Risks of maternal cardiopulmonary events associated with ritodrine for tocolysis: A national database linkage study in 1 831 564 pregnant women.

OBJECTIVE: Real-world data on cardiopulmonary events among pregnant women receiving ß-agonist therapy are scarce. In the present study, we aimed to examine the absolute and relative risks of maternal cardiopulmonary events associated with the use of ß-agonist ritodrine during pregnancy. METHODS: By linking Taiwan's National Birth Certificate Application Database with National Health Insurance data, 1 831 564 pregnancies at ≥20 weeks' gestation were identified. Age-standardized incidence rates of cardiopulmonary events among pregnant women exposed to ritodrine were estimated. Nested case-control analyses were conducted to evaluate the relative risk of pulmonary edema, heart failure, and arrhythmia associated with prior ritodrine use. Cases and controls were matched using risk set sampling, and adjusted odds ratios were estimated using conditional logistic regression models. RESULTS: A total of 189 cases of pulmonary edema, 126 cases of heart failure, and 162 cases of arrhythmia were identified (corresponding age-standardized incidence rates: 20.90, 8.35, and 16.63 per 100 000 among pregnant women only exposed to oral ritodrine; 91.28, 36.01, and 14.61 per 100 000 among those ever exposed to intravenous ritodrine). Exposure to oral ritodrine was associated with a lower increased risk of pulmonary edema (aOR 1.76; 95% CI: 1.12-2.76) and arrhythmia (2.21; 1.47-3.32) whereas exposure to ritodrine injection was associated with a significantly higher risk of pulmonary edema (10.56; 6.39-17.45), arrhythmia (4.15; 1.99-8.64), and heart failure (5.58; 2.27-13.74). CONCLUSIONS: Pregnant women receiving intravenous ritodrine therapy had higher cardiopulmonary risks and should be intensively monitored. While the relative risk associated with oral ritodrine is not pronounced, it should be used judiciously among pregnant women as well.

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

PURPOSE: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. METHODS: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. RESULTS: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. CONCLUSIONS: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.

Hyperkalemia Recurrence Following Medical Nutrition Therapy in Patients with Stage 3-4 Chronic Kidney Disease: The REVOLUTIONIZE I Real-World Study.

INTRODUCTION: The REVOLUTIONIZE I study aimed to characterize the relationships between medical nutrition therapy (MNT) and hyperkalemia recurrence in patients with stage 3-4 chronic kidney disease (CKD) and hyperkalemia who received MNT in real-world clinical practice. METHODS: This observational cohort study used de-identified electronic health record data from patients aged ≥ 18 years with stage 3-4 CKD who received MNT between January 2019 and October 2022 and had hyperkalemia (serum potassium > 5.0 mmol/L) within 30 days before MNT. Patients were followed for 6 months or until the first censoring event (death, prescription of outpatient potassium binder, or study end). The primary outcome was the percentage of patients with ≥ 1 hyperkalemia recurrence during follow-up. Secondary outcomes included the number of hyperkalemia recurrences per patient, time to each recurrence, and hyperkalemia-related healthcare resource utilization. Exploratory outcomes included all-cause healthcare resource utilization and mortality. RESULTS: The final cohort comprised 2048 patients; 1503 (73.4%) patients remained uncensored after 6 months. During the 6-month follow-up period, 56.0% of patients had ≥ 1 hyperkalemia recurrence and 37.4% had ≥ 1 recurrence within the first month. Patients with ≥ 1 hyperkalemia recurrence during follow-up had a mean ± standard deviation (SD) of 2.6 ± 2.2 recurrences. The mean ± SD time to first hyperkalemia recurrence was 45 ± 46 days; the time between recurrences decreased with subsequent episodes. Hyperkalemia-related hospitalizations and emergency department visits were recorded for 13.7% and 1.5% of patients, respectively. Sensitivity analyses showed that results were consistent across patient subgroups, including those with comorbid heart failure and patients receiving renin-angiotensin-aldosterone system inhibitor therapy at baseline. CONCLUSION: Most patients with stage 3-4 CKD had hyperkalemia recurrence, and MNT alone was inadequate to prevent recurrence. These patients may require additional long-term treatment, such as novel potassium binders, to maintain normokalemia and prevent hyperkalemia recurrence following MNT. Infographic available for this article. INFOGRAPHIC.

Patients with chronic kidney disease (CKD) typically receive dietary counseling from a registered dietician, referred to as medical nutrition therapy, to help reduce their risk of complications of CKD while addressing their specific nutritional needs. Patients with CKD have an increased risk of elevated blood potassium levels (hyperkalemia), which has potentially life-threatening consequences. Although medical nutrition therapy may help patients with hyperkalemia to manage their dietary potassium intake, its effects in preventing recurrence are unclear. Our aim was to determine whether medical nutrition therapy can help prevent hyperkalemia recurrence after an initial event in patients with non-dialysis-dependent (stage 3­4) CKD in real-world clinical practice. We used data from de-identified electronic health records to study hyperkalemia recurrence over 6 months in patients with stage 3­4 CKD who received medical nutrition therapy within 30 days after experiencing hyperkalemia. Over half of the patients (56.0%) had at least one hyperkalemia recurrence within an average of 45 days during the 6 months after medical nutrition therapy; these patients had an average of 2.6 distinct recurrences in 6 months. In patients with two or more hyperkalemia recurrences, the time between these became shorter than 30 days. Our real-world study results show that hyperkalemia is a chronic, recurring condition in patients with stage 3­4 CKD, and that medical nutrition therapy is not enough to prevent its recurrence. This suggests that these patients may need additional long-term treatment for hyperkalemia, such as novel potassium binder therapy, to prevent hyperkalemia recurrence.

Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database.

BACKGROUND: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. OBJECTIVES: We examined the incidence of serious infection and infection mortality in patients with psoriasis. METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). RESULTS: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. CONCLUSION: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.

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.

Association between maternal benzodiazepine or Z-hypnotic use in early pregnancy and the risk of stillbirth, preterm birth, and small for gestational age: a nationwide, population-based cohort study in Taiwan.

BACKGROUND: Benzodiazepines and Z-hypnotics are commonly prescribed for anxiety and insomnia during pregnancy, but the evidence regarding potential adverse neonatal outcomes is insufficient because of poor control for confounding factors in previous studies. We therefore aimed to evaluate the association between the use of benzodiazepines or Z-hypnotics during early pregnancy and adverse neonatal outcomes (stillbirth, preterm birth, and small for gestational age). METHODS: We did a nationwide, population-based cohort study in Taiwan using three data sources: Taiwan's National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database. The study cohort included all singleton pregnancies of females aged 15-50 years who gave birth between Jan 1, 2004, and Dec 31, 2018. Pregnancies without valid information were excluded. Benzodiazepine and Z-hypnotic use was defined as at least one benzodiazepine or Z-hypnotic prescription during early pregnancy (the first 20 weeks of pregnancy). The primary outcomes were stillbirth (fetal death at or after 20 weeks' gestation), preterm birth (<37 weeks' gestation), and small for gestational age (birthweight below the 10th percentile for gestational age by sex). Logistic regression models with propensity score fine stratification weighting were used to control for potential confounders and examine the association between benzodiazepines or Z-hypnotics use during early pregnancy and the risk of adverse neonatal outcomes. Odds ratios (ORs) and 95% CIs were reported. We used confounding by indication control analyses, a sibling control study, and a paternal negative control design to account for unmeasured confounders. The risk associated with exposure during late pregnancy was also assessed. FINDINGS: Between Oct 7, 2021, and June 10, 2022, we analysed the study data. The cohort included 2 882 292 singleton pregnancies; of which, 75 655 (2·6%) of the mothers were dispensed one or more benzodiazepines or Z-hypnotics during early pregnancy. Women exposed during pregnancy were older (mean age at delivery was 31·0 years [SD 5·3] for exposed women vs 30·6 years [4·9] for unexposed women), had a higher prevalence of psychiatric disorders, and were more likely to have unhealthy lifestyle behaviours than unexposed women. Information about ethnicity was not available. Early pregnancy exposure was associated with adverse neonatal outcomes compared with non-exposure. The propensity score-weighted OR was 1·19 (95% CI 1·10-1·28) for stillbirth, 1·19 (1·16-1·23) for preterm birth, and 1·16 (1·13-1·19) for small for gestational age. After controlling for confounding by indication, there was no significant association between drug exposure and stillbirth risk; however, this attenuation was not observed for preterm birth and small for gestational age. In models with sibling controls that accounted for familial confounding and genetic factors, early exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of stillbirth and preterm birth, but it remained significantly associated with small for gestational age. The paternal negative control analyses with point estimates close to the null indicated no strong evidence of unmeasured confounding shared by the mother and the father. Substantially increased risks of stillbirth and preterm birth were observed for late pregnancy exposure. INTERPRETATION: Benzodiazepine or Z-hypnotic use in early pregnancy is not associated with a substantial increase in the risk of stillbirth and preterm birth after accounting for unmeasured confounding factors. Clinicians should be aware of the increased risk of small for gestational age and caution should be taken when prescribing these medications during late pregnancy. FUNDING: National Science and Technology Council, Taiwan. TRANSLATION: For the Taiwanese translation of the abstract see Supplementary Materials section.

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.

Mortality among acute myocardial infarction patients admitted to hospitals on weekends as compared with weekdays in Taiwan.

Weekend effect has been considered to be associated with poorer quality of care and patient's survival. For acute myocardial infarction (AMI) patients, the question of whether patients admitted during off-hours have worse outcomes as compared with patients admitted during on-hours is still inconclusive. We conducted this study to explore the weekend effect in AMI patients, using a nationwide insurance database in Taiwan. Using Taiwan National Health Insurance (NHI) claims database, we designed a retrospective cohort study, and extracted 184,769 incident cases of AMI through the NHI claims database between January 2006 and December 2014. We divided the patients into weekend admission group and weekday admission group. Patients were stratified as ST elevation/non-ST elevation AMI and receiving/not receiving percutaneous coronary intervention (PCI). We used a logistic regression model to examine the relative risk of in-hospital mortality and 1-year mortality which were obtained from the Taiwan National Death Registry between study groups. We found no difference between weekend group and weekday group for risk of in-hospital mortality (15.8% vs 16.2%, standardized difference 0.0118) and risk of 1-year mortality (30.2% vs 30.9%, standardized difference 0.0164). There was no statistically significant difference among all the comparisons through the multivariate logistic regression analysis adjusting for all the covariates and stratifying by the subtypes of AMI and whether or not executing PCI during hospitalization. As for AMI patients in Taiwan, admission on weekends or weekdays did not have a significant impact on either in-hospital mortality or 1-year cumulative mortality.

Characteristics, Treatment Patterns, and Clinical Outcomes of Chronic Hepatitis B Across 3 Continents: Retrospective Database Study.

INTRODUCTION: The prevalence of chronic hepatitis B virus (HBV) infection is high in many countries; however, robust, real-world epidemiological data are lacking. This study describes the prevalence, characteristics, treatment patterns, and long-term clinical outcomes of patients with chronic HBV infection in the US, Germany, and Taiwan. METHODS: This was a retrospective cohort analysis of three healthcare/insurance claims databases. Individuals were identified as patients with chronic HBV infection if their records contained HBV diagnostic codes from 1 January 2010 to 31 December 2012 (Germany and Taiwan) or 1 January 2013 (USA). Included patients were indexed on 1 January 2013. Patients' demographics, clinical characteristics, and healthcare utilisation were described. Treatment patterns and long-term clinical outcomes over follow-up (to 31 December 2016 or loss to follow-up) were estimated. RESULTS: The prevalence of chronic HBV infection was 0.10%, 0.17%, and 2.39% in the US, Germany, and Taiwan respectively. Prevalence was very low in children, increased rapidly in adulthood, and peaked in 50- < 65 year olds before declining in the elderly. More US (16.6%) and German (15.4%) patients were HIV ± HCV coinfected than in Taiwan (4.1%). Baseline clinical characteristics and healthcare utilisation were broadly similar between countries. In total, 19.2%, 11.1%, and 5.9% of non-coinfected adult patients received treatment at index in the US, Germany, and Taiwan, respectively; most frequently with nucleos(t)ide analogue monotherapy (94.4%, 97.2%, 99.8% of treated patients, respectively) and rarely with interferons (0.27%, 1.63%, and 0.06%, respectively). Untreated Taiwanese patients were more likely to remain untreated than elsewhere, and treated Taiwanese patients were less likely to persist with therapy. Generally, the cumulative incidence of long-term clinical outcomes was lowest in Germany. CONCLUSION: This study provides a contemporary, real-world, intercontinental snapshot of chronic HBV infection. Long-term sequelae occurred in all populations, and treatment levels were low, suggesting an unmet need for (or access to) effective treatments.

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.

Inhaled Zanamivir vs Oral Oseltamivir to Prevent Influenza-related Hospitalization or Death: A Nationwide Population-based Quasi-experimental Study.

BACKGROUND: Meta-analyses of individual patient data from randomized, controlled trials show that early oseltamivir treatment for influenza cut the risk of pneumonia and hospitalization by 44% and 63%, respectively. However, data on the effectiveness of inhaled zanamivir in preventing hospitalization and death are lacking. METHODS: This nationwide, population-based, cohort study included all outpatients treated with inhaled zanamivir or oral oseltamivir within 48 hours after a clinical diagnosis of influenza before and after the rollout of inhaled zanamivir as the first-line antiviral in Taiwan. The main outcome was influenza-related hospitalization or death within 14 days. Those who developed the outcome within 2 days were excluded from analyses. Propensity score stratification was used to control confounding from covariates. RESULTS: A total of 865 032 eligible influenza outpatients were included in the analysis. The risk of developing the main outcome (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], .96 to 1.06) did not differ between the inhaled zanamivir group (n = 595 897, 68.9%, the reference) and the oral oseltamivir group (n = 269 135, 31.1%). Prespecified analysis on high-risk subgroups further showed that inhaled zanamivir is not inferior to oral oseltamivir in either patients aged ≥65 years (aHR, 1.14; 95% CI: 1.05 to 1.25) or patients with chronic lung diseases (aHR, 1.23; 95% CI: 1.08 to 1.41). CONCLUSIONS: Inhaled zanamivir is not inferior to oral oseltamivir as outpatient treatment in preventing influenza-related hospitalization or death for patients whose conditions do not require hospitalization within 2 days.

Mortality of major cardiovascular emergencies among patients admitted to hospitals on weekends as compared with weekdays in Taiwan.

BACKGROUND: Several studies have found a so-called weekend effect that patients admitted at the weekends had worse clinical outcomes than patients admitted at the weekdays. We performed this retrospective cohort study to explore the weekend effect in four major cardiovascular emergencies in Taiwan. METHODS: The Taiwan National Health Insurance (NHI) claims database between 2005 and 2015 was used. We extracted 3811 incident cases of ruptured aortic aneurysm, 184,769 incident cases of acute myocardial infarction, 492,127 incident cases of ischemic stroke, and 15,033 incident cases of pulmonary embolism from 9,529,049 patients having at least one record of hospitalization in the NHI claims database within 2006 ~ 2014. Patients were classified as weekends or weekdays admission groups. Dates of in-hospital mortality and one-year mortality were obtained from the Taiwan National Death Registry. RESULTS: We found no difference in in-hospital mortality between weekend group and weekday group in patients with ruptured aortic aneurysm (45.4% vs 45.3%, adjusted odds ratio [OR] 1.01, 95% confidence interval [CI] 0.87-1.17, p = 0.93), patients with acute myocardial infarction (15.8% vs 16.2%, adjusted OR 0.98, 95% CI 0.95-1.00, p = 0.10), patients with ischemic stroke (4.1% vs 4.2%, adjusted OR 0.99, 95% CI 0.96-1.03, p = 0.71), and patients with pulmonary embolism (14.6% vs 14.6%, adjusted OR 1.02, 95% CI 0.92-1.15, p = 0.66). The results remained for 1 year in all the four major cardiovascular emergencies. CONCLUSIONS: We found no difference in either short-term or long-term mortality between patients admitted on weekends and patients admitted on weekdays in four major cardiovascular emergencies in Taiwan.

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.

Red Cell Distribution Width and Mortality in Patients Undergoing Percutaneous Coronary Intervention.

Red cell distribution width (RDW) can effectively predict prognosis in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI). There is currently no relevant research to demonstrate a linear or non-linear association between RDW and mortality. This is a multi-center, retrospective cohort study, with data collected from 2006 to 2017. Source data included electronic medical records of the Integrated Medical Database of National Taiwan University Hospital, and health insurance claims from the National Health Insurance Administration. Patients were stratified into five groups according to RDW values (13.4%, 14.1%, 14.8%, and 15.9%). Multivariable logistic and Cox regression analyses were used to determine 1-year all-cause and cardiovascular (CV) mortalities. Data of 10,669 patients were analyzed and those with the lowest RDW (≤13.3%) served as the reference group. The adjusted odds ratios (ORs) of 1-year all-cause mortality from the second to fifth RDW group were 1.386, 1.589, 2.090, and 3.192, respectively (p for trend < 0.001). The adjusted ORs of 1-year CV mortality were 1.555, 1.585, 1.623, and 2.850, respectively (p for trend = 0.015). The adjusted hazard ratios (HRs) of 1-year all-cause mortality were 1.394, 1.592, 2.003, and 2.689, respectively (p for trend = 0.006). The adjusted HRs of 1-year CV mortality were 1.533, 1.568, 1.609, and 2.710, respectively (p for trend = 0.015). RDW was an independent predicting factor and had a linear relationship with the 1-year all-cause and CV mortalities in patients undergoing PCI. Thus, RDW may be a clinically useful parameter to predict the mortality in those patients.

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.