A cohort study evaluating the risk of stroke associated with long-term exposure to ambient fine particulate matter in Taiwan.

BACKGROUND: Evidences have shown that the stroke risk associated with long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) varies among people in North America, Europe and Asia, but studies in Asia rarely evaluated the association by stroke type. We examined whether long-term exposure to PM2.5 is associated with developing all strokes, ischemic stroke and hemorrhagic stroke. METHODS: The retrospective cohort study consisted of 1,362,284 adults identified from beneficiaries of a universal health insurance program in 2011. We obtained data on air pollutants and meteorological measurements from air quality monitoring stations across Taiwan in 2010-2015. Annual mean levels of all environmental measurements in residing areas were calculated and assigned to cohort members. We used Cox proportional hazards models to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing stroke associated with 1-year mean levels of PM2.5 at baseline in 2010, and yearly mean levels from 2010 to 2015 as the time-varying exposure, adjusting for age, sex, income and urbanization level. RESULTS: During a median follow-up time of 6.0 years, 12,942 persons developed strokes, 9919 (76.6%) were ischemic. The adjusted HRs (95% CIs) per interquartile range increase in baseline 1-year mean PM2.5 were 1.03 (1.00-1.06) for all stroke, 1.06 (1.02-1.09) for ischemic stroke, and 0.95 (0.89-1.10) for hemorrhagic stroke. The concentration-response curves estimated in the models with and without additional adjustments for other environmental measurements showed a positively linear association between baseline 1-year mean PM2.5 and ischemic stroke at concentrations greater than 30 µg/m3, under which no evidence of association was observed. There was an indication of an inverse association between PM2.5 and hemorrhagic stroke, but the association no longer existed after controlling for nitrogen dioxide or ozone. We found similar shape of the concentration-response association in the Cox regression models with time-varying PM2.5 exposures. CONCLUSION: Long-term exposure to PM2.5 might be associated with increased risk of developing ischemic stroke. The association with high PM2.5 concentrations remained significant after adjustment for other environmental factors.

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study.

BACKGROUND: Osteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan. METHODS: We identified 13,520 women with OA aged 20-99 newly diagnosed in 2000-2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort. RESULTS: The incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09-1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37-2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24-4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin. CONCLUSION: Women with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Derivation and validation of a discharge disposition predicting model after acute stroke.

BACKGROUND: Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. METHODS: We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. RESULTS: Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). CONCLUSIONS: The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Patients with chronic kidney disease are at an elevated risk of dementia: a population-based cohort study in Taiwan.

BACKGROUND: Chronic kidney disease (CKD) is more prevalent in Taiwan than in most countries. This population-based cohort study evaluated the dementia risk associated with CKD. METHODS: Using claims data of 1,000,000 insured residents covered in the universal health insurance of Taiwan, we selected 37049 adults with CKD newly diagnosed from 2000-2006 as the CKD cohort. We also randomly selected 74098 persons free from CKD and other kidney diseases, frequency matched with age, sex and the date of CKD diagnosed. Incidence and hazard ratios (HRs) of dementia were evaluated by the end of 2009. RESULTS: Subjects in the CKD cohort were more prevalent with comorbidities than those in the non-CKD cohort (p <0.0001). The dementia incidence was higher in the CKD cohort than in the non-CKD cohort (9.30 vs. 5.55 per 1,000 person-years), with an overall HR of 1.41 (95% confidence interval (CI), 1.32-1.50), controlling for sex, age, comorbidities and medicaitions. The risk was similar in men and women but increased sharply with age to an HR of 133 (95% CI, 68.9-256) for the elderly. However, the age-specific CKD cohort to non-CKD cohort incidence rate ratio decreased with age, with the highest ratio of 16.0 (95% CI, 2.00-128) in the youngest group. Among comorbidities and medications, alcoholism and taking benzodiazepines were also associated with dementia with elevated adjusted HRs of 3.05 (95% CI 2.17-4.28) and 1.23 (95% CI 1.14-1.32), respectively. CONCLUSIONS: Patients with CKD could have an elevated dementia risk. CKD patients with comorbidity deserve attention to prevent dementia.

Anxiety and depression risk in Taiwan women with breast cancer and cervical cancer.

Background: Studies comparing mental disorder risks between women with breast cancer and cervical cancer are lacking. This study compared risks of developing anxiety and depression between women with breast cancer (BC cohort) and women with cervical cancer (CC cohort) using insurance claims data of Taiwan. Methods: From the 2000 to 2016 data, we identified a BC cohort and BC controls (N = 96,862) and a CC cohort and CC controls (N = 26,703), matched by propensity scores. Incident mental disorders and the Cox method estimated the related cancer cohort to control cohort hazard ratios (HRs), and 95% confidence intervals (CIs) were estimated by the end of 2016. Results: Compared to the CC cohort, the BC cohort had slightly higher incident anxiety (15.9 versus 15.5 per 1,000 person-years) and depression (6.92 vs. 6.28 per 1,000 person-years). These mental disorders were higher in respective cancer cohorts than controls. The BC cohort to BC control adjusted HRs of anxiety and depression were 1.29 (95% CI = 1.25-1.33) and 1.78 (95% CI = 1.69-1.87), respectively. The corresponding adjusted HRs for the CC cohort were 1.12 (95% CI = 1.06-1.18) and 1.29 (95% CI = 1.18-1.41). The combined incidence rates of both disorders were 1.4-fold greater in the BC cohort than in BC controls (22.8 vs. 15.8 per 1,000 person-years), and 1.2-fold greater in the CC cohort than in the CC controls (21.7 vs. 18.3 per 1,000 person-years). Conclusion: Women with breast cancer or cervical cancer are at an elevated likelihood of developing anxiety and depression disorders. These incident disorders are slightly higher in those with breast cancer.

Roles of Ambient Temperature and PM2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 µg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 µg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 µg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 µg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

Population-based study on birth outcomes among women with hypertensive disorders of pregnancy and gestational diabetes mellitus.

To evaluate birth outcomes in women with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), we used insurance data of Taiwan to evaluate 11 adverse neonatal outcomes of infants born to women with HDP (N = 7775) and with both HDP and GDM (HDP/GDM) (N = 1946), comparing to women with neither disorder (N = 19,442), matched by age. The impacts of preeclampsia/eclampsia were also evaluated. Results showed that Caesarean section delivery was near 1.7-fold greater in the HDP/GDM and HDP groups than in comparisons. The preterm delivery rates were more than threefold greater in HDP/GDM group and HDP group than in comparisons with adjusted odds ratios (aORs) of 4.84 (95% confidence interval (CI) 4.34-5.40) and 3.92 (95% CI 3.65-4.21), respectively, followed by jaundice (aORs 2.95 (95% CI 2.63-3.33) and 1.90 (95% CI 1.76-2.06)), and small gestation age (SGA) (aORs 6.57 (95% CI 5.56-7.75) and 5.81 (95% CI 5.15-6.55)). Incidence rates of birth trauma, patent ductus arteriosus, atrial septal defect, respiratory distress syndrome, and neonatal hypoglycemia were also higher in the HDP/GDM and HDP groups than in the comparison group. Most adverse outcomes increased further in women with preeclampsia or eclampsia. In conclusion, women with HDP are at elevated risks of adverse neonatal outcomes. Risks of most adverse outcomes increase further for women with both HDP and GDM. Preeclampsia or eclampsia may also contribute to these outcomes to higher risk levels. Every pregnant woman with these conditions deserves specialized prenatal care.

Population-Based Study on Cancer Incidence in Pharmacist: A Cohort Study in Taiwan.

Cancer is increasing in rate globally and is leading cause of death among no communicable chronic diseases (NCDs) after cardiovascular disease (CVD). Most of the research focuses on the risk of occupational injury, job stress, mental illness, substance abuse and workplace safety in physicians and nurses. However, fewer studies have investigated the risk of cancer in pharmacists. We compared the matched general population to investigate the risk of cancer in pharmacists in Taiwan. Data were obtained from the Health and Welfare Data Science Center of the Ministry of Health and Welfare in Taiwan. We established a pharmacist group that included 11,568 pharmacists and selected a 4-fold comparison (n = 46,272) for the non-clinics comparison group, frequency being matched by age, gender and Charlson Comorbidity Index (CCI) score. The pharmacists had a lower but non-significant risk of all cancer (Adjusted hazard ratio [aHR] = 0.96; 95% confidence interval [CI] = 0.85-1.07) compared with the general population. Female pharmacists had a higher risk of cancer than male pharmacists ([aHR] = 1.23; 95% CI = 1.06-1.43). Pharmacists had higher risks of breast cancer in females (aHR = 1.68; 95% CI = 1.35-2.08) and of prostate cancer in males (aHR = 2.18; 95% CI = 1.35-2.08) when compared with the general population. Occupational risk factors could play a role, but they were not evaluated. These epidemiological findings require additional studies to clarify cancer risk mechanisms in pharmacists.

Risk of Glaucoma Associated with Components of Metabolic Disease in Taiwan: A Nationwide Population-Based Study.

PURPOSE: This retrospective cohort study was conducted to determine the glaucoma risk associated with metabolic disease (MetD) using insurance claims data of Taiwan. METHODS: From the database, we identified patients with newly diagnosed hypertension, diabetes and/or hyperlipidemia from the years 2000 to 2002 as the MetD cohort (N = 42,036) and an age-gender-diagnosis-date matched control cohort without MetD with a two-fold sample size than that of the MetD cohort. Both cohorts were followed until the development of glaucoma, death, or withdrawal, until 31 December 2013. The incidence of glaucoma, and the Cox method estimated hazard ratio (HR) of glaucoma were calculated. Results showed that the incidence of glaucoma was two-fold higher in the MetD cohort than in the controls (1.99 versus 0.99 per 1000 person-years), with an adjusted HR of 1.66 (95% CI: 1.50-1.85). The glaucoma incidence was higher in patients with diabetes than those with hypertension and hyperlipidemia (2.38 versus 1.95 and 1.72 per 1000 person-years, respectively). The incidence increased to 5.67 per 1000 person-years in patients with all three comorbidities, with an aHR of 4.95 (95% CI: 2.35-10.40). We also found higher incidence rates of primary open-angle glaucoma and primary angle-closure glaucoma with aHRs of 2.03 and 1.44, respectively. It was concluded that glaucoma risk increased with the number of MetD. Health providers need to monitor patients with MetD to prevent glaucoma.

Childhood Rotavirus Infection Associated with Temperature and Particulate Matter 2.5 µm: A Retrospective Cohort Study.

No study has ever investigated how ambient temperature and PM2.5 mediate rotavirus infection (RvI) in children. We used insurance claims data from Taiwan in 2006-2012 to evaluate the RvI characteristics in children aged ≤ 9. The RvI incidence rates were higher in colder months, reaching the highest in March (117.0/100 days), and then declining to the lowest in July (29.2/100 days). The age-sex-specific average incident cases were all higher in boys than in girls. Stratified analysis by temperature (<20, 20-24, and ≥25 °C) and PM2.5 (<17.5, 17.5-31.4, 31.5-41.9, and ≥42.0 µg/m3) showed that the highest incidence was 16.4/100 days at average temperatures of <20 °C and PM2.5 of 31.5-41.9 µg/m3, with Poisson regression analysis estimating an adjusted relative risk (aRR) of 1.26 (95% confidence interval (CI) = 1.11-1.43), compared to the incidence at the reference condition (<20 °C and PM2.5 < 17.5 µg/m3). As the temperature increased, the incident RvI cases reduced to 4.84 cases/100 days (aRR = 0.40, 95% CI = 0.35-0.45) when it was >25 °C with PM2.5 < 17.5 µg/m3, or to 9.84/100 days (aRR = 0.81, 95% CI = 0.77-0.93) when it was >25 °C with PM2.5 > 42 µg/m3. The seasonal RvI is associated with frequent indoor personal contact among children in the cold months. The association with PM2.5 could be an alternative assessment due to temperature inversion.

Population based retrospective cohort study on risk of retinopathy of prematurity in twins.

BACKGROUND: Twin infants are likely at great risk for ROP, but studies reported conflicting findings and population studies examining the risk of retinopathy of prematurity (ROP) in twins is limited. We aimed to evaluate the ROP risk in the cohort of one of twins, comparing to singletons. MATERIAL AND METHODS: Using insurance claims data of a half of children in Taiwan ages 18 and less, we established a twin cohort (N = 27830) born in 1998-2009 and a randomly selected singleton cohort (N = 111080) frequency matched by sex, birth year, residential area and parental occupation and followed up to 2012 years. RESULTS: The overall incidence rate of ROP was 13.6-fold greater in the twin cohort than in the singleton cohort (35.1 vs. 2.58 per 10,000 person-years; adjusted HR = 13.4, 95% CI = 11.7-15.3; p <0.0001). The ROP incidence was slightly higher in boys than in girls, higher in children in more urbanized areas and born to mothers without works. The incident ROP increased with decreasing birthweight. For children with birthweight <1000 grams, the ROP incidence was 1.2-fold greater in the twin cohort than in the singleton cohort (1243.2 vs. 1016.3 per 10,000 person-years). The use of mechanical ventilation was associated with increased ROP risk for both cohorts, particularly for infants who were under invasive treatment. CONCLUSION: Infants who were born as twins or born with low birthweight were at an elevated risk of developing ROP. Extreme cautious and close monitor are required for new born with low birthweight and have undergone with mechanical ventilation.

Stroke risks in women with dysmenorrhea by age and stroke subtype.

BACKGROUND: Dysmenorrhea and stroke are health problems affecting women worldwide in their day-to-day lives; however, there is limited knowledge of the stroke risk in women with dysmenorrhea, and there have been no studies assessing the specific distribution of stroke subtypes. This case-control study assessed stroke subtypes by age and the role of comorbidities in women with dysmenorrhea. METHODS AND FINDINGS: Data obtained between 1997 and 2013 from Taiwan's health insurance database identified 514 stroke cases and 31,201 non-stroke controls in women with dysmenorrhea aged 15-49 years. Proportional distributions of subtypes and odds ratios (ORs) of stroke associated with comorbidities by age and subtype were measured. We found that the stroke risk in dysmenorrheal patients increased with age, and that hypertension was nine-fold more prevalent in the stroke cases than in the controls and was associated with an adjusted OR of 4.53 (95% confidence interval (CI) = 3.46-5.92) for all stroke cases. Moreover, the proportion of hemorrhagic stroke was greater than that of ischemic stroke in younger dysmenorrheal patients between 15-24 years old (50.5% vs. 11.4%), whereas this was reversed in those aged 30-49 years old (16.1% vs. 21.0%). Overall, 25.3% of the stroke cases consisted of transient cerebral ischemia and 31.3% were other acute but ill-defined cerebrovascular diseases, in which the prevalence increased with age for both types of strokes. Hypertension was the comorbidity with the highest OR associated with each subtype stroke; diabetes, hyperlipidemia, arrhythmia, and thyroid disease were also comorbidities that were significantly associated with ill-defined cerebrovascular diseases. CONCLUSIONS: The stroke type varies by age in dysmenorrheal patients, and hypertension is the most important comorbidity associated with all types of stroke; therefore, more attention for stroke prevention must be paid to women with dysmenorrhea, particularly when combined with comorbidities.

Trend of subsequent epilepsy in children with recurrent febrile seizures: A retrospective matched cohort study.

PURPOSE: Trends of epilepsy in children were correlated with febrile seizure (FS) in a previous retrospective study. In the present study, the authors obtained relevant data from a nationwide cohort database to investigate trends in subsequent epilepsy in children with a history of recurrent FS. METHODS: A total of 10,210 children with FS comprised the cohort. The diagnosis date was used as the index date. A comparison cohort was randomly matched with each case based on age, sex, urbanization level, parents' occupation, and index date. Cox proportional hazard regression was performed to estimate the hazard ratio and confidence interval of FS-associated epilepsy. RESULTS: This retrospective cohort study included 7729 children with FS and a comparison cohort of 30,916 children. The incidence of epilepsy was 11.4-fold higher in the FS cohort than in the comparison cohort (5.67 vs. 0.49 per 1000 person-years, respectively). Compared with the comparison cohort, the epilepsy incidence rate ratio increased in children with admissions for FS, from 8.62 at 1 admission to 26.2 at ≥2 admissions (95% CI 6.80-10.9, and 19.78-34.8, respectively; p for trend < 0.0001). CONCLUSION: FS may increase the risk for subsequent epilepsy in children. Recurrent FS increased the cumulative incidence of epilepsy.

Population study evaluating fracture risk among patients with chronic osteomyelitis.

BACKGROUND: Studies investigating the fracture risk in patients with chronic osteomyelitis (COM) limited to case reports. This study evaluated the association between COM and subsequent fracture risk using population-based data. METHODS: A subset claims data of the Taiwan National Health Insurance was used to identify 7,147 patients with COM newly diagnosed in 1999-2005 without fracture history and 28,588 general population controls, frequency matched by sex, age and diagnosis date. The incident fractures was measured by the end of 2013. RESULTS: The incidence density of fracture was 1.94-fold greater in the COM cohort than in controls (21.5 vs. 11.1 per 1000 person-years), with the adjusted hazard ratio (HR) of 1.81 (95% CI: 1.67-1.95) for COM patients compared to controls after controlling for sex, age, and comorbidities of diabetes, osteoporosis, depression and end-stage renal disease in Cox proportional hazards regression. The fracture risk increased with age and women were at greater risk than men. The fracture incidence increased substantially in those with osteoporosis, 40.2 per 1000 person-years in COM patients. Site specific analysis showed a higher portion of incident fractures for lower limbs, 52.7% in COM cohort and 46.3% in controls. CONCLUSION: Findings in this 15-year follow-up observation support our hypothesis that patients with COM are at an elevated risk of subsequent fracture. COM patients and the elderly deserve adequate consultation and awareness for fracture prevention.

Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus: A Nationwide, Retrospective, Taiwanese-Registry, Cohort Study.

With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD).We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts.In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, α-glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46-0.97; P < 0.05).This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke.

Retrospective cohort evaluation on risk of pneumonia in patients with pulmonary tuberculosis.

Pulmonary tuberculosis (PTb) and pneumonia are diseases that may exist concomitantly. Population study investigating the subsequent pneumonia development in PTb patients is limited. This study compares the risk of pneumonia between cohorts with and without PTb.We used the claims data of the Taiwan National Health Insurance to identify a cohort with PTb (N = 3417) newly diagnosed in 2000-2006 without pneumonia history, and a randomly selected comparison cohort (N = 6834) free of PTb and pneumonia, frequency matched by propensity score. Incidence rates and hazard ratios of pneumonia were calculated by sex, age, and comorbidity starting in the 7th month after the cohorts being established until the end of 2011.We found the incidence of pneumonia to be 1.9-fold higher in the PTb cohort than in the PTb free cohort (51.6 vs 27.0 per 1000 person-years). The PTb cohort had a Cox method estimated adjusted hazard ratio of 2.14 (95% confidence interval = 1.96-2.32). We also found that the risk was greater for men than for women, but lower for young adults aged 20-39 years. Comorbidity interacted with PTb by aggravating the pneumonia risk, particularly for those with asthma. For PTb patients comorbid with asthma, the pneumonia incidence was 2.5-fold higher than for PTb patients free of comorbidities (75.9 vs 29.3 per 1000 person-years).Our results display that PTb patients have an elevated risk of developing pneumonia. Adequate follow-up should be provided to the PTb patients, especially those with comorbidity.

Risk of Subsequent Hypertension and Diabetes in Women With Hypertension During Pregnancy and Gestational Diabetes.

OBJECTIVE: To assess risks of postpartum hypertension and diabetes mellitus (DM) for women with hypertension during pregnancy (HDP) with and without gestational DM (GDM). PATIENTS AND METHODS: From insurance data of 15- to 44-year-old women with pregnancy in 2000-2011, we established an HDP/GDM cohort (n=1270), an HDP/non-GDM cohort (n=5077), and a comparison cohort without either disorder (n=12,594), frequency matched by age and year of pregnancy. Postpartum hypertension and DM were assessed before 2012. RESULTS: The postpartum hypertension incidence increased with age in all cohorts, with overall rates of 13.1, 8.82, and 0.79 per 1000 person-years in the HDP/GDM, HDP/non-GDM, and comparison cohorts, respectively. The adjusted hazard ratios (aHRs) of hypertension were 16.8 (95% CI, 11.8-24.1) for the HDP/GDM cohort and 11.2 (95% CI, 8.19-15.2) for the HDP/non-GDM cohort relative to the comparison cohort. The corresponding incident DM rates were 41.9 and 8.06 vs 2.55 per 1000 person-years in the 3 cohorts, respectively, with aHRs of 16.2 (95% CI, 13.2-19.9) for the HDP/GDM cohort and 3.15 (95% CI, 2.55-3.89) for the HDP/non-GDM cohort relative to the comparison cohort. Incident DM in the HDP/GDM cohort was 44% greater in 15- to 29-year-old women vs 40- to 44-year-old women (49.1 vs 34.2 per 1000 person-years), with aHRs of 39.2 (95% CI, 24.5-62.7) and 5.52 (95% CI, 2.92-10.4), respectively, relative to comparisons of respective age groups. CONCLUSION: Subsequent hypertension and DM risks are greater in women with HDP/GDM than in women with HDP only compared with women without these complications. Younger women with HDP/GDM should be particularly cautious.

Integrative traditional Chinese medicine therapy reduces the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Life-long insulin is the standard treatment for type 1 diabetes mellitus (T1DM). The role of traditional Chinese medicine (TCM) in T1DM is still not clear. The aim of this study is to explore the prescription pattern of TCM and its impact on the risk of diabetic ketoacidosis (DKA) in patients with T1DM. MATERIALS AND METHODS: We retrieved samples from the registry for catastrophic illness patients from the National Health Insurance Research Database (NHIRD). Based on a frequency (1:4) matched case-control design, patients with T1DM in 2000-2011 were designated as cases (TCM users) and controls (non-TCM users). TCM treatment for patients with T1DM was analyzed. The incidence of DKA and the annual costs of emergency visits and hospitalizations were evaluated for all causes. RESULTS: Overall, 416 subjects were TCM users, whereas a total of 1608 matched subjects were classified as non-TCM users. The most common Chinese herbal formula and single herb is Liu-wei-di-huang-wan (Six-ingredient pill of Rehmannia) and Huang-qi (Radix Astragali; Astragalus membranaceus (Fisch.) Bunge, Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao), respectively. Compared with non-TCM users, we found a 33% reduction in DKA incidence for all TCM users (aHR 0.67, 95% CI 0.56-0.81, p <0.000) and a 40% reduction for users receiving TCM treatment for more than 180 days (aHR 0.58, 95% CI 0.41-0.82, p <0.01). There were no significant differences between TCM users and non-users in the frequency and medical costs of emergency visits and hospitalizations. CONCLUSIONS: Integrative TCM use may reduce the risk of DKA in patients with T1DM. Our results suggest that TCM may have a substantial positive impact on the management of TIDM.

Long-Term Use of Antihypertensive Agents and Risk of Breast Cancer: A Population-Based Case-Control Study.

INTRODUCTION: To evaluate the risk of breast cancer associated with long-term use of antihypertensive agents (AHs) in Taiwanese women with hypertension. METHODS: A search of the Taiwan National Health Insurance Research Database identified 330,699 patients with hypertension who were treated with antihypertensive drugs between January 1, 1998 and December 31, 2011. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) between the use of AHs and breast cancer risk, adjusted for other types of antihypertensive drugs, statins and co-morbidities. RESULTS: Among the AHs used to treat the hypertensive women enrolled in our study, our analysis revealed that those treated with one specific particular class of beta-blockers (beta-1 selective beta-blockers) had an increased risk for breast cancer. We also found that the ever-use of calcium channel blockers (CCBs; i.e. for 13 years) was associated with breast cancer in an adjusted model (OR 1.09; 95% CI 1.03-1.16). However, the use of nonselective beta-blockers, selective and nonselective alpha-blockers, angiotensin-converting enzyme inhibitors and angiotensin II antagonists were not associated with breast cancer risk. CONCLUSION: Based on the results of our analysis, long-term use of CCBs or beta-1 selective beta-blockers are likely to be associated with the risk of breast cancer. Further large comprehensive population-based studies to support our findings are required for confirmation of this conclusion.

Incidence of Non-Traumatic Subconjunctival Hemorrhage in a Nationwide Study in Taiwan from 2000 to 2011.

OBJECTIVE: To determine the nationwide incidence of non-traumatic subconjunctival hemorrhage (NTSCH) in Taiwan from 2000-2011 and to analyze the risk factors for NTSCH using a case-control analysis. METHODS: This is a population-based cohort administrative database study. Randomly selected 1,000,000 residents from the Taiwan National Health Insurance Research Database in 2000 and followed for 12 years to determine the population incidence of NTSCH. Individuals with the first diagnosis of subconjunctival hemorrhage were identified by the corresponding International Classification of Diseases code (ICD) 372.72. Traumatic subconjunctival hemorrhages (ICD-9 codes 921, 871, 850-854 and 959.01) were excluded. The association of NTSCH with various demographic factors, comorbidities and use of medications was studied by a population based case-control analysis using data of 2008-2011. RESULTS: A total of 67,720 patients with a first-time diagnosis of NTSCH were identified during the 12 years period. The mean annual incidence was 65 per 10,000 individuals (crude incidence) and 60 per 10,000 individuals (age- and sex-standardized incidence). The incidence rate of NTSCH was higher in women than in men, [men-women ratio: 0.80 (95% confidence interval: 0.78-0.81)]. The age-specific incidence decreased from childhood to the group of teenagers, after which it increased to a maximal value of 136.2 per 10,000 people in the age group of 60-69 years. Case-control analysis showed that comorbidities of hypertension, purpura and thrombocytopenia, and the use of aspirin were significantly associated with the risk of NTSCH. CONCLUSIONS: This study indicates that NTSCH is a common eye disease that occurs once in 167 individuals in a general East Asian population per year. It occurs more often in women than in men and the age-specific incidence peaked in the age group of 60-69 years. Hypertension, purpura and thrombocytopenia, and the use of aspirin are the major risk factors for NTSCH.