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Background Women with endometriosis (EM) have increased vulnerability to certain psychiatric disorders, including depression and anxiety, as well as bipolar disorder (BD). This study investigates the risk of BD development in EM patients. Also, the impact of EM treatment on the risk of developing BD is examined. Methods A total of 17,832 EM patients and 17,832 non-EM controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000–2012 and followed to the end of 2013. Participants newly diagnosed as BD by board-certified psychiatrist were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the BD incidence rate between two studied groups. Results EM patients were associated with an increased risk of BD development compared with non-EM controls after adjusting for age, CCI score, and different treatment options (1.04 versus 0.56 per 1,000 person-years, HR: 2.34, 95% CI: 1.75–3.12). Also, there was no significant difference in the risk estimate between different hormonal or surgical treatment groups, suggesting a limited impact of EM treatment on the risk of BD development. Limitations This study deals with the duration of hormonal treatment, whether operated or not, which reduces the chances of showing the effect of individual EM treatment on the risk of BD development. Conclusion This study shows that EM patients are associated with an increased risk of BD development. Further studies would be needed to elucidate the mechanism linking the EM and BD.

Objectives Narcolepsy symptoms, such as excessive daytime sleepiness or cataplexy, can pose a risk to safety. Stimulants or antidepressants have been used to treat these symptoms. The study investigated the risk of bone fractures in narcolepsy patients. Also, the exposure pattern of stimulants and antidepressants to the risk of bone fractures was examined. Methods In all, 493 narcolepsy patients and 490 controls matched by gender, age, index year, and comorbidity severity were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed bone fractures were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) for the incidence rates of bone fractures between narcolepsy patients and unaffected controls. Results Narcolepsy patients had a significantly increased risk of bone fractures compared with unaffected controls (19.6 versus 12.3 per 1000 person-years, HR: 1.74, 95% CI: 1.29–2.35). In addition, the use of stimulants in narcolepsy patients showed lower incidence rates of bone fractures compared to non-users (incidence rates were 14.2, 11.9, and 20.0 per 1000 person-years, respectively, among frequent users, infrequent users, and non-users), but the risk estimate was not statistically significant. The evidence for associations between antidepressant use in narcolepsy patients and bone fractures was contradictory. Conclusion This study highlights the need to pay attention to the risk of bone fractures in narcolepsy patients, and the importance of adequate stimulants use might reduce the risk of bone fractures.

Patients with schizophrenia (SCZ) have a higher prevalence of known risk factors for obstructive sleep apnea (OSA). This study aims to determine if SCZ patients are at increased risk of incident OSA. A total of 5092 newly diagnosed SCZ patients and 5092 non-SCZ controls matched by gender, age, and index year were included between 2000 and 2012 and followed to 2013. Participants newly diagnosed with OSA were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence intervals (CI) of the OSA incidence rate between the two groups studied. SCZ patients were at increased risk of OSA compared to non-SCZ controls after adjusting for gender, age, comorbidities, and duration of antipsychotic use (2.12 versus 1.01 per 1000 person-years, HR: 1.97, 95% CI: 1.36–2.85). Also, this study confirmed the existence of some known risk factors for OSA, including male gender (HR 1.65, 95% CI 1.14–2.37), obesity (HR 2.62, 95% CI 1.19–5.80), hypertension (HR 1.61, 95% CI 1.06–2.47), hyperlipidemia (HR 1.55, 95% CI 1.04–2.38), diabetes (HR 1.53, 95% CI 1.01–2.38), and antipsychotic use (duration

To investigate whether patients with polycystic ovary syndrome (PCOS) are at increased risk for incident schizophrenia and whether PCOS treatment (clomiphene, cyproterone, or metformin) affects the incidence of schizophrenia.An overall of 7146 PCOS patients and 28,580 non-PCOS controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000 and 2012 and followed up until 2013 using a validated nationally representative sample from Taiwan. Participants newly diagnosed as schizophrenia were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of the schizophrenia incidence rate between the two studied groups.PCOS patients were at increased risk of incident schizophrenia compared to non-PCOS controls after adjusting for age, CCI score, comorbidities, and different treatment options (0.49 versus 0.09 per 1000 person-years, HR: 6.93, 95% CI: 3.25-14.7). After adjusting for above-mentioned covariates, metformin treatment had a protective effect against the incident schizophrenia compared to non-users (HR: 0.16, 95% CI: 0.06-0.41). Also, treatment with clomiphene and cyproterone had only a limited impact on the incident schizophrenia.This study shows PCOS patients are at increased risk of incident schizophrenia, and the metformin treatment has a protective effect against incident schizophrenia.

Background The study investigated the risk of newly developed bipolar disorder (BD) in patients with polycystic ovary syndrome (PCOS) and examined the relationship between PCOS treatment (hormone therapy (clomiphene or cyproterone) or metformin) and risk of BD development. Methods In all, 7175 PCOS patients and 28,697 non-PCOS controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000 and 2012, then followed until the end of 2013. Participants newly diagnosed as BD by board-certified psychiatrists were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the BD incidence rate between two studied groups. Results PCOS patients had a significantly increased risk of developing BD compared to unaffected controls after adjusting for age, CCI score, and different treatment options (1.05 vs. 0.12 per 1,000 person-years, HR: 8.29, 95% CI: 4.65–14.7). Also, the use of metformin in PCOS patients showed a significantly reduced risk of developing BD compared to non-users after adjusting for the above-mentioned variables (HR: 0.36, 95% CI: 0.16–0.81). Although hormone therapy in PCOS patients showed a lower incidence rate of BD development compared to non-users, the risk estimate was not statistically significant (HR: 0.68, 95% CI: 0.35–1.32). Limitations This study didn't assess the PCOS severity, which reduced the chances of showing the effects of PCOS severity on BD development. Conclusion This study shows PCOS patients have an increased risk of developing BD, and the use of metformin may reduce its risk.

Narcolepsy is a rare brain disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Stimulants have been used to relieve the symptoms of EDS. Narcolepsy symptoms may pose a risk to burn injury. The study aimed to investigate the risk of burn injury in narcolepsy patients and to examine the relationship between the use of stimulants and the risk of burn injury. In all, 507 narcolepsy patients and 504 controls matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed burn injury were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the burn incidence rate between narcolepsy patients and unaffected controls. Narcolepsy patients had a significantly increased risk of burn injury compared to unaffected controls (5.37 versus 2.69 per 1,000 person-years, HR: 2.04, 95% CI: 1.13–3.67) after adjusting for gender, age, CCI score, urbanization degree, and duration of stimulants use. Also, the use of stimulants in narcolepsy patients was associated with a lower incidence rate of developing burn injury, but the risk estimate was not statistically significant after adjusting for the above-mentioned variables. This study shows narcolepsy patients have an increased risk of burn injury and the use of stimulants may reduce the burn incidence rate, providing a reference for developing prevention interventions.

Objective: Obstructive sleep apnea (OSA) is a sleep disorder which results in daytime sleepiness and impaired memory function. The aim of this study was to investigate the effect of continuous positive airway pressure (CPAP) on sleepiness and memory function in OSA patients. We also investigated whether CPAP compliance impacted the effect of this treatment.Methods: The case-control study enrolled sixty-six patients with moderate to severe OSA subjects. All subjects completed a polysomnographic study, sleepiness questionnaires (the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index), and four memory function tests (WM: working memory; PS: processing speed; LM: logical memory; FM: face memory).Results: Prior to CPAP treatment, no significant differences (p< 0.05) were noted in the demographic data, daytime sleepiness, or memory function between the two groups (with/without CPAP). However, OSA patients treated with CPAP for two months showed significant improvements in daytime sleepiness, PS, LM, and FM compared to those who did not receive CPAP treatment. A significant improvement in LM was observed in subjects who exhibited good compliance with CPAP treatment compared to those with poor compliance. Conclusions: In conclusion, CPAP treatment for two months improved daytime sleepiness and memory function in OSA patients. Patients exhibiting good CPAP compliance demonstrated greater improvements in daytime sleepiness and LM function.

BACKGROUND Hormonal fluctuations may trigger the onset of bipolar disorder. We designed a longitudinal follow-up study to evaluate the association between hysterectomies and bipolar disorder risk. METHODS We conducted a large retrospective cohort study using Taiwan's National Health Insurance Research Database. A total of 4,337 women aged 30 to 50 years who underwent the hysterectomy during 2000-2013 were selected and 17,348 patients without hysterectomy were selected for comparison (1:4 match). Poisson regression analysis was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI). RESULTS During the follow-up of 7.93 years, 20 participants with hysterectomy and 28 without hysterectomy developed bipolar disorder. Receiving hysterectomy was associated with the risk of developing bipolar disorder (adjusted IRR = 2.80; 95% CI = 2.54-3.09). Women with hysterectomy had a higher risk of bipolar disorder in follow-up durations of

Objectives Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. Methods Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). Results The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23–2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07–6.72), rheumatoid arthritis (2.89, 1.97–4.23), dermatomyositis (5.85, 1.32–25.94) and autoimmune vasculitis (2.44, 1.17–5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. Conclusions This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.

In order to determine whether Taiwanese vegetarian diets reduce the risks of depression, we analyzed data from the Tzu Chi Vegetarian Study (TCVS), which is a prospective cohort study following 12,062 participants from the Buddhist Tzu Chi Foundation of Taiwan since 2005. The cohort was prospectively followed by linking to the National Health Institute Research Database (NHIRD) of Taiwan and hazard ratios of depression between vegetarian and non-vegetarian groups were calculated by Cox proportional hazards regression. We assessed dietary intake using a detailed food frequency questionnaire (FFQ). Incident depression was ascertained through linkage to NHIRD which had claim records with the International Classification of Diseases, and a total of 3,571 vegetarians and 7,006 non-vegetarians were included in this analysis. Compared with non-vegetarians, the vegetarian group had a lower incidence of depressive disorders (2.37 vs. 3.21 per 10,000 person-years, adjusted hazard ratio (aHR): 0.70, 95% confidence interval (95% CI): 0.52–0.93). Thus, Taiwanese vegetarians had a lower risk of developing subsequent depressive disorders compared with non-vegetarians. This indicated that diet may be an important measure for the prevention of depression. However, to generalize to the global population requires further study.

Background: Abnormalities in the immune system of endometriosis has been demonstrated and may reflect the chronic inflammatory response or the autoimmune reaction to the presence of ectopic endometrial tissue. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease of an autoimmune nature. The study aimed to investigate the risk of incident RA in patients with endometriosis. Materials and Methods: A total of 17,913 patients with endometriosis and 17,913 unaffected controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed RA were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of RA incidence rate between patients with endometriosis and unaffected controls. Results: Patients with endometriosis were associated with an increased risk of incident RA compared with unaffected controls after adjusting for age, CCI score, and hormonal and surgical treatments (3.56 vs. 1.30 per 10,000 person-years, HR: 3.71, 95% CI: 2.91-5.73). Among these adjusted variables, hormonal and surgical treatments were treated as time-dependent covariates. Stratification analyses also revealed similar risk associations linking endometriosis to subsequent RA in all stratified age and CCI score subgroups (adjusted HR all >1, although not all were significant) Conclusions: Patients with endometriosis was associated with an increased risk of incident RA. Additional prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm this relationship.

Hyperthyroidism contributes to many other disease conditions, including neurodegenerative diseases. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hyperthyroidism. A total of 8788 patients with hyperthyroidism and 8788 controls (without hyperthyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% CI of PD incidence rate between patients with hyperthyroidism and unaffected controls. Patients with hyperthyroidism had a significantly increased risk of PD compared with unaffected controls (1.21 vs 0.45 per 1000 person-years, HR: 2.69, 95% CI: 1.08–6.66) after adjusting for age, gender, CCI score, comorbidities, and antithyroid therapy. Hyperthyroidism and PD may share common manifestations. After excluding the first year of observation, a similar result is obtained (HR: 2.57, 95% CI: 1.61–4.01). Also, this study found that older age (HR: 3.74–8.53), more comorbidities (HR: 1.58–1.63), and specific comorbidities (brain injury (HR: 1.57) and cerebrovascular disease (HR: 3.44)) were associated with an increased risk of developing PD. Patients with hyperthyroidism have an increased risk of developing PD. Additional prospective clinical studies are warranted to examine the relationship between hyperthyroidism and PD and determine if there is an intervention that could reduce PD risk.

Objective Previous case reports have linked Graves' disease to incident systemic lupus erythematosus (SLE). It has also been reported that antithyroid drugs used to treat Graves' disease can induce SLE development. The purpose of this study was to investigate the risk of SLE in patients with Graves' disease. Methods A total of 8779 patients with Graves' disease and 8779 controls (without Graves' disease) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000-2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed SLE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of SLE incidence rate between patients with Graves' disease and unaffected controls. Results Patients with Graves' disease had a significantly increased risk of SLE than unaffected controls (8.81 vs 2.83 per 10 000 person-years, HR: 5.45, 95% CI: 1.74-17.0) after adjusting for antithyroid therapies (antithyroid drugs, radioactive iodine ablation, and surgery). Diagnostic bias may be present as patients with Graves' disease may seek more help from healthcare providers. After excluding the first 0.5 and 1 year of observation period, similar results were obtained (excluding 0.5 year - HR: 4.30, 95% CI: 2.78-8.57; excluding 1 year - HR: 4.63, 95% CI: 2.33-7.79). Conclusion This study shows that Graves' disease is associated with an increased risk of incident SLE. Further studies on the underlying pathogenesis linking Graves' disease and SLE are warranted.

Introduction Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea (OSA). To date, the link between CPAP usage and incident stroke has been inconsistent. Objective This nationwide population study is designed to examine the effect of CPAP on stroke incidence in OSA patients. Methods Using Taiwan's National Health Insurance Research Database (NHIRD), this study collected data from 4275 OSA patients diagnosed between 2000 and 2011 and divided them into two groups according to whether they received CPAP treatment. After matching baseline demographics and comorbidities, both cohorts contained 959 OSA patients and were followed to a newly diagnosed stroke or until the end of 2013. Cox regression analysis was performed to examine the incidence of stroke between patients with OSA receiving CPAP or no CPAP treatment. Results CPAP treatment for OSA patients predicted a lower incidence rate (3.41 vs 5.43 per 1000 person-years) and tended to protect against the development of stroke (hazard ratio (HR): 0.68, 95% confidence interval (95% CI): 0.38-1.23) compared to those without CPAP treatment, but the estimate was not statistically significant. Similar results were also observed by dividing stroke into ischemic (2.65 vs 4.30 per 1000 person-years; HR: 0.67, 95% CI: 0.35-1.31) or hemorrhagic origin (0.76 vs 1.12 per 1000 person-years; HR: 0.67, 95% CI: 0.19-2.40). Conclusions It is possible that treatment with CPAP might be beneficial for protection against stroke, but this conclusion should be interpreted with caution. Future studies with satisfactory CPAP quality and duration are needed to validate this observation.

The etiology of endometriosis is mostly under-explored, but abnormalities in the immune system leading to an autoimmune reaction have been suggested. The systemic lupus erythematosus (SLE) is one of the most common autoimmune diseases. The purpose of this study was to investigate the risk of SLE in patients with endometriosis. A total of 17,779 patients with endometriosis and 17,779 controls (without endometriosis) matched by age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database, at which time participants who developed SLE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of SLE incidence rate between patients with endometriosis and unaffected controls. After adjusting for age, CCI score, and different treatment options, patients with endometriosis were at increased risk of SLE compared to unaffected controls (0.85 versus 0.57 per 1000 person-years, HR 1.86, 95% CI 1.36–2.53). Also, higher baseline CCI scores (CCI score 1–2 and ≥ 3 vs. 0—HR 2.33–4.98) were at increased risk of SLE. During follow-up, hormonal treatment for endometriosis could reduce the risk of SLE (short-term and long-term vs. non-use HR 0.48–0.62), while surgical treatment appeared to have a limited impact on the risk of SLE. Patients with endometriosis were at increased risk of SLE, and adequate hormonal treatment could reduce the risk of SLE, providing a reference for developing prevention interventions.

Background The capacity to regulate emotion is important for individuals' ability to adapt to society, the long-term lack of which can lead to related emotional disorders. However, evaluating whether an emotion-regulation strategy is appropriate requires consideration of the individual's distinct culture and situation. In this study, we compared the anger regulation strategies employed in various interpersonal situations by psychiatric outpatients and a community control group in Taiwan. Methods We surveyed 150 psychiatric outpatients (mean age = 45.30, SD = 12.48, 73.3% female) and 150 community controls (mean age = 45.05, SD = 12.24, 73.3% female) congruent in age and sex. Participants evaluated their emotion regulation in two interpersonal contexts by completing a set of questionnaires related to a recent incident of anger they experienced with family and friends, respectively. Results Outpatients used the emotion-regulation strategies of cognitive reappraisal and expressive suppression equally in various relationships; while the community control group made more use of cognitive reappraisal to regulate anger, which arose in their relationships with both family and friends. Relationship intimacy influenced the strategy adopted, and the community control group was more likely to use suppression to regulate anger towards friends than family members, which reflected a cultural belief—maintaining harmony in social relationships. Limitations Context-specific emotion regulation was assessed via a retrospective self-report measure, which is subject to recall bias. Conclusions Our findings highlight the importance of considering interpersonal contexts when studying emotion regulation and developing psychological interventions that target anger or other negative emotion regulation., Psychology; Emotion regulation; Cognitive reappraisal; Suppression; Depressed mood

Hypothyroidism has been implicated in many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hypothyroidism.A total of 4725 patients with hypothyroidism and 4725 controls (without hypothyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of PD incidence rate between patients with hypothyroidism and unaffected controls.Patients with hypothyroidism had a significantly increased risk of PD compared with unaffected controls (2.00 versus 1.10 per 1,000 person-years, HR: 1.77, 95% CI: 1.13-2.76) after adjusting for age, gender, CCI score, physical comorbidities (brain injury, cerebrovascular disease, hypertension, dyslipidemia, and diabetes mellitus), and duration of levothyroxine use. Also, older age (≥50 vs.50 - HR:14.83), higher CCI score (CCI score 1-2≥3 vs. 0 - HR: 1.66-1.74), and specific comorbidities (brain injury (HR: 1.78) and cerebrovascular disease (HR: 2.46)) significantly increased the risk of PD after adjusting for the variables mentioned above.Patients with hypothyroidism have an increased risk of developing PD. Other prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm their relationship.

Obstructive sleep apnea (OSA), a sleep disorder, results in decreased daytime alertness and neurocognitive dysfunction. Obesity is considered a major risk factor for the development and progression of OSA and the resulting cognitive dysfunction. However, the effect of obesity on neurocognitive dysfunction in OSA has been rarely investigated. Eighty-three patients with moderate to severe OSA syndrome were recruited in our study. After matching for education, age, and body mass index (BMI), 40 patients were enrolled into our study with matched obese (BMI ≧ 30) and non-obese (BMI

Background Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. Methods Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. Results The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. Limitations The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. Conclusion This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Graphene oxide (GO), a derivative of graphene, and its related nanomaterials have attracted much attention in recent years due to the excellent biocompatibility and large surface area of GO with abundant oxygen functional groups, which further enable it to serve as a nano-bio interface. Herein, we demonstrate the induction of blue fluorescence in GO suspensions via a mild thermal annealing procedure. Additionally, this procedure preserves the oxygen functional groups on the graphene plane which enables the conjugation of cancer drugs without obvious cytotoxicity. Consequently, we demonstrate the capability of GO to simultaneously play the dual-role of a: (i) cellular imaging agent and (ii) drug delivery agent in CT26 cancer cells without the need for additional fluorescent protein labeling. Our method offers a simple, controllable strategy to tune and enhance the fluorescence property of GO, which shows potential for biomedical applications and fundamental studies.

Aim Under-management of diabetes can lead to a hyperglycaemic episode (HCE), which could be further strengthened in the presence of schizophrenia and the use of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with schizophrenia. Additionally, the duration of antipsychotic use on the risk of HCE is examined. Materials and methods A total of 13858 diabetic patients with schizophrenia and 55407 controls (without schizophrenia) matched by gender, age, index year, and Charlson Comorbidity Index score were included between 1999 and 2010 and followed to the end of 2013 using from the Taiwan National Health Insurance Research Database. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (95% CI) of the HCE incidence rate between the two groups studied. Results Diabetic patients with schizophrenia were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic use (4.73 versus 2.43 per 1,000 person-years, HR: 2.16, 95% CI: 1.85-2.51). Also, in diabetic patients with schizophrenia, a longer duration of antipsychotic use was associated with a lower risk of HCE after adjustment for the above-mentioned variables, suggesting a protective effect of antipsychotics against HCE during prolonged use. Conclusion This study highlights the need to pay more attention to the risk of HCE in diabetic patients with schizophrenia and the importance of proper use of antipsychotics may reduce the risk of HCE.

Background Suboptimal management of diabetes can lead to a hyperglycemic crisis episode (HCE), which could be further enhanced in the presence of bipolar disorder (BD) and the prescription of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with BD. Additionally, the duration of antipsychotic prescription on HCE risk is examined. Methods Using the Taiwan National Health Insurance Research Database, 6099 diabetic patients with BD and 24,378 diabetic patients without BD matched by gender, age, index year, and Charlson Comorbidity Index score were enrolled between 1999 and 2010 and followed to the end of 2013. Participants who developed HCE during the follow-up period were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between two groups studied. Results Diabetic patients with BD were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic prescription (3.84 versus 2.71 per 1,000 person-years, HR: 1.41, 95% CI: 1.15–1.71). Also, this study revealed that male gender, more comorbidities, and a longer duration of antipsychotic prescription were potential risk factors for developing HCE. Limitations This study only deals with data on the duration of antipsychotic prescription, without showing the effects of different antipsychotics on HCE risk. Conclusion This study highlights the need to pay attention to the risk of HCE in diabetic patients with BD and the importance of careful prescription of antipsychotics to reduce the HCE incident.

Introduction Violent motor tics or severe self-harm behaviors have been reported in patients with Tourette's syndrome (TS) and leading to traumatic brain injury (TBI). The study aimed to determine the risk of TBI in TS patients, the effects associated with concurrent psychiatric disorders (attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or depressive disorder), and the effects of medication treatment (antipsychotics, antidepressants, or clonidine) on the risk of TBI. Methods Using the National Health Insurance Research Database of Taiwan, 2261 TS patients and 20349 non-TS controls matched by gender and age were enrolled between 2000 and 2012, and followed until the end of 2013. Participants who developed TBI during the follow-up period were identified. Cox regression analysis was performed to examine the risk of TBI between TS patients and non-TS controls. Results TS patients were associated with an increased risk of TBI compared to non-TS controls (hazard ratio (HR): 1.59, 95% confidence interval (95% CI): 1.37–1.85). Also, this study revealed TS patients with ADHD, OCD, or depressive disorder predicted a higher TBI incidence rate than those who did not, but the estimate was not statistically significant. Moreover, this study found that TS patients with frequent use of antipsychotics were associated with a lower risk of TBI than infrequent users (HR: 0.76, 95% CI: 0.57–0.99). Conclusions This study highlights the need to pay more attention to the risk of TBI in TS patients, and the importance of adequate antipsychotic medication may reduce the risk of TBI.

Arachnoid cyst is a benign, congenital space-occupying brain lesion, which has been found in patients with schizophrenia. The association between arachnoid cyst and schizophrenia remains controversial, but the location of the arachnoid cyst may give rise to a specific symptom presentation in schizophrenia. We present a 31-year-old woman with an established diagnosis of schizophrenia coexisting with a large cerebellar arachnoid cyst who presented mainly with delusions of control. This cerebellar arachnoid cyst and schizophrenia may have been found together coincidentally or brain dysfunction due to this cerebellar arachnoid cyst may have caused or contributed to the appearance of psychotic symptoms. The patient had an unsteady gait accompanied by delusions of control, and she showed a poor response to high-dose olanzapine treatment, suggesting the arachnoid cyst was associated with her schizophrenic symptoms. The cyst was over the right posterior fossa with cerebellum compression, which may have caused abnormality in the cerebellar–parietal network resulting in her delusions of control. This case indicates that there might be relationships between cerebellar lesions, schizophrenia, and delusions of control.

Aims This study aims to investigate the risk of hyperglycemic crisis episode (HCE) in diabetic patients with depression and to examine the relationship between the duration of antidepressants use and the risk of HCE. Methods In all, 26,746 diabetic patients with depression and 106,853 controls (without depression) matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were included between 1999 and 2010, then followed until the end of 2013. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between the two groups studied. Results Diabetic patients with depression had a significantly increased risk of HCE compared to unaffected controls after adjusted for gender, age, CCI score, and duration of antidepressants use (2.87 versus 2.50 per 1000 person-years, HR: 1.78, 95% CI: 1.56–2.03). Also, long-term use of antidepressants in diabetic patients with depression showed a significantly reduced risk of HCE compared to non-users after adjusting for the above-mentioned variables (HR: 0.44, 95% CI: 0.35–0.55). Conclusions This study shows diabetic patients with depression have an increased risk of HCE, and the use of antidepressants may reduce its risk.

BackgroundSeveral features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population.ObjectiveThe study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan.MethodsOverall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls.ResultsPatients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18–34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4).ConclusionGiven the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan’s mental health clinics.

Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31–0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44–1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.

Background Previous studies have suggested that sexually transmitted infections (STI) tend to increase in patients with bipolar disorder during a manic or hypomanic episode. However, in the long-term course of this disease, it is unclear whether patients with bipolar disorder have a higher risk of incident STI. Methods Using the National Health Insurance Research Database of Taiwan, 3721 patients with bipolar disorder and 14,884 controls without bipolar disorder matched by gender and age were enrolled between 2000 and 2010 and followed up until the end of 2013. Participants who developed any STI (human immunodeficiency virus [HIV], syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between patients with bipolar disorder and comparative controls. Results Patients with bipolar disorder were prone to develop STI (hazard ratio [HR], 1.67, 95% confidence interval [95% CI], 1.27-2.18) especially for HIV (HR, 3.59; 95% CI, 1.16-11.08) and syphilis (HR, 2.26; 95% CI, 1.06-4.85). In addition, this study found that the incidence of STI was higher among women than men (HR, 1.83; 95% CI, 1.41-2.39). Conclusions This study shows that bipolar disorder is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in patients with bipolar disorder.