Diabetic retinopathy as a potential risk factor for ptosis: A 13-year nationwide population-based cohort study in Taiwan.

Purpose: To determine the risk of ptosis among diabetic retinopathy (DR) patients. Methods: This is a population-based, retrospective, matched-cohort study where DR patients were recruited from the Taiwan National Health Insurance Research Database (NHIRD) to investigate the risk of developing ptosis. Preexisting co-factors of interest included smoking status and medical comorbidities of hyperlipidemia and hypertension. Statistical analysis was performed using T-test, Cox-proportional hazard ratios adjusted for comorbidities (aHR), Wilcoxon rank sum test, Kaplan-Meier estimators, and log rank tests. Results: Follow-up data of 9,494 patients with DR and 37,976 matched control cohort (non-DR) from 2000 to 2012 were analyzed. DR patients were found to have significantly increased risk of developing ptosis (adjusted hazard ratio (HR) [95% CI]: 2.76 [1.74-4.38], p < 0.001) when compared to the control cohort. From analysis in different strata, adult age and non-smokers were shown to have higher risk for ptosis development among DR patients. Furthermore, DR patients was also found to have increased risk of developing ptosis when compared to matched controls, regardless of whether they had medical comorbidities of lipid metabolism disorders or hypertension. Conclusions: In this large-scale study using real-world data, our results showed that DR patients were found to have increased risk of developing ptosis. Female gender, adult age, and non-smokers were also shown to increase the risk of ptosis among DR patients. This has implications towards the care of diabetic patients, complications such as ptosis should be properly screened for when encountering such patients. Before ptosis surgery, the possibility of underlying diabetes or DR should be also scrutinized and treated properly to avoid undesirable postoperative dissension.

Chronic Kidney Disease as A Potential Risk Factor for Uveitis: A 13-Year Nationwide Population-Based Cohort Study in Taiwan.

PURPOSE: To investigate whether patients with chronic kidney disease (CKD) are at increased risk of uveitis. METHODS: Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with CKD between 2000 and 2012. The endpoint of interest was a diagnosis of uveitis. RESULTS: 30,256 CKD patients and 121,024 matched comparisons were analyzed. CKD patients were found to have a significantly higher cumulative uveitis incidence. Through multivariate Cox regression analysis, the CKD group was found to have higher risk of developing uveitis (adjusted hazard ratio 1.51). After stratified by gender, age, and comorbidities (hypertension, diabetes, and hyperlipidemia), the increased risk of uveitis in CKD patients remained significant. CONCLUSIONS: Patients with CKD were found to have higher risk of developing uveitis. For patients over 18 years old and with hypertension, diabetes, or hyperlipidemia, the presence of CKD was demonstrated as an additional crucial factor for uveitis development.

Thiazolidinedione Use in Individuals With Type 2 Diabetes and Chronic Obstructive Pulmonary Disease.

Few studies have investigated the effects of various antidiabetic agents on individuals with both type 2 diabetes mellitus (T2DM) and Chronic obstructive pulmonary disease (COPD). This study compared mortality, cardiovascular events and respiratory outcomes in individuals with both T2DM and COPD taking TZD vs. those not taking TZD. From Taiwan's National Health Insurance Research Database, 12 856 propensity-score-matched TZD users and non-users were selected between January 1, 2000, and December 31, 2012. Cox proportional hazards models were used to calculate the risks of investigated outcomes. Compared with non-use of TZD, the adjusted hazard ratios (95% CI) of TZD use were stroke 1.63 (1.21-2.18), coronary artery disease 1.55 (1.15-2.10), heart failure 1.61 (1.06-2.46), non-invasive positive pressure ventilation 1.82 (1.46-2.27), invasive mechanical ventilation 1.23 (1.09-1.37), bacterial pneumonia 1.55 (1.42-1.70), and lung cancer 1.71 (1.32-2.22), respectively. The stratified analysis disclosed that rosiglitazone, not pioglitazone, was associated with significantly higher risk of major cardiovascular events than TZD non-users. In patients with concomitant T2DM and COPD, TZD use was associated with higher risks of cardiovascular events, ventilation use, pneumonia, and lung cancer. Use of TZD in these patients should be supported by monitoring for cardiovascular and respiratory complications.

Population-based retrospective cohort study on risk of age-related macular degeneration in people with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and age-related macular degeneration (AMD) are both common diseases of the elderly people. COPD induced systemic inflammation and hypoxia may have an impact on the development of AMD. This study investigated the possible association between COPD and subsequent risk of AMD. A retrospective cohort study was conducted based on the data from the National Health Insurance Research Database in Taiwan. The COPD cohort comprised 24,625 adult patients newly diagnosed during 2000-2012, whereas age-, gender-, and the year of diagnosis-matched non-COPD cohort comprised 49,250 individuals. Incident AMD was monitored to the end of 2013. A Cox proportional hazards model was applied to evaluate the risk of AMD. The COPD cohort showed 1.25 times higher AMD incidence than the non-COPD cohort (4.80 versus 3.83 per 1000 person-years, adjusted hazard ratio (HR) = 1.20 [95% confident interval (CI) = 1.10-1.32]). Stratified analyses for age, gender, and presence of comorbidity resulted in significant adjusted HRs in most subgroups. Further analysis revealed that the COPD group had an increased risk of both the exudative and non-exudative types of AMD (adjusted HRs = 1.49 [95% CI = 1.13-1.96] and 1.15 [95% CI = 1.05-1.26], respectively). COPD patients have an increased risk for AMD development. Clinicians should provide adequate care for the ocular health to these patients.

Traditional Chinese Medicine Reduces the Incidence of Chemotherapy-Induced Stroke: A Five-Year Nationwide Population-Based Cohort Study From Taiwan.

Background: Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks. Methods: We analyzed stroke incidence rates in Taiwan's Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke. Results: In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52-3.20; p < 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53-2.46; p < 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26-0.79; p < 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44-0.68; p < 0.001). Conclusion: These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.

Risk of schizophrenia in patients with polycystic ovary syndrome: a nationwide population-based cohort study from Taiwan.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This study shows PCOS patients are at increased risk of incident schizophrenia, and the metformin treatment has a protective effect against incident schizophrenia.

Association of laparoscopy and laparotomy with adverse fetal outcomes: a retrospective population-based case-control study.

BACKGROUND: This study aimed to evaluate fetal adverse outcomes of laparoscopy and laparotomy in pregnant women to determine the safety of these surgical approaches. METHODS: This was a retrospective nationwide case-control study of women who became pregnant for the first time between 2000 and 2012 in Taiwan. The case (with adverse fetal outcomes) and control groups comprised 208,604 and 417,124 participants, respectively. Participants who underwent appendectomy, cholecystectomy, ovarian cystectomy, or myomectomy were treated with either laparoscopy or laparotomy. A conditional logistic regression model was used to calculate the odds ratios (ORs) for adverse fetal outcomes. RESULTS: The laparotomy and laparoscopy groups comprised 632 and 536 patients, respectively. Women who underwent laparoscopy had a significantly higher risk of adverse fetal outcomes (adjusted OR [AOR] = 2.33; 95% CI 1.66-2.99) than those who underwent laparotomy. Adverse fetal outcomes were found to be significantly associated with laparoscopy among women aged 20-39 years (AOR = 2.30; 95% CI 1.70-3.31). Regarding surgical indication, unlike laparotomy, laparoscopic cholecystectomy and appendectomy were not associated with adverse fetal outcomes. However, laparoscopic myomectomy and ovarian surgeries were associated with a higher incidence of adverse fetal outcomes than the laparotomy group (AOR = 2.29 [95% CI 1.57-3.35, p < 0.0001] and AOR = 2.52 [95% CI 1.58-4.04, p = 0.0001], respectively). CONCLUSIONS: Pregnant women who underwent laparoscopic surgery experienced significantly more adverse fetal outcomes than those who underwent laparotomy. Therefore, pregnant women undergoing either laparotomy or laparoscopy should be informed of the risk of adverse fetal outcomes.

Relationship between Uveitis and Thyroid Disease: A 13-Year Nationwide Population-based Cohort Study in Taiwan.

Purpose: To investigate whether patients with thyroid disease are at increased risk of uveitis.Methods: Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with thyroid disease from 2000 to 2012. The endpoint of interest was a diagnosis of uveitis.Results: In analyzing 21,396 patients with thyroid disease, yielding 85,584 matched comparisons, patients with thyroid disease to have a significantly higher cumulative incidence of uveitis when compared to the control cohort with the Kaplan-Meier analysis. This result was further confirmed by Cox regression analysis. The increased risk was persistent in both genders. The association between thyroid disease and uveitis was stronger in patients without diabetes or hypertension.Conclusion: Patients with thyroid disease were found to have a higher risk for uveitis. For certain age groups or patients without diabetes or hypertension, the role of thyroid disease might be more crucial for uveitis development.

Association between Graves' disease and risk of incident systemic lupus erythematosus: A nationwide population-based cohort study.

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.

Aspirin associated with a decreased incidence of uterine cancer: A retrospective population-based cohort study.

Aspirin (ASA) exerts an anti-tumor effect via the COX pathway. Clinical studies on the chemopreventive effects of ASA on uterine cancer (UC) remain inconsistent. We used population-based retrospective cohort study to evaluate the UC in ASA users in Taiwanese women. From insurance claims data, we identified 23,342 women received ASA treatment between 2000 and 2010 and a comparison group of same sample size randomly selected from the same database matched by the propensity score. The incidence of UC in the ASA cohort was 10% of that in the comparison group (0.28 vs 2.73 per 10,000 person-years). The Poisson regression analysis estimated adjusted incidence rate ratio (IRR) was 0.10 (95% confidence interval (CI) = 0.09-0.11) for ASA users relatives to comparisons after controlling for covariates. The UC incidence in ASA users decreased with age, from 0.61 per 10,000 person-years in the 20 to 39 years old (adjusted IRR = 0.21, 95% CI = 0.15-0.29) to 0.21 per 10,000 person-years in the 65 to 80 years old (adjusted IRR = 0.15, 95% CI = 0.12-0.16). The incidence was higher in longer term users. Hormone therapy of estradiol was associated with the increase of UC risk in both cohorts, but less in ASA users than comparisons (1.34 vs 4.75 per 10,000 person-years). This study suggests that ASA use was associated with a decreased risk of UC. Further prospective randomized clinical trials are warranted to confirm the association.

Respiratory outcomes of metformin use in patients with type 2 diabetes and chronic obstructive pulmonary disease.

Few studies investigated the respiratory outcomes of metformin use in patients with coexistent type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We want to compare the long-term respiratory endpoints of metformin use and nonuse in patients with T2DM and COPD. This retrospective cohort study enrolled patients with T2DM and COPD from Taiwan's National Health Insurance Program between January 1, 2000, and December 31, 2012. Main outcomes were hospitalized bacterial pneumonia, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV), and lung cancer. In total, 20,644 propensity score-matched metformin users and nonusers were assessed. The adjusted hazard ratios (95% confidence intervals) of metformin use relative to nonuse for bacterial pneumonia, hospitalization for COPD, NIPPV, IMV, and lung cancer were 1.17 (1.11-1.23), 1.34 (1.26-1.43), 0.99 (0.89-1.10), 1.10 (1.03-1.17), and 1.12 (0.96-1.30). Metformin use also exhibited significant dose-response relationship with respect to the risks of bacterial pneumonia, hospitalization for COPD and IMV. Consistent results were found in the sensitivity test. This nationwide cohort study demonstrated that in patients with T2DM and COPD, metformin use was associated with higher risks of pneumonia, hospitalization for COPD, and IMV. If patients with COPD use metformin, vigilance with regard to their pulmonary condition may be required.

Risk of Parkinson's disease in patients with hypothyroidism: A nationwide population-based cohort study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk of bipolar disorder in patients with polycystic ovary syndrome: A nationwide population-based cohort study.

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.

Risk of Polycystic Ovary Syndrome in Women Exposed to Fine Air Pollutants and Acidic Gases: A Nationwide Cohort Analysis.

BACKGROUND: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. METHODS: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. RESULTS: In total, 91,803 women were enrolled in this study; of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (±1.44) ppb, 20.41 (±6.65) ppb, 9.25 (±4.36) ppb, 20.99 (±3.33) ppb, and 30.85 (±6.16) µg/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35-12.7), 3.37 times (95% CI = 2.86-3.96), 4.18 times (95% CI = 3.57-4.89), 7.46 times (95% CI = 6.38-8.71), and 3.56 times (95% CI = 3.05-4.15), respectively. CONCLUSION: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.

Risk of hyperglycemic crisis episode in diabetic patients with bipolar disorder: A nationwide population-based cohort study.

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.