Early cardiovascular risk and all-cause mortality following an incident of severe hypoglycaemia: A population-based cohort study.

AIMS: Severe hypoglycaemia is associated with a high risk of cardiovascular events in patient with diabetes. The aim of this study was to clarify the temporal relationship between hypoglycaemia and cardiovascular events. MATERIALS AND METHODS: This observational cohort study was conducted using Taiwan's Longitudinal Cohort of Diabetes Patients Database, which included 360 000 patients with newly diagnosed diabetes during the period 1999 to 2001. Patients with the first severe hypoglycaemia after 2002 served as the study cohort. Each patient in the study cohort was matched with two control patients without severe hypoglycaemia, based on a propensity score. A joinpoint regression model was used to determine trends in all-cause mortality and incidence of cardiovascular disease (CVD) events in both cohorts. RESULTS: A total of 10 157 patients with severe hypoglycaemia and 20 314 matched controls were recruited. Patients with severe hypoglycaemia had a significantly higher risk of CVD (HR, 7.28; 95% CI, 5.19-10.20) and all-cause mortality (HR, 19.92; 95% CI, 13.42-29.56) during the first month compared with those without. In patients with severe hypoglycaemia, the incidence of CVDs dropped by 17.29% monthly during the first 4 months and slowly decreased (-0.67%) during subsequent months. All-cause mortality decreased by 16.55% and 3.24% monthly during months 0-6 and months 6-17, respectively. CONCLUSIONS: Severe hypoglycaemia is associated with a greater risk of cardiovascular events and death, especially during the first month following a hypoglycaemic episode. Patients prone to severe hypoglycaemia should be made aware of the elevated risk of subsequent cardiovascular events.

THE TRENDS OF HYPERTHYROIDISM TREATMENT IN TAIWAN: A NATIONWIDE POPULATION-BASED STUDY.

OBJECTIVE: Few studies on hyperthyroidism treatment have been reported in the past 3 decades. We used a nationwide population-based database to evaluate the current practices and management of hyperthyroidism in Taiwan. METHODS: This retrospective study included a random selection of 1 million people in Taiwan between 2004 and 2010. We identified patients with hyperthyroidism who received antithyroid drugs (ATD), radioactive iodine (RAI), or surgery. We calculated the proportions and treatment trends of those 3 treatment options annually. A Poisson regression model was used to determine whether trends changed. RESULTS: The prevalence of overt hyperthyroidism in Taiwan steadily increased from 2,666 (0.27%) in 2004 to 3,464 (0.37%) in 2010. The incidence of hyperthyroidism (per 1,000 persons) also increased from 0.97 in 2004 to 1.06 in 2010. The major proportion of hyperthyroidism in this study was Graves disease (95%), followed by toxic nodular goiter (2%), and other causes (3%). ATD is the most commonly used (96-97%) treatment for hyperthyroidism, followed by surgery (2-3%) and RAI (<1%). There was a significant decreasing trend for surgery, from 2.9% in 2004 to 2% in 2010, especially in female patients (3.3% in 2004 to 2.3% in 2010, P<.01) and patients younger than 40 (3.8% in 2004 to 2.9% in 2010, P<.01). Meanwhile, the proportions of ATD and RAI remained unchanged. The most common ATD prescription was methimazole (45-50%), followed by propylthiouracil (30-32%) and carbimazole (19-21%). CONCLUSION: Between 2004 and 2010, ATD was the treatment of choice in Taiwan, followed by surgery and RAI. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; LHID2005 = Longitudinal Health Insurance database 2005 dataset; NHI = National Health Insurance; RAI = radioactive iodine.

The effect of benzodiazepine and nonbenzodiazepine prescriptions for diabetes mellitus type 2 in elderly Taiwanese with depressive symptoms.

BACKGROUND: This study examined the relationship between depression, benzodiazepine (BZD)/nonbenzodiazepine hypnotics (non-BZD), and other risk factors in a national sample of Taiwan's elderly diabetic patients. METHODS: Data were drawn from the 2005 Taiwan National Health Interview Survey and adults aged 65 years and older. A total of 1331 subjects were included in this study. The Chinese version of Center for Epidemiologic Studies Depression Scale was used to evaluate patients' depression symptoms. RESULTS: The rates of depression in the diabetes mellitus (DM) and non-DM groups were 13.5% (39/288) and 9.8% (102/1043) and the average ages were 73.7 and 73.4 years, respectively. In multivariate regression, the odds ratio of depression was 1.66-fold higher among BZD/non-BZD users (95% confidence interval: 1.10-2.51, model 2) than among those without BZD/non-BZD use. In addition, hyperlipidaemia, poor physical function, and antidepressant use were associated with a higher risk of depressive symptoms. Meanwhile, a monthly household income of NT$30 000-NT$49 999, exercise, and betel chewing were associated with a lower risk of depression. We performed an additional logistic analysis for which the odds ratio of depression significantly increased to 1.52 in non-DM elderly patients (95% confidence interval: 1.06-2.19) who were prescribed BZD/non-BZD. In contrast, there was no significant difference in the odds ratio of depression in the DM elderly regardless of BZD/non-BZD use, although there was a slight tendency for depression among those who used BZD/non-BZD. CONCLUSION: Depression in non-DM Taiwanese elderly patients was found to be associated with BZD/non-BZD use, whereas depression in DM Taiwanese elderly patients was not found to be associated with BZD/non-BZD use.

Benzodiazepine & nonbenzodiazepine prescriptions for Taiwanese elderly with type 2 diabetes contributes to cognitive dysfunction.

BACKGROUND: This study examined the relationship of cognitive function and benzodiazepine/nonbenzodiazepine hypnotics (BZD/nonBZD) and other risk factors in a national sample of Taiwan's elderly diabetic patients. METHODS: Data were drawn from the "2005 Taiwan National Health Interview Survey (NHIS)", a population-based study of a national sample of adults aged 65 years and older. A total of 653 participants were included in this study. The Mini-Mental State Examination (MMSE) was used to evaluate patient's cognitive function for which the cut-off score is education-adjusted. RESULTS: There were 130 participants left in the diabetic group and 523 participants in the control group. The average age was 74.2 and 73.3 respectively. The rate of cognitive dysfunction in DM and non DM participants was 11.5% (15/130) and 8.4% (44/523). Compared with those without diabetes in multivariate logistic regression, the odds ratio of cognitive impairment was 1.87-fold higher for diabetic patients (95% CI 1.04-3.61) after adjusting for sociodemographic characteristics, comorbidities, and BZD/nonBZD. Other factors were not significant. We performed an additional logistic analysis for which the odds ratio of cognitive impairment in diabetic patients with BZD/nonBZD was significantly increased to 2.41 (95% CI 1.08-5.40) than for patients without diabetes and BZD/nonBZD. CONCLUSION: In our research, cognitive dysfunction was associated with diabetes. BZD/nonBZD may have conferred additional risk of cognitive impairment in our elderly diabetic patients. We should consider examining the mental function of DM patients regularly and try our best to avoid potentially inappropriate medications (PIMs).

Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway.

N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.

High risk of osteoporosis and fracture following solid organ transplantation: a population-based study.

Background: Osteoporosis and fractures increase morbidity and mortality rates after solid organ transplantation (SOT), but few studies have analyzed the risk of osteoporosis and related fractures after SOT. In this retrospective cohort study, we investigated the risk of osteoporosis and fractures in different SOT recipients. Methods: This study was a retrospective cohort study using a nationally representative database in Taiwan. We collected the data of SOT recipients and used the propensity score matching method to obtain a comparison cohort. To reduce bias, we excluded patients who had been diagnosed with osteoporosis or fracture before inclusion. All participants were followed up until the date of diagnosis as having a pathological fracture, death, or the end of 2018, whichever occurred first. The Cox proportional hazards model was used to investigate the risk of osteoporosis and pathological fracture in SOT recipients. Results: After adjustment for the aforementioned variables, SOT recipients were observed to have a higher risk of osteoporosis (hazard ratio (HR) = 1.46, 95% confidence interval (CI): 1.29-1.65) and fracture (HR: 1.19, 95% CI: 1.01-1.39) than the general individuals. Among the different SOT recipients, the highest risk of fractures was noted in heart or lung transplant recipients, with a HR of 4.62 (95% CI: 2.05-10.44). Among the age groups, patients aged >61 years had the highest HRs for osteoporosis (HR: 11.51; 95% CI, 9.10-14.56) and fracture (HR: 11.75, 95% CI: 8.97-15.40). Conclusion: SOT recipients had a higher risk of osteoporosis and related fractures than the general population, with the highest risks observed in patients receiving heart or lung transplants, older patients, and patients with CCI scores of >3.

Risk of Non-Hodgkin Lymphoma among Patients with Hepatitis B Virus and Hepatitis C Virus in Taiwan: A Nationwide Cohort Study.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with an increased risk of developing non-Hodgkin lymphoma (NHL); however, adequate data corroborating these associations are lacking. Therefore, a study based on the national database was performed to investigate the correlation between HBV and HCV with NHL in Taiwan. This research was a retrospective cohort study using a nationally representative database established by the Health and Welfare Data Science Center of the Ministry of Health and Welfare, Taiwan. The participants were patients with HBV and HCV, analyzed using the propensity score matching method. The study results indicated that the incidence rate of NHL (0.13%) was significantly higher than that in patients from the general population. After controlling related variables, the hazard ratio (HR) of the incidence of NHL in patients with hepatitis was 2.37 (95% CI, 1.93-2.91). Furthermore, the incidence of NHL in patients with HBV was significantly higher than in patients from the general population (HR, 2.49; 95% CI, 1.94-3.19). The incidence of NHL in patients with HCV was significantly higher than in patients from the general population (HR, 2.36; 95% CI, 1.73-3.22). This study indicated that HBV and HCV significantly increase the risk of NHL.

The Impact of Pharmaceutical Home Care on Medical Utilization for Frequent Users of Outpatient Services in Taiwan.

Due to the high-accessibility and low-copayment of healthcare system in Taiwan, the clinical visit frequency of people is relatively high, which often leads to an excessively high healthcare expenditure. The aim of this research was to explore the effectiveness of pharmaceutical home care for frequent users of outpatient service and to analyze the impact of pharmaceutical home care on medical utilization. The study was based on the Taiwan National Health Insurance Research Database. Patients with over 100 clinical visits during 2010 to 2012 were selected as subjects. Whether these patients participate the experimental plan of pharmaceutical home care in the following year and the medical utilization of the research subjects were analyzed to compare the difference between participating group and non-participating group in this plan. The generalized estimating equation was employed to examine the difference of medical utilization. A total of 3943 subjects were included in this study, including 591 patients (14.99%) participating in the experimental plan. The average number of physician visits during the following year of the participating group was higher than that of the non-participating group by 0.12 visits, and the outpatient medical expense was lower than the non-participating group by 18,302 points (1 point = 0.03 US dollars). After participating in the plan, the average number of clinical visits of frequent users of outpatient services was significantly reduced by 6.63 visits, and the outpatient expense was significantly decreased by 9871 points. After joining the experimental plan of pharmaceutical home care, the average number of outpatient visits decreased significantly and the medical expense was lower when compared with those who did not participate in the plan.

Progress of diabetes severity associated with severe hypoglycemia in Taiwan.

OBJECTIVES: The association between the progression of diabetes severity and risk of severe hypoglycemia is unknown. This study aimed to evaluate the association between the progression of diabetes severity and severe hypoglycemia in patients with diabetes. STUDY DESIGN: A 13-year population-based retrospective cohort study of patients with diabetes in Taiwan. METHODS: Diabetes progression was evaluated by the adapted Diabetes Complications Severity Index (aDCSI) score from index date to end of follow-up. The progression of diabetes severity was divided into 3 categories: slow, moderate, and rapid increase in aDSCI score. We further compared those 3 categories and evaluated the risk of first hospitalization due to severe hypoglycemia. RESULTS: A total of 330,831 patients with diabetes were recruited. The mean age of patients in this study was 56.8 years, and mean follow-up duration was 9.3 years. The mean initial aDCSI score was 0.7, whereas the mean aDCSI score at the event date or end date was 2.9. A rapid increase in aDCSI score was associated with higher risk of severe hypoglycemia compared with a slow increase (hazard ratio, 4.91; 95% CI, 4.65-5.18). The incidence densities of severe hypoglycemia (per 1000 person-years) for slow, moderate, and rapid increase in aDCSI score were 2.3, 2.5, and 11.4, respectively. CONCLUSIONS: This study demonstrated that rapid progression of diabetes complications was associated with higher risk of severe hypoglycemia. It is imperative that treating physicians identify patients with acute worsening of diabetes severity and provide proper hypoglycemia education and prevention care.

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

PURPOSE: Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. METHODS: This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. RESULTS: We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (<8,600 mg) and medium (8,600-88,900 mg) cumulative doses of aspirin did not reduce the risk of breast cancer. CONCLUSIONS: Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Association of asthma and anxiety: A nationwide population-based study in Taiwan.

BACKGROUND: Few studies have investigated the bidirectional relationship between asthma and anxiety; we sought to investigate asthma and anxiety in a large national sample. METHODS: Cases were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) aged more than 15 years between 2000 and 2007. Case status required the presence of any inpatient diagnosis of asthma and/or at least one year diagnosis of asthma in outpatient service. These 22,797 cases were compared to 22,797 sex-, age-, residence- and insurance premium-matched controls and both groups were followed until the end of 2008 for instances of anxiety, defined as ICD-9 codes 300.0, 300.01, 300.02, 300.2, 300.21, 300.23, 300.3. Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, cardiovascular disease, diabetes, depression disorder, and hospital admission days for any disorder. The effect of asthma on the risk of panic disorder and the effect of anxiety disorder on the risk of later asthma were also examined as competing risk adjusted Cox regression analyses RESULTS: Of the 45,594 subjects, 2792 were ascertained as having anxiety during a mean (SD) follow-up period of 5.3 (2.5) years. Asthma, females, older age, rural residence, depression disorder, and prednisone use were independent risks on anxiety in the fully adjusted model. Anxiety, older age, rural residence, and prednisone use were independent risks on asthma in the fully adjusted model. LIMITATIONS: The severity of asthma and anxiety disorder, the duration of prednisone treatment and adherence, stressful life events, smoking, family history and relationship were not evaluated. CONCLUSIONS: Bidirectional relationship between asthma and anxiety disorder was confirmed in this population, in dependent of a number of potential confounding factors.

Impact of potentially inappropriate medication and continuity of care in a sample of Taiwan elderly patients with diabetes mellitus who have also experienced heart failure.

AIMS: Continuity of care (COC) and potentially inappropriate medication (PIM) can affect the elderly healthcare outcome. We evaluated the COC and PIM effects in older diabetes mellitus (DM) patients with heart failure (HF). METHODS: The Longitudinal Health Insurance Database of 2005 was multiple-year claim data collected from 2005 to 2010 in Taiwan. There were both 823 DM and non-DM subjects aged 65 years and older in this observational study. The COC index and 2012 Beers criteria were applied to evaluate the COC and HF-PIM in older DM patients with heart failure. The dependent variables were either hospital admissions or emergency department visits. Generalized estimating equation was used to adjust all covariates. RESULTS: During 2005-2010, the rate of HF-PIM in the elderly DM group was 86.1%, the mean COC index was 0.28 ± 0.19, the admission rate was 31.9% and the emergency department rate was 38.8 %. Lower COC index was associated with HF-PIM and HF-PIM duration in older DM patients with HF. Lower COC index was associated with hospitalizations (OR 0.07, 95% CI 0.05-0.11) and ED visits (OR 0.10, 95% CI 0.07-0.13), but HF-PIM was not significant. The duration of HF-PIM was related with poor health outcomes over 90 and 180 days for hospitalization and emergency department visit, respectively. CONCLUSION: Among elderly DM patients with HF, COC had positive effects on healthcare outcomes. Improving COC and reducing PIM duration for elderly DM patients with HF seems warranted. Geriatr Gerontol Int 2016; 16: 1117-1126.

Iodinated Contrast Media-Induced Thyroid Dysfunction in Euthyroid Nodular Goiter Patients.

BACKGROUND: The risks of thyroid dysfunction after iodinated contrast media exposure in patients with euthyroid nodular goiter are largely unknown. METHODS: This observational, retrospective cohort study included a random selection of one million people in Taiwan. All patients with iodinated contrast media exposure during this study period were selected. Patients with euthyroid nodular goiter were identified as cases, while patients without thyroid nodule were selected as controls. We followed these patients until the first event of thyroid dysfunction including hyperthyroidism or hypothyroidism after iodinated contrast media exposure. RESULTS: A total of 334 cases and 2672 matched controls were selected in this study. The mean age of cases and controls were 58.6 and 58.4 years old, and mean follow-up durations were 2.1 and 2 years respectively. After adjustment, patients with euthyroid nodular goiter had a higher risk of thyroid dysfunction (hazard ratio 5.43, [confidence interval (CI) 3.01-9.80]) compared with controls after iodinated contrast media exposure. In the subgroup analysis, the risks of hyperthyroidism and hypothyroidism in cases compared with controls were 5.77 [CI 2.64-12.62] and 4.95 [CI 2.15-11.40] respectively. Half of the euthyroid nodular goiter cases developed thyroid dysfunction within one year after iodinated contrast media exposure. Interestingly, all thyroid-related comorbidities and drug prescriptions did not increase the risk of thyroid dysfunction. CONCLUSIONS: Presence of euthyroid nodular goiter was associated with higher risk of thyroid dysfunction including hyperthyroidism and hypothyroidism after iodinated contrast media exposure.

Iodinated Contrast Media Increased the Risk of Thyroid Dysfunction: A 6-Year Retrospective Cohort Study.

CONTEXT: The risks of thyroid dysfunction after iodinated contrast media (ICM) exposure are largely unknown, especially in Asian populations. OBJECTIVE: The objective was to determine whether ICM exposure in patients with normal thyroid would increase the risk of thyroid dysfunction, including hyperthyroidism or hypothyroidism. DESIGN: This was a retrospective cohort study including a random selection of 1 million people in 2005. SETTING: General population of Taiwan was studied. PATIENTS: Patients with ICM exposure were identified as cases, whereas patients without any ICM exposure were selected as controls. INTERVENTION: Interventions included ICM exposure or nonexposure in normal thyroid function patients. MAIN OUTCOME: The primary endpoint was the composite risk of thyroid dysfunction associated with ICM exposure. RESULTS: A total of 19 642 cases and 78 568 matched controls were recruited in this study. The mean ages of ICM exposure and nonexposure were 53.9 and 53.6 years, respectively, and mean follow-up durations were 4.1 and 5.6 years, respectively. After adjustment, patients with ICM exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval [CI], 1.29-1.66). In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism compared with controls were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44), respectively. CONCLUSIONS: ICM exposure was associated with higher risk of thyroid dysfunction, including hyperthyroidism and hypothyroidism.