Longitudinal Trajectory of Opioid Prescribing and its Associated Serious Adverse Events: A Population-Wide Cohort Study in Taiwan.

Chronic opioid prescribing (COP) for noncancer pain is highly restricted in Taiwan, but tramadol is not listed in the regulation on chronic prescribing. This study investigated the trajectories of COP in noncancer pain when considering tramadol in Taiwan and identified the risk of serious adverse events. This population-wide longitudinal cohort study used the Taiwan National Health Insurance claims records from 2001 to 2016. Adults prescribed opioids (including tramadol) and without cancer were selected. Patients who received COP (opioid supply days for 28 days or continuous opioid supply for 14 days) in the first patient quarter were included, and serious adverse events were identified. Group-based trajectory models were applied to identify patients with a similar trajectory of quarterly COP. The Cox proportional hazard model was applied to assess the association between adverse events and patients' trajectories. Of the 2,360,358 noncancer opioid users, 476,934 (20.2%) received COP in the first quarter. Four groups of COP trajectory were identified, and 59,310 (12.8%) patients received COP quarterly over 2 years. Patients categorized into the trajectory of long-term COP had a significantly higher crude incidence rate of cardiovascular death, seizure, and hypoglycemia. Still, there is no newly developed opioid use disorder. There was a substantial underestimate in COP in Taiwan when tramadol was not considered. Notably, 10% of them could receive COP for over 2 years. The result raises concern about unmet pain management needs and the limited accessibility of alternative treatments for noncancer pain.

Sex-specific incidence of hepatitis B virus flares among Bcr-Abl tyrosine kinase inhibitor users in Taiwan.

BACKGROUND: The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS: Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS: Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION: Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.

Validation of diagnosis codes in healthcare databases in Taiwan, a literature review.

PURPOSE: To compile validation findings of diagnosis codes and related algorithms for health outcomes of interest from National Health Insurance (NHI) or electronic medical records in Taiwan. METHODS: We carried out a literature review of English articles in PubMed® and Embase from 2000 through July 2022 with appropriate search terms. Potentially relevant articles were identified through review of article titles and abstracts, full text search of methodology terms "validation", "positive predictive value", and "algorithm" in Subjects & Methods (or Methods) and Results sections of articles, followed by full text review of potentially eligible articles. RESULTS: We identified 50 published reports with validation findings of diagnosis codes and related algorithms for a wide range of health outcomes of interest in Taiwan, including cardiovascular diseases, stroke, renal impairment, malignancy, diabetes, mental health diseases, respiratory diseases, viral (B and C) hepatitis, and tuberculosis. Most of the reported PPVs were in the 80% ~ 99% range. Assessment of algorithms based on ICD-10 systems were reported in 8 articles, all published in 2020 or later. CONCLUSIONS: Investigators have published validation reports that may serve as empirical evidence to evaluate the utility of secondary health data environment in Taiwan for research and regulatory purpose.

Incidence, Prevalence, and Mortality of People with Psoriasis and Psoriatic Arthritis in Taiwan: A Nationwide Cohort Study.

There is a recognized need to better understand changes in the epidemiology of psoriasis and psoriatic arthritis (PsA) over time in Asia. Using the Taiwan National Health Insurance claim records this population-based study examined changes in the prevalence, incidence, and mortality rates in patients with psoriasis or psoriatic arthritis in Taiwan over 12 years. Patients with ≥1 diagnosis code for psoriasis or psoriatic arthritis, recorded either by dermatologists or rheumatologists, were identified. Annual age- and sex-standardized prevalence and incidence rates were calculated using the Taiwan general population as reference. To investigate mortality, each patient in the incident cohort was matched to 10 comparators from the general population by sex and age (at diagnosis). The risk of mortality between study cohorts and comparators was analysed by Cox proportional hazard regression. The prevalence of psoriasis (0.18-0.86%) and psoriatic arthritis (0.01-0.08%) increased steadily between 2006 and 2017. The incidence rates, however, remained stable (psoriasis: 62-65 per 100,000 person-years; psoriatic arthritis: 6-5 per 100,000 person-years). The risk of all-cause mortality for patients with psoriasis (hazard ratio 1.16; 95% confidence interval: 1.13-1.19) was higher than the general population, despite a decreasing trend over time in the all-cause mortality rates for both groups. The steady increase in the prevalence of psoriasis despite stable incidence rates suggests that improvements in life expectancy may be the key determinant of this increase.

Soft tissue sarcoma incidences and clinical characteristics are significantly different in France and Taiwan.

BACKGROUND: The incidence of different soft tissue sarcoma (STS) histotypes among ethnic and geographic populations has not been comprehensively investigated. METHODS: Data from 2013 to 2016 were obtained from national cancer registry databases in France and Taiwan. Liposarcoma (LPS), leiomyosarcoma (LMS), angiosarcoma (AS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumor (MPNST) were selected as index STSs to estimate the age-standardized incidence rates (ASRs) and other clinical features between patients. RESULTS: In total, 9398 patients (7148 from France and 2250 from Taiwan) were included. The ASRs of AS (5.4 vs. 2.8) and MPNST (2.0 vs. 1.0) were significantly higher in Taiwan; France had significantly higher ASRs for LPS (12.0 vs. 10.0), LMS (9.7 vs. 7.6), and SS (1.7 vs. 1.2). Patients in Taiwan with LMS or LPS were younger than their French counterparts. With regard to the distribution according to primary anatomic site, French patients had higher odds for extremity and truncal LMS (odds ratio [OR], 2.84; p < .001), AS (OR, 2.67; p < .001), MPNST (OR, 1.55; p = .027), and LPS (OR, 1.38; p < .001) and for breast AS (OR, 10.58; p < .001). Taiwanese patients had higher odds for liver AS (OR, 10.72; p < .001) and uterine LMS (OR, 3.21; p < .001). SS age and distribution according to primary anatomic site did not differ significantly between the French and Taiwanese populations. CONCLUSIONS: Significant differences in the incidence and clinical characteristics of index STS suggested that geographic (environmental) and ethnicity factors likely play a vital role in the pathogenesis of STS.

Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan.

Importance: The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. Objective: To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Design, Setting, and Participants: This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. Exposure: Use of Bcr-AbL TKIs. Main Outcomes and Measures: Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Results: Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). Conclusions and Relevance: These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.

Increasing tramadol utilisation under strict regulatory control of opioid prescribing - A cross-sectional study in Taiwan from 2002 through 2016.

BACKGROUND/PURPOSE: Prescribing of opioids to patients with non-cancer pain is strictly regulated in Taiwan, but tramadol is not included in the regulation on chronic opioid prescribing. This study aims to identify the utilization trend of prescribing tramadol and other opioid analgesics and investigate the influence of government regulation on opioid prescribing in Taiwan. METHODS: This cross-sectional study used the Taiwan National Health Insurance claims database and the cancer registry from 2001 through 2016. The annual number of adult opioid users, opioid utilization (Defined Daily Doses [DDDs]/1000 registrants) and the number of supply days were enumerated for each calendar year and stratified by cancer or non-cancer patients. Descriptive statistics were used to report the trends in utilization for each calendar year. RESULTS: The regulation strictly limited persistent use of opioids for patients with non-cancer pain, of which only a small proportion of fentanyl (20%) and morphine (<2%) users were prescribed with an annual number of supply days greater than 28 days. The annual utilization of morphine (6.4-53.5 vs. 1.1 to 9.6 DDD/1000 registrants) and fentanyl (8.3-37.0 vs. 0.16 to 1.8 DDD/1000 registrants) to patients with cancer was consistently higher than patients without cancer. In contrast to morphine and fentanyl, the utilization of tramadol prescribed to patients without cancer increased 92.2-fold (3.7-341.2 DDD/1000 registrants) from 2002 to 2016. CONCLUSION: The regulation in Taiwan limited the prescribing of selective opioids for patients with non-cancer pain and the substitution of tramadol for other opioids may have safety implications.

Association Between Low-Dose Aspirin Use and Colorectal Cancer Incidence in Taiwan.

Importance: Population-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC). Objective: To evaluate the association between duration and recency of low-dose aspirin use and CRC risk. Design, Setting, and Participants: This nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin. Data were collected from Taiwan National Health Insurance and Taiwan Cancer Registry from 2000 through 2015. CRC cases were age- and sex-matched in a 1:4 ratio with individuals in a control group, identified from a cohort of individuals who used and did not use aspirin through risk-set sampling. Data analysis was conducted from June 2018 to July 2019. Exposures: Low-dose aspirin use was defined as receiving less than 150 mg per day, whereas 100 mg/d was most commonly used. Based on duration and recency of low-dose aspirin use between cohort entry (initiation date of low-dose aspirin for aspirin use group or randomly assigned date for those who did not use aspirin) and index date (CRC diagnosis date for individuals in the case group and the diagnosis date for the 4 corresponding matched individuals in the control group), the 3 following mutually exclusive exposure groups served as the basis for analysis: (1) long-term current low-dose aspirin use, (2) episodic low-dose aspirin use, and (3) no low-dose aspirin use (the reference group). Main Outcomes and Measures: CRC risk among the 3 exposure groups. Results: Among 4 710 504 individuals (2 747 830 [51.7%] men; median [interquartile range] age at cohort entry in initiator group, 61 [52-71] years; median [interquartile range] age at cohort entry in nonuse group, 59 [51-68] years), 79 095 CRC cases (1.7% of study cohort) were identified. Compared with no low-dose aspirin use, the adjusted odds ratio (OR) for long-term current low-dose aspirin use and CRC risk was 0.89 (95% CI, 0.85-0.93); for episodic use, 0.88 (95% CI, 0.86-0.89). Adjusted ORs of 0.69 (95% CI, 0.63-0.76) and 0.64 (95% CI, 0.61-0.67) were observed for long-term current use and episodic low-dose aspirin use within the subcohort of individuals who initiated low-dose aspirin between age 40 and 59 years. Conclusions and Relevance: In this study, low-dose aspirin use was associated with 11% lower CRC risk in an East Asian population, and this association was larger when low-dose aspirin use started before age 60 years.

Intensive Care Unit Admission and Survival in Stage IV Cancer Patients with Septic Shock: A Population-Based Cohort Study.

Background: The impact of intensive care unit (ICU) admission during life-threatening critical illness on survival of patients with advanced cancer remains unknown. Methods: We identified incident stage IV cancer patients from Taiwan Cancer Registry during 2009-2013 and ascertained the first episode of septic shock after cancer diagnosis. Patient was classified as ICU admission and no ICU admission during the index hospitalization. Primary outcome of interest was overall survival. Propensity score (PS) and proportional hazards regression were used to control potential confounders. Results: A total of 11,825 stage IV cancer patients with septic shock were identified. Among them, 6,089 (51.5%) patients were admitted to ICU during the index hospitalization and 3,626 (30.7%) patients survived the index hospitalization. A 1:1 propensity score (PS)-matched cohort of 7,186 patients were created for patients with/without ICU admission among the total study population. Both the PS-stratified analysis among the overall population (pooled hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.74-0.81) and analysis among the PS-matched population (HR: 0.76, 95% CI: 0.72-0.79) showed association between ICU admission and better overall survival. ICU admission was also associated with a lower risk of in-hospital mortality in both PS-stratified analysis (pooled odds ratio [OR]: 0.69, 95% CI: 0.63-0.75) and PS-matched analysis (OR: 0.61, 95% CI: 0.55-0.68). In PS-stratified analysis for long-term survival after discharge among hospital survivors, ICU admission was associated with improved long-term survival after discharge (pooled HR: 0.73, 95% CI: 0.68-0.80). Also ICU admission was associated with better long-term survival after discharge (HR: 0.77, 95% CI: 0.70-0.85) in PS-matched analysis. Conclusions: Though ICU admission with aggressive treatment may be associated with improved survival, the majority (70%) of stage IV cancer patients with septic shock were unable to survive until hospital discharge.

Commensurate incidence and outcomes of liver enzyme elevation between anti-tumor necrosis factor users with or without prior hepatitis B virus infections.

BACKGROUND AND OBJECTIVE: Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus. METHODS: We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg-/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort. RESULTS: Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg-/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3-8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg-/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users. CONCLUSIONS: In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg-/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg-/HBcAb+ patients is probably safe.

Burden of asthma and COPD overlap (ACO) in Taiwan: a nationwide population-based study.

BACKGROUND: Patients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO). ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone. Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only. This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan. METHODS: This was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009-2011. Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims. Eligible patients were ≥40 years of age with 12 months' continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim). RESULTS: Patients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293). Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting ß2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting ß2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index. Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]). CONCLUSIONS: Patients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.

Population-Based Cohort Study Reveals Distinct Associations Between Female Lung Cancer and Breast Cancer in Taiwan.

PURPOSE: Associations between Asian lung cancer (LC) and breast cancer (BC) are unknown. This study evaluates associations between LC and BC in the Taiwan population. METHODS: This study was based on the Taiwan National Health Insurance data and Taiwan Cancer Registry. The cohorts included women with newly diagnosed LC or BC between 2000 and 2011 and an age- and sex-stratified random sample as a noncancer comparison cohort during the same period. Cox proportional hazards regression analysis was used to determine the risks. The National Taiwan University Hospital (NTUH) cohort, which comprised patients with confirmed pathology diagnoses of double BC/LC, was reviewed. RESULTS: In 32,824 women with LC, there were increased risks for synchronous BC in patients younger than age 50 years (hazard ratio, 5.80; 95% CI, 1.83 to 18.73), age 50 to 59 years (HR, 2.37; 95% CI, 1.02 to 5.54), and age 60 to 69 years (HR, 4.42; 95% CI, 1.91 to 10.2). In the 88,446 women with BC, there were increased risks for synchronous LC in patients age 40 to 59 years (HR, 5.86; 95% CI, 3.05 to 11.3) and older than 60 years (HR, 1.98; 95% CI, 1.04 to 3.77). In the 128-patient NTUH double LC/BC cohort, 77 (60%) had both cancers diagnosed within 5 years of each other. CONCLUSION: LC is associated with an increased risk for synchronous BC in Taiwan and vice versa. Radiotherapy might not be a major risk factor for LC in BC survivors. Etiology for double LC/BC deserves additional exploration and cross-racial genomic studies.

Assessing risk of liver enzyme elevation in patients with immune-mediated diseases and different hepatitis B virus serostatus receiving anti-TNF agents: a nested case-control study.

BACKGROUND: Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. METHODS: At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n = 368) of cases with serum alanine aminotransferase (ALT) > 40 international units/L ≤ 12 months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. RESULTS: Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg+) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16-31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg-/HBcAb+) patients (adjusted odds ratio 1.00, 95% CI 0.33-3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52-56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32-45.75). CONCLUSIONS: HBsAg+ patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg-/HBcAb+ serostatus had a risk similar to that of uninfected patients.

Pregnancy-associated breast cancer in Taiwanese women: potential treatment delay and impact on survival.

This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.

Impacts of drug reimbursement reductions on utilization and expenditures of oral antidiabetic medications in Taiwan: an interrupted time series study.

OBJECTIVES: To control increasing pharmaceutical expenditures, Taiwan's National Health Insurance has implemented a series of drug reimbursement price reductions since 2000. This study examined changes in use and expenditures of oral antidiabetic medications following the price regulation in November 2006. METHODS: We obtained claims data between January 2006 and August 2007 from Taiwan's National Health Insurance Research Database. We categorized oral antidiabetic products as affected by the reimbursement reduction ("targeted") or not ("non-targeted"), by level of relative price reduction, and by manufacturer type (international vs. local manufacturers). We used an interrupted time series design and segmented regression models to estimate changes in monthly per capita prescribing rate, volume, and insurance reimbursement expenditures following the policy. RESULTS: The majority (129/178; 72.5%) of oral antidiabetic products were targeted by this round of price reductions. There was a relative reduction of 9.5% [95%CI: -12.68, -6.32] in total expenditures at ten months post-policy compared to expected rates. For targeted products, there were 2.04% [95%CI: -4.15, 0.07] and 13.26% [95%CI: -16.64, -9.87] relative reductions in prescribing rate and expenditures, respectively, at ten months post-policy. Non-targeted products increased significantly (22% [95%CI: 10.49, 33.51] and 22.85% [95%CI: 11.69, 34.01] relative increases in prescribing rate and expenditures respectively). Larger reimbursement cuts led to greater reductions in prescribing rate, volume, and insurance reimbursement expenditures of targeted products. Prescribing rates of both targeted and non-targeted products by international manufacturers declined after the policy while rates of prescribing non-targeted products by local manufacturers increased. CONCLUSIONS: While total government expenditures for oral antidiabetic medications were contained by the policy, our results indicate that prescribing shifted at the margin from targeted to non-targeted products and from international to local products. Further research is warranted to understand how changes in medication use due to price regulation policies affect medication adherence and patient health outcomes.

Development and validation of a pharmacy-based comorbidity measure in a population-based automated health care database.

STUDY OBJECTIVE: To develop the Pharmacy-Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis-based Deyo version of the Charlson Index in predicting subsequent-year hospitalization in adults. DESIGN: Retrospective cohort analysis. DATA SOURCE: Longitudinal health insurance database derived from the national health insurance system in Taiwan. PATIENTS: Two adult populations were identified: 697,823 individuals who were at least 18 years of age on January 1, 2005 (dataset 2005), and 714,072 who were at least 18 years of age on January 1, 2006 (dataset 2006). MEASUREMENTS AND MAIN RESULTS: Based on the Chronic Disease Score framework and the Anatomical Therapeutic Chemical classification system, we developed the PBDI, a comorbidity measure that is a function of 37 drug categories that correspond to major diseases in Taiwan. The relationship between individuals' PBDI score and subsequent-year hospitalization was evaluated by use of logistic regression models. Covariates in the models included age group, sex, PBDI score, and Deyo score. Using the two overlapping adult populations, we calculated both the PBDI score and the Deyo score for each individual in each year. Using subsequent-year hospitalization as the outcome and each comorbidity measure as the predictor, we demonstrated that the c statistic of the PBDI versus the Deyo version of the Charlson Index was 0.72 versus 0.69 for both the 2005 and 2006 populations. The Akaike information criterion, Bayesian information criterion, model calibration, and reclassification measures also confirmed the utility of the PBDI. CONCLUSION: The PBDI demonstrated acceptable predictive performance for subsequent-year hospitalization. It can be used as a general comorbidity measure to describe the health status of populations based on data derived from population-based automated health care databases.

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance.

OBJECTIVES: As part of a regulatory postmarketing commitment, we assessed the risk of claims for thyroid and pancreatic cancer among users of exenatide using an active drug safety surveillance system. METHODS: This active surveillance assessment used cohort methodology and commercial health insurance claims data to identify initiators of exenatide and propensity score-matched initiators of metformin or glyburide between June 2005 and September 2009, with up to 1 year of follow up through December 2009. The primary analysis estimated absolute and relative risk (RR) of inpatient or outpatient claims with diagnosis codes for thyroid neoplasm (benign or malignant) or pancreatic malignancies after exclusion of patients with a history of the same diagnosis at baseline. RESULTS: Among the matched comparison cohorts (N ≈ 32,800 each), there were 37 claims-suggested thyroid malignancies among exenatide initiators and 26 among metformin or glyburide initiators [RR 1.4; 95% confidence interval (CI) 0.8-2.4]. This association was attenuated when limited to inpatient thyroid cancer claims (RR 0.9; CI 0.3-2.6). Exenatide use was not associated with an increased risk of benign thyroid neoplasm (RR 0.7; CI 0.3-1.7), or pancreatic cancer (RR 0.8; CI 0.5-1.6). CONCLUSIONS: Use of exenatide was associated with a modestly higher incidence of inpatient and outpatient claims, but not inpatient claims for thyroid malignancies. Exenatide was not associated with higher risk of benign thyroid neoplasm or pancreatic cancer. Misclassification of outcomes and exposure, and residual confounding remain limitations of this analysis to be considered when interpreting the results. We have initiated a formal epidemiologic investigation to explore these relationships.

Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus.

UNLABELLED: The objective of this nationwide case-control study was to evaluate the risk of specific malignancy in diabetic patients who received thiazolidinediones (TZDs). A total of 606,583 type 2 diabetic patients, age 30 years and above, without a history of cancer were identified from the Taiwan National Health Insurance claims database during the period between January 1 2000 and December 31 2000. As of December 31 2007, patients with incident cancer of liver, colorectal, lung, and urinary bladder were included as cases and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between TZDs and cancer incidence. A total of 10,741 liver cancer cases, 7,200 colorectal cancer cases, and 70,559 diabetic controls were included. A significantly lower risk of liver cancer incidence was found for any use of rosiglitazone (OR: 0.73, 95% CI: 0.65-0.81) or pioglitazone (OR: 0.83, 95% CI: 0.72-0.95), respectively. The protective effects were stronger for higher cumulative dosage and longer duration. For colorectal cancer, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk (OR: 0.86; 95% CI: 0.76-0.96). TZDs were not associated with lung and bladder cancer incidence, although a potential increased risk for bladder cancer with pioglitazone use ≥3 years could not be excluded (OR: 1.56; 95% CI: 0.51-4.74). CONCLUSION: The use of pioglitazone and rosiglitazone is associated with a decreased liver cancer incidence in diabetic patients. The effects on occurrence of specific cancer types may be different for pioglitazone and rosiglitazone.

Evidence-based consensus development and reduction of rate of endoscopic thoracic sympathectomy: a national study.

BACKGROUND: Endoscopic thoracic sympathectomy (ETS) was overused for treating patients with hyperhidrosis in Taiwan. OBJECTIVES: To determine whether use of evidence and a consensus-building exercise can reduce rates of surgery. METHODS: We invited all surgeons in Taiwan who performed five or more ETSs per year for treating patients with hyperhidrosis to join this study. A structured questionnaire was mailed to surgeons asking about their management decisions based on clinical scenarios. Then we provided surgeons with evidence synopses and used the Delphi method to reach consensus. We analyzed healthcare utilization data during 2000 to 2005 and calculated total numbers of ETSs performed per 12 months to examine the effect on surgeons' behavior. RESULTS: Of 155 surgeons invited, 61 (40%) completed this study. They agreed that observation or topical therapy was appropriate for patients with mild palmar hyperhidrosis, whereas ETS was appropriate for children, adolescents, and young and middle-aged adults who had severe symptoms. Surgeons became more willing to recommend botulinum toxin injection after we provided evidence synopses. We found a 52% reduction in mean total ETSs per 12 months in surgeons receiving evidence synopses. A higher percentage of reduction occurred in patients younger than 12 and aged 60 and older. CONCLUSION: Evidence-based consensus development is helpful in decreasing overuse of ETS in treating patients with hyperhidrosis in Taiwan.

Statin use and risk of colorectal cancer in a cohort of middle-aged men in the US: a prospective cohort study.

BACKGROUND: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer. OBJECTIVE: To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization. METHODS: We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45-69 years who enrolled in the California Men's Health Study in 2002-3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders. RESULTS: During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of >or=5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers. CONCLUSION: These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for >or=5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.