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Schizophrenia is highly comorbid with obsessive–compulsive disorder (OCD); both conditions share numerous pathophysiological etiologies. We, thus, examined the risk of mental disorders in the parents of probands with schizophrenia, OCD, or both conditions. Between 2001 and 2011, we enrolled a nationwide cohort of 69,813 patients with schizophrenia, OCD, or both. The control cohort included 698,130 individuals matched for demographics. Poisson regression models were employed to examine the risk of six mental disorders in their parents, including schizophrenia, bipolar disorder, depressive disorder, OCD, alcohol use disorder, and substance use disorder. We stratified patients into schizophrenia-only, OCD-only, and dual-diagnosis groups, and the dual-diagnosis group was further divided into schizophrenia-first, OCD-first, and simultaneously diagnosed groups. Compared with controls, the schizophrenia, OCD, and dual-diagnosis groups had higher risks for the six mental disorders in their parents (range of odds ratio [OR] 1.50–7.83). The sub-analysis of the dual-diagnosis group showed that the schizophrenia-first, OCD-first, and simultaneously diagnosed groups had higher odds for schizophrenia, bipolar disorder, depressive disorder, and OCD (range of OR 1.64–6.45) in their parents than the control group; the simultaneously diagnosed and OCD-first diagnosed groups had a higher odds of parental substance use disorder, while the schizophrenia-first diagnosed group had a higher odds of parental alcohol use disorder. The interrelationship between OCD and schizophrenia is linked to bipolar disorder, depressive disorder, alcohol use disorder, and substance use disorder. The results have implications for mental health policy and future research. [ABSTRACT FROM AUTHOR]

Background: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown. Methods: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified. Results: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02–1.44), especially daughters (HR: 1.30, 95% CI: 1.06–1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29–1.67) compared with those having no parents with severe mental disorders. Discussion: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group. [ABSTRACT FROM AUTHOR]

In this study, we examined the risk of sexually transmitted infections (STIs) among adolescents and young adults (AYAs) with borderline personality disorder (BPD). A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was conducted to examine the risk of contracting any STI among both patients and controls. A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI (ICD-9-CM code 042, 091–097, 087.11, 078.8, 078.88, 131, and 054.1) during the follow-up period were identified. Cox regression and sub-analyses stratified by sex, age, psychiatric comorbidity subgroups, and psychotropic medication usage were conducted to assess STI risk. AYAs with BPD were at a higher risk of contracting any STI (hazard ratio [HR] = 50.79, 95% confidence interval [CI] = 33.45–77.11) in comparison with controls, including HIV, syphilis, genital warts, gonorrhea, chlamydia, trichomoniasis, and genital herpes. The association of BPD with an increased risk of any STI was prevalent in both sexes, adolescents, and young adult patients. BPD with or without psychiatric comorbid subgroup were all associated with an elevated risk of contracting any STI relative to the control group. AYAs with BPD are highly susceptible to contracting STIs. Future studies should examine the role of the core symptoms of BPD, sexual orientation, risky sex behaviors, depressive and anxiety symptoms, and substance use before sex in the risk of STIs among AYAs with BPD. [ABSTRACT FROM AUTHOR]

Purpose: Both metabolic syndrome (MetS) and cognitive dysfunction impair health-related quality of life (HRQOL). This study aims to determine whether individuals experiencing both MetS and cognitive dysfunction have lower HRQOL. Methods: This cross-sectional study enrolled 567 participants who attended outpatient clinics at a medical center in northern Taiwan. MetS was diagnosed according to the modified criteria for the Asian population. Cognitive function was categorized as normal, mild cognitive dysfunction, and advanced cognitive dysfunction according to the score of the Montreal Cognitive Assessment, Taiwanese version. HRQOL was assessed using the SF-36v2® Health Survey (SF-36v2). The associations of the comorbidity status of MetS and cognitive dysfunction with HRQOL were analyzed using linear regression models, adjusting for age, sex, marital status, education level, income groups, and activities of daily living. Results: Out of 567 participants, 33 (5.8%) had MetS with mild cognitive dysfunction, and 34 (6.0%) had MetS with advanced cognitive dysfunction. Participants with both MetS and advanced cognitive dysfunction exhibited the lowest scores in the physical component summary and almost all scales of HRQOL. MetS exacerbated the inverse association between mild cognitive dysfunction and the mental component summary. For those with MetS, the scores on scales of role physical, bodily pain, vitality, and social functioning worsened as cognitive function deteriorated (all Ptrend<0.05). Conclusion: As the severity of comorbidity between MetS and cognitive dysfunction varies, patients exhibited poorer performance in different aspects of HRQOL. Future research is needed to find solutions to improve HRQOL for patients with both MetS and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Although several studies have examined a diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BD), only a few studies specifically focused on adolescents and young adults who are at the peak ages of BD onset. Data from participants (N = 130,793) aged 10–29 years who were diagnosed with MDD were extracted from the Taiwan National Health Insurance Research Database. We applied demographic analyses, survival analysis, Aalen Johansen curves, and Cox regression, investigating the diagnostic conversion rate and factors that were most or less predictive of conversion. Among the adolescents and young adults with MDD, the number of participant conversion subsample is 14,187 and the conversion rate was 13.80% (95% confidence interval: 13.54–14.06%) during the 11-year follow-up. The conversion rate was highest in the first year (4.50%; 4.39–4.61%) and decreased over time. The significant predictors were younger age of diagnosis with MDD (p < 0.001), moderate and high antidepressant resistance (p < 0.001), obesity (p < 0.001), psychiatric comorbidities (attention-deficit/hyperactivity disorder, substance use disorder, and cluster B and C personality disorder, all p < 0.001), a family history of mental disorders (schizophrenia and mood disorders, all p < 0.05), lower monthly income (p < 0.001), and more mental health visits to the clinic each year (p < 0.001). A composite of demographic characteristics, antidepressant resistance, physical and psychiatric comorbidities, and family history significantly predicted diagnostic conversion from MDD to BD (area under the curve = 0.795, p < 0.001). Compared to adult population, the adolescents and young adults had different factors that were most or less predictive of conversion, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Although a growing number of studies have investigated the relationship between psychosocial factors and periodontitis, studies investigating the association between bipolar disorder (BD) and periodontitis are lacking. Using the Taiwan National Health Insurance Research Database, 4251 adolescents with BD and 17,004 age- and sex-matched controls were included. They were followed up from enrollment to the end of 2011 or death. Periodontitis was diagnosed during the follow-up. Cox regression analysis indicated that adolescents with BD had a higher risk of periodontitis (hazard ratio [HR]: 2.96, 95% confidence interval [CI] 2.77–3.17) than did controls. Subanalyses stratified by sex revealed a higher risk of periodontitis in male (HR: 2.83, 95% CI 2.56–3.14) and female (HR: 3.01, 95% CI 2.74–3.30) adolescents with BD than their respective controls. The long-term use of mood stabilizers was associated with a higher risk of periodontitis (HR: 1.19, 95% CI 1.06–1.35) in the BD cohort. Our study highlighted an increased risk of periodontitis in adolescents with BD compared with controls during the follow-up. We recommend that more attention should be paid to the prevention of periodontitis in adolescents with BD, especially those who are female or receiving mood stabilizers. [ABSTRACT FROM AUTHOR]

This longitudinal study aimed to investigate the risk of subsequent autoimmune disease in patients with post-traumatic stress disorder (PTSD) in Asian population. Between 2002 and 2009, we enrolled 5273 patients with PTSD and 1:4 matched controls from the National Health Insurance Database of Taiwan, and followed up the patients until December 31, 2011, or death. The investigated autoimmune diseases included thyroiditis, lupus, rheumatic arthritis, inflammatory bowel disease, Sjogren's syndrome, dermatomyositis, and polymyositis. The Cox regression model was used to estimate the risk of developing autoimmune diseases, with adjustment for demographics and psychiatric and medical comorbidities. Furthermore, we examined the psychiatric clinics utility of patients with PTSD indicating the severity of PTSD in association with autoimmune diseases. After adjusting for confounders, patients with PTSD had a 2.26-fold higher risk of developing any autoimmune diseases (reported as hazard ratios with 95% confidence intervals: 1.82–2.80) than the controls. For specific autoimmune diseases, patients with PTSD had a 2.70-fold higher risk (1.98–3.68) of thyroiditis, a 2.95-fold higher risk (1.20–7.30) of lupus, and a 6.32-fold higher risk (3.44–11.60) of Sjogren's syndrome. Moreover, the PTSD severity was associated with the risk of autoimmune diseases in a dose-dependent manner. The patient with the highest psychiatric clinics utility was associated with an 8.23-fold higher risk (6.21–10.90) of any autoimmune diseases than the controls. Patients with PTSD had an increased risk of autoimmune diseases, and such risk was associated with the severity of PTSD in a dose-dependent manner. However, the present study did not provide a direct effect between PTSD and autoimmune diseases, but rather an association. Further studies are warranted to examine the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

It remains unclear how major psychiatric comorbidities and parental psychiatric disorders differ in males and females with autism spectrum disorder (ASD). Between 2001 and 2011, 17,627 children and 5071 adolescents with ASD (ICD-9-CM code: 299) were identified from Taiwan's National Health Insurance Research Database and assessed for major psychiatric comorbidities and parental psychiatric disorders. Compared with females with ASD, males with ASD were more likely to be diagnosed as having attention deficit hyperactivity disorder (relative risk [RR], 95% confidence interval [CI] 1.63, 1.51–1.75) and disruptive behavior disorder (1.38, 1.17–1.62) and less likely to be diagnosed as having schizophrenia (0.45, 0.36–0.56), bipolar disorder (0.58, 0.45–0.74), or intellectual disability (0.53, 0.49–0.58). Furthermore, compared with women, having a parental history of schizophrenia (RR, 95% CI 0.66, 0.49–0.89) or intellectual disability (0.34, 0.19–0.61) was less associated with ASD among men. However, the difference in ASD diagnosis between ICD-9-CM and ICD-10/11-CM systems may reflect the different, but surely overlapping, entity of ASD, which may limit the generalization of our results. Additional studies should be performed. [ABSTRACT FROM AUTHOR]

The association between autism spectrum disorder (ASD) and subsequent sexually transmitted infections (STIs) and the potential effects of medications on STI risk remain unknown. In all, 5076 adolescents and young adults with ASD and 57,060 age-/sex-matched individuals without ASD were enrolled between 2001 and 2009 and followed-up to the end of 2011 for identification of subsequent STIs. The results revealed that patients with ASD were prone to acquiring an STI [hazard ratio (HR) 3.36] compared with the comparison group. Long-term use of atypical antipsychotics was associated with a lower risk of acquiring an STI later in life compared with nonuse (HR 0.34). We recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD. [ABSTRACT FROM AUTHOR]

Teenage pregnancy is a major public health concern. However, few studies have investigated the relationship between pediatric bipolar disorder and early pregnancy, and whether bipolar disorder medications reduce the risk of early pregnancy remains unknown. In total, 3218 adolescent girls with bipolar disorder and 32,180 controls matched for age, family income, residence, and time of enrollment were enrolled in this study from 2001 to 2009. Early pregnancy, defined as pregnancy occurring in patients younger than 20 years old, was identified during the follow-up period from enrollment until the end of 2011. After adjustment for demographic data, psychiatric comorbidities, and bipolar disorder medications, adolescent girls with bipolar disorder had 20 times the risk of early pregnancy (hazard ratio [HR] = 20.63, 95% confidence interval [CI] [15.68, 27.16]) and about 25 times the risk of repeated early pregnancy (HR = 24.59, 95% CI [15.20, 39.78]) compared with those without bipolar disorder. Long-term use of both mood stabilizers (HR = 0.34, 95% CI [0.23, 0.52]) and atypical antipsychotics (HR = 0.32, 95% CI [0.20, 0.51]) was associated with a reduced risk of early pregnancy. Bipolar disorder was associated with an increased risk of early pregnancy in adolescent girls. Bipolar disorder medications reduced this risk. The results suggest that interventions targeting the vulnerable population of adolescent girls with bipolar disorder are warranted to prevent early pregnancies. [ABSTRACT FROM AUTHOR]

This Taiwan study examined the associations of parental age and mental disorders with the offspring risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), and bipolar disorder (BD). Children born between January 1991 and December 2004 in Taiwan were enrolled as the birth cohort (n = 4,138,151) and followed up until December 2011. A logistic regression analysis was performed to identify the odds ratio (OR). The advanced age effects were significant in ADHD (range of OR: 1.04 to 1.49) and ASD (range of OR: 1.35 to 2.27). Teenage mothers, teenage fathers, and fathers ≥ 50 years had higher offspring risks of MDD (range of OR: 1.24 to 1.46); and teenage mothers and fathers ≥ 50 years had increased offspring risks of BD (range of OR: 1.23 to 1.87). Both paternal and maternal mental disorders were associated with higher risks of within-disorder transmission for ADHD, ASD, MDD, and BD (range of OR: 2.64 to 30.41). Besides, parents with one of these four mental disorders (ADHD, ASD, MDD, and BD) might have higher risk of cross-disorder transmission to at least one of the other three mental disorders in the offspring (range of OR: 1.35 to 7.15). Parental age and mental disorders had complex and nuanced patterns in association with offspring mental disorders. [ABSTRACT FROM AUTHOR]

Evidence suggests a continuity between obsessive–compulsive disorder (OCD) and schizophrenia. However, the factors that may predict diagnostic progression from OCD to schizophrenia remain unclear. A total of 35,255 adolescents and adults with OCD (ICD-9-CM code: 300.3) were enrolled between 2001 and 2010 and followed up at the end of 2011 for the identification of de novo schizophrenia (ICD-9-CM code: 295). The Kaplan–Meier method was used to estimate incidence rates, and the Cox regression was used to determine the significance of candidate predictors. At the end of the 11-year follow-up period, the crude cumulative progression rate from OCD to schizophrenia was 6%, and the estimated progression rate totaled 7.80%. Male sex (hazard ratio: 1.23), obesity (1.77), autism spectrum disorder (1.69), bipolar disorder (1.69), posttraumatic stress disorder (1.65), cluster A personality disorder (2.50), and a family history of schizophrenia (2.57) also were related to an elevated likelihood of subsequent progression to schizophrenia in patients with OCD. Further study is necessary to elucidate the exact pathomechanisms underlying diagnostic progression to schizophrenia in patients with OCD. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to examine the risk of T1D, major depressive disorder (MDD), attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), in first-degree relatives (FDRs) of patients with T1D. Methods: We enrolled 24,555 FDRs of individuals with T1D and 1:4 matched controls (N = 98,220) based on age and sex using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. Poisson regression analyses were performed to estimate the risks of MDD, attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder among the FDRs. Finally, we assessed the impact of DKA in the familial coaggregation. Results: After adjusting for demographic characteristics, FDRs of individuals with T1D had higher risk of T1D (reported as relative risk with 95% confidence interval: 46.07, 33.36–63.63) and MDD (1.17, 1.04–1.32) than controls. Stratified by sex, female FDRs had increased risk of MDD (1.30, 1.13–1.51), while male FDRs had increased risk of ADHD (1.21, 1.01–1.44). Stratified by kinship, parents of individuals with T1D had increased risk of MDD (1.24, 1.06–1.44); offspring of individuals with T1D had increased risk of ADHD (1.41, 1.11–1.79). Importantly, FDRs of individuals with T1D and DKA had higher risk of MDD (1.35, 1.11–1.64) and ADHD (1.40, 1.07–1.82) than controls; however, such risks were not observed in FDRs of individuals with T1D but without DKA. Conclusions: The individual risks of T1D, MDD, and ADHD were increased in families that included patients with T1D, and DKA might play a role in such coaggregation with MDD and ADHD. Future studies are warranted to investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

All severe mental disorders, namely schizophrenia, bipolar disorder, and major depression, are associated with dementia. However, a head-to-head comparison study of severe mental disorders and dementia risk is lacking. This study was a retrospective analysis from Taiwan National Health Insurance Database. In the current study, we included 14,137, 14,138, and 14,137 patients aged 45–69 years diagnosed with schizophrenia, bipolar disorder, and major depressive disorder, respectively, between 2001 and 2009 and 42,412 matched controls. Four groups were age-matched based by age of identification. Any dementia, including Alzheimer disease and vascular dementia, was diagnosed from the identification date to the end of 2011. Alzheimer disease was more likely in patients with bipolar disorder (hazard ratio [HR]: 10.37, 95% confidence interval [CI]: 6.93–15.52) and major depression (HR: 8.92, 95% CI: 5.93–13.41) than in those with schizophrenia (HR: 4.50, 95% CI: 2.84–7.13) and in controls. The likelihood of developing vascular dementia during the follow-up period was greater in patients with schizophrenia (HR: 4.55, 95% CI: 3.14–6.59) and bipolar disorder (HR: 4.45, 95% CI: 3.13–6.31) than in those with major depression (HR: 3.18, 95% CI: 2.21–4.58) and in controls. However, the overlapped CIs indicated the non-significant between-category differences. There was an increased risk of Alzheimer disease and vascular dementia in all groups compared with controls. For Alzheimer disease risk was greater bipolar and depression compared with schizophrenia while for vascular dementia risk was greater for bipolar and schizophrenia compared with depression. Our findings may encourage clinicians to closely monitor the trajectory of cognitive function in middle-aged and elderly patients with schizophrenia, bipolar disorder, and major depressive disorder. [ABSTRACT FROM AUTHOR]

Studies have suggested that maternal autoimmune diseases are associated with an increased risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, research on the association of paternal autoimmune diseases with ADHD and ASD risk has remained inconclusive. Using the Taiwan National Health Insurance Research Database, we selected 708,517 family triads (father–mother–child) between 2001 and 2008 and followed them until the end of 2011. Parental autoimmune diseases as well as ADHD and ASD in children were identified during the study period. Increased ADHD risk in children in terms of hazard ratios (HRs) and 95% confidence intervals (CIs) was associated with prenatal exposure to paternal autoimmune diseases, including Sjögren's syndrome (HR: 8.41, 95% CI: 2.72–26.05), psoriasis (HR: 1.95, 95% CI: 1.05–3.63), and ankylosing spondylitis (HR: 2.02, 95% CI: 1.29–2.15), as well as maternal autoimmune diseases, such as systemic lupus erythematosus (HR: 1.53, 95% CI: 1.09–2.15), type 1 diabetes mellitus (HR: 1.55, 95% CI: 1.02–2.36), inflammatory bowel disease (HR: 2.37, 95% CI: 1.59–3.52), psoriasis (HR: 1.70, 95% CI: 1.00–2.87), and ankylosing spondylitis (HR: 2.07, 95% CI: 1.11–3.86). However, ASD was only associated with paternal inflammatory bowel disease (HR: 3.08, 95% CI: 1.15–8.28) and ankylosing spondylitis (HR: 2.65, 95% CI: 1.10–6.39). Both paternal and maternal autoimmune diseases were associated with increased likelihood of ADHD in children. However, only paternal autoimmune diseases were related to offspring ASD risk. The precise pathomechanism underlying the correlation between parental autoimmunity and child neurodevelopment requires further investigation. [ABSTRACT FROM AUTHOR]

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]

Previous studies have shown an association between early parental death and the risk of subsequent major mental disorders (MMDs) among the bereaved children and adolescents; however, it is unclear whether this risk exists in young adults and in individuals with premorbid mental comorbidities. We aimed to explore differences between children, adolescents, and young adults in the risk of MMDs after parental death. We analyzed data from the Taiwan National Health Research Database. The index cohort was offspring (divided into four groups: aged < 6, 6–11, 12–17, and 18–29 years) whose parents had died. The control cohort was demographically matched offspring whose parents were still alive. Cox regression with adjustments for demographics was used to estimate the risk of subsequent MMDs between the index and control cohorts, including schizophrenia, bipolar disorder, and depressive disorder. We included 202,837 cases and 2,028,370 matched controls. As with the bereaved children and adolescents, the bereaved young adults had a significantly higher risk of schizophrenia (hazard ratio with 95% confidence interval: 5.63; 5.01–6.33), bipolar disorder (3.37; 2.96–3.84), and depressive disorder (2.78; 2.68–2.90) than the control cohort. The risk of MMDs was similar for maternal death and paternal death. Among premorbid mental comorbidities, bereaved individuals with premorbid substance use disorder were associated with the highest risk of schizophrenia (10.43; 8.57–12.71), bipolar disorder (12.93; 10.59–15.79), and depressive disorder (10.97; 10.22–11.78). Healthcare workers should be aware that young adults and individuals with premorbid mental comorbidities are at a higher risk of subsequent MMDs than those without premorbid mental comorbidities after parental death. [ABSTRACT FROM AUTHOR]

Background: The annual cut-off birthdate for entry into school in Taiwan is August 31. Thus, children and adolescents born in August are typically the youngest in their grades. The potential effect of relative age on the diagnosis of autism spectrum disorder (ASD) remains uncertain. Methods: A total of 9,548,393 individuals aged 3–17 years during the study period (from September 1, 2001, to August 31, 2011) identified from the Taiwan National Health Insurance Research Database were enrolled into our study. Logistic regression analysis was used to examine the likelihood of receiving ASD diagnosis for those who were born in August (the youngest) compared with those who were born in September (the oldest). Results: Both boys and girls born in August had a higher likelihood of being diagnosed with ASD (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.16–1.32; OR: 1.23, 95% CI 1.06–1.42) than did those born in September. Sensitivity analysis conducted over different periods revealed consistent findings. Discussion: Relative age, as an indicator of neurocognitive maturity, is a crucial contributor to the risk of being diagnosed with ASD among children and adolescents. Our findings highlight the importance of considering the age of a child within a grade when diagnosing ASD. [ABSTRACT FROM AUTHOR]

Studies have suggested that unaffected siblings of patients with autism spectrum disorder (ASD) have some other neurodevelopmental abnormalities. However, the risks of mental and developmental disorders have rarely been investigated among unaffected siblings. Using Taiwan's National Health Insurance Research Database, 1304 unaffected siblings born between 1980 and 2010 with ASD probands and 13,040 age-/sex-/family structure-matched controls were included in our study and followed up from 1996 or birth to the end of 2011. Developmental delay, language delay, developmental coordination disorder, attention-deficit hyperactivity disorder (ADHD), anxiety disorders, disruptive behavior disorders, unipolar disorder, and bipolar disorder were identified during the follow-up period. Unaffected siblings were more likely to develop any developmental delay, developmental speech or language disorder, developmental coordination disorder, intelligence disability, ADHD, anxiety disorders, unipolar depression, and disruptive behavior disorders compared with the control group. Brothers of patients with ASD had a higher risk of neurodevelopmental abnormalities, ADHD, anxiety disorders, and disruptive behavior disorders; sisters were prone to having neurodevelopmental abnormalities, ADHD, anxiety disorders, unipolar depression, and disruptive behavior disorders. Unaffected siblings of patients with ASD were prone to developing any developmental or mental disorder later in life. Clinicians and public health officials should pay more attention to the developmental condition and mental health of unaffected siblings of patients with ASD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) may share genomic risks with certain mental disorders. This study aimed at investigating associations between parental RA and risks of mental disorders in offspring. Using the National Health Insurance Research Database (2001–2010), we conducted a matched cohort study involving two parent–child cohorts (i.e., RA-parent–child cohort and non-RA-parent–child cohort) between which risks of major mental disorders in offspring were compared. There were 23,981 parent–child pairs in the RA-parent–child cohort and 239,810 in the non-RA-parent–child cohort. Preliminary analysis demonstrated increased risks of autism spectrum disorders (ASDs) [Odds ratio (OR) 1.47; 95% confidence interval (CI) 1.05–2.07], attention-deficit/hyperactivity disorder (ADHD) [OR 1.34; (95% CI 1.17–1.54)], bipolar disorder [OR 1.41 (95% CI 1.17–1.70)], and major depressive disorder [OR 1.20 (95% CI 1.07–1.35)] associated with parental RA. Sub-group analysis further showed higher risks of the four disorders in children of mothers with RA but not those from fathers with RA. Higher risks of ASDs and ADHD were not noted in children of mothers with RA before childbirth. Maternal RA, but not paternal RA or mothers diagnosed with RA before childbirth, was associated with increased risks of multiple mental disorders in their offspring, suggesting potential contributions of maternal genetic factors to ASDs and ADHD development in offspring. [ABSTRACT FROM AUTHOR]

Background: The bleeding risk profile of patients with atrial fibrillation (AF) may change over time, and the increment of HAS-BLED score is perceived to result in discontinuations of oral anticoagulants (OACs). Objectives: To investigate the changes of HAS-BLED scores of AF patients initially with a low bleeding risk. The associations between continuation or discontinuation of OACs and clinical outcomes after patients' bleeding risk profile worsened (ie HAS-BLED increased) were studied. Methods: The present study used Taiwan nationwide health insurance research database. From year 2000 to 2015, a total of 24,990 AF patients aged ≥ 20 years with a CHA2DS2-VASc score ≥ 1 (males) or ≥ 2 (females) having an HAS-BLED score of 0–2 who were treated with OACs were identified and followed up for changes of the HAS-BLED scores. Patients who did not refill OACs within 90 days after their HAS-BLED scores increased to ≥ 3 were defined as discontinuations of OACs. The risks of clinical outcomes were compared between patients who continued or stopped OACs once their HAS-BLED scores increased to ≥ 3. Results: Mean HAS-BLED score of study population increased from 1.54 to 3.33. At end of 1 year, 5,229 (20.9%) patients had an increment of their HAS-BLED scores to ≥ 3, mainly due to newly diagnosed hypertension, stroke, bleeding, and concomitant drug therapies. Among 4777 patients who consistently had an HAS-BLED score ≥ 3, 1,062 (22.2%) stopped their use of OACs. Patients who kept on OACs (n = 3715; 77.8%) even after their HAS-BLED scores increased to ≥ 3 were associated with a lower risk of ischemic stroke (aHR 0.60, 95%CI 0.53–0.69), major bleeding (aHR 0.78, 95%CI 0.67–0.91), all-cause mortality (aHR 0.88, 95%CI 0.79–0.97), and any adverse events (aHR 0.75, 95%CI 0.68–0.82) adjusted for age, sex, heart failure, and HAS-BLED score. These results were consistent among the cohorts after propensity matching. Conclusions: For patients whose HAS-BLED scores increased to ≥ 3, the continuation of OACs was associated with better clinical outcomes. An increased HAS-BLED score in anticoagulated AF patients may not be the only reason to withhold OACs, but reminds physicians to correct modifiable bleeding risk factors and follow up patients more closely. Associations between Continuation or Discontinuation of Oral Anticoagulants and Risks of Clinical Outcomes after HAS-BLED Scores Increased AF atrial fibrillation; aHR adjusted hazard ratio; ICH intra-cranial hemorrhage; OACs oral anticoagulants [ABSTRACT FROM AUTHOR]

Objectives: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD. Materials and methods: Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest. Results: A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49–1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75–1.10), or MACE (aHR: 1.18, 95% CI: 0.91–1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures. Conclusions: Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD. Clinical relevance: These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that conduct disorder is related to risky sexual behaviors, the dominant risk factor for contracting a sexually transmitted infection (STI). However, the association between conduct disorder and STIs remains unclear. Using the Taiwan National Health Insurance Research Database, 5733 adolescents with conduct disorder and 22,932 age- and sex-matched controls without conduct disorder were enrolled from 2001 to 2009 and were subject to follow-up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was performed to examine the likelihood of subsequently contracting an STI for patients and controls. Patients with conduct disorder were more likely than controls to develop any STI (HR 3.95, 95% CI 2.97–5.26) after adjusting for demographic data, psychiatric comorbidities, and use of medications. Long-term use of second-generation antipsychotics (SGAs) was related to a reduced risk (HR 0.36, 95% CI 0.14–0.91) of developing an STI among patients with conduct disorder. Adolescents with conduct disorder had an increased risk of developing any STI later in life compared with those without conduct disorder. Long-term use of SGAs was associated with a lower risk of subsequent STI. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) has long been associated with thyroid diseases; however, the temporality of their association remains unclear. This study aimed to investigate the bidirectional association between AA and thyroid diseases. In analysis 1, we included 5929 AA patients and 59,290 matched controls to assess the risk of thyroid diseases. In analysis 2, we included 35,071 patients with thyrotoxicosis, 19,227 patients with Graves' disease, 5460 patients with thyroiditis, 3352 patients with Hashimoto's thyroiditis, and their matched controls (1:10) to assess the risk of AA. Incidence of thyroid diseases and AA were the outcomes in analysis 1 and analysis 2, respectively. After adjusting the potential confounders, AA patients had an increased risk of all thyroid diseases, including toxic nodular goiter, (aHR 10.17; 95% confidence interval [CI] 5.32–19.44), nontoxic nodular goiter (aHR 5.23; 95% CI 3.76–7.28), thyrotoxicosis (aHR 7.96; 95% CI 6.01–10.54), Graves' disease (aHR 8.36; 95% CI 5.66–12.35), thyroiditis (aHR 4.04; 95% CI 2.12–7.73), and Hashimoto thyroiditis (aHR 4.35; 95% CI 1.88–10.04). On the contrary, a significantly increased risk of developing AA was observed among patients with thyrotoxicosis (aHR 9.29; 95% CI, 7.11–12.14), Graves' disease (aHR 8.66; 95% CI 6.03–12.42), and thyroiditis (aHR 6.42; 95% CI 3.15–13.11) but not in patients with Hashimoto's thyroiditis. In conclusion, our study found a bidirectional association between AA and thyroid diseases, suggesting shared biological mechanisms underlying these two diseases. [ABSTRACT FROM AUTHOR]

Background: Association of proton pump inhibitor (PPI) exposure with acute myocardial infarction (AMI) risk in the Caucasian population remains under debate. Here, we clarified whether PPI exposure might be related to an increased new-onset AMI risk in an Asian population. Method: Data of 27,624 patients with PPI exposure followed by new-onset AMI development were extracted from Taiwan National Health Insurance Research Database and age- and sex-matched with 27,624 controls with PPIs exposure, but without subsequent AMI and ischemic heart disease development. The amount of PPI exposure was calculated based on the cumulative defined daily dose (cDDD) during the follow-up period. Subsequent AMI risk was measured after adjustments of demographic data and indication of PPI use. Results: AMI risk increased with an increase in PPI exposure: with cDDD ≤ 30 as the reference, the odds ratios (95% confidence intervals) for cDDDs of > 365 was 1.56 (1.45–1.69). All five PPI categories, including pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, increased AMI risk. Conclusions: Our study demonstrated long-term or high-dose PPI exposure associated with increased new-onset AMI risk in patients without a history of any ischemic heart disease. The underlying mechanisms of PPI-related cardiovascular effects deserve more investigation. [ABSTRACT FROM AUTHOR]

ADHD comorbidity has been associated with delayed diagnosis of ASD, but no study has investigated this association in an Asian country. Children with ASD were included and divided into three groups: ADHD before ASD, ADHD same/after ASD, and ASD only. Timing of ASD and ADHD diagnoses were assessed. The logistic regression model was performed to investigate the likelihood of being diagnosed with ASD after 6 years of age between three groups. ADHD before ASD (OR 10.93) group was more likely to being diagnosed with ASD after 6 years of age compared with ADHD same/after ASD (OR: 1.37) and ASD only groups. ADHD comorbidity would delay the diagnosis of ASD in the general clinical settings in Taiwan. [ABSTRACT FROM AUTHOR]

Background: The effects of cigarette smoking and alcohol consumption on the risk of alopecia areata (AA) are unclear. Objective: The aim was to examine the association of cigarette smoking and alcohol consumption with AA. Methods: We collected participants from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident AA cases were identified from the National Health Insurance database. Results: Of the 60,055 participants, 154 developed AA during the 647,902 person-years of follow-up. After controlling for confounders, current smokers had a higher risk of incident AA than never smokers [adjusted hazard ratio (aHR) 1.88; 95% confidence interval (CI) 1.22–2.88]. There was a trend toward an increased risk of AA with increasing numbers of years of smoking and cumulative pack-years of smoking among current smokers. The aHRs (95% CIs) of current smokers of > 5 and ≤ 15 cigarettes per day, > 10 and ≤ 20 years of smoking, ≤ 10, and > 10 and ≤ 20 pack-years of smoking were 2.03 (1.17–3.51), 2.25 (1.21–4.18), 1.86 (1.12–3.09), and 2.04 (1.04–4.01), respectively. Conversely, social and regular drinkers had significantly lower risks of AA than never drinkers [aHRs (95% CIs) 0.65 (0.43–0.98) and 0.49 (0.26–0.93), respectively]. Conclusion: Current smokers had an increased risk of developing AA, while alcohol consumption was associated with a decreased risk of AA. [ABSTRACT FROM AUTHOR]

The independent risk factors for death in patients admitted for asthma exacerbation have not been thoroughly investigated. This study aimed to investigate these independent risk factors and the relationship between mortality and the prescription patterns of anti-asthmatic medications in patients admitted for asthma exacerbation. Using a nested case–control design, we identified 267 cases (death after asthma admission) and 1035 controls (survival after asthma admission) from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2010. Conditional logistic regressions were used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs). We identified the independent risk factors for death as the comorbidities of pneumonia (aOR 3.82, 95% CI 2.41–6.05), genitourinary disease (aOR 1.75, 95% CI 1.17–2.62), septicemia (aOR 4.26, 95% CI 2.61–6.94), diabetes mellitus (aOR 2.10, 95% CI 1.30–3.38), arrhythmia (aOR 2.00, 95% CI 1.14–3.50), and a history of asthmatic hospitalization (aOR 4.48, 95% CI 2.77–7.25). Moreover, the use of short-acting β2-agonist (SABA) and the dosage of oral corticosteroids (OCSs) >70 mg prednisolone during previous hospitalization (all p < 0.05) and the dosage of OCSs ≥110 mg prednisolone/month (aOR 2.21, 95% CI 1.08–4.50) during outpatient treatment independently increased the risk of death. The inhaled corticosteroids (ICSs) ≥4 canisters/year (aOR 0.39, 95% CI 0.19–0.78) independently reduced the risk of death. Specific comorbidities, asthma severity, and prescription patterns of SABA, OCSs, and ICSs were independently associated with mortality in patients admitted for asthma exacerbation. These results can be utilized to help physicians identify asthmatic patients who are at a higher mortality risk and to refine the management of the condition. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients. Materials and methods: We used Taiwan's National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio. Results: Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06–2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57–2.29), being male (aHR 1.98, 95% CI 1.36–2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05–1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06–1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05–33.14), chemotherapy (aHR 1.41, 95% CI 1.15–1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57–2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients. Conclusion: Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. Clinical relevance: High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas. [ABSTRACT FROM AUTHOR]

Several studies have shown a strong association between atopic diseases and autism spectrum disorder (ASD). However, the risk of atopic diseases in individuals having ASD-affected siblings has never been investigated. This nationwide population-based cohort study included 2762 individuals with ASD-affected siblings and 11,048 controls. Diagnoses of atopic diseases, including asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis, were ascertained from 1996 or the birth data to the end of 2011. Individuals with ASD-affected siblings had a higher risk for asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and multiple atopic diseases compared with controls. In conclusion, individuals with ASD-affected siblings were more likely than were the controls to develop atopic diseases, suggesting shared familial mechanisms underlying the two conditions. [ABSTRACT FROM AUTHOR]

Previous studies suggested that menopausal transition played an important role in the clinical course of major depression and bipolar disorder. However, the role of symptomatic menopausal transition in diagnostic conversion from major depression to bipolar disorder was still unknown. Using the Taiwan National Health Insurance Research Database, 50,273 midlife women aged between 40 and 60 years in 2002∼2008 with major depression were enrolled in our study and divided into two subgroups based on the presence ( n = 21,120) or absence ( n = 29,153) of symptomatic menopausal transition. Subjects who had subsequent bipolar disorder during the follow-up were identified. Midlife women with major depression and symptomatic menopausal transition had a higher incidence of the diagnostic conversion to bipolar disorder (7.3 vs. 6.6%, p = 0.003) than those with major depression alone. Cox regression analysis after adjusting for demographic data and psychiatric comorbidities further showed that symptomatic menopausal transition was associated with an increased risk of developing bipolar disorder (HR 1.14, 95% CI 1.07∼1.23) among midlife women with major depression. Sensitivity test after excluding the 1-year and 3-year observation exhibited the consistent findings (HR 1.18, 95% CI 1.09∼1.28; HR 1.20, 95% CI 1.08∼1.34). Midlife women with the dual diagnoses of major depression and symptomatic menopausal transition had an increased risk of the diagnostic conversion to bipolar disorder compared to those with major depression alone. Further studies may be required to investigate the underlying mechanisms among menopausal transition and the diagnostic conversion from major depression to bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available.Methods: Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population.Results: We identified 52,639 patients with lung cancer and excluded 34,267 patients who had expired within one year after diagnosis. The study included 18,372 subjects with a median follow-up period of 2.24 years. 590 patients developed an SPM. The overall cancer risk was significantly increased (SIR 1.33, 95% confidence interval [CI]: 1.22-1.44, p < 0.001), and there was a significant increase in the incidences of head and neck (SIR 1.60, 95% CI 1.21-2.07, p = 0.001), bone and soft tissue (SIR 2.65, 95% CI 1.27-4.87, p = 0.011), genitourinary (SIR 1.50, 95% CI 1.27-1.76, p < 0.001), and thyroid (SIR 3.85, 95% CI 2.28-6.08, p < 0.001) cancers. Importantly, after multivariate adjustment, the use of tyrosine kinase inhibitors (TKIs) statistically significantly reduced SPM incidence (HR, 0.41; 95% CI, 0.21-0.79; p = 0.008).Conclusions: Our study indicates that lung cancer may be a risk factor for SPM. TKI use was associated with a significantly lower risk of SPM development. However, because patients with epidermal growth factor receptor mutant lung adenocarcinoma (associated with non-smokers) tend to receive TKI treatment, they might have fewer smoking-related SPMs. [ABSTRACT FROM AUTHOR]

Background: Recurrence of hepatocellular carcinoma (HCC) with unsatisfactory survival is common after surgical resection. Antiplatelet therapy with aspirin or clopidogrel was recently shown to prevent hepatic carcinogenesis in a murine model, but its effect in humans had not been clarified. This study aimed to investigate the association between antiplatelet therapy and the outcomes for patients with hepatitis B virus (HBV)-related HCC after liver resection. Methods: By analyzing data from the Taiwan National Health Insurance Research Database, 9461 HBV-related HCC patients who had undergone liver resection between January 1997 and December 2011 were identified. After one-to-four matching by sex, age, and propensity score, 442 patients with antiplatelet therapy and 1768 patients without antiplatelet therapy were enrolled for the analysis. The Kaplan-Meier method and modified Cox proportional hazards models were used for survival and multivariable, stratified analyses. Results: Recurrence-free survival and overall survival after resection surgery were significantly better after 5 years in the treated cohort than in the untreated cohort (52.8 vs 47.9 %; p = 0.021 and 80.3 vs 65.4 %; p < 0.001, respectively). Besides, antiplatelet therapy reduced the risk of HCC recurrence (hazard ratio [HR] 0.73; p < 0.001) and overall mortality (HR 0.57; p < 0.001) in the multivariable analysis. However, antiplatelet use significantly increased the risk of upper gastrointestinal bleeding (odds ratio [OR] 1.91; p < 0.001). Conclusions: Use of aspirin or clopidogrel was associated with better recurrence-free survival and overall survival among patients with HBV-related HCC after liver resection. However, these agents should be used with caution due to the adverse effects of upper gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) are liable to develop significant comorbidities, including lung cancer. Whether they are at a higher risk for cancer of other types remains debatable, especially for Asians. We studied the risk of incident cancer in COPD patients using a nationwide representative database, the Taiwan National Health Insurance Research Database. Methods: From 1995 to 2008, 50,875 COPD patients who were free of antecedent malignancy were identified and followed up to development of malignancy, death or end of 2008, whichever came first. The risk of cancer was determined with the standardized incidence ratio (SIR), which is based on comparison to the national cancer incidence among the general population. Results: During a median follow-up period of 5.61 years, 3623 (7.02 %) patients developed cancer and the SIR was 1.2 [95 % confidence interval (CI) 1.16-1.24, p < 0.001]. The risk remained higher at <1, 1-5, and even ≥5 years after the diagnosis of COPD (SIR 1.83, 1.07, and 1.11, respectively). Furthermore, the risk was significantly higher for some specific types of cancer, including head and neck cancer (SIR 1.23, 95 % CI 1.08-1.39, p = 0.002), esophageal cancer (SIR 1.35, 95 % CI 1.08-1.67, p = 0.010), lung and mediastinal cancer (SIR 1.86, 95 % CI 1.74-1.99, p < 0.001), breast cancer (SIR 1.19, 95 % CI 1.01-1.4, p = 0.041), prostate cancer (SIR 1.20, 95 % CI 1.06-1.35, p < 0.001), cancer of the central nervous system (SIR 1.58, 95 % CI 1.05-2.28, p = 0.030), lymphoma (SIR 1.53, 95 % CI 1.22-1.90, p < 0.001), and multiple myeloma (SIR 1.95, 95 % CI 1.31-2.80, p = 0.001). Conclusion: COPD patients had increased risk for incident cancers, including lung cancer and several extrapulmonary cancers. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients. Methods: Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables. Results: During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin's lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not. Conclusions: Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered. [ABSTRACT FROM AUTHOR]

Background: The association between amyloidosis and cancer remains unclear. Participants and methods: Using the Taiwan National Health Insurance Research Database we conducted a population-based cohort study. Patients newly diagnosed with amyloidosis between 1997 and 2009 were enrolled. Patients with antecedent cancer were excluded. Standardized incidence ratios (SIR) of cancers were calculated for the study cohort and compared with cancer incidence among the general population. We used a multivariate Cox regression model to evaluate the predictors of cancer development for patients with amyloidosis. Results: The study included 1,693 subjects with median follow-up of 5.63 years. A total of 68 patients developed cancer. The incidence of kidney cancer (SIR 3.42; 95 % CI 1.11-7.97; p = 0.034) and hematologic malignancies (SIR 3.88; 95 % CI 1.86-7.14; p < 0.001) were significantly higher for patients with amyloidosis. Conclusion: This is currently the largest study to evaluate cancer risk among patients with amyloidosis. The results indicate that amyloidosis may be associated with an increased risk of kidney cancer and hematologic malignancies. [ABSTRACT FROM AUTHOR]

Background: Tablet splitting or pill splitting frequently occurs in daily medical practice. For drugs with special pharmacokinetic characters, such as drugs with narrow therapeutic index (NTI), unequal split tablets might lead to erroneous dose titration and it even cause toxicity.Objective: The aim of this study was to investigate the frequency of prescribing split NTI drugs at ambulatory setting in Taiwan.Setting: A population-based retrospective study was conducted using the National Health Insurance Research Database in Taiwan. All ambulatory visits were analyzed from the longitudinal cohort datasets of the National Health Insurance Research Database.Methods: The details of ambulatory prescriptions containing NTI drugs were extracted by using the claims datasets of one million beneficiaries from National Healthcare Insurance Research Database in 2010 in Taiwan. The analyses were stratified by dosage form, patient age and the number of prescribed tablets in a single dose for each NTI drugs. Main outcome measures Number and distinct dosage forms of available NTI drug items in Taiwan, number of prescriptions involved split NTI drugs, and number of patients received split NTI drugs.Results: A total of 148,548 patients had received 512,398 prescriptions of NTI drugs and 41.8 % (n = 62,121) of patients had received 36.3 % (n = 185,936) of NTI drug prescriptions in form of split tablets. The percentage of splitting was highest in digoxin prescriptions (81.0 %), followed by warfarin (72.0 %). In the elderly patients, split tablets were very prevalent with digoxin (82.4 %) and warfarin (84.5 %).Conclusion: NTI drugs were frequently prescribed to be taken in split forms in Taiwan. Interventions may be needed to provide effective and convenient NTI drug use. Further studies are needed to evaluate the clinical outcome of inappropriate split NTI drugs. [ABSTRACT FROM AUTHOR]

Purpose: There are 26 teaching hospitals in Taiwan that provide anesthesia residency training programs (one program per hospital), and only an average of 40 medical graduates are accepted for residency training per year. The aim of this study is to understand how this situation affects the learning and working conditions of anesthesia residents in Taiwan. Methods: A self-structured survey was mailed to all 178 anesthesia residents receiving training in Taiwan in April 20, 2012. Survey questions included resident characteristics, working and learning conditions, satisfaction with resident training programs, and reasons for choosing anesthesiology as a career. In addition to descriptive statistics, linear regression was used to test correlation between working conditions and satisfaction with training programs. Results: The survey was completed by 136 residents. Although the residents' expected optimal working time was 54.1 ± 12.2 h per week, their actual working time was an average of 64.0 ± 15.7 h per week. In addition, the workload included managing 4.2 ± 1.3 operating rooms simultaneously. The ratio of working vs. learning time was 2.2 ± 1.1. Less than 40 % of the residents were satisfied with their training in critical care and pain management. Anesthesia residents with heavier workloads and higher ratios of work vs. learning time had significantly lower satisfaction with their training programs, especially with training environments ( R = 0.169). General interest in anesthesiology and related work (66.1 %) was the main factor in choosing anesthesia as their career. Conclusions: Anesthesia residents in Taiwan are treated as an integral part of hospital manpower. This may limit the effectiveness of their learning and cause dissatisfaction with their training environment. To improve the current status, anesthesia residents should perform anesthesia in one operating room at a time and some of the anesthesia training hospitals should be suggested for removal. [ABSTRACT FROM AUTHOR]

Background: The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients. Objective: To assess the risk of comorbid anxiety and depressive disorders after the diagnosis of esophageal cancer compared with a matched cohort by using the Taiwan National Health Insurance Research Database (NHIRD). Methods: We conducted a retrospective study of 28,454 patients (14,227 patients with esophageal cancer and 14,227 matched patients) who were selected from the NHIRD. Patients were observed for a maximum of 12 years to determine the incidence of new-onset anxiety and depressive disorders for which antidepressants had been prescribed. A Cox regression analysis was performed to identify the risk factors associated with anxiety and depressive disorders in esophageal cancer patients. Results: The cumulative incidence of anxiety and depressive disorders in the esophageal cancer patients was significantly higher than that in the matched cohort ( P < .001). The adjusted hazard ratio (HR) was 2.24 (95 % confidence interval, CI = 1.95-2.56, P < .001) in the esophageal cancer cohort compared with the matched cohort. Independent risk factors for developing anxiety and depressive disorders among the patients with esophageal cancer included cirrhosis, cerebrovascular disease, and surgical treatment. Conclusion: Esophageal cancer may be a prominent risk factor for anxiety and depressive disorders. Based on our data, we suggest that attention should be focused on esophageal cancer patients with comorbid cirrhosis and cerebrovascular disease and those who have received surgical interventions. [ABSTRACT FROM AUTHOR]

Background: There is evidence suggesting that migraine may be associated with vertigo. The aim of this study was to assess the risk of benign paroxysmal positional vertigo (BPPV), the most common form of vertigo, in patients with migraine using a population-based dataset. Methods: The National Health Insurance Research Database in Taiwan was searched for migraine patients and was also used to select an age- and sex-matched cohort of subjects without migraine. The analyses included 8266 migraine patients and 8266 controls. The incidence rates of BPPV in the two cohorts were compared. Cox proportional hazard models were used to identify risk factors for BPPV in migraine patients. Results: In the migraine cohort, 1.11% of the patients developed BPPV compared to 0.5% of the controls. The incidence rate ratio was 2.03 (95% CI 1.41-2.97; p <0.001). Cox proportional hazards analysis showed that age =40 years (HR 2.20; 95% CI 1.40-3.45; p = 0.001), coronary artery disease (HR 4.62; 95% CI 1.12-19.01; p = 0.034), and the number of outpatient department visits to neurologists because of migraine (HR 2.93; 95% CI 2.50-3.44; p >0.001) were associated with an increased risk for BPPV. Conclusion: The results showed that patients with migraine had a 2.03-fold increased risk of developing BPPV compared with age- and sex-matched controls. Although BPPV may not be a common condition in migraine patients, migraine sufferers with vestibular symptoms should alert physicians to the possibility of BPPV, particularly if patients are aged =40 years, have a history of coronary artery disease, or have frequent visits to neurologists clinics because of migraine. [ABSTRACT FROM AUTHOR]

Few studies are available on the risk of ischemic stroke after a diagnosis of primary Sjögren's syndrome (PSS). This study investigated whether PSS increased the risk of ischemic stroke in a large, nationwide cohort. Data for 4,276 patients who were newly diagnosed with PSS from 2000 to 2006 and who did not have a stroke prior to diagnosis of PSS were obtained from the Registry of Catastrophic Illness in Taiwan. For each PSS patient, data for ten controls (matched by age, gender, comorbidities, and enrollment date) without systemic autoimmune disease or previous stroke were obtained from the Longitudinal Health Insurance 2000 database. All study subjects were followed up from the date of enrollment until they developed ischemic stroke, died, or until the end of 2006, whichever was earliest. To investigate if PSS was an independent factor in determining the risk of developing ischemic stroke, a Cox regression model was used with adjustment for age, gender, and comorbid disorders. Among 4,276 PSS patients and 42,760 controls, 669 subjects (51 PSS patients and 618 controls) developed ischemic stroke during the mean 3.7-year follow-up period (interquartile range 2.2-5.2 years). Patients with PSS and controls had a similar incidence of ischemic stroke occurrence (3.17/1,000 vs. 3.90/1,000 person years). Multivariate analysis adjusted for baseline covariates indicated that PSS did not increase the risk of ischemic stroke (adjusted hazard ratio: 0.84, 95 % confidence interval: 0.63-1.12, P = 0.244). PSS is not associated with an increased risk of ischemic stroke subsequent to diagnosis. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease and may complicate with interstitial lung disease. The risk of Mycobacterium tuberculosis (TB) infection in patients with pSS has not been determined. This nationwide population-based study aimed to explore the incidence and risk factors of TB infection in patients with pSS. We identified 4,822 pSS patients from the Taiwan National Health Insurance database and compared the incidence rates of TB infection in these patients with 48,220 randomly selected age-, sex-, and comorbidity-matched subjects without pSS. The Cox proportional hazard model was used to identify risk factors for TB in patients with pSS. The risk of TB was higher in the pSS cohort than in the control cohort with an incidence rate ratio (IRR) of 1.58 (95 % confidence interval [95 % CI] 1.13-2.18, p = 0.006). The risk factors for TB in the pSS cohort were age ≥60 years (hazard ratio [HR] 3.22, 95 % CI 1.78-5.84; p < 0.001), and corticosteroid usage, which had a dose-dependent effect in the pSS patients compared to the nonusers (daily prednisolone dose or equivalent less than 5 mg/day: HR 2.34; p = 0.020, 95 % CI 1.14-4.78; 5 mg/day to less than 10 mg/day: HR 4.79, 95 % CI 2.15-10.68; p < 0.001; 10 mg/day or more: HR 12.19, 95 % CI 4.42-33.63; p < 0.001). Patients with pSS had a higher risk of pulmonary TB in Taiwan, which was related to age ≥60 years and corticosteroid usage. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence and risk of stroke after lumbar spinal fusion surgery. Method: Study subjects were identified from a nationwide cohort of 1 million people from 2000 to 2005 and were divided into the lumbar spinal fusion group ( n = 2,015), who received posterior lumbar spinal fusion surgery, and the comparison group ( n = 16,120) composed of age-, sex-, and propensity score-matched control subjects. The matching process was intended to adjust for demographics, comorbidities, and other immeasurable covariates to minimize selection bias. All subjects were followed up for 3 years for stroke, including hemorrhagic and ischemic strokes. Kaplan-Meier and Cox regression analyses were performed. Results: The overall incidence rate of stroke in the cohort was 9.99 per 1,000 person-year. The lumbar spinal fusion group was less likely to have any stroke (adjusted hazard ratio (HR) = 0.83, p = 0.293), hemorrhagic stroke (adjusted HR = 0.74, p = 0.739) and ischemic stroke (adjusted HR = 0.81, p = 0.250) than the comparison group, but without significance. Conclusions: Three years post-operatively, patients who received lumbar spinal fusion had stroke incidence rates similar to those without surgery. Posterior lumbar spinal fusion surgery is not associated with increased risks for any kind of stroke. [ABSTRACT FROM AUTHOR]

The rapid economic growth in East Asia might have an impact on the development of research output. Because previous bibliometric analysis about anesthesiology in this region had been limited to research within anesthesiology journals or anesthesia-related research, the total publications from anesthesia departments might not be well displayed. In this study, the databases of Web of Science and PubMed were used to assess the academic productivity and distribution of research diversity of anesthesia departments from four major countries in East Asia and compared those with the USA. From 2001 to 2010 the volume of scientific research from anesthesia departments in East Asia has stably increased. Although Japan was the most productive contributor in East Asia, its share declined annually. China increased most rapidly and exceeded Japan in 2010 in terms of annual number of papers. Research attributed to anesthesia departments in East Asia was diverse and present in a wide range of non-anesthesia field journals. Notably the annual number of randomized controlled trials in East Asia also had a strong growth. [ABSTRACT FROM AUTHOR]

The trend to use administrative health care databases as research material is increasing but not well explored. Taiwan's National Health Insurance Research Database (NHIRD), one of the largest administrative health care databases around the world, has been used widely in academic studies. This study analyzed 383 NHIRD studies published between 2000 and 2009 to quantify the effects on overall growth, scholar response, and spread of the study fields. The NHIRD studies expanded rapidly in both quantity and quality since the first study was published in 2000. Researchers usually collaborated to share knowledge, which was crucial to process the NHIRD data. However, once the fundamental problem had been overcome, success to get published became more reproducible. NHIRD studies were also published diversely in a growing number of journals. Both general health and clinical science studies benefited from NHIRD. In conclusion, this new research material widely promotes scientific production in a greater magnitude. The experience of Taiwan's NHIRD should encourage national- or institutional-level data holders to consider re-using their administrative databases for academic purposes. [ABSTRACT FROM AUTHOR]

China has made great progress in economy and science in the last two decades. Its scientific development in gastroenterology has been seldom reported. Using two authoritative bibliographic databases, Science Citation Index Expanded (SCI-E) and Medline, we analyze China's research output in gastroenterology journals from 1990 to 2004. After detailed analysis, we found that China have greatly advanced in gastroenterology research, but the growth of Chinese articles in gastroenterology journals can largely be attributed to the selection of China-based journals into international bibliographic databases. [ABSTRACT FROM AUTHOR]