients below the age of 40 years. The correlation between the two diseases and the subsequent risk of disease development should be considered when caring for patients. [ABSTRACT FROM AUTHOR]

BackgroundWhether or not patients with gastroesophageal reflux disease (GERD) have a higher risk of developing subsequent dementia remains unknown, and no observational evidence from population-based data is available. This study was to determine whether patients with GERD have a higher future risk of developing dementia.MethodsFor the period 2000–2012, datasets from the Longitudinal Health Insurance Database (LHID, subset of National Health Insurance Research Database in Taiwan) were analyzed. Definition of GERD was based on ICD-9-CM codes 530.11 and 530.81 and prescriptions for PPIs. After matching gender, age, index year, and comorbidities, each GERD patient was matched with four control patients without GERD. Future risk of dementia was evaluated, and sensitivity analysis of subgroups was conducted to clarify the potential association.ResultsIn the present study, 13,570 patients were included in the GERD cohort and 54,280 patients were included in the control cohort. Patients with GERD showed higher risk developing dementia than control group, with an aHR of 1.34 (95% C.I., 1.07, 1.67). In GERD patients between above 70 years old, the risk of developing dementia was higher than that of the control groups (aHR = 1.34; 95% C.I., 1.01, 1.77).ConclusionPatients with GERD showed higher incidence of dementia, and elder patients had the highest risk of developing dementia. Clinicians should be concern of the association between GERD and dementia and should develop strategies to prevent dementia while managing patients with GERD.

ObjectiveWe investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).MethodsBCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting β2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}.ResultsCompared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25–4.33), 2.65 (1.87–3.75), 2.66 (1.74–4.05), 2.53 (1.61–3.99), 1.76 (1.43–2.18), 9.88 (3.27–30.5), and 1.73 (1.15–2.58), respectively except fludiazepam 1.33 (0.73–2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs 30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78–3.29), 2.43 (0.90–6.55), 5.02 (1.76–14.3), and 2.28 (1.43–3.62), respectively.ConclusionThe bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.

BackgroundAssociation between nonalcoholic fatty liver disease (NAFLD) and future psoriasis has not yet been confirmed, although the two diseases partially share a common pathogenesis pathway. Studies have revealed an association between psoriasis and subsequent NAFLD; however, these studies were limited to small sample sizes and a cross-sectional study design. Hence, the main objective of this population-based longitudinal cohort study was to evaluate the bidirectional association between psoriasis and NAFLD.MethodsData were retrieved from Taiwan’s National Health Insurance Research Database. Patients with new-onset NAFLD and psoriasis were respectively enrolled in two cohorts. For each comparison cohort, propensity-score-matched controls with no record of NAFLD or psoriasis were selected. An adjusted hazard ratio (aHR) was applied to evaluate subsequent risks.ResultsThe risk of patients with new-onset NAFLD developing psoriasis was statistically significant, with an HR of 1.07 (95% CI, 1.01–1.14). For younger patients with NAFLD, the risk of developing psoriasis was 1.3-fold higher. The risk of patients with new-onset psoriasis developing NAFLD in the future was 1.28-fold higher than that of patients without psoriasis (95% CI, 1.21–1.35), and patients in younger psoriasis subgroups below the age of 40 years were at a higher risk than those in older subgroups, with an aHR of 1.55 (95% CI, 1.40–1.71).ConclusionEvidence supports a bidirectional association between NAFLD and psoriasis, especially in patients below the age of 40 years. The correlation between the two diseases and the subsequent risk of disease development should be considered when caring for patients.

BackgroundCandida infection is prevalent in patients with Sjögren's syndrome (SjS), which usually takes years to reach diagnosis. Is the link a two-way street? The role of Candida infection before SjS has not been examined clearly. This study was conducted to provide epidemiological evidence regarding the relationship between the first acquisition of Candida infection and subsequent SjS.MethodsTotally, 23,494 individuals newly diagnosed with Candida infection were enrolled from 2000, to 2012. Controls (N = 93,976) were selected at a 1:4 ratio through propensity score matched (PSM) using the greedy algorithm. Exposure was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.Main Outcomes and MeasuresSjS was recorded in the Registry for Catastrophic Illness Patients Database (RCIPD). Cox proportional hazard model was used to analyze the association and sensitivity analyses for cross-validation.ResultsOf 117,470 individuals (106,077 [89%] women), 23,494 individuals (20.0%) had Candida infection and 104 individuals (0.1%) developed SjS. The incidence of SjS was higher in the exposed group compared with the controls (1.92 vs. 0. 98 per 10,000 person-years) with adjusted hazard ratio (aHR) 1.90 (95% CI, 1.25–2.87). The aHRs in subgroups of aged 18–30 years, oral candidiasis and depression were 4.30 (95% CI, 1.60–11.55), 4.70 (4.70–13.93) and 6.34 (2.16–18.66). Sensitivity analyses yield consistent results.ConclusionsResidents in Taiwan with Candida infection have higher risk of SjS. For early diagnosis of SjS, clinicians are advised to take Candida infection into account in some situation.

Objective: We investigated the correlation between nontyphoidal S almonella (NTS) infection and systemic lupus erythematosus (SLE) risk. Methods: This case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups. Results: The mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren's syndrome; and developed intensive and severe NTS infection during admission. Conclusions: Exposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren's syndrome also contributed to the risk of developing SLE. [ABSTRACT FROM AUTHOR]

ObjectiveWe investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk.MethodsThis case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups.ResultsThe mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome; and developed intensive and severe NTS infection during admission.ConclusionsExposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome also contributed to the risk of developing SLE.

IntroductionInfections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus.ObjectiveTo investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis.MethodsRetrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25–6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82–7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68–5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups.ConclusionsSymptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

Introduction: Infections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus. Objective: To investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis. Methods: Retrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25–6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82–7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68–5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups. Conclusions: Symptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases. [ABSTRACT FROM AUTHOR]

Postoperative sepsis is a major type of sepsis. Sociodemographic characteristics, incidence trends, surgical procedures, comorbidities, and organ system dysfunctions related to the disease burden of postoperative sepsis episodes are unclear.

Ing-Luen Shyu,1,2 Li-Yu Hu,3 Yi-Jen Chen,1,4,5 Peng-Hui Wang,1,4,5 Ben-Shian Huang1,4,5 1Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Obstetrics and Gynecology, Chi-Mei Hospital, Tainan City, Taiwan; 3Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Obstetrics and Gynecology, School of Medicine, Taipei, Taiwan; 5Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Introduction: Depression might affect women with cervical cancer and can deteriorate their quality of life or even their compliance with cancer treatments. The aim of this study was to investigate the incidence of depression and risk factors for developing depression among women with cervical cancer in Taiwan. Patients and methods: This study enrolled patients with newly diagnosed cervical cancer from the National Health Insurance Research Database in Taiwan. From a population of 21,400,826 residents, each cervical cancer patient was matched with one subject without cervical cancer according to sex, age, and comorbidities with the same diagnostic index. The International Classification of Diseases, Ninth Revision, code 180.9 was used to identify patients with cervical cancer, and 296.0X–296.1X, 296.4X–296.8X, 296.2X–296.3X, 300.4, and 311.X codes were used to identify those with depressive disorders.Results: In total, 19,316 newly diagnosed cervical cancer patients were enrolled from January 2000 to December 2005, and the median follow-up period was 5.23 years (1.75–8.48 years). The prevalence of depressive disorder was 4.21% (813 of 19,316) in the cervical cancer cohort, and it was 3.85% (744 of 19,316) in the control cohort. The incidence risk ratio of depressive disorders was 1.35 (95% CI =1.22–1.49, P

ObjectiveThe aim of this study was to investigate the relationship between non-typhoidal Salmonella (NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan.MethodsIn this retrospective cohort study, we enrolled 69,116 patients under 18 years of age, with NTS from January 1st, 2000, to December 31st, 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 31st, 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.ResultsAfter 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.ConclusionsNTS is associated with an increased risk of KD in Taiwanese children.

Objective: The aim of this study was to investigate the relationship between non-typhoidal Salmonella (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 1st, 2000, to December 31st, 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 31st, 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. [ABSTRACT FROM AUTHOR]

ObjectivesClinically, associations have been observed between Sjögren’s syndrome and fibromyalgia. Nonetheless, population-based evidence evaluating the risk of Sjögren’s syndrome in fibromyalgia patients is lacking. The main purpose of this retrospective cohort study was to determine the association between fibromyalgia and subsequent development of Sjögren’s syndrome.MethodsThis retrospective cohort study extracted data from the Longitudinal Health Insurance Database (LHID) of the Taiwan National Health Insurance (NHI). During 2000-2012, patients with newly-diagnosed fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1) were defined as the exposure cohort. Age- and gender-matched individuals without fibromyalgia were used as the comparison cohort. The adjusted hazard ratios (aHR) for the occurrence of Sjögren’s syndrome in those with fibromyalgia were evaluated along with stratified analyses of different subgroups.ResultsOf the 149,706 subjects whose data were extracted from the LHID, 74,853 subjects had coded fibromyalgia and 74,853 control subjects were without fibromyalgia. Compared to the control group, patients with fibromyalgia had an aHR of 2.00 (95% Confidence Interval [CI], 1.52-2.61) for developing Sjögren’s syndrome. In fibromyalgia patients aged 20-49 years, the aHR for future Sjögren’s syndrome was 3.07 (95% CI, 1.92-4.89).ConclusionPatients with fibromyalgia, both males and females, have a higher risk for developing Sjögren’s syndrome than those without fibromyalgia, especially those aged 20-49 years. While managing patients, clinicians should be aware of the bidirectional association between the two diseases, which helps to understand the impact of the association on disease activity and diagnosis.

Objectives: The main purpose of this retrospective cohort study was to provide an evaluation of Ankylosing spondylitis (AS) patients' fibromyalgia risk in different age and sex subgroups by analyzing large study samples.Methods: Datasets from the National Taiwan Insurance Research Database (NHIRD) were retrieved in this retrospective cohort study. This study was approved by the Institutional Review Board of Chung Shan Medical University (IRB permit number CS15134). Within the Longitudinal Health Insurance Database (LHID), and the subset of NHIRD, we identified AS patients to explore the risk of further fibromyalgia. The exposure cohort included patients with newly-diagnosed AS (ICD-9-CM:720.0) during 2000–2013. After 1:4 age-sex matching and 1:2 propensity score matching, and adjusting potential confounders, individuals without AS were identified as a comparison cohort. The adjusted hazard ratio of subsequent development of fibromyalgia in people with AS was evaluated. Further stratification analyses of different ages and genders were then undertaken to validate the results.Results: In total, 17 088 individuals were included in the present study, including 5,696 patients with AS and 11,392 individuals without AS. Respective incidence rates (per 1,000 person-months) of fibromyalgia was 0.52 (95% CI, 0.46–0.59) in the AS cohort and 0.39 (95% CI, 0.35–0.44) in the non-AS cohort. Compared with the non-AS cohort, aHR of developing fibromyalgia was 1.32 (95% CI, 1.12–1.55) in people with AS. This association was consistent in both statistical models of 1:4 age–sex matching and 1:2 propensity score matching.Conclusion: Patients with AS were associated with a higher risk of fibromyalgia, especially those over 65 years old. In managing patients with AS, clinicians should be aware of this association, which could impact diagnosis, disease activity evaluation, and treatment.

Background: To investigate the relationship between pleural empyema (PE) and peripheral arterial disease (PAD).Methods: We conducted a retrospective cohort study using data from the National Health Institute Research Database. Univariable and multivariable Cox's proportional hazard regressions were performed to investigate the association between PE and the risk of PAD. Kaplan–Meier method and the differences were assessed using a log-rank test.Results: The overall incidence of PAD was higher in the PE cohort than in the non-PE cohort (2.76 vs. 1.72 per 1,000 person-years) with a crude hazard ratio (HR) of 1.61 [95% confidence interval (CI) = 1.41–1.83]. After adjustment for age, gender, and comorbidities, patients with PE were noted to be associated with an increased risk of PAD compared with those without PE [adjusted HR (aHR) = 1.18, 95% CI = 1.03–1.35]. Regarding the age-specific comparison between the PE and non-PE cohorts, PAD was noted to be significantly high in the ≤ 49 years age group (aHR = 5.34, 95% CI = 2.34–10.1). The incidence of PAD was higher in the first 2 years, with an aHR of 1.35 (95% CI = 1.09–1.68) for patients with PE compared with those without PE.Conclusion: The risk of PAD was higher if patients with PE were younger than 49 years and within the 2-year diagnosis of PE.

Objectives: Clinically, associations have been observed between Sjögren's syndrome and fibromyalgia. Nonetheless, population-based evidence evaluating the risk of Sjögren's syndrome in fibromyalgia patients is lacking. The main purpose of this retrospective cohort study was to determine the association between fibromyalgia and subsequent development of Sjögren's syndrome. Methods: This retrospective cohort study extracted data from the Longitudinal Health Insurance Database (LHID) of the Taiwan National Health Insurance (NHI). During 2000-2012, patients with newly-diagnosed fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1) were defined as the exposure cohort. Age- and gender-matched individuals without fibromyalgia were used as the comparison cohort. The adjusted hazard ratios (aHR) for the occurrence of Sjögren's syndrome in those with fibromyalgia were evaluated along with stratified analyses of different subgroups. Results: Of the 149,706 subjects whose data were extracted from the LHID, 74,853 subjects had coded fibromyalgia and 74,853 control subjects were without fibromyalgia. Compared to the control group, patients with fibromyalgia had an aHR of 2.00 (95% Confidence Interval [CI], 1.52-2.61) for developing Sjögren's syndrome. In fibromyalgia patients aged 20-49 years, the aHR for future Sjögren's syndrome was 3.07 (95% CI, 1.92-4.89). Conclusion: Patients with fibromyalgia, both males and females, have a higher risk for developing Sjögren's syndrome than those without fibromyalgia, especially those aged 20-49 years. While managing patients, clinicians should be aware of the bidirectional association between the two diseases, which helps to understand the impact of the association on disease activity and diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The major burden of diseases in childhood has shifted from infectious diseases to chronic health conditions in recent decades. Although the rates of infectious diseases have decreased, the incidence of chronic diseases stemming from infectious agents continues to grow. Enterovirus is a major infectious disease of childhood and has been linked to numerous chronic diseases. We analyzed population-based data from Taiwan's National Health Insurance Research Database (NHIRD) to investigate the correlations between enterovirus infection and major chronic health conditions in children.Method: Children diagnosed with enterovirus (EV) infection during 1999–2003 were identified from the Longitudinal Health Insurance Database 2000 (LHID 2000), a subdataset of Taiwan's National Health Insurance Research Database (NHIRD). A total of 14,168 patients were selected after excluding patients with existing chronic diseases and missing data. Another 14,168 children matched by age and sex were selected as the control group. Five primary outcomes, including attention deficit and hyperactivity disorder (ADHD), epilepsy, asthma, allergic rhinitis, and atopic dermatitis, were recorded.Results: The risks of ADHD, asthma, allergic rhinitis, and epilepsy were significantly increased in the EV group compared with the control group. The risk of atopic dermatitis was significantly increased in the crude model. However, there were no significant differences in the adjusted model. The risks of ADHD, asthma, allergic rhinitis, and epilepsy were also significantly increased in patients with severe EV infection compared with patients with non-severe EV infection.Conclusion: Chronic diseases, such as ADHD, epilepsy, asthma, allergic rhinitis, and atopic dermatitis were shown to be associated with enterovirus infection during childhood. EV infection during early childhood might have long-term public health implications and thus prevention strategies should be implemented.

Abstract Background Pay-for-Performance programs have shown improvement in indicators monitoring adequacy and target achievement in diabetic care. However, less is known regarding the impact of this program on the occurrence and long-term effects of diabetic retinopathy. The objective of this study was to determine the effect of pay-for-performance program on the development of treatment needed for diabetic retinopathy in type 2 diabetes patients. Methods We conducted a nationwide retrospective cohort study with a matching design using the Taiwan National Health Insurance Research Database from 2000 to 2012. The outcome was defined as the treatment needed diabetic retinopathy. We matched Pay-for-Performance and non-Pay-for-Performance groups for age, gender, year diabetes was diagnosed and study enrollment, and duration of follow-up. Results A total of 9311 patients entered the study cohort, of whom 2157 were registered in the Pay-for-Performance group and 7154 matched in the non-Pay-for-Performance group. The incidence of treatment needed diabetic retinopathy was not significantly different in two groups. However, the incidence of treatment needed diabetic retinopathy was significantly different if restricted the non-Pay-for-Performance group who had at least 1 eye examination or optical coherence tomography within 1 year (adjusted hazard ratio, 0.78; 95% confidence interval, 0.64–0.94). Conclusions Pay-for-Performance is valuable in preventing the development of treatment needed diabetic retinopathy, which could be attributed to the routine eye examination required in the Pay-for-Performance program. We could improve our diabetic care by promoting eye health education and patient awareness on the importance of regular examinations.

Ying-Hsu Chang,1,2,* Su-Wei Chang,3,4,* Chung-Yi Liu,1,2 Po-Hung Lin,1,2 Kai-Jie Yu,1,2 See-Tong Pang,1,2 Cheng-Keng Chuang,1,2 Hung-Cheng Kan,1,2 I-Hung Shao1,2 1Division of Urology, Department of Surgery, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan *These authors contributed equally to this work Introduction: Renal cell carcinoma (RCC) is one of the most lethal urological malignancies, and surgeries remain the mainstay for localized RCC. This study aimed to compare the selection of open surgery and minimally invasive kidney surgery for RCCs for the aspects of complication, medical costs, and patient preference. Materials and methods: We conducted a population-based case–control study by using the National Health Insurance Research Database of Taiwan, which included data from 23 million Taiwanese residents. Patients newly diagnosed with RCC during 2006–2012 were included. We compared the general characteristics, underlying disease, complications, hospital stay, postoperative analgesic dosage, and medical costs between open group and minimally invasive group. Results: A total of 3,172 patients who received radical nephrectomy (RN) or partial nephrectomy (PN) for RCC were included. The mean age was 61.1 years, with a male to female ratio of 1.88. In the minimally invasive groups, the mean hospital stay was significantly shorter than in open groups (12.4 days in open RN versus 10.3 days in minimally invasive RN, and 9.7 days in open PN versus 8.2 days in minimally invasive PN). There was no significant difference between the medical costs and the incidence of major bleeding complication between the open group and the minimally invasive group. Female patients and patients with higher monthly income were more likely to receive minimally invasive surgery. Conclusion: During past decades, open RN has gradually been replaced by minimally invasive surgeries and PN. Compared to open surgeries, minimally invasive surgeries could lead to less postoperative pain and faster recovery. Economic status of the patients potentially hinders them from receiving minimally invasive surgeries, which may cost more. Keywords: renal cell carcinoma, minimally invasive, open surgery, complication, NHIRD

Abstract Background Bipolar disorder (BD), a type of psychiatric mood disorder, is manifested by chronic and recurrent mood fluctuations. This study aims to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for BD. Methods A total of 48,215 patients with newly diagnosed viral hepatitis from 2000 to 2010 were identified and frequency-matched with 192,860 people without hepatitis. Both groups were followed until diagnosis with BD, withdrawal from the national health insurance program, or the end of 2011. Patients with viral hepatitis were grouped into 3 cohorts: HBV infection, HCV infection, and HBV/HCV coinfection. The association between viral hepatitis and BD were examined using Cox proportional hazards regression models. Results The incidence of BD was higher in HBV/HCV coinfection than in the control group, with an adjusted hazard ratio of 2.16 (95% confidence interval 1.06–4.41) when adjusted for sex, age, and comorbidity. After further adjustment, we noted that an age more than 65 years and female may be associated with an increased risk of BD in patients with chronic hepatitis B and C. Conclusion Viral hepatitis may be associated with increased risk of subsequent BD.

Parkinson's disease (PD) is a common associated motor dysfunction nervous system disease. Low-level occupational mercury vapor exposure is a commonly known critical factor that increases the risk of PD. Dental amalgams, used for dental restoration, are a major source of mercury exposure for people. However, the relationship between PD and the use of amalgam fillings (AMFs) has yet to be clarified. This paper of retrospective case--control aimed to examine the relationship between AMF use and the risk of PD; it analyzed Taiwan's NHIRD (National Health Insurance Research Database) based on population administrative database, for the 2000-2013 period. For the case and control groups, Charlson Comorbidity Index, age, urbanization level, sex and monthly income were all matched by a propensity score method for a 1:1 ratio; 5712 cases and 5712 controls participated in this study. This results of case--control based on nationwide population revealed no significant association between PD and AMF in Taiwanese people. This result provides meaningful implications despite being statistically not significant. [ABSTRACT FROM AUTHOR]

Diseases can be interconnected. In the recent years, there has been a surge of multidisease studies. Among them, HDN (human disease network) analysis takes a system perspective, examines the interconnections among diseases along with their individual properties, and has demonstrated great potential. Most of the existing HDN analyses are based on either molecular information (which may be unreliable and have limited clinical relevance) or phenotypic measures (which may have limited implications for disease management and not directly reflect disease severity). In this study, we take advantage of the uniquely valuable Taiwan NHIRD (National Health Insurance Research Database) data and conduct an HDN analysis of disease treatment cost. Complementing the existing literature, treatment cost can serve as a surrogate of disease severity (and hence be clinically highly relevant) and also directly describe the financial burden of illness (and hence be uniquely informative for disease management). With inpatient and outpatient treatment data on close to 1 million randomly selected subjects and collected during the period of 2000 to 2013, the human disease cost network is constructed using a novel copula-based approach and the weighted correlation-based network construction technique. Extensive analysis is conducted, and the results are found to be biomedically sensible. [ABSTRACT FROM AUTHOR]

Abstract Background N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate. Methods Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan’s National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells. Results The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days. Conclusions BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen.

Background Antipyretics are widely prescribed in pediatric practice. Some reports have mentioned that acetaminophen and non-steroid anti-inflammatory drugs may negatively affect asthma control by causing asthma exacerbation (AE). However, many confounding factors can also influence the risks. We assessed the impact of using acetaminophen or ibuprofen on AE in asthmatic children, especially those with strong risk factors. Methods We used the 2010 Taiwan National Health Insurance Research Database and identified 983 children with persistent asthma aged 1–5 years old; among them, 591 used acetaminophen alone and 392 used ibuprofen alone in 2010. Then, we analyzed the risk of AE over 52 weeks in the patients with and without severe AE in the previous year. Results The ibuprofen group had a higher risk of an emergency room (ER) visit or hospitalization for AE (odds ratio (OR) = 2.10, 95% confidence interval (CI) [1.17–3.76], P = 0.01). Among asthmatic children who had severe AE in the previous year, the risk of AE was higher in the ibuprofen group than in the acetaminophen group (OR = 3.28, 95% CI [1.30–8.29], P = 0.01), where as among those who did not, the risks of AE were similar between the acetaminophen and ibuprofen groups (OR = 1.52, 95% CI [0.71–3.25], P = 0.28). Conclusions Among young asthmatic children, use of ibuprofen was associated with a higher risk of AE than acetaminophen, if they had severe AE with ER visit or hospitalization in the previous year. Pediatricians should use antipyretics among children with asthma after a full evaluation of the risk.

Purpose: The aim of this study was to evaluate the influence of bariatric surgery on gallstone disease in obese patients.Materials and Methods: This large cohort retrospective study was conducted based on the Taiwan National Health Insurance Research Database. All patients 18-55 years of age with a diagnosis code for obesity (ICD-9-CM codes 278.00-278.02 or 278.1) between 2003 and 2010 were included. Patients with a history of gallstone disease and hepatic malignancies were excluded. The patients were divided into non-surgical and bariatric surgery groups. Obesity surgery was defined by ICD-9-OP codes. We also enrolled healthy civilians as the general population. The primary end point was defined as re-hospitalization with a diagnosis of gallstone disease after the index hospitalization. All patients were followed until the end of 2013, a biliary complication occurred, or death.Results: Two thousand three hundred seventeen patients in the bariatric surgery group, 2331 patients in the non-surgical group, and 8162 patients in the general population were included. Compared to the non-surgery group (2.79%), bariatric surgery (2.89%) did not elevate the risk of subsequent biliary events (HR = 1.075, p = 0.679). Compared to the general population (1.15%), bariatric surgery group had a significantly higher risk (HR = 4.996, p < 0.001). In the bariatric surgery group, female gender (HR = 1.774, p = 0.032) and a restrictive procedure (HR = 1.624, p = 0.048) were risk factors for gallstone disease.Conclusion: The risk for gallstone disease did not increase after bariatric surgery, although the risk was still higher than the general population. The benefit of concomitant cholecystectomy during bariatric surgery should be carefully evaluated. [ABSTRACT FROM AUTHOR]

Background Dry eye disease (DED), a chronic ocular disease, is associated with numerous medical issues, including asthma. However, studies on these associations are limited. In this study, we investigated the incidence of DED among patients with asthma and its correlation with other allergic comorbidities. Methods We retrospectively analyzed data from the National Health Insurance Research Database of Taiwan. We compared the data of 41,229 patients with asthma with those of 164,916 sex- and age-matched non-asthma controls. We followed up the patient and control groups from 1998 to 2010, and compared the rate of DED in these two groups. We further analyzed the allergic comorbidities and asthma-related medication use among the patients with asthma to verify whether these factors were associated with DED. Results The patients in the asthma group were more likely to have DED than were the controls (6.35% vs. 4.92%, p < 0.0001). In the asthma group, female had a higher risk of DED (odds ratio (OR) = 1.70, 95% confidence interval (CI) [1.57–1.85]) than males did. After adjustment for sex, age, income, urbanization, and the other two allergic comorbidities, patients with allergic rhinitis (adjusted OR = 1.58, 95% CI [1.46–1.72]) and urticaria (adjusted OR = 1.25, 95% CI [1.12–1.38]) were more likely to have DED, but not patients with atopic dermatitis (adjusted OR = 1.17, 95% CI [0.98–1.40]). Patients with asthma who had prescriptions of leukotriene receptor antagonists (LTRAs) (adjusted OR = 1.29, 95% CI [1.01–1.64]), oral antihistamines (adjusted OR = 2.02, 95% CI [1.84–2.21]), and inhaled corticosteroids (adjusted OR = 1.19, 95% CI [1.04–1.36]) exhibited association with DED. Discussion Our findings reveal that patients with asthma—particularly females—were more likely to have DED, with comorbidities such as allergic rhinitis and urticaria, and prescriptions including LTRAs, antihistamines, and inhaled corticosteroids. The results suggest that in clinical practice, physicians should pay attention to DED, particularly in patients with a high risk of DED.

Background: Postoperative sepsis is a major type of sepsis. Sociodemographic characteristics, incidence trends, surgical procedures, comorbidities, and organ system dysfunctions related to the disease burden of postoperative sepsis episodes are unclear. Methods: We analyzed epidemiological characteristics of postoperative sepsis based on the ICD-9-CM codes for the years 2002 to 2013 using the Longitudinal Health Insurance Databases of Taiwan’s National Health Insurance Research Database. Results: We identified 5,221 patients with postoperative sepsis and 338,279 patients without postoperative sepsis. The incidence of postoperative sepsis increased annually with a crude mean of 0.06% for patients aged 45–64 and 0.34% over 65 years. Patients with postoperative sepsis indicated a high risk associated with the characteristics, male sex (OR:1.375), aged 45–64 or ≥ 65 years (OR:2.639 and 5.862), low income (OR:1.390), aged township (OR:1.269), agricultural town (OR:1.266), and remote township (OR:1.205). Splenic surgery (OR:7.723), Chronic renal disease (OR:1.733), cardiovascular dysfunction (OR:2.441), and organ system dysfunctions had the highest risk of postoperative sepsis. Conclusion: Risk of postoperative sepsis was highest among men, older, and low income. Patients with splenic surgery, chronic renal comorbidity, and cardiovascular system dysfunction exhibited the highest risk for postoperative sepsis. The evaluation of high-risk factors assists in reducing the disease burden. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether percutaneous endoscopic gastrostomy (PEG) tube placement is associated with increased risk of gastric cancer.Methods: We conducted a nationwide population-based retrospective study in Taiwan. Inpatient data from 1997 to 2010 were collected from Taiwan National Health Insurance Research Database. Patients with age less than 20 years; those with histories of PEG before 2000; those with histories of cancers; and those diagnosed with gastric cancer before or within 6 months of the first PEG procedure were excluded. Finally, 3505 patients who underwent PEG were included (PEG cohort), along with 7010 randomly-selected individuals, matched by age, sex, and year of index date, as the control cohort.Results: After adjusting for age, sex, peptic ulcer, gastritis, hypertension, diabetes and coronary artery disease, risk of gastric cancer was significantly higher in the PEG cohort (adjusted hazard ratio, 5.31; 95% confidence interval, 4.12-6.00; p = 0.011). Patients with 2 or more PEG procedures were significantly associated with increasingly developing gastric cancer risk (adjusted hazard ratio, 2.73; 95% confidence interval, 1.91-3.85; p < 0.001). The possible hypothesis may be due to chronic inflammation caused by chemical and physical conditions of the tube.Conclusions: Patients with PEG might be associated with a greater risk of subsequent gastric cancer in Taiwan. Physicians should be aware of the link when assessing patients with PEG. [ABSTRACT FROM AUTHOR]

Background The reported incidence of shoulder redislocation varies among different reports. This was a nationwide study to investigate the recurrence rate of shoulder dislocation after closed reduction. Methods We performed a cohort study to analyze the incidence of first dislocation as well as second and third repeated dislocations in a nationwide dataset from the National Health Insurance Research Database of Taiwan. Patients who had any shoulder dislocation event and received closed reduction from 2000 to 2013 were included. Results From this dataset of 1 million persons, we identified 1074 patients who had a shoulder dislocation. Of these, 210 had a second shoulder dislocation and 93 had a third shoulder dislocation. The shoulder redislocation rates were 9.4%, 12.7%, and 17.0% at 1 year, 2 years, and 5 years, respectively, after the first shoulder dislocation and 19.6% at overall follow-up. Patients in the youngest age group and male patients had higher risks of redislocation (adjusted hazard ratios, 3.28 and 1.41, respectively). The mean time to recurrence was 13.1 months. However, the patients who had a second shoulder dislocation had a shorter time to recurrence and a higher risk of redislocation (44%), with no statistical differences in risk among any age or sex groups. Conclusions After the first shoulder dislocation, male patients and younger patients had higher shoulder redislocation rates. However, after the second shoulder dislocation, all groups shared a similar high shoulder redislocation rate regardless of age or sex. Surgical treatment should be considered for patients with multiple episodes of shoulder dislocation. [ABSTRACT FROM AUTHOR]

Summary: Is gout a risk factor for future osteoporosis? This large population-based study comprising two matched groups of individuals with and without gout demonstrates that patients with gout have a 20% increase in the risk of developing osteoporosis in future through an 8-year follow-up.Introduction: To examine if gout is associated with an increased risk of osteoporosis.Methods: We conducted a nationwide population-based retrospective matched-cohort study. Two matched cohorts (n = 36,458 with gout and 71,602 without gout) assembled and recruited from the Longitudinal Health Insurance Dataset containing 1 million subjects. Exclusion criteria were missing data, age < 20 years, short follow-up period, and pre-existing osteoporosis. Both cohorts were followed up until incident osteoporosis, death, or the end of the study. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for socioeconomic proxy, geographical difference, glucocorticoid and allopurinol exposure, various prespecified medical conditions, and comorbidities.Results: Men comprised 72.8% of the cohorts. With a follow-up of 183,729 and 359,900 person-years for the gout and non-gout cohorts, 517 and 811 incidents of osteoporosis occurred, respectively, after excluding osteoporosis incidents in the first 3 years of follow-up. The cumulative incidence of osteoporosis was statistically higher in the gout cohort than in the non-gout cohort, at 3.3 versus 2.1% (P = 0.0036, log-rank). Our Cox model showed a 1.2-fold increase in the incidence of osteoporosis in the gout cohort, with an aHR of 1.2 (95% confidence interval, 1.06-1.35).Conclusions: This first population-based epidemiologic study supports the hypothesis that compared with individuals without gout; those with gout have a modest increase in the risk of developing osteoporosis in future. [ABSTRACT FROM AUTHOR]

Objective Tinnitus is a common disorder that may cause psychological distress and anxiety. The aim of this study was to investigate the association between anxiety disorders (ADs) and tinnitus in a large population. Method We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. Study subjects included 14,772 patients with tinnitus and 709,963 people in the general population who sought treatment in 2005. Distributions in ADs, age, sex, and medical comorbidities were compared between groups using chi-squared tests. Multivariate logistic regression models adjusted for age, sex, and medical comorbidities were used to analyze the association between tinnitus and ADs. Results Prevalence of ADs in tinnitus and general population groups was 3.9% and 1.5%, respectively, and this difference was significant ( P < 0.001). Diabetes mellitus, hypertension, hyperlipidemia, concussion or head injury, Meniere's disease, sensorineural hearing impairment, renal disease, coronary artery disease, and cerebrovascular disease were significantly more prevalent in the tinnitus group (all P -values < 0.001). Multivariate logistic regression model demonstrated that patients with tinnitus were significantly associated with increased risk of ADs (adjusted OR = 1.99; 95% CI = 1.81–2.19; P < 0.001). Conclusion Because the risk of ADs was significantly higher in patients with tinnitus than in the general population, physicians should be aware of the importance of psychological factors in tinnitus management. [ABSTRACT FROM AUTHOR]

Purpose Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. Methods This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Results Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Conclusions Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. [ABSTRACT FROM AUTHOR]

Background: Uremia is likely a risk factor for deep neck infection (DNI). However, only a few relevant cases have been reported, and evidence sufficient to support this hypothesis is lacking. The aim of the study is to investigate the effects of end-stage renal disease (ESRD) on DNI.Methods: We used the database of the Registry for Catastrophic Illness Patients (RFCIP), a subset of the National Health Insurance Research Database (NHIRD) in Taiwan, to conduct a retrospective follow-up study. Between 1997 and 2013, a total of 157,340 patients in Taiwan with ESRD who received dialysis were registered in the RFCIP, whom were matched with a database consisting of 1,000,000 randomly selected patients who represented the national population, to conduct the follow-up study for investigating the incidence of DNI in the ESRD and control cohorts.Results: In the ESRD group, 280 DNIs were identified with an incidence rate of 43 per 100,000 person-years. In the comparison group, 194 DNIs were identified with an incidence rate of 20 per 100,000 person-years. The incidence rate ratio was 2.16 (p < 0.001). Kaplan-Meier analysis indicated that the ESRD group had a significantly higher cumulative incidence of DNI (p < 0.001). According to Cox regression analysis, the hazard ratio of ESRD for DNI was 2.23 (p < 0.001). The therapeutic methods (non-surgery and surgery), performance of tracheostomy, duration of hospitalization did not differ significantly between the two groups, except more ESRD-DNI patients were admitted to intensive care units. The mortality rate of patients with DNI in the ESRD group was significantly higher than that in the control group (8.6% for ESRD vs 3.6% for control, p = 0.032). Furthermore, the Kaplan-Meier analysis demonstrated a poorer survival outcome in the ESRD group (p = 0.029). However, the individual survival outcomes following non-surgical and surgical therapies in the ESRD group did not differ significantly (p = 0.31).Conclusions: ESRD is a predisposing factor for DNI, increasing its risk by twofold. In the patients with ESRD, DNI was not associated with higher rates of surgical debridement, tracheostomy, and mediastinal complications or longer hospital stays; however, it was associated with poorer survival outcomes, regardless of the therapeutic method. [ABSTRACT FROM AUTHOR]

Background and objective Return visits (RVs) to the emergency department (ED) consume medical resources and may represent a patient safety issue. The occurrence of unexpected RVs is considered a performance indicator for ED care quality. Because children are susceptible to medical errors and utilize considerable ED resources, knowing the factors that affect RVs in pediatric patients helps improve the quality of pediatric emergency care. Methods We collected data on visits made by patients aged ≤18 years to EDs from the National Health Insurance Research Database. The outcome of interest was a RV within 3 days of the initial visit. Potential factors were categorized into demographics, medical history, features of ED visits, physician characteristics, hospital characteristics, and treatment-seeking behavior. A multivariate logistic regression was used to identify independent predictors of RVs. We compared the performance of various data mining techniques, including Naïve Bayes, classification and regression tree (CART), random forest, and logistic regression, in predicting RVs. Finally, we developed a decision tree to stratify the risk of RVs. Results Of 125,940 visits, 6,282 (5.0%) were followed by a RV within 3 days. Predictors of RVs included younger age, higher acuity, intravenous fluid, more examination types, complete blood count, consultation, lower hospital level, hospitalization within one week before the initial visit, frequent ED visits in the past one year, and visits made in Spring or on Saturdays. Patients with allergic diseases and those underwent ultrasound examination were less likely to return. Decision tree models performed better in predicting RVs in terms of area under curve. The decision tree constructed using the CART technique showed that the number of ED visits in the past one year, diagnosis category, testing of complete blood count, and age were important discriminators of risk of RVs. Conclusions We identified several factors which are associated with RVs to the ED in pediatric patients. The knowledge of these factors may help assess risk of RVs in the ED and guide physicians to reevaluate and provide interventions to children belonging to the high risk groups before ED discharge. [ABSTRACT FROM AUTHOR]

Purpose. Acute myeloid leukemia (AML) is the most deadly subtype of leukemia, and many patients with this disease seek other complementary therapies, one of which is Chinese medicine. We set out to provide reliable data regarding the benefit of Chinese herbal medicine (CHM) for AML patients, using mortality as the main outcome measure. We also characterized the herbal prescriptions of patients. Methods. Using the Taiwanese National Health Insurance Research Database, we performed a nationwide population-based cohort study among AML patients from 1997 to 2010. The Cox regression model was used to adjust for comorbidities and other variables, and the hazard ratios (HRs) of CHM users and non–CHM users were compared. Results. After 1:1 matching, 498 patients were included into the study. The HR of the CHM group was 0.41 (95% CI = 0.26-0.65; P = .0001) compared with the non-CHM group. This decrease in HR was also shown to be dose dependent (P < .001). The 3 single-herbs most commonly prescribed were Salvia miltiorrhiza (Dan Shen), Astragalus membranaceus (Huang Qi), and Spatholobus suberectus (Ji Xue Teng). The 3 mutli-herb products most commonly prescribed were Jia Wei Xiao Yao San, Gui Pi Tang, and Qi Ju Di Huang Wan. Conclusion. Prospective controlled clinical data is still needed, however, this study provides real-world data regarding the benefit AML patients may have from CHM. This study suggests that all AML patients, regardless of age or other prognostic factors, may achieve longer survival times when receiving CHM in addition to standard therapy. [ABSTRACT FROM AUTHOR]

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary. [ABSTRACT FROM AUTHOR]