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Background After isotretinoin's approval to treat patients with recalcitrant acne, there have been continued debates around its psychiatric safety profile. This study aimed to assess the risk of psychiatric disorders in patients with acne who are taking isotretinoin. Methods We used de-identified information from Taiwan's National Health Insurance Research Database from 2000 to 2015 to examine the risk for psychiatric disorders among patients with acne who were taking isotretinoin. We performed subgroup analyses based on the dosage and duration of isotretinoin administration. Results This study included 29,943 participants during a 16-year follow-up period. We found no significantly increased risk for psychiatric disorders among patients taking isotretinoin compared with patients who did not receive isotretinoin treatment (adjusted hazard ratio [aHR]: 1.009, 95% confidence interval [CI]: 0.422–1.696). Subgroup analyses showed no significantly increased risk for psychiatric disorders in patients taking different doses of isotretinoin (≤ 20 mg per day, aHR: 0.892, 95% CI: 0.371–1.501; > 20 mg per day, aHR: 1.068, 95% CI: 0.446–1.798). There was also no significant increase in risk for patients undergoing isotretinoin treatment over different periods (≤ 6 months, aHR: 0.924, 95% CI: 0.392–1.612; > 6 months, aHR: 1.196, 95% CI: 0.488–2.004). Limitations We did not analyze the risk of suicidal ideation, and it could be underestimated in medical claims databases. Conclusions We found no increased risk of psychiatric disorders among Taiwanese patients with acne who were taking isotretinoin. Higher dosage or longer duration of isotretinoin treatment did not increase the risk for developing a psychiatric disorder.

PURPOSE To investigate the risk of poor delivery events (PDEs; premature delivery, abortion, and stillbirth) in female subjects with obstructive sleep apnea (OSA). METHODS The study identified 8346 female subjects with PDEs as cases between January 1, 2000 and December 31, 2015 from the Longitudinal Health Insurance Database 2005 in Taiwan. A total of 33,384 controls were also identified based on frequency matching for age and year of index date. Diagnoses of OSA and PDEs were determined according to the International Classification of Diseases, 9th Revision. The risk of PDEs in female subjects with OSA was estimated with conditional logistic regression analyses. FINDINGS The mean age of the 41,730 female subjects was 35.53 years. The overall incidence rate of PDEs was 506.22 per 100,000 person-years for subjects with OSA, which was significantly higher than that for the controls (501.95 per 100,000 person-years). The risk of PDEs was higher in subjects with OSA than in controls (adjusted odds ratio [AOR] = 1.19; 95% confidence interval [CI] [95% CI]: 1.08-1.43), including for premature delivery (AOR = 1.20; 95% CI: 1.16-1.50), and abortion (AOR = 1.19; 95% CI: 1.09-1.47). OSA showed no relation to stillbirth (AOR = 1.04; 95% CI: 0.99-1.31). The findings indicate that the longer a subject has been experiencing OSA, the higher the probability of PDEs. CONCLUSIONS The risk of PDEs associated with OSA was found in this study. In particular, the longer a subject has OSA, the higher the likelihood of PDEs, exhibiting a dose-response effect. CLINICAL RELEVANCE To effectively promote maternal health in clinical practice, health providers need to recognize OSA as a risk factor associated with negative pregnancy outcomes. Furthermore, OSA symptoms should be assessed and managed in all pregnant women to enable more comprehensive maternal care.

There is little comprehensive education for people with end-stage renal disease (ESRD) progress. We investigated the differences in terms of outcomes between patients with CKD stages 3–5 who enrolled and did not enroll in the pre-ESRD care education in Taiwan. This retrospective cohort study was conducted using data from the National Health Insurance Research Database (NHIRD). All patients diagnosed with CKD stages 3–5 who received the pre-ESRD care education through the pay for performance (P4P) program were enrolled. Based on whether or not they participated in the program, they were categorized into P4P or non-P4P groups. All analyses were performed from January 2006 through December 2015. Study outcomes were risk of hemodialysis dependency, hospitalization, and all-cause mortality. In this study of 29,337 patients, those with CKD stages 3–5 in the P4P group had lower events of hemodialysis, hospitalization, and all-cause mortality compared to patients in the non-P4P group. This study suggested that pre-ESRD care education is associated with increased patient outcomes, resulting in lower hemodialysis and hospitalization events and a higher overall survival rate in patients with CKD stages 3–5. Patient education could raise opportunities to improve pre-ESRD care by reaching patients outside the traditional health care setting.

Tien-Yu Chen,1– 3,&ast; Vincent Yi-Fong Su,4,5,&ast; Chung-Hsin Lee,6 Chi-Hsiang Chung,7– 9 Chia-Kuang Tsai,3,10 Chung-Kan Peng,3,11 Hsiao-Ching Lai,1 Wu-Chien Chien,7– 9,12 Nian-Sheng Tzeng1,13 1Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 2Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; 3Sleep Medicine Center, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 4Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 5Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; 6Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan; 7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8School of Public Health, National Defense Medical Center, Taipei, Taiwan; 9Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 10Department of Neurology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 12Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 13Student Counseling Center, National Defense Medical Center, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Wu-Chien ChienDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei, 11490, TaiwanTel +886 2-87923311, Ext. 19189Fax +886 2-87927235Email chienwu@mail.ndmctsgh.edu.twNian-Sheng TzengDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, TaiwanTel +886 2-87927299Fax +886 2-87927221Email pierrens@mail.ndmctsgh.edu.twPurpose: Asthma, which is caused by inflammation of the airways, affects the sensitivity of nerve endings. Narcolepsy is a chronic sleep disorder that may be caused by autoimmunity. Recent studies have reported a positive association between narcolepsy and asthma. We aimed to examine the association between asthma and narcolepsy and determine the effects of therapeutic corticosteroid or bronchodilator use.Materials and Methods: We conducted a nationwide population-based, nested case-control study using Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2013. Subjects with narcolepsy (ICD-9-CM code 347) were enrolled, with 1:3 estimated propensity score-matched controls based on sex, age, and index year. The association between narcolepsy and asthma was assessed using multiple logistic regression analyses. The covariates included sex, age, monthly insurance premiums, geographical area of residence, urbanization level of residence, level of care, and presence of diseases related to immune response and central nervous system. The effects of corticosteroid and bronchodilator use were also analyzed.Results: Overall, 2008 subjects were identified from the NHIRD (502 patients with narcolepsy and 1506 controls). The participants with narcolepsy had almost three times the level of previous asthma diagnosis than controls. Compared to those without asthma, patients with asthma had an adjusted odds ratio (OR) of 3.181 for narcolepsy comorbidity (95% confidence interval [CI]: 2.048– 4.941, p< 0.001). The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity, with an adjusted OR of 0.465 (95% CI, 0.250– 0.634; p< 0.001), in patients with asthma when compared to those without treatment.Conclusion: This study demonstrated a significantly higher level of previous asthma diagnosis in patients with narcolepsy. The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity in asthma patients, compared to those without treatment.Keywords: asthma, narcolepsy, corticosteroid, bronchodilators

Background This study aimed to investigate the association between posttraumatic stress disorder and the risk of developing erectile dysfunction. Methods In this population-based retrospective cohort study, we used Taiwan’s National Health Insurance Research Database to analyze patients who were newly diagnosed with posttraumatic stress disorder (PTSD) between 2000 and 2013, with a 1:3 ratio by age and index year matched with patients in a non-PTSD comparison group, for the risk of erectile dysfunction. Results In total, 5 out of 1079 patients in the PTSD group developed erectile dysfunction, and 3 out of 3237 patients in the non-PTSD group (47.58 vs. 9.03 per 100,000 per person-year) developed erectile dysfunction. The Kaplan–Meier analysis showed that the PTSD cohort had a significantly higher risk of erectile dysfunction (log-rank, p, Highlights Utilizing a nationwide, population-based database, the Longitudinal Health Insurance Database in 2000–2015 in Taiwan, which comprised 2 million people, we conducted a study to clarify the association between posttraumatic stress disorder and erectile dysfunction.Posttraumatic stress disorder was associated with the risk of erectile dysfunction.Psychotropic medications in the subjects with PTSD were not associated with the risk of erectile dysfunction. Supplementary Information The online version contains supplementary material available at 10.1186/s12991-021-00368-w.

Purpose The aim of this study was to examine the association between obstructive sleep apnea (OSA) diagnosis and diverse types of injuries. Design This population-based retrospective cohort study compared records from 2000 to 2013 in the Taiwan National Health Insurance Research Database. Methods 3025 patients identified with OSA were compared against the control cohort consisting of 12,100 age- and sex-matched patients. Cox proportional hazards regression analysis was performed to estimate the effects of OSA on injury risk. Findings Patients with OSA exhibited a significantly higher overall incidence of injury of 2599 per 100,000 person-years compared to the control cohort (2248 per 100,000 person-years). After the confounding factors were considered, subjects with OSA showed a higher risk of injury than subjects in the control group (adjusted hazard ratio [HR] = 1.78, 95% confidence interval [CI] = 1.64-1.93). The risk of unintentional injury (traffic, poisoning, falls) and intentional injury (suicide) in the group of patients with OSA was higher than that in the controls. Conclusions Our study strongly supports the conclusion that adults with OSA are at increased risk of injury. Clinical relevance The present results indicate the significance of OSA as a predictor of injury risk, which will provide valuable information for clinical practice and injury prevention.

Jen-Ta Shih,1,2 Tsu-Te Yeh,1 Pei-Hung Shen,1 Chih-Chien Wang,1 Sheng-Hao Wang,1 Wu-Chien Chien,3– 6 Chi-Hsiang Chung,3– 5 Chia-Chun Wu1 1Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei, Taiwan; 3School of Public Health, National Defense Medical Center, Taipei, Taiwan; 4Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 5Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 6Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanCorrespondence: Chia-Chun WuDepartment of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Road, Neihu Dist, Taipei City, 11472, TaiwanTel +886-953-086-492Fax +886-2-8792-7186Email orthopedicsintsgh@gmail.comPurpose: With recent advances in surgical techniques and instruments, orthopedic surgeons are better equipped to treat metastatic bone disease. There has also been considerable progress in the non-surgical treatment of cancers, specifically in improving the survival rate of patients with advanced cancer. However, it remains unclear whether surgical resection of a metastatic bone lesion poses additional risk to the survival of patients with advanced cancer.Patients and Methods: This study utilized data from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. Patients aged ≥ 18 years, who had been recently diagnosed with bone metastases (BM), were enrolled and assigned to either the surgery or non-surgery groups. The demographic characteristics were analyzed, and the adjusted hazard ratios (aHR) of mortality were calculated using Cox regression analysis.Results: Of the 4,549,226 individuals in the inpatient database of the NHIRD, 83,536 patients with BM were enrolled in this study. Among them, 8802 underwent surgical resection for skeletal metastatic lesion and 66,098 did not. Altogether, 28,691 patients died, including 2798 (31.8%) in the surgery group and 25,893 (39.2%) in the non-surgery group. The aHR for mortality was 0.7-fold lower in the surgery group (p < 0.001).Conclusion: This study demonstrates that surgical resection of metastatic bone lesions did not pose any additional risk to survival outcomes. Thus, we believe that surgery, if indicated, could have a competitive role in the management of metastatic bone disease.Keywords: bone metastasis, surgical resection, mortality, bone resorption inhibitor

Yi-Jen Huang,1,2 Senyeong Kao,1,3 Li-Ting Kao,1,3– 5 Chih-Feng Chian,6 Chi-Hsiang Chung,3,7 Wu-Chien Chien,1,3,7,* Kwua-Yun Wang1,8,9,* 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 2Department of Nursing, University of Kang Ning, Taipei, Taiwan; 3School of Public Health, National Defense Medical Center, Taipei, Taiwan; 4Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; 5School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri‐Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8School of Nursing, National Defense Medical Center, Taipei, Taiwan; 9Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Wu-Chien ChienDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, Taiwan, Republic of ChinaTel +886-2-87923311, Ext. 19189Fax +886-2-87927235Email chienwu@ndmctsgh.edu.twKwua-Yun WangGraduate Institute of Life Sciences, National Defense Medical Center, 9314R, No. 161, Section 6, Min-Chuan East Road, Neihu District, Taipei City, 11490, TaiwanTel +886-2-87923100 ext.18766Email kywang7@vghtpe.gov.twPurpose: The role of statins as anti-inflammatory drugs in chronic obstructive pulmonary disease (COPD) is controversial. This study aimed to determine the efficacy of statins used with or without corticosteroids in COPD patients.Patients and Methods: This was a retrospective cohort study and used the two million outpatients and inpatients in Taiwan’s Longitudinal Health Insurance Database covering 2000 to 2015. A total of 92,460 patients were identified in this study. We divided COPD patients into four groups by auditing each patient’s medication (statins used or not; corticosteroids used or not) and used Cox regression to analyze and compare the effects of statins in COPD patients with or without corticosteroids.Results: In terms of all COPD patients, our findings were consistent with previous studies showing that statins decreased COPD-related hospitalization and mortality rates. However, the beneficial effects were only observed in younger patients or those not taking corticosteroids in further analysis. Statins significantly decreased hospitalization and mortality rates in the non-corticosteroids groups. The hazard ratios increased with age and were not statistically significant for patients > 70 years old. Statins did not significantly decrease ED visits, hospitalization, and mortality in corticosteroids groups.Conclusion: Statins decreased hospitalization and mortality rates in COPD patients not taking corticosteroids but were not efficacious in patients on corticosteroids therapy. Furthermore, the beneficial effects of statins gradually decreased with patient age. Based on the findings, statins used in COPD patients may need to consider the patient age and corticosteroids used or not.Keywords: COPD, exacerbation, statins, corticosteroids, mortality

Yao-Ching Huang,1 Wu-Chien Chien,2– 5,* Chi-Hsiang Chung,2– 4 Hsin-An Chang,6,7 Yu-Chen Kao,6,8 Fang-Jung Wan,6 Shi-Hao Huang,1 Ren-Jei Chung,1,* Richard S Wang,9 Bing-Long Wang,2,* Nian-Sheng Tzeng,7,8,* Chien-An Sun10,11 1Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 6Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 7Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 8Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan; 9Program of Data Analytic and Business Computing, Stern School of Business, New York University, USA; 10Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 11Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Nian-Sheng TzengDepartment of Psychiatry, School of Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-2-87923311 Ext 17484Fax +886-2-87927221Email pierrens@mail.ndmctsgh.edu.twBing-Long WangDepartment of Public Health, National Defense Medical Center, 116, Section 6, Minchuan E. Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-980-794951Email billwang1203@gmail.comBackground: Multiple sclerosis (MS) is a demyelinating disease that can damage neurons in the brain and spinal cord and is associated with several psychiatric disorders. However, few studies have evaluated the risk of psychiatric disorders in patients with MS by using a nationwide database. This study investigated the association between MS and the risk of psychiatric disorders.Methods: Using data from the Taiwan National Health Insurance Research Database from 2000 to 2015, we identified 1066 patients with MS. After adjustment for confounding factors, Fine and Gray’s competing risk model was used to compare the risk of psychiatric disorders during 15 years of follow-up.Results: Of the patients with MS, 531 (4622.86 per 105 person years) developed psychiatric disorders; by contrast, 891 of the 3198 controls (2485.31 per 105 person years) developed psychiatric disorders. Fine and Gray’s competing risk model revealed an adjusted hazard ratio (HR) of 5.044 (95% confidence interval = 4.448– 5.870, p < 0.001) after adjustment for all the covariates. MS was associated with depression, anxiety, bipolar disorder, sleep disorders, schizophrenia, schizophreniform disorder, and other psychotic disorders (adjusted HR: 12.464, 4.650, 6.987, 9.103, 2.552, 2.600, 2.441, and 2.574, respectively; all p < 0.001). Some disease-modifying drugs were associated with a lower risk of anxiety or depression.Conclusion: Patients with MS were determined to have a higher risk of developing a wide range of psychiatric disorders.Keywords: multiple sclerosis, psychiatric disorders, depression, anxiety

Background In 2010, the American Heart Association recommended that postcardiac arrest care should be included in the chain of survival to reduce permanent neurological damage, improve quality of life, and reduce health care expenses of postcardiac arrest care. Objectives To investigate post-in-hospital cardiac arrest (IHCA) survival prior to and after modification of the chain of survival in 2010, with subgroup analyses per age and concomitant coronary heart disease (CHD). Methods We retrospectively searched the National Health Insurance Research Database for the 2007–2015 period to collect case data coded as “427.41” or “427.5” per International Classification of Disease Clinical Modification, Ninth revision codes and analyzed the data with SPSS v22.0. Results The 1-day survival rate in the 2011–2015 period was 2% higher than that in the 2007–2010 period (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.04). Moreover, in the 2011–2015 period, the survival-to-discharge rate was increased by 1% in patients under 65 years (OR 1.01, 95% CI 1.00–1.02) and 1% in CHD patients (OR 1.01, 95% CI 1.01–1.02) compared with that in the 2007–2010 period. Conclusion For patients with IHCA, the overall short-term survival improved significantly after modification of the chain of survival. Younger patients and patients with CHD had better long-term survival.

Objective We have conducted a study to clarify the association between amphetamine‐related disorders (ARD) and the risk of developing dementia. Methods This study used a retrospective cohort design by using Taiwan’s National Health Research Institute Database. A random sample of 68,300 subjects between January 1, 2000, and December 31, 2015, was obtained, comprising of 17,075 patients with ARD, and 51,225 controls without ARD (1:3), matched for gender and age group. After adjusting for covariates, a Fine and Gray’s survival analysis (competing with mortality) was used to compare the risk of dementia during a 15‐year follow‐up period. Results In the present study, 1,751 of 17,075 patients with ARD and 2,147 of 51,225 in the control group without ARD (883.10 vs 342.83 per 100,000 person‐years) developed dementia. ARD cohort was more likely to develop dementia (hazard ratio = 4.936 [95% CI: 4.609–5.285, P

BACKGROUND Authors of several studies have reported differences in the prevalence of metabolic syndrome (MetS) between men and women. However, information is lacking on gender difference among military personnel. OBJECTIVE The aim of this study was to examine the prevalence of MetS and its component abnormalities among Taiwanese Air Force personnel by gender and age groups. METHODS A population-based study was conducted including 14 872 Taiwanese Air Force personnel. Data were retrieved from the military's Health Management Information System. Analyses were performed using Student t test, χ test, and linear-by-linear χ test. Statistical significance was defined as P < .05. RESULTS The MetS prevalence was 14.0% (15.1% in men and 5.3% in women). Metabolic syndrome was associated with age for both men and women (both Ptrend < .001), with a greater prevalence of MetS in men aged 18 to 44 years than in women, but not in the age group of 45 years or older. In men, MetS was most prevalent in those with increased waist circumference (78.2%), followed by those with elevated blood pressure (75.6%). By contrast, in women, it was most prevalent in those with increased waist circumference (86.5%), followed by those with reduced high-density lipoprotein cholesterol (84.3%). CONCLUSIONS Our findings suggest that military nurses and other health providers should consider the gender- and age-based MetS prevalence trend among Taiwanese Air Force personnel when designing interventions to identify vulnerable subgroups at a high risk of MetS. Health management programs should be adapted to minimize metabolic risks.

Background To examine the association between the usage of agomelatine in patients with major depressive disorder and the usage of sedative-hypnotics. Methods This population-based, cross-sectional study used Taiwan's National Health Insurance Research Database (NHIRD) between 2012 and 2015. The agomelatine-only group and matched control (1:3) with the usage of other antidepressants were enrolled. The association between the usage of the agomelatine and other antidepressants and the usage of sedative-hypnotics in the patients were also assessed. Results A total of 7961 subjects were enrolled comprising 1985 with the usage of agomelatine only, and 5976 with other antidepressants. In the present study, a total of 3322 subjects who used the sedative-hypnotics were recorded, with 811 (40.86%) from the agomelatine-only group and 2511 (42.02%) from the non-agomelatine group, which have used sedative-hypnotics. After adjusting for covariates, the odds ratio (OR) of the usage of sedative-hypnotics in the agomelatine only-group was 0.892 (95% CI: 0.306-1.601, p = 0.533), in comparison to the controls, and the relative risk (RR) of the usage of sedative-hypnotics in the agomelatine only-group was 0.910 (95% CI: 0.312-1.633, p = 0.520), in comparison to the controls. No matter as to whether the treatment duration was

Purpose: This nationwide population-based retrospective cohort study evaluated the protective effect of N-acetylcysteine against prosthetic joint infection after hip or knee joint replacement. Methods: Patients receiving N-acetylcysteine after hip or knee joint replacement between 2000 and 2015 were identified from the Taiwan National Health Insurance Research Database. Each patient receiving N-acetylcysteine was matched to four controls based on age, sex, and index year. All subjects were followed-up from the index date to December 31, 2015. The Cox proportional hazards regression model was used to assess the risk of prosthetic joint infection. Results: A total of 1478 patients were included in the study group, and 5912 matched subjects not receiving N-acetylcysteine were included in the control group. After adjusting for age, sex, insured premium, comorbidities, and immunosuppressive agent use, no significant difference in the risk of prosthetic joint infection was found between the two groups. A higher N-acetylcysteine dose (>360 cumulative defined daily dose) significantly decreased the risk of prosthetic joint infection (adjusted hazard ratio = 0.891; 95% confidence interval = 0.599–0.989; p = 0.042). The protective effect of N-acetylcysteine was observed only in the group of prosthetic joint infection within 5 years (adjusted hazard ratio = 0.801; 95% confidence interval = 0.581–0.980; p = 0.040). Conclusions: High cumulative dose of N-acetylcysteine (>360 cumulative defined daily dose) can effectively reduce the risk of prosthetic joint infection in patients undergoing knee or hip joint replacement surgery within 5 years. Keywords: Biofilm, N-acetylcysteine, Prosthetic joint infection

Background The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. Methods Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. Results During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817–2.505; P < 0.001). Conclusion Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P

The clavicle hook plate has been commonly used to treat distal clavicle fractures and acromioclavicular (AC) joint dislocations; however, midshaft clavicle fracture at the medial end of the hook plate remains an underestimated complication. We aimed to discover the risk factors for this complication and the influence of these risk factors on patients and to suggest preventive surgical techniques. We retrospectively reviewed the records of 150 patients with acute distal clavicle fractures or acute AC joint dislocations treated by internal fixation with a clavicle hook plate. The patient demographics, the occurrence of midshaft clavicle fracture at the medial end of the hook plate, and functional outcomes were analyzed. The functional outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score and grading of the Constant shoulder score after the hook plate was removed. In total, 17 patients had complicating midshaft clavicle fractures at the medial end of the hook plate. Elderly patients had a higher risk of developing this complication than young patients. The odds ratio was 4.4 (p

Genital warts are a common sexually transmitted disease caused by human papillomavirus (HPV) infections. The prevalence of dementia is 4-8% in those aged 65 years or older in Taiwanese community studies, with a high social and economic burden for patients, family caregivers, the community and society. Previous studies have shown that viral infections such as herpes simplex and herpes zoster were associated with dementia. This study aimed to investigate the association between dementia and HPV infections. A population-based cohort study using data from Taiwan's National Health Insurance Research Database was conducted. Fine and Grays's survival analysis was employed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between genital warts and dementia. From all of the potential participants aged 50 years or more, a total of 16 116 patients were enrolled, including 4029 genital warts-infected patients, with 12 087 sex-, age- and indexed date-matched controls (1:3). The cumulative incidences of dementia were 10.72 per 103 person-years and 6.43 per 103 person-years in the genital warts and control group, respectively. There were 475 dementia cases from the genital warts cohort during the follow-up period of 15 years. The adjusted HR for dementia was 1.485 (95% CI, 1.321-1.668; P

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.

Vitiligo is an autoimmune skin disease that has a major impact on the quality of life of patients. However, a nationwide study of the association between vitiligo and the incidence of inclusive psychiatric diseases has not been conducted in the Asian population. Therefore, this study aimed to analyze the association between vitiligo and the risk of psychiatric disorders using a nationwide database in Taiwan. Data were collected from the National Health Insurance Research Database of Taiwan from 2000 to 2013. In total, 1432 subjects with vitiligo and 5728 age-, sex- and index year-matched controls were enrolled in this study. Patients with vitiligo tend to have more coexisting psychiatric disorders than healthy individuals, regardless of their sex, age group and facility level of care. After adjusting for sex, age, comorbidity, urbanization and facility level of care, the adjusted hazard ratio of overall psychiatric disorders for patients with vitiligo was 2.926 (95% confidence interval [CI], 2.646-3.236; P < 0.001). Among them, the highest adjusted hazard ratios were found for obsessive-compulsive disorder, at 10.790 (95% CI, 9.756-11.932; P < 0.001). Vitiligo is associated with an increased risk of various psychiatric disorders. By providing a better understanding of the psychosocial burden associated with vitiligo, these results emphasize the need to evaluate the mental health of patients with vitiligo by treating physicians.

This study aimed to investigate the association between traumatic spinal cord injury (TSCI) and the risk of affective and other psychiatric disorders, and the role of the rehabilitation therapies.In this population-based, retrospective cohort study, we used Taiwan's National Health Insurance Research Database to analyze the patients who were newly diagnosed with TSCI between 2000 and 2015 were included, with a 1:3 ratio by age, sex, and index year matched in the non-TSCI comparison group, for the risk of affective and other psychiatric disorders.In total, 5375 out of 16,151 patients with TSCI developed psychiatric disorders, and 1467 out of 48,543 patients in the non-TSCI group developed psychiatric disorders (2930.88 vs 2823.29 per 100,000 persons/year). The Kaplan-Meier analysis showed that the TSCI cohort had a significantly higher risk of psychiatric disorders (log-rank, p 0.001). Fine and Gray's survival analysis revealed that the adjusted hazard ratio was 1.977 (95% CI: 1.914-2.042, p 0.001). Rehabilitation therapies, including physical and occupational therapies, within 90 days after the injury, was associated with a lowered risk of psychiatric disorders, including anxiety, depression, and bipolar disorder, in the TSCI cohort (adjusted HR = 0.702 [95% CI: 0.661-0.746, p 0.001]). In the subgroups with low, medium, and high intensity, rehabilitation therapies were associated with a lowered risk of psychiatric disorders.TSCI was associated with the risk of affective and other psychiatric disorders, and rehabilitation therapies were associated with a lowered risk of these in the TSCI cohort.

Background To examine the association between narcolepsy and anxiety disorders. Methods This population-based, retrospective case-control study analyzed Taiwan's National Health Insurance Research Database between 2000 and 2013. We included narcoleptic patients aged at least 12 years, diagnosed according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 347. The cases and the propensity score-matched controls were selected in a 1:4 ratio. Each subject with anxiety disorders (ICD-9-CM code 300) was required to visit the outpatient clinic at least three times within a year. Multivariate logistic regression and interaction analyses were used to calculate the association between anxiety disorders and narcolepsy. Results This study enrolled 478 and 1912 subjects with and without narcolepsy, respectively. After adjusting for covariates, patients with anxiety disorders had an approximately 2.7 odds ratio of developing narcolepsy when compared to the control subjects (adjusted odds ratio [aOR)] = 2.7; 95% confidence interval [CI] = 1.699–4.344). Interaction analysis and subgroup analysis showed a higher incidence of previously diagnosed anxiety disorders in narcoleptic patients aged 12 to 17 years and female patients (aOR = 25.9; 95% CI = 15.194–42.896; aOR = 3.6; 95% CI = 1.818–7.062, respectively). Limitations The narcolepsy and anxiety disorders were not distinguished by validated structural diagnostic instruments. Conclusions The results of this study revealed higher comorbidity rates of anxiety disorders in narcoleptic patients. The incidence of previously diagnosed anxiety disorders was higher in narcoleptic patients aged 12 to 17 years and female patients.

OBJECTIVE To examine the risk of developing benign or malignant colorectal tumors in patients with periodontitis within 15 years using Taiwan's National Health Insurance Database. BACKGROUND Studies have shown that colorectal carcinoma often develops under inflammatory conditions and changes of microbiota in the gut. Recently, a link between Fusobacterium nucleatum, a periodontal pathogen, and colorectal carcinoma has been proposed. However, whether periodontitis is a risk of developing colorectal tumor remains uncertain. METHODS In total, 35 124 participants were enrolled from 2000 to 2015 to examine the development risk of benign colorectal tumors, including 11 708 patients with periodontitis who received therapy (group 1), 11 708 patients with periodontitis not receiving periodontal treatment (group 2), and 11 708 non-periodontitis controls after matching for gender, age, and index year. To examine the risk of developing colorectal malignancy, 11 720 participants were assigned to each of the three groups. Cox proportional hazards model and Kaplan-Meier methods were used to compare the risks. Sensitivity analysis was performed, excluding the diagnoses during the first 1 or 5 years. RESULTS After the follow-up, 177, 154, and 63 participants in group 1, group 2, and control group had benign colorectal tumors. Patients with periodontitis tended to be associated with a greater rate of having a benign colorectal tumor. The adjusted hazard ratios (aHRs) were 3.77 (95% confidence interval [CI] 2.01-4.82, p

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model.Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29–1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users.Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

BACKGROUND The effect of radical hysterectomy for patients with cervical cancer on voiding function remains controversial. The purpose of this study was to examine the association between radical hysterectomy for patients with cervical cancer and the odds of developing neurogenic bladder by using data from the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS We identified 17 936 patients who underwent radical hysterectomy for cervical cancer between 2000 and 2013 among inpatients registered in the Longitudinal Health Insurance Database in Taiwan. Of the patients, those diagnosed as having cervical cancer without radical hysterectomy were selected and compared as a matched control group. Patients diagnosed as having cervical cancer before the index date, those with neurogenic bladder dysfunction before tracking, and those aged

Tuberculosis (TB) can cause chronic inflammation. The occurrence of aortic aneurysm (AA) and aortic dissection (AD) may be associated with chronic inflammatory disease, but whether TB increases the risk of AA and AD remains to be determined. This study aimed to investigate the association between TB and the development of AA and AD. We conducted a population-based cohort study using data obtained from the Taiwan National Health Insurance Database. We selected 31,220 individuals with TB and 62,440 individuals without TB by matching the cohorts according to age, sex, and index year at a ratio of 1:2. Cox regression analysis revealed that the TB cohort had a 1.711-fold higher risk of AA and AD than the non-TB cohort after adjustment for sex, age, socioeconomic status, and comorbidities (adjusted hazard ratio = 1.711, 95% confidence interval = 1.098–2.666). Patients with pulmonary, extrapulmonary, and miliary TB had a 1.561-, 1.892-, and 8.334-fold higher risk of AA and AD, respectively. Furthermore, patients with TB at &lt, 6 months, 6–12 months, and 1–5 years of follow-up had a 6.896-, 2.671-, and 2.371-fold risk of AA and AD, respectively. Physicians should consider the subsequent development of AA and AD while treating patients with TB.

Background: Ischemic optic neuropathy (ION) is a possible extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD). We investigate the relation between IBD and ION and possible risk factors associated with their incidence.Methods: Medical records were extracted from the National Health Insurance Research Database (NHIRD) from January 1, 2000, to December 31, 2013. The main outcome was ION development. Univariate and multivariate Cox regression analyses were performed.Results: We enrolled 22,540 individuals (4,508 with IBD, 18,032 without). The cumulative risk of developing ION was significantly greater for patients with IBD vs. patients without (Kaplan–Meier survival curve, p = 0.009; log-rank test). Seven (5%) and five (0.03%) patients developed ION in the IBD and control groups, respectively. Patients with IBD were significantly more likely to develop ION than those without IBD [adjusted hazard ratio (HR) = 4.135; 95% confidence interval: 1.312–11.246, p = 0.01]. Possible risk factors of ION development were age 30–39 years, diabetes mellitus (DM), hypertension, ischemic heart disease (IHD), atherosclerosis, and higher Charlson comorbidity index revised (CCI_R) value.Conclusion: Patients with IBD are at increased risk of subsequent ION development. Moreover, for patients with comorbidities, the risk of ION development is significantly higher in those with IBD than in those without.

Background This study aimed to investigate the association between posttraumatic stress disorder and the risk of developing erectile dysfunction. Methods In this population-based retrospective cohort study, we used Taiwan’s National Health Insurance Research Database to analyze patients who were newly diagnosed with posttraumatic stress disorder (PTSD) between 2000 and 2013, with a 1:3 ratio by age and index year matched with patients in a non-PTSD comparison group, for the risk of erectile dysfunction. Results In total, 5 out of 1079 patients in the PTSD group developed erectile dysfunction, and 3 out of 3237 patients in the non-PTSD group (47.58 vs. 9.03 per 100,000 per person-year) developed erectile dysfunction. The Kaplan–Meier analysis showed that the PTSD cohort had a significantly higher risk of erectile dysfunction (log-rank, p p = 0.003) after adjusting for age, monthly income, urbanization level, geographic region, and comorbidities. Psychotropic medications used by the patients with PTSD were not associated with the risk of erectile dysfunction. Conclusions Patients who suffered from PTSD had a higher risk of developing erectile dysfunction.

Background Previous studies have presented an unclear association between major depressive disorder (MDD) and tinnitus. Therefore, in this study, we aimed to demonstrate the actual association between MDD and new-onset tinnitus using a large, population-based dataset in Taiwan. Method This case–control study used the data from the National Health Insurance Database. In total, 18,365 patients with tinnitus were recruited as cases, and 18,365 propensity score-matched patients without tinnitus were identified as controls. Logistic regression models were constructed to calculate the odds ratios (ORs) and to estimate the association between prior MDD and tinnitus. Results MDD was found in 396 (2.16%) patients with tinnitus and 228 (1.24%) controls without tinnitus. The logistic regression model indicated that prior MDD was associated with tinnitus (adjusted OR, 1.74; 95% CI, 1.47–2.05). Moreover, MDD was positively associated with tinnitus among most subgroups. Notably, a significant association between MDD and tinnitus was observed among patients with diabetes (adjusted OR, 2.05) and hyperlipidemia (adjusted OR, 1.94). Furthermore, sensitivity analyses consistently found a relationship between prior MDD and tinnitus. Limitations The database used in this study does not provide information regarding the lifestyle and gene factors. Conclusions Our results showed a positive association between prior MDD and tinnitus. In addition, MDD may be one of the risk factors for tinnitus onset. Therefore, we recommended that the clinicians should be alert about the tinnitus condition among patients with MDD and provide appropriate interventions for them.

Background The risk of injury directly related to hospitalization for motor vehicle accidents (MVAs) in the obstructive sleep apnea (OSA) patients has not been thoroughly understood. Our study aimed to examine the association between the OSA and the hospitalization for an MVA injury. Methods This retrospective cohort study used Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2015. The OSA patients aged ≥20 years by age, sex, and index-year matched by non-OSA controls were enrolled (1:3). We used the Cox proportional regression model to evaluate the association between the OSA and the hospitalization for an MVA injury. Results The incidence rate of hospitalization for an MVA injury was higher in the OSA cohort (N = 3025) when compared with the non-OSA controls (N = 9075), as 575.3 and 372.0 per 100,000 person-years, respectively (p p p Conclusions This study provides evidence that patients with OSA are at a two-fold higher risk of developing hospitalization for an MVA injury, and the usage of modafinil and methylphenidate was associated with a lower risk of an overall hospitalization for the MVA injury.

Objective Aortic aneurysms (AAs) and intracranial aneurysms (IAs) share several clinical risk factors, a genetic predisposition, and molecular signaling pathways. Nonetheless, associations between IAs and AAs remain to be thoroughly validated in large-scale studies. In addition, no effective medical therapies exist for unruptured IAs or AAs. Methods Data for this nationwide, population-based, retrospective, cohort study described herein were obtained from the National Health Insurance Research Database in Taiwan. The study outcomes assessed were (1) the cumulative incidence of IAs, which was compared between AA and patients without an AA and (2) the cumulative incidence of IAs in patients with AAs during the 13-year follow-up period, which was further compared among those who underwent open surgical repair (OSR), endovascular aneurysm repair or nonsurgical treatment (NST). Results Our analyses included 20,280 patients with an AA and 20,280 propensity score-matched patients without an AA. Compared with the patients without an AA, patients with AA exhibited a significantly increased risk of an IA diagnosis (adjusted hazard ratio [HR], 3.395; P Conclusions We demonstrated an association between IAs and AAs, even after adjusting for several comorbidities. We also found that OSR was associated with fewer recognized IAs than NST.

Background: Sjogren's syndrome (SS) is a chronic autoimmune disease with lymphocytic exocrine gland infiltration causing dry mouth and eyes. The disease can develop alone (primary SS, PSS) or with other autoimmune diseases (secondary SS, SSS). PSS has been suggested to increase the acute pancreatitis risk. However, whether all patients with SS share this higher risk remains uncertain. This nationwide population-based cohort study aimed to detect associations between SS and acute pancreatitis. Methods: We identified 11,922 individuals with SS cohort and 47,688 individuals without SS (non-SS cohort) between 2000 and 2010 from the Taiwan National Health Insurance database. We matched the individuals between the SS and non-SS cohorts according to age, gender, and index year at a 1:4 ratio. We used a Cox multivariable proportional-hazards model to determine the effects of SS on the acute pancreatitis risk. Results: The SS cohort had a higher acute pancreatitis risk than the non-SS cohort after covariate adjustments (adjusted hazard ratio [HR], 3.374; 95% confidence interval [CI], 2.869–3.969). Patients with PSS exhibited a 2.872-fold risk (95% CI, 2.611–3.901) and patients with SSS a 4.121-fold risk (95% CI, 3.752–5.124) for acute pancreatitis. Our subgroup analyses revealed that patients with SS and systemic lupus erythematosus (adjusted HR, 3.85; 95% CI, 3.259–4.999), rheumatoid arthritis (adjusted HR, 4.298; 95% CI, 3.862–5.286), systemic sclerosis (adjusted HR, 2.765; 95% CI, 2.26–3.68), or polymyositis (adjusted HR, 2.641; 95% CI,1.847–3.101) and dermatomyositis (adjusted HR, 3.77; 95% CI, 2.894–4.502) had higher acute pancreatitis risk. Conclusions: Patients with SS presented increased acute pancreatitis risks than patients without SS, and patients with SSS had higher acute pancreatitis risks than patients with PSS. Physicians should be aware of this increased risk in patients with SS.

Recent studies revealed the risk of bullous pemphigoid (BP) in patients with diabetes mellitus (DM) taking dipeptidyl peptidase 4 (DPP-4) inhibitors. To clarify the relationship between taking DPP-4 inhibitors and the risk of BP among patients with DM, we conducted a cohort study by using the National Health Insurance Research Database of Taiwan from 1 January 2009 to 31 December 2015. We identified 6340 patients with DM taking DPP-4 inhibitors and 25 360 DM patients who had not taken DPP-4 inhibitors during the 7-year follow-up period. Compared with the non-DPP-4 inhibitor group, patients taking DDP-4 inhibitors had a higher risk of BP (adjusted hazard ratio [aHR], 2.382; 95% confidence interval (CI), 1.163-4.883; P = 0.017]. Among the DPP-4 inhibitors available in Taiwan, vildagliptin showed the highest risk of BP (aHR, 2.849; 95% CI, 1.893-4.215; P < 0.001), followed by saxagliptin (aHR, 2.657; 95% CI, 1.770-3.934; P < 0.001). Subgroup analysis revealed that the higher risk of BP was observed in patients older than 65 years (aHR, 2.403; 95% CI, 1.590-3.627; P < 0.001). This study revealed that treatment with DPP-4 inhibitors, especially vildagliptin, was significantly associated with an increased risk of BP among DM patients.

Objective The study aim was to investigate the risk of venous thromboembolism (VTE) in patients with concurrent depressive, bipolar, and schizophrenic disorders. Methods A population-based cohort study was conducted in which information regarding psychiatric illnesses and medical comorbidities in 29,467 patients with concurrent depressive, bipolar, and schizophrenic disorders and regarding 117,868 controls were extracted. We compared the incidence of VTE between the study and control cohorts. Cox proportional hazard regression models were used to analyze the risk of VTE after adjusting for potential confounders, including sex, age, and comorbidities. Results Compared with the control cohort, the overall study cohort had a 2.995-fold higher adjusted hazard ratio (aHR) for development of deep vein thrombosis (DVT) and a 2.591-fold higher aHR for development of pulmonary embolism (PE). Moreover, patients with depressive, bipolar, and schizophrenic disorders all exhibited higher aHRs for development of both DVT and PE. Conclusion The relative risks of DVT and PE were higher in patients with concurrent depressive, bipolar, and schizophrenic disorders than those of the general population. Further research is needed to develop effective prevention strategies for different patient populations.

Background The associations between the human immunodeficiency virus (HIV) and dementias are as yet to be studied in Taiwan. The aim of this study is to clarify as to whether HIV infections are associated with the risk of dementia. Methods A total of 1,261 HIV-infected patients and 3,783 controls (1:3) matched for age and sex were selected between January 1 and December 31, 2000 from Taiwan's National Health Insurance Research Database (NHIRD). Fine and Gray's survival analysis (competing with mortality) analyzed the risk of dementias during the 15-year follow up. The association between the highly active antiretroviral therapy (HAART) and dementia was analyzed by stratifying the HAART status among the HIV subjects. Results During the follow-up period, 25 in the HIV group (N= 1,261) and 227 in the control group (N= 3,783) developed dementia (656.25 vs 913.15 per 100,000 person-years). Fine and Gray's survival analysis revealed that the HIV patients were not associated with an increased risk of dementia, with the adjusted hazard ratio (HR) as 0.852 (95% confidence interval [CI]: 0.189-2.886, p=0.415) after adjusting for sex, age, comorbidities, geographical region, and the urbanization level of residence. There was no significant difference between the two groups of HIV-infected patients with or without HAART in the risk of dementia. Conclusion This study found that HIV infections, either with or without HAART, were not associated with increased diagnoses of neurodegenerative dementias in patients older than 50 in Taiwan.

OBJECTIVE To examine the risk of ocular complications following radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS We adopted 1:1 propensity score matching and identified an NPC cohort (n = 736) and a comparison cohort (n = 736) that comprised non-NPC head and neck cancer patients who received radiotherapy in the National Health Insurance Research Database from 1997 to 2010. The follow-up period was terminated upon developing ocular complications (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]360-379) or on December 31, 2010. RESULTS After adjusting for the confounding factors of the study, the NPC cohort had a higher adjusted hazard ratio (HR) for developing ocular complications than the comparison cohort (adjusted HR = 2.786, 95% confidence interval [CI] = 1.805-4.112, P

Aim: This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders. Method: A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. Results: Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214–9.480, p

STUDY OBJECTIVES: To examine the risk of hospitalization for motor vehicle accident injury (MVAI) in patients with narcolepsy and the effects of stimulant use on MVAI occurrence in patients with narcolepsy. METHODS: This is a population-based, retrospective cohort study using Taiwan's National Health Insurance Research Database between 2000 and 2013. We included patients with narcolepsy based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, 347. The case and matched control participants were selected in a ratio of 1:3, and the traffic accident (ICD-9-CM codes: E810–E819) plus injury codes (ICD-9-CM codes: 800.xx–999.xx) due to MVAI following hospitalization were used for the study outcome. The type of injury, causes, intentionality, and the effects of stimulant use on patients with narcolepsy were also assessed. RESULTS: A total of 1,316 participants were enrolled, including 329 participants with narcolepsy and 987 participants without narcolepsy. During a 14-year follow-up period, a total of 104 participants had MVAI, of whom 47 (1,559.54 per 100,000 person-years) belonged to the narcolepsy cohort and 57 (556.21 per 100,000 person-years) to the non-narcolepsy cohort. After adjusting for covariates, the risk of hospitalization for MVAI among participants with narcolepsy was still significantly higher than those without narcolepsy (adjusted hazard ratio = 6.725; 95% confidence interval = 4.421–10.231; P < .001). The use of modafinil or methylphenidate, as monotherapy or combined treatment, was associated with a lower risk of MVAI in the narcolepsy cohort. CONCLUSIONS: Patients with narcolepsy may have a higher risk of hospitalization for MVAI and stimulant use could mitigate such risk. CITATION: Tzeng NS, Hsing SC, Chung CH, Chang HA, Kao YC, Mao WC, Yang CC, Kuo TB, Chen TY, Chien WC. The risk of hospitalization for motor vehicle accident injury in narcolepsy and the benefits of stimulant use: a nationwide cohort study in Taiwan. J Clin Sleep Med. 2019;15(6):881–889.

Background Primary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed to a great risk for developing sleep apnoea (SA). Methods In this retrospective longitudinal study, the data obtained from the Longitudinal Health Insurance Database in Taiwan were analysed. The study included 1346 patients with PHDs who were initially diagnosed and 5348 patients who were randomly selected and age/sex matched with the study group as controls. PHDs, SA, comorbidities and other confounding factors were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification. Cox proportional hazards regressions were employed to examine adjusted HRs after adjusting with confounding factors. Results Our data revealed that patients with PHDs had a higher risk (HR 2.17, 95% CI 1.259 to 3.739, p Conclusion Our results suggest that PHDs are linked to an increased risk for SA with sex-dependent and time-dependent characteristics.

Dementia and aortic aneurysms share clinical risk factors and molecular signaling pathways. However, the association between dementia and aortic aneurysms has not been examined. The potential effects of open surgical repair (OSR) of aortic aneurysms on future dementia events are unknown.We conducted this nationwide population-based, retrospective cohort study using the Taiwanese National Health Insurance Research Database (NHIRD). The cumulative incidence of dementia over a 13-yearfollow-up period was compared among 1)aortic aneurysms and non-aortic aneurysm patients and 2)aortic aneurysm patients who underwent OSR, endovascular aneurysm repair (EVAR) or nonsurgical treatment (NST).This study enrolled 19,921 aortic aneurysms patients and 19,921 matched controls. The aortic aneurysm cohort exhibited a significantly increased incidence of dementia compared with the controls (adjusted hazard ratio (HR)=3.559, p0.001). Furthermore, 5409 aortic aneurysm patients were treated with surgical intervention, whereas 5409 matched aortic aneurysm patients were not. Aortic aneurysm patients who underwent OSR had a significantly lower incidence of dementia than those who underwent NST (adjusted HR=0.638, 95% confidence interval (CI)=0.411-0.764, p0.001). Patients who underwent EVAR did not have a lower incidence of dementia than those who underwent NST.OSR was associated with a reduced incidence of dementia in patients with aortic aneurysms compared to NST.

Background:Chlamydia pneumoniae (CPn) is a common community-acquired pneumonia. In the literature, CPn infection is demonstrated to exhibit an association with Alzheimer dementia (AD). We executed the present nationwide, population-based research with the goal of probing the association of CPn infection and antibiotic therapy with AD risk.Methods: We conducted a cohort study using a database extracted from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each enrolled individuals were categorized using the International Classification of Diseases, ninth Revision classifications. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CPn pneumonia-associated hospitalizations and AD were estimated using Fine and Gray's survival analysis and adjusted for comorbidities. The effects of the antibiotics on the HRs for AD in the patients with CPn pneumonia-associated hospitalization were also analyzed.Results: Our analyses included 6,628 individuals, including 1,657 CPn-infected patients, as well as 4,971 controls matched by age, index date, and sex (1:3). In this study, patients hospitalized for CPn pneumonia exhibited a significantly higher AD risk (adjusted HR = 1.599, 95% CI = 1.284–1.971, p < 0.001). We also noted an association of macrolide use (≥15 days) and fluoroquinolone use (≥15 days) with decreased AD risk.Conclusions: We determined CPn pneumonia to be associated with a relatively high AD risk. The result in this study confirmed the findings from previous literatures, by using a large, nationwide, population-based database. Appropriate macrolide and fluoroquinolone treatment may attenuate this risk.

Background: Trichomonas vaginalis infection is one of the most widespread sexually transmitted infections in the world. There are approximately 276 million cases worldwide. Most men remain undiagnosed and untreated because they are asymptomatic. The chronic inflammation induced by persistent infection may increase the risk of developing genitourinary cancers. In this study, we aimed to investigate the association between trichomoniasis and benign prostate hyperplasia (BPH), prostate cancer (PCa), and bladder cancer (BC) in Taiwan.Material and method: We designed a case-control study by using the database of the National Health Insurance program in Taiwan. We used the International Classification of Diseases, 9th Revision classifications to classify all the medical conditions in the case and control groups. All odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using multivariable logistic regression to adjust for all comorbidities and variables.Result: From 2000 to 2015, we enrolled a total of 62,544 individuals as the case group and 187,632 as the control group. Trichomoniasis exposure had a significant association with BPH and PCa (adjusted OR: BPH = 2.685, 95% CI = 1.233–4.286, P = 0.013; PCa = 5.801, 95% CI = 1.296–26.035, P = 0.016). The relative risk was much higher if patients had both trichomoniasis and depression (adjusted OR = 7.682, 95% CI = 5.730–9.451, P < 0.001).Conclusion: Men with trichomoniasis had a significantly higher risk of developing BPH and PCa than those without. Healthcare professionals should not only pay more attention to disease treatment, but also to public health education.

BACKGROUND Nephrotic syndrome (NS) is characterized by various etiologies that damage the glomerulus. Central serous chorioretinopathy (CSCR) is a retinal disease characterized by neurosensory detachment of the retina. Several case reports have described the relationship between both. Therefore, we try to analyze the epidemiological associations between NS and CSCR using the National Health Insurance Research Database in Taiwan. METHODS Data spanning 14 years were extracted from the National Health Insurance Research Database and sub-grouped. The variables were analyzed using Pearson's chi-squared test and Fisher's exact test. The risk factors for disease development with or without comorbidities were examined using an adjusted hazard ratio (aHR). Kaplan-Meier analysis was performed to evaluate the cumulative incidence of CSCR with or without NS. RESULTS A total of 14 794 patients with NS and 14 794 matched controls without NS were enrolled in this cohort study. The incidence rate of CSCR was higher in the study cohort than in the control cohort (aHR = 3.349, p

ObjectivesTo investigate the effect of botulinum toxin A (BTA) on the development of hip dislocation and scoliosis, surgical rates for hip and spine, and mortality in cerebral palsy (CP).Study designA cohort study was conducted using CP data from a Taiwan National Insurance Health Research Database. Diagnoses were defined using the International Classification of Diseases codes, 9th revision. Adjusted hazard ratios for outcomes were calculated using Cox regression analysis and adjusted for the following variables: BTA injection, sex, age, severities of CP, comorbidities, location, urbanization level, and level of care.ResultsA total of 1,405 CP children (670 female vs. 735 male), 281 in the BTA group and 1,124 in the controls, were followed-up for a mean of 5 years 4 months. There were no significant differences in the outcomes in both groups, in the incidence rates of hip dislocation and scoliosis, nor in the surgical rates for hip and spine surgery. Mortality rate in the BTA group was 0.49 times lower than that in the controls (p= 0.001). Moderate to severe types of CP had higher incidence rates of hip dislocation, scoliosis, hip surgery, spine surgery, and mortality.ConclusionModerate to severe types of CP had poorer outcomes in all aspects, including a higher risk of hip dislocation, scoliosis, surgical rate for hip and spine, and mortality. Although BTA injection in children with CP proved to not significantly reduce hip dislocation and scoliosis, it is considered safe as an anti-spasticity treatment and may be beneficial for survival.

Background Calcific tendinopathy of the rotator cuff is a common cause of painful disability in the shoulder with unclear aetiology. Diabetes mellitus (DM) is associated with calcific tendinopathy; however, large epidemiological data are lacking. Thus, we conducted a nationwide population-based matched cohort study to investigate the risk for calcific tendinopathy of the shoulder in diabetic patients. Methods The National Health Insurance Research Database of Taiwan was used to include 42 915 patients newly diagnosed with DM between 1 January 2000 and 31 December 2015 and randomly extract the data of 171 660 individuals, as a matched control group. All individuals were followed-up until the development of calcific tendinopathy or the end of 2015. Results Overall, 122 patients from the DM group (0.284%) developed calcific tendinopathy compared with 340 individuals from the non-DM group (0.198%). The Kaplan-Meier analysis indicated that patients with DM had a higher risk of calcific tendinopathy since the eighth year of follow-up (log-rank test, P = .006). Cox proportional hazard regression revealed that the adjusted hazard ratio of calcific tendinopathy in diabetic patients to that in non-diabetic patients was 1.276 (95% confidence interval 1.037-1.571, P = .002). Moreover, the stratified analysis disclosed that DM was a strong independent risk factor for calcific tendinopathy irrespective of the existing comorbidities. Conclusions This study demonstrated that patients with DM had a 27% increased risk of developing calcific tendinopathy of the shoulder, 8 years after initially being diagnosed with DM.

We conducted a retrospective group study to evaluate the potential systemic risk factors for major postoperative complications of cataract surgery. Individuals diagnosed with (n = 2046) and without (n = 8184) serious complications after cataract surgery were matched 1:4 for age, sex, and index date obtained using Taiwan’s National Health Insurance Research Database. The outcome was defined as at least one new inpatient or outpatient diagnosis of systemic disease one year before the index date. The effect of demographic data on postoperative complications was also analyzed in the multivariable model. Data were analyzed using univariate and multivariate conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals of the risk of developing serious complications. After the entire study interval, the major postoperative complications of cataract surgery were associated with the following systemic diseases: hypertension (adjusted OR (aOR) = 2.329, p &lt, 0.001), diabetes mellitus (aOR = 2.818, p &lt, 0.001), hyperlipidemia (aOR = 1.702, p &lt, 0.001), congestive heart failure (aOR = 2.891, p &lt, 0.001), rheumatic disease (aOR = 1.965, p &lt, 0.001), and kidney disease needing hemodialysis (aOR = 2.942, p &lt, 0.001). Additionally, demographic data including old age, higher urbanization level, higher level of care, and more frequent inpatient department visits were associated with a higher rate of postoperative complications. In conclusion, metabolic syndrome, chronic heart failure, end-stage renal disease, rheumatic disease, older age, and frequent inpatient department visits are correlated with the development of severe postoperative complications of cataract surgery. Therefore, cataract surgery patients should be informed about a higher possibility of postoperative complications.

One recent study showed that atomoxetine-oxybutynin combination (AOC) use is effective in reducing obstructive sleep apnea (OSA) severity. We used a nationwide database to examine the association between AOC use and the risk of OSA incidence. This retrospective cohort study used Taiwan’s National Health Insurance Research Database between the years 2000 and 2015. The patients who used atomoxetine or oxybutynin were included as an exposed cohort. The exposed and unexposed groups were selected in a ratio of 1:3 with sex, age, and index year matching. We used the multivariate Cox proportional regression model to evaluate the association between AOC use and the risk of an incident diagnosis of OSA. The incidence rates of OSA in the exposed cohort (N = 8940) and the unexposed cohort (N = 26,820), were 21.92 and 22.93 per 100,000 person-years, respectively. The adjusted hazard ratio of oxybutynin use only and AOC with a treatment duration of ≥ 366 days were 0.307 (95% CI 0.204–0.995, P = 0.045) and 0.299 (95% CI 0.102–0.933, P = 0.002), respectively. Long-term atomoxetine-oxybutynin combination therapy may be beneficial to reduce the risk of obstructive sleep apnea. Further studies to examine these mechanisms are warranted.

This study aimed to investigate whether orbital fracture increases the risk of dry eye syndrome (DES) and identified the profile of prognostic factors. We studied a cohort from the Taiwan National Health Insurance Research Database (NHIRD). Overall, 46,179 and 184,716 participants were enrolled in the study and control groups, respectively. Each patient in the case group was age- and gender-matched to four individuals without orbital fracture that served as the control group. Cox proportional hazards analysis regression was used to estimate the risks of incident DES. During the follow-up period, the case group was more likely to develop incident DES (0.17%) than the control group (0.11%) (p = 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 4.917-fold increased risk of DES compared to the controls. In the stratified age group, orbital fracture had the highest impact on patients aged 18–29 years. Furthermore, patients with orbital roof fracture have a greater risk of developing DES. Regardless of whether having received surgery or not, the patients with orbital fracture have higher risks of DES. Our study demonstrated that orbital fracture increases the risk of developing subsequent DES. Early recognition by thorough examinations with raised awareness in the clinical setting could preserve visual function and prevent further complications.

Background: Premenstrual syndrome (PMS) is a common disorder affecting the quality of life of women of reproductive age. In a previous study, sex hormone imbalances and alterations in autonomic function were present in PMS, with parasympathetic dysfunction and sympathetic overactivity during the late luteal phase. Palmar hyperhidrosis (PH) presents with oversweating, heat and emotional stimulation, sympathetic hyperactivity and parasympathetic hypofunction. We hypothesized that the incidence of PMS is increased in females with PH. Methods: Data were retrieved from the Taiwanese National Health Insurance Database. The patients with PH were identified by the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) disease code 780.8. Female patients matched by age and index day were used as the control group. The incidence of PMS was considered an outcome by the ICD-9-CM disease code 625.4. The factors related to PMS were analyzed by Cox regression. Results: The adjusted hazard ratio for the incidence of PMS was 1.276 (95% confidence interval: 1.05–1.488) in females with PH. Conclusions: This study found a positive correlation between PMS and female PH patients. Patients and physicians must understand the relationship of PMS with autonomic function alterations and other risk factors to prevent this problematic disorder.

BACKGROUND Central serous chorioretinopathy (CSCR) and liver cirrhosis share numerous risk factors and may have possible connections. We aimed to investigate whether patients with liver cirrhosis and the severity of cirrhosis have an increased incidence of CSCR. METHODS This population-based retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database from January 1, 2000, to December 31, 2015. We included patients who were newly diagnosed with cirrhosis and selected an equal number of sex- and age-matched control subjects. The effect of cirrhosis on the risk of CSCR was examined via a Cox proportional hazard regression analysis. The cumulative incidence of CSCR was assessed with the Kaplan-Meier method and the log-rank test. RESULTS Both groups in this study comprised a total of 25 925 individuals. The cirrhotic patients had a significantly higher cumulative risk of developing CSCR in following years than patients without cirrhosis (log-rank test < 0.001). Furthermore, compared with noncirrhotic patients, the risk of CSCR was increased 3.59-fold (95% confidence interval [CI], 2.31-5.28) in cirrhotic patients with complications, and 2.34-fold (95% CI, 1.27-3.24) in cirrhotic patients without complications. Additionally, male sex, springtime, diabetes mellitus, hepatitis B virus, and hepatitis C virus statistical significantly increased the incidence of CSCR. CONCLUSION Cirrhosis is an independent indicator of CSCR. Among the cirrhotic population, patients with ascites and other complications have a higher incidence of CSCR than those with uncomplicated cirrhosis. Physicians should be observant when managing cirrhotic patients with visual disturbances.

Background Alcohol has dual effects on many systems, including the pain system. We will test whether and how chronic alcohol consumption enhances pain sensation to develop pain disorder. Methods We conducted a retrospective matched cohort study using data from the National Health Insurance Research Database (NHIRD) in Taiwan, in patients with and without alcohol use disorder (AUD). This study enrolled 19,174 individuals with AUD as study cohort and 19,174 propensity score-matched individuals without AUD as comparison cohort. The outcome was the incidence of pain disorders and the need for analgesics. The hazard ratios of pain disorders and the need for analgesics were evaluated using Cox proportional hazard regression analysis after adjusting for age, sex, index year, comorbidities, urbanization, areas of residence, and insurance premium. Results The 14 years of follow-up showed that AUD patients had a higher adjusted hazard ratio (aHR) for developing pain disorders than in non-AUD controls [aHR= 1.290, 95% confidence interval (CI): 1.045-1.591]. Besides, AUD patients had a higher risk of analgesic use (aHR = 1.081, 95% CI: 1.064-1.312), including opioids and non-opioid analgesics. Most importantly, AUD patients required more days of analgesic use, increased dose of analgesics, and higher costs of analgesics. Moreover, AUD patients had more anemia (aHR=2.772, 95% CI: 2.581-2.872), which could be a mediating factor. Conclusions AUD patients had higher risks of developing pain disorders and subsequently increased analgesic demand. These results suggest that AUD worsened pain, and pain syndrome is correlated with the duration of chronic alcohol exposure.