The epidemiology, treatments and outcomes of patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive early breast cancer in Taiwan.

Aim: Estimate patient counts, treatment patterns and outcomes of a subset of patients with early breast cancer (EBC) presenting with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive features, who are at high-risk of recurrence, in Taiwan.Materials & methods: Data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry from 1 January 2011 to 31 December 2020 were analyzed.Results: There were 4500 patients with high-risk EBC (10.4% of all patients with EBC) from 2012 to 2018, with an annual average incidence of 643 that increased over time. Five-year progression was 24.8% in patients with high-risk EBC and 8-year survival was low (69.6%).Conclusion: Patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive high-risk EBC clinical features are an increasing high-risk subset of all patients with EBC.

[Box: see text].

Higher cumulative dose of topical corticosteroids is associated with osteoporosis and major osteoporotic fracture: A nationwide case-control study.

BACKGROUND: Connections between long-term use of topical corticosteroids (TCSs) of varying potency and osteoporosis and major osteoporotic fracture (MOF) are unclear. Susceptibility to adverse bone effects of TCSs in different sex, age and ethnic groups is unknown too. OBJECTIVES: To demonstrate the association between cumulative dose of TCSs of varying potency and osteoporosis and MOF in Taiwanese population, with stratified analysis of sex and age. METHODS: We conducted a nationwide case-control study and obtained data from Taiwan National Health Insurance Research Database. Cumulative TCS doses in different exposure periods were calculated, and the potency of TCSs was converted to prednisolone equivalent. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for osteoporosis and MOF associated with TCS use. RESULTS: From 2017 to 2020, 129,682 osteoporosis cases and 34,999 MOF cases were selected and randomly matched with 518,728 and 139,996 controls by sex and age. We found clear dose-response relationships between long-term TCS exposure and osteoporosis and MOF. For example, compared to no TCS use, adjusted ORs of osteoporosis were 1.216 (95% CI 1.189-1.243), 1.260 (95% CI, 1.241-1.280) and 1.341 (95% CI, 1.314-1.369) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Adjusted ORs of MOF were 1.118 (95% CI 1.069-1.170), 1.191 (95% CI, 1.156-1.227) and 1.288 (95% CI, 1.238-1.340) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Stratified analysis showed women had higher ORs of osteoporosis and MOF compared to men. Younger people (<50 years) had highest OR of osteoporosis compared to other age groups. CONCLUSIONS: Higher cumulative TCS dose was associated with increased risk of osteoporosis and MOF. Long-term use of TCSs should be cautious, especially in susceptible populations such as women and young people.

Economic Burden of Atopic Dermatitis in Taiwan.

Atopic dermatitis is a prevalent inflammatory skin disease that manifests clinically as pruritus and eczema. Severe forms of atopic dermatitis can be chronic and relapsing or associated with other dermatological complications and comorbidities, resulting in lifelong impacts across multiple aspects for patients. This study was conducted to calculate the atopic dermatitis-related economic burden in Taiwan. First, the out-of- pocket costs incurred by 200 patients with atopic dermatitis were estimated using a specifically designed questionnaire. Secondly, work impairment was converted into quantifiable costs. The costs reimbursed by the Taiwan National Health Insurance (NHI), which were estimated in our previous work, were included in the final calculation. The atopic dermatitis-related economic burden for patients in Taiwan in 2018 was estimated as (2018 New Taiwan dollars; NT$) 37.90 billion, which is 0.207% of Taiwan's gross domestic product. This substantial economic burden suggests an existing need for more effective and equitable treatment for atopic dermatitis.

Efficacy and immunogenicity of insulin biosimilar compared to their reference products: a systematic review and meta-analysis.

BACKGROUND: To ascertain the efficacy, safety, and immunogenicity from existing evidence via conducting a meta-analysis of randomized controlled trials between biosimilar and originator insulins. METHODS: The PubMed, Cochrane Library, EMBASE, and ClinicalTrails.gov were searched to identify head-to-head randomized controlled trials (RCTs) that directly compare the efficacy and safety of biosimilar insulin and its originator. Efficacy was assessed by change of HbA1C, fasting plasma glucose (laboratory or self-monitoring of blood glucose (SMBG)), and change all mean of 7 points- or 8 points- SMBG. Safety was assessed by change in proportion hypoglycemia and serious hypoglycemia. The occurrence of anti-insulin antibodies (AIAs) was also evaluated. RESULTS: Fourteen RCTs with 6188 patients from different countries were included. Data were pooled using a random-effects model and were expressed as the mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). In efficacy, Insulin biosimilar products showed similar in change of HbA1C at weeks 26 and 52, the MD were 0.03 (95% CI - 0.02 to 0.07, p = 0.28), and 0.05 (95% CI - 0.05 to 0.15, p = 0.36), respectively. The proportion of HbA1C less than 7% at endpoint, the OR were 1.04 (95% CI 0.89 to 1.20, p = 0.64). The change of fasting plasma glucose (laboratory or SMBG) mmol/L in 24-52 weeks and change all mean of 7 points-/8 points- SMBG mmol/L in 24-52 weeks, the MD were 0.02 (95% CI - 0.20 to 0.24, p = 0.87) and - 0.34 (95% CI - 1.35 to 0.67, p = 0.51), respectively. In occurrence of hypoglycemia (≥ 1 events) and severe hypoglycemia, the OR were 0.96 (95% CI 0.85 to 1.09, p = 0.52) and 1.06 (95% CI 0.85 to 1.31, p = 0.62). The AIA was 1.02 (95% CI 0.90 to 1.16, p = 0.76). Analysis stratified by type of diabetes and duration of insulin. There was no significant difference between the biosimilar and their reference group in a different type of diabetes and different duration of insulin. CONCLUSIONS: Insulin biosimilar showed comparable characteristics with the reference drug in terms of efficacy, safety, immunogenicity, through comprehensive and specific conventional meta-analysis.

Healthcare utilization and costs of atopic dermatitis in Taiwan.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease. Only relatively scant studies from Asian countries have attempted to quantify AD-associated healthcare utilization and costs by using population-based databases. This study aims to evaluate the AD-associated annual healthcare utilization and costs in Taiwan. METHODS: A retrospective matched-cohort study was conducted by matching the AD cases with controls at a 1:4 (cases:controls) ratio, with the data for both the cases and controls being sourced from the 2017 National Health Insurance Research Database (NHIRD). The AD patients were stratified by disease severity based on their treatments. Differences in the regression-adjusted frequency of care and costs between the cases and controls were compared using t-tests by the severity level of AD. RESULTS: The incremental frequency of outpatient visits per year increased with AD severity (9.60, 11.28, and 16.23 for mild, moderate, and severe cases, respectively). However, the frequency of inpatient care and emergency room visits per year showed no consistent pattern associated with disease severity. The incremental total costs per year were NT$9,511.64, NT$9,705.20, and NT$15,762.09 for mild, moderate, and severe cases, respectively, and the outpatient and drug costs accounted for 46.65%-54.82% and 17.01%-31.20% of the total costs, respectively. CONCLUSION: AD was found to impose significant healthcare costs, with estimated total cost burdens of NT$3.61 billion in 2017, which is 0.314% of Taiwan's national health expenditure and 0.020% of Taiwan's gross domestic product.

The impact of atopic dermatitis on health-related quality of life in Taiwan.

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a common skin disease. At present, there is little evidence regarding its impact on patients' health-related quality of life (HRQoL) in Taiwan. Therefore, this study investigated the relationship between AD severity and patients' HRQoL in Taiwan. METHODS: Patients with AD were recruited from three hospitals in Taiwan from April 2018 to April 2019. AD severity was measured using the Scoring of AD (SCORAD) scale, and HRQoL was assessed using the Dermatology Life Quality Index (DLQI) and the five-level version of EuroQol five-dimension questionnaire (EQ-5D-5L). RESULTS: A total of 200 patients (mean age: 34.4 years) were recruited, including 103 males and 97 females. They were further classified as 79 mild, 72 moderate, and 58 severe AD patients according to their SCORAD scores. There was a positive correlation between their SCORAD and DLQI scores (Spearman's r = 0.77, p < 0.001). Patients with severe AD had higher scores in all the DLQI questions, particularly the symptoms, feelings, and work/school. In addition, both the EQ-5D visual analogue scale (VAS) scores and utility index values were negatively correlated with the SCORAD scores (Spearman's r = -0.46 and -0.60, respectively, both p < 0.001). Patients with higher AD severity had more problems with mobility, usual activity, pain/discomfort, and anxiety/depression, while demographic characteristics did not significantly affect HRQoL. CONCLUSION: Higher AD severity is associated with poorer HRQoL in Taiwanese AD patients, with AD's effects on symptoms, feelings, and work/school being the most troublesome. Meanwhile, demographic factors did not affect HRQoL significantly.

Relationship between transfusion burden, healthcare resource utilization, and complications in patients with beta-thalassemia in Taiwan: A real-world analysis.

BACKGROUND: This study utilized a population-based claims database to identify patients with beta-thalassemia and evaluate associations between transfusion burden, healthcare resource utilization (HCRU), and complications. STUDY DESIGN AND METHODS: Taiwan's National Health Insurance Research Database was used to identify patients with beta-thalassemia (ICD-10 D56.1) in 2016. Patients with a beta-thalassemia claim in 2016 were indexed into the study at their first claim on or after January 1, 2001 in the dataset through to December 31, 2016 and followed until the end of study. During the follow-up period, red blood cell transfusion (RBCT) units, HCRU, iron chelation therapy use, and beta-thalassemia-related complications incidence were recorded. Patients were grouped into transfusion burden severity cohorts based on average number of RBCT units per 12 weeks during follow-up: 0 RBCT units, >0 to <6 RBCT units (mild), ≥6 to <12 RBCT units (moderate), and ≥12 RBCT units (severe). RESULTS: A total of 2984 patients were included with mean follow-up of 6.95 years. Of these, 1616 (54.2%) patients had no claims for RBCT units, 1112 (37.3%) had claims for >0 to <6 RBCT units, 112 (3.8%) for ≥6 to <12 RBCT units, and 144 (4.8%) for ≥12 RBCT units per 12 weeks. Transfused patients had significantly more all-cause HCRU and iron chelation therapy compared with non-transfused patients during follow-up. Thalassemia-related HCRU and risk of liver, endocrine, cardiac, and renal complications were significantly and positively correlated with increases of RBCT units. DISCUSSION: Clinical and healthcare resource burden of patients with beta-thalassemia is closely related to transfusion burden.

Impact of Atopic Dermatitis on Work and Activity Impairment in Taiwan.

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

Treatment evolution and improved survival in multiple myeloma in Taiwan.

The incidence of multiple myeloma (MM) is increasing worldwide, but the rate of increase is greatest in Asia. Few data describe the epidemiology and treatment of MM in Asia. Building on a cohort study from 2007 to 2012 using the Taiwan National Healthcare Insurance Research database, we extended our analysis to estimate the disease burden and treatment patterns of patients with MM in Taiwan through 2015. A further 1664 patients with newly diagnosed MM from 2013 to 2015 (total 4387 patients from 2007 to 2015) were enrolled and followed up until death or end of the observation period (December 31, 2016), whichever occurred first. The age distribution of the 2013-2015 cohort was similar to that for previous years, but there were fewer men (52.1% versus 58.0%), and more patients had renal impairment at diagnosis (19.7% versus 16.4%). From 2007 to 2015, crude annual incidences per 100,000 population of newly diagnosed MM increased from 1.74 to 2.48 and age-adjusted incidences from 1.41 to 1.65. Crude all-cause mortality rates increased over time. Case fatality decreased from 25.5 to 18.3% and median survival increased from 2.10 to 3.12 years. From 2007 to 2015, the percentage of patients receiving first-line therapy with novel agents increased from 0.4 to 89.4%, autologous stem cell transplantation doubled, and chemotherapy use decreased by 81%. Comprehensive national data covering 9 years of follow-up demonstrate continuing change in the disease burden, treatment, and survival of MM in Taiwan. Despite increased use of new treatments, MM remains largely incurable.

Postarrest Steroid Use May Improve Outcomes of Cardiac Arrest Survivors.

OBJECTIVES: To evaluate the ramifications of steroid use during postarrest care. DESIGN: Retrospective observational population-based study enrolled patients during years 2004-2011 with 1-year follow-up. SETTING: Taiwan National Health Insurance Research Database. PATIENTS: Adult nontraumatic cardiac arrest patients in the emergency department, who survived to admission. INTERVENTIONS: These patients were classified into the steroid and nonsteroid groups based on whether steroid was used or not during hospitalization. A propensity score was used to match patient underlying characteristics, steroid use prior to cardiac arrest, the vasopressors, and shockable rhythm during cardiopulmonary resuscitation, hospital level, and socioeconomic status. MEASUREMENTS AND MAIN RESULTS: There were 5,445 patients in each group after propensity score matching. A total of 4,119 patients (75.65%) in the steroid group died during hospitalization, as compared with 4,403 patients (80.86%) in the nonsteroid group (adjusted hazard ratio, 0.74; 95% CI, 0.70-0.77; p < 0.0001). The mortality rate at 1 year was significantly lower in the steroid group than in the nonsteroid group (83.54% vs 87.77%; adjusted hazard ratio, 0.73; 95% CI, 0.70-0.76; p < 0.0001). Steroid use during hospitalization was associated with survival to discharge, regardless of age, gender, underlying diseases (diabetes mellitus, chronic obstructive pulmonary disease, asthma), shockable rhythm, and steroid use prior to cardiac arrest. CONCLUSIONS: In this retrospective observational study, postarrest steroid use was associated with better survival to hospital discharge and 1-year survival.

Increased Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Patients on Chronic Dialysis: A Cancer Registry-based Study in Taiwan.

This study investigated the predominant skin cancer subtype among organ transplant recipients, patients on chronic dialysis, and patients with chronic kidney disease in Asian subjects. Among 23,644 patients with skin cancer, identified from Taiwan Cancer Registry Database, 53 were organ transplant recipients, 255 were on chronic dialysis, 1,792 had chronic kidney disease, and 21,544 were in the control group. The proportions of squamous cell carcinoma were 52.8%, 47.8%, 40.1%, and 33.5%, respectively. Compared with the control group, organ transplant recipients (1.99-fold) and patients on chronic dialysis (1.25-fold) were at higher risk of developing squamous cell carcinoma than other skin cancers after adjustment for potential confounders. Subgroups or covariates associated with increased squamous cell carcinoma compared with other skin cancer risk included patients with chronic kidney disease aged < 70 years (vs. control group; 1.3-fold), old age (vs. young age; 2.8-fold), male sex (vs. female sex; 1.1-fold), and south Taiwan residency (vs. north Taiwan residency; 1.1-fold). Organ transplant recipients and patients on chronic dialysis had immune dysregulation, resulting in a higher risk of squamous cell carcinomas.

Effect of glucocorticoid use on survival in patients with stage I-III breast cancer.

PURPOSE: Glucocorticoids (GCs) are commonly used in breast cancer patients to ameliorate emesis induced by chemotherapy. Some preclinical studies have suggested that systemic GCs might promote survival of estrogen receptor (ER)-negative breast cancer cells. This study aims to clarify their clinical effect on patient survival. METHODS: A total of 18,596 women with newly diagnosed stage I-III breast cancer in 2002-2006 were identified from the Taiwan Cancer Database and drug treatment was examined from the Taiwan National Health Insurance Claims Database. Of these, 3989 who did not receive adjuvant chemotherapy (non-chemotherapy cohort) and 3237 patients who received six cycles of adjuvant anthracycline-based chemotherapy (anthracycline cohort) were included. The impact of GC use on survival was analyzed separately in these two cohorts using Cox proportional hazards models. RESULTS: In the non-chemotherapy cohort, GC use was associated with aggressive clinicopathological features of breast cancer. High-dose GC was associated with shorter overall survival in univariate analysis but not in multivariate analysis. In the anthracycline cohort, multivariate analysis showed that GC use at each dose level was significantly associated with longer breast cancer-specific survival (HR 0.65, 0.70, and 0.70 for low-dose, median-dose, and high-dose GC, respectively) and overall survival (HR 0.72, 0.76, and 0.73, respectively) when compared with those receiving no GC. The associations were significant in both ER-positive and ER-negative subgroups for breast cancer-specific survival, and in ER-negative subgroup for overall survival. CONCLUSION: Concomitant use of GC improved survival in patients receiving adjuvant anthracycline-based chemotherapy for stage I-III breast cancer.

Assessing the relationship between healthcare market competition and medical care quality under Taiwan's National Health Insurance programme.

Background: There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods: In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results: Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (ß = -0.05, P < 0.01) and less competitive markets (ß = -0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions: Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated.

Migraine and incidence of ischemic stroke: A nationwide population-based study.

Background The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. Method A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Results Both cohorts ( n = 119,017 each) were followed for a mean period of 3.6 ± 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. Compared to the comparison cohort, patients with migraine were at an increased risk of ischemic stroke (aHR: 1.24, 95% CI: 1.12-1.38, p < 0.001). Subgroup analysis by age and sex revealed the highest risk in women aged ≤ 45 years (aHR: 3.44, 95% CI: 2.20-5.39, p < 0.001), especially among those with migraine with aura (aHR: 4.58, 95% CI: 2.45 - 8.56, p < 0.001). A trend for increased stroke risk was observed in men aged ≤ 45 years (aHR: 1.54, 95% CI: 0.96-2.48, p = 0.075). Conclusion Migraine is associated with an increased risk of ischemic stroke, especially in younger (age ≤ 45 years) women with migraine with aura. The trend toward ischemic stroke in younger men merits further exploration.

Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and Calcium Channel Blocker.

BACKGROUND: In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. METHODS: A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004-2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. RESULTS: After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051-2.307; p < 0.05) as compared with the A + B + C group. CONCLUSION: Adding a diuretic may be better than adding a beta-blocker for treating hypertensive patients with prior CVA history who have already received ACEIs/ARBs and CCBs.

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus.

This study investigated the risk of non-melanoma skin cancer (NMSC) in pre-dialysis patients with chronic kidney disease (CKD) and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR) for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold), and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold). A higher SIR for NMSC was found in younger patients with CKD (age < 70 years, 1.34-fold; age 20-39 years, 1.63-fold), stage 5 CKD with anaemia (age < 70 years, 2.09-fold), and uraemic pruritus (age <70 years, 2.22-fold). Pre-dialysis patients with CKD are at higher risk of NMSC, especially those with advanced-stage CKD, and those with uraemic pruritus.

Effect of pulmonary tuberculosis on clinical outcomes of long-term dialysis patients: Pre- and post-DOTS implementation in Taiwan.

BACKGROUND AND OBJECTIVE: The link between tuberculosis (TB) and dialysis is known; however, the impact of TB on the clinical outcomes remains to be elucidated. This study aims to determine the clinical consequences of pulmonary TB among patients under long-term dialysis. METHODS: A retrospective propensity-scores matched (1:4) cohort study was conducted by retrieving patient data for pulmonary TB after long-term dialysis commencement from the Taiwan National Health Insurance Research Database between 1999 and 2013. Patients with TB (n = 1993) or without TB (n = 7972) were compared for 3-year morbidity and mortality. The effect of Directly Observed Treatment, Short-Course (DOTS) implementation was also evaluated. Cox proportional hazards models were used to determine adjusted hazard ratios (HRs). RESULTS: TB patients had a significantly higher risk of mortality than non-TB patients even after multivariate adjustment (HR: 1.48; 95% CI: 1.36-1.60; P < 0.001). DOTS implementation reduced the risk of some morbidities such as pneumonia, hospitalization and intensive care unit stay >7 days, but not inotropic agent usage, ventilator therapy >21 days and mortality in TB patients. In pulmonary TB patients with treatment duration ≥180 days, DOTS implementation also lowered the risk of TB relapse (HR: 0.33; 95% CI: 0.19-0.55; P < 0.001), irrespective of treatment duration (180-224 or ≥225 days). CONCLUSION: Pulmonary TB increases the risk of morbidity and mortality in dialysis patients; DOTS implementation reduces some morbidities and TB relapse. Continuing DOTS implementation should be encouraged to improve clinical outcomes in dialysis patients.

Association between migraine and risk of venous thromboembolism: A nationwide cohort study.

BACKGROUND: -The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. METHODS: -We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. RESULTS: -During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92-1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40-4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.

Increased risk of urinary calculi in patients with migraine: a nationwide cohort study.

OBJECTIVE: Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi. METHODS: We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010. RESULTS: The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52-1.63; p < 0.001, irrespective of the influence of topiramate. The risk was higher in younger and female patients. The magnitude of the risk was proportional to the annual frequency of clinic visits for headache (≥6 vs. <3, aHR = 1.11; 95% CI, 1.04-1.17; p = 0.002), but did not differ between migraine patients with and without aura. CONCLUSIONS: Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk.

Proton pump inhibitor-related headaches: a nationwide population-based case-crossover study in Taiwan.

BACKGROUND: Headaches resulting from proton pump inhibitor (PPI) use could cause discontinuation of PPI in as many as 40% of patients who experience such headaches. Previous studies focusing on acute headache risk from PPI use are rare and limited to clinical trials of a single PPI. OBJECTIVES: To investigate the association between PPI use and headache with a nationwide population-based case-crossover study. METHODS: Records containing the first diagnosis of any headache, including migraine and tension-type headaches, were retrieved from Taiwan National Health Insurance Database (1998-2010). We compared the rates of PPI use for cases and controls during time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios (ORs) and 95% confidence intervals (CIs) from a conditional logistic regression model were used to determine the association between PPI use and headache. RESULTS: Overall, 314,210 patients with an initial diagnosis of any headache during the study period were enrolled. The adjusted ORs for headache risk after PPI exposure were calculated for three time periods (within 7 days=1.41, p=0.002, 95% CI 1.14-1.74; within 14 days=1.36, p<0.001, 95% CI 1.16-1.59; within 28 days=1.20, p=0.002, 95% CI 1.07-1.35). Subgroup analyses showed female patients had an increased risk of headache. Among PPIs, lansoprazole and esomeprazole had the highest risks of headache incidence, which were similar to that of nitrates. CONCLUSION: PPI usage is associated with an increased risk for acute headache. Female patients and use of lansoprazole or esomeprazole present the greatest risks of headache.