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.

Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Endodontic malpractice litigations in the United States from 2000 to 2021.

Background/purpose: Little is known regarding the outcomes and distinguishing characteristics of lawsuits related to endodontic procedures. This study used a verdict-based data from United States of America to analyze the factors associated with endodontic malpractice lawsuits and mitigate the risk of litigation. Materials and methods: The LexisNexis legal database was used to search for endodontic malpractice cases from January 1, 2000 to December 31, 2021 using the terms "medical malpractice" and (I) "endodontist" (II) "endodontics" (III) "root canal" (IV) "dental pulp." Each case was reviewed for reported medical characteristics and litigation outcomes. Results: A total of 650 cases were initially identified, and 97 cases were included in the final analysis. Eighty-four (86.6%) of the 97 defendants were general practitioners; 42 cases favored the plaintiff, 53 (54.6%) favored the defendant, 1 was partial win/loss, and 1 was settled. The annual case mean was 4.41 ± 2.17 (Mean ± SD). The major allegations favored for the patients involving paresthesia, root perforation, rubber dam not use, wrong tooth therapy, and infections. Plaintiffs who claimed with post-procedural reasons had a significantly higher winning rate than non-post-procedural reasons (P < 0.05). Conclusion: In the present study, 54.6% of endodontic litigation favored the dentists in the US. The authors recommend that general practitioners refer complicated cases to endodontists and treat carefully to avoid paresthesia, canal perforation and infections. Clinicians should always diagnose and treat correctly, shared decision making with the patient, use rubber dam routinely, and timely management to prevent malpractice claims.

Efficacy of free gingival grafting to augment keratinized mucosa around dental implants in posterior regions after restorative procedures: A retrospective clinical study.

STATEMENT OF PROBLEM: Data on the shrinkage of free gingival grafts (FGGs) vary. Most studies have analyzed grafts in nonmolar sites because of measurement limitations and have addressed the changes in grafts and keratinized mucosa width (KMW) only in the early healing phase. PURPOSE: The purpose of this retrospective clinical study was to assess the dimensional changes of an FGG in the posterior regions and their influencing factors, with the aim of obtaining sufficient and stable KMW after restoration. MATERIAL AND METHODS: A total of 77 implants in 40 participants who had undergone an FGG surgery were recruited. Graft sizes during surgery and the surface areas of keratinized mucosa at the follow-up visit after restorations were compared by digital analysis and verified by clinical measurements and photographs. The association between shrinkage and the graft sizes, implant location, and sex and age of the participants was evaluated. The influence of the shrinkage of FGG on the KMW after restoration was analyzed by multivariable linear regression with generalized estimating equation (GEE) models. RESULTS: The mean ±standard deviation shrinkage of FGG around implants in the posterior regions was 24.76 ±14.77%, and the mean ±standard deviation KMW was 4.16 ±1.77 mm at the follow-up visit. Larger grafts had a statistically higher shrinkage ratio (P<.001). No statistically significant difference was found regarding the effect of implant location, sex, and age on the shrinkage of FGG and final KMW (P>.05). The mean ±standard deviation follow-up period after restoration was 12.45 ±7.73 months CONCLUSIONS: Free gingival grafting was found to be a predictable treatment approach for augmentation of KMW around implants in the posterior region after the fabrication of prostheses as long as grafts of sufficient size were placed. Stable outcomes were shown in the study participants in the follow-up period of up to 3 years.

The Relationship between Obesity-Related Factors and Graves' Orbitopathy: A Pilot Study.

Background and Objectives: The aim of this study was to investigate the relationships between obesity-related factors including body mass index (BMI), diabetes or prediabetes, hyperlipidemia, fasting plasma glucose, fasting plasma insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), highly sensitive C-reactive protein (hs-CRP) and Graves' orbitopathy (GO). Materials and Methods: Eighty-four patients with Graves' disease (GD) (42 without GO and 42 with GO) were enrolled in this cross-sectional cohort study. Gender, age, GD treatment history, height, body weight, waist circumference, smoking status, co-morbidities, levels of free thyroxin, thyroid-stimulating hormone, thyroid-stimulating hormone receptor (TSHR) antibodies, fasting plasma glucose and insulin, and hs-CRP were recorded. The eye condition was evaluated using the consensus statement of the European Group of Graves' Orbitopathy (EUGOGO) and the NOSPECS classification. Results: In this study, multivariate regression analysis showed that BMI, fasting plasma insulin, and HOMA-IR were associated with the presence of GO after adjusting the age, gender, smoking, TSHR antibodies, and steroid usage (adjusted odd's ratio (aOR) 1.182, 95% confidence interval (95% CI), 1.003-1.393, p = 0.046; aOR 1.165, 95% CI, 1.001-1.355, p = 0.048; and aOR 1.985, 95% CI, 1.046-3.764, p = 0.036, respectively). In addition, BMI, fasting plasma glucose, fasting plasma insulin, HOMA-IR, and hs-CRP levels were positively correlated with the severity of GO. Conclusions: The findings of this study suggest that obesity-related factors, especially fasting plasma insulin and HOMA-IR, are related to GO. Our study highlighted the importance of obesity-related factors in GO. Obesity-related factors may cause the development of GO or occur simultaneously with GO.

The Association between Physical Activity and Cardiovascular Implantable Electronic Device-Detected Atrial High Rate Episodes.

BACKGROUND: Atrial fibrillation is the most common arrhythmia and it is associated with a higher risk of mortality and morbidity. The goal of this study was to assess the correlation between physical activity (PA) and atrial high rate episodes (AHREs) detected by cardiovascular implantable electronic devices (CIEDs). METHODS: We prospectively collected data from 81 patients from March 2017 to June 2019. Device-detected PA (hours per day) through an accelerometer and occurrence/burden of AHREs were determined at each outpatient clinic visit. Modest AHREs and long AHREs were defined as at least 1 episode of AHREs lasting ≥ 12 hours and 24 hours, respectively. The percentage of total AHREs in the follow-up period was defined as the burden of AHREs. Generalized estimating equations were used to explore the association between PA and occurrence/burden of AHREs to account for repeated measures within a participant. RESULTS: The patients had 336 follow-up visits (mean 4.1 visits each). The prevalence rates of device-detected modest AHREs and long AHREs were 4.8% and 3.9%, respectively. More PA (hours per day) was associated with a lower risk of modest AHREs [odds ratio (OR) 0.671, 95% confidence interval (CI) 0.452-0.997, p = 0.048] and long AHREs (OR 0.536, 95% CI 0.348-0.824, p = 0.004) after adjusting for age, sex, and basic characteristics. More PA had a trend of association with fewer AHREs (ß -0.255, 95% CI -0.512 to 0.001, p = 0.051). CONCLUSIONS: More PA was associated with a lower risk of AHREs detected by CIEDs in older patients. PA may reduce the risk of AHREs.

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.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

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.

Retrospective evaluation of gingival thickness and tissue stability after connective tissue grafting in Asian populations: 1 month to 3.5 years.

BACKGROUND/PURPOSE: The objectives of this retrospective study are to analyze post-surgical gingival thickness after connective tissue grafting in the Asian population and to assess its tissue stability for up to approximately 3.5 years. METHODS: A total of 111 grafted teeth and 57 nearby nongrafted teeth in 28 Asian patients who had undergone connective tissue grafting surgery were selected. Gingival thickness was measured by transgingival probing. The mean gingival thickness of the grafted teeth was compared with adjacent nongrafted teeth in the same individuals. The mean gingival thickness of the grafted teeth in different tooth types and at various time intervals were statistically analyzed. RESULTS: The average gingival thickness following connective tissue grafting is 1.99 ± 0.62 mm compared to 0.96 ± 0.40 mm with nongrafted teeth (P < .0001). The maxillary premolar is the tooth type that underwent connective tissue grafting most frequently in our study. Among different tooth types, mandibular molars showed the thickest gingival tissues whereas mandibular incisors presented the thinnest tissues. No statistically significant difference in the mean tissue thickness at different time intervals was observed. CONCLUSION: Connective tissue grafting is a predictable treatment modality for gingival phenotype conversion, even in Asians, achieving nearly 2 mm of gingival thickness on average, post-operation. Tissue stability after connective tissue grafting has been presented in our study. This quantitative assessment of the gingival thickness in Asians may encourage clinicians to deal with soft tissue architecture ahead of main surgical, restorative and orthodontic treatments in order to achieve pleasing treatment outcomes.

Modified paramedian versus conventional paramedian technique in the residency training: an observational study.

BACKGROUND: Residency training includes positive and negative aspects. Well-trained doctors must be educated, but the process may bring additional risks to patients. Anesthesiologists' performance when conducting neuraxial anesthesia is related to their experience. We hypothesized that a modified neuraxial anesthesia method would improve both residency training and patient safety. METHODS: We recruited 518 patients who were scheduled for a cesarean section and used spinal anesthesia (n = 256), epidural anesthesia (n = 154), and combined spinal-epidural anesthesia (SEA; n = 108). We observed and evaluated the anesthesia performance of five second-year resident anesthesiologists in elective cesarean sections using the conventional and modified methods. The number of attempts, implant error rate, and the incidence of complications were recorded and analyzed. RESULTS: Better success puncture attempts occurred in all three groups when the modified method was applied. For the groups with an implant assessment, the complication rate and implant error rate were lower when using the modified method. We employed generalized estimating equation (GEE) analysis to correct for possible confounding factors. When using the conventional method, the resident anesthesiologists required more attempts, made more implant errors, and caused more complications in patients. CONCLUSIONS: We found that a modified method for neuraxial anesthesia could improve residency performance and patient safety. The modified method may be a suitable training process for resident anesthesiologists when practicing neuraxial anesthesia. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of National Taiwan University (IRB:200812040R) Clinicaltrials register: NCT03389672 .

Statin adherence and persistence on secondary prevention of cardiovascular disease in Taiwan.

BACKGROUND: Evidence and treatment guidelines support the use of statins in patients with established atherosclerotic cardiovascular disease (ASCVD) for secondary prevention of subsequent cardiovascular (CV) event. However, treatment adherence and persistence are still a concern. METHODS: We constructed a retrospective population-based cohort of patients, who initiated statin treatment within 90 days after discharge from hospital for ASCVD using the claims database of Taiwan National Health Insurance. Proportion of days covered (PDC) was used to measure statin adherence, and PDC ≥80% was defined as good adherence. The study outcomes were subsequent rehospitalisation or in-hospital death due to composite ASCVD, myocardial infarction or ischaemic stroke. Their associations with statin prescription adherence or persistence were analysed using time-dependent Cox proportional hazards model. RESULTS: The study cohort included 185 252 postdischarge statin initiators. There were 50 015 subsequent ASCVD rehospitalisations including 2858 in-hospital death during 7 years of study period. Good adherence was significantly associated with lower risk of ASCVD rehospitalisation (adjusted HR (aHR) 0.90; 95% CI 0.87 to 0.92) and significantly lower risk of in-hospital death (aHR 0.59; 95% CI 0.53 to 0.65). Compared with constant use of statin, patients in the three less persistent states (recent stop, non-persistence and intermittent use) were associated with higher risk of subsequent ASCVD rehospitalisation, aHRs were 1.16, 1.13 and 1.26, respectively (all p<0.05). The increased risks were consistent with specific outcome of acute myocardial infarction and ischaemic stroke. Also, patients in the recent stop period had significantly higher risk for fatal CV event. CONCLUSIONS: Good adherence and persistence to statin therapy are significantly associated with lower risk of secondary ASCVD rehospitalisation and in-hospital death.

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.

Reinforcement of patient education improved physicians' adherence to guideline-recommended medical therapy after acute coronary syndrome.

BACKGROUND: Prescription of guideline-recommended medicines after acute coronary syndrome (ACS) has been suboptimal. Tools for improving the use of medications have been developed, but they mainly targeted physicians. OBJECTIVE: We evaluated the effects of reinforcement of patient and family education on the usage of guideline-recommended secondary prevention medications. METHODS: This was a retrospective analysis of a prospectively collected registry of patients with ACS who were admitted to a regional teaching hospital in Taiwan between February 2015 and April 2017. The control group included 76 patients discharged before implementing the electronic-based patient and family education (PFE) system. The intervention group included 206 patients discharged after implementation. The primary outcome was the prescription rate of all four guideline-recommended drugs. Predictors of adherence were also evaluated. RESULTS: The study cohort included 282 ACS patients (188 men and 94 women) with a mean age of 68.5 years (standard deviation, 14.2). The intervention group patients were younger, had more family history of premature cardiovascular disease, more dyslipidemia, and underwent more reperfusion therapy. The intervention group was prescribed more guideline-recommended drugs than the control group: dual antiplatelet agents, 79.61% vs. 47.37% (p<0.001); statins, 74.76% vs. 34.21% (p<0.001); beta-blockers, 81.07% vs. 46.05% (p<0.001); angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 62.62% vs. 38.16% (p<0.001); and a combination of all four medications, 39.32% vs. 14.47% (p<0.001). After adjusting baseline variables, the PFE system remained a significant contributor to adherence to these drugs use (P = 0.02). CONCLUSIONS: Reinforcement of patient education was associated with significant improvements in physicians' adherence to guideline-recommended medical therapy after acute coronary syndrome.

Re-evaluating Safety and Effectiveness of Dabigatran Versus Warfarin in a Nationwide Data Environment: A Prevalent New-User Design Study.

INTRODUCTION: The new user cohort design is widely used to assess the effects of a new drug, such as dabigatran, but inherently excludes some users due to prior use of the comparator drug, for example warfarin. The prevalent new-user design offers a solution that includes all eligible users of the new drug. OBJECTIVE: To evaluate the safety and effectiveness of dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients with prevalent new-user design. METHODS: Taiwan National Health Insurance and mortality data from 2011 through 2015 were utilized. From an incident NVAF cohort, we identified dabigatran initiators as either incident or prevalent (switchers from warfarin) new users. Time- and prescription-based exposure sets were formed for dabigatran initiators to account for prior warfarin prescriptions. A comparable warfarin user was matched on the time-conditional propensity score to the dabigatran initiator in each set. The matched patients were followed for clinical outcomes, with Cox proportional hazards model used to estimate hazard ratios (HRs). RESULTS: There were 10,811 dabigatran initiators, including 22% prevalent new users (switchers), who formed the exposure sets and were matched 1:1 to warfarin users. Dabigatran use was associated with lower risks of intracranial hemorrhage (HR 0.51; 95% confidence interval [CI] 0.39, 0.66) and gastrointestinal bleeding (HR 0.81; 95% CI 0.70, 0.92), compared with warfarin use. These effects were similar between the incident and prevalent new users. CONCLUSION: Using a design that includes both incident and prevalent new users of dabigatran, the use of dabigatran is associated with lower major bleeding risk than warfarin use among patients with incident NVAF.

Metformin was associated with lower all-cause mortality in type 2 diabetes with acute coronary syndrome: A Nationwide registry with propensity score-matched analysis.

BACKGROUND: No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agents users. METHODS: Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. The Cox proportional hazards model was used to compare mortality outcomes among the PS-matched cohort as the primary analysis. The Cox proportional hazards models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as the secondary analyses. RESULTS: Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0.50, 95% confidence interval [CI] 0.26-0.95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0.30, 95% CI 0.17-0.54 while adjusting for all pre-determined covariates, and aHR 0.34, 95% CI 0.19-0.59 while adjusting for quintiles of the PS). CONCLUSIONS: Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. However, a detrimental effect of any of the comparators could not be excluded.

Long-term statin adherence in patients after hospital discharge for new onset of atherosclerotic cardiovascular disease: a population-based study of real world prescriptions in Taiwan.

BACKGROUND: Despite the recommendations of statins treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), treatment adherence and persistence are still a concern. This study examined the real world practice of long-term adherence and persistence to statins treatment initiated after hospital discharge for ASCVD, and their associated factors in a nationwide cohort. METHODS: Post discharge statin prescriptions between 2006 and 2012 were extracted from the Taiwan National Health Insurance claims database. Good adherence, defined as proportion of days covered (PDC) ≥0.8 and mean medication possession ratio (MPR), was measured every 180-day period. Non-persistence was defined on the date patients failed to refill statin for 90 days after the end of the last prescription. Their associations with influential factors were analyzed using a generalized estimating equation and Cox's proportional hazard model. RESULTS: There was a total of 185,252 post-discharge statin initiations (from 169,624 patients) and followed for 467,398 patient-years in the study cohort. Percentage of good adherence (mean MPR) was 71% (0.87) at 6-months; declined to 54% (0.68), 47% (0.59), and 42% (0.50) at end of year 1, 2, and 7, respectively. Persistence in statin treatment was 86, 67, 50, and 25% at 6-month, 1-, 2-, and 7-year, respectively. Comparing the statin-cohort initiated from year 2006 to 2012, 1-year persistence increased from 58 to 73%, and 1-year good adherence improved from 45 to 61%. Factors associated with sub-optimal adherence and non-persistence included: prescription by primary care clinics or non-cardiology specialties; patients' age > 75 years; no history of previous statin use; ASCVD events with ischemic stroke diagnosis; comorbidities of renal disease, liver disease, depression, and chronic obstructive pulmonary disease. CONCLUSIONS: Despite the improving trends, long-term adherence and persistence of statin treatment were suboptimal in Taiwan. Strategies to maintain statin treatment adherence and persistence need to be implemented to further enhance the positive trend.

Direct Comparison of Low-Dose Dabigatran and Rivaroxaban for Effectiveness and Safety in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to examine the comparative effectiveness and safety between low-dose dabigatran and rivaroxaban in atrial fibrillation (AF) patients. METHODS: Using the National Health Insurance claims database in Taiwan, we conducted head-to-head comparisons among adult non-valvular AF patients prescribed with dabigatran 110 mg or rivaroxaban 15 mg between June 1, 2012 and May 31, 2015. A propensity score was derived using logistic regression to model the probability of receiving different non-VKA oral anticoagulants (NOACs) as a function of potential confounders, and an inverse-probability- of-treatment-weighted (IPTW) pseudo-cohort was created. A Cox proportional hazards model was used to compare clinical outcomes in the IPTW pseudo-cohort as the primary analysis. The propensity score-matched analysis was applied as the secondary analysis. RESULTS: Overall, 13505 dabigatran 110 mg users and 6551 rivaroxaban 15 mgusers were identified. In the primary analysis, the rivaroxaban 15 mg users had a higher risk of all-cause death [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.02-1.38]. In addition, the rivaroxaban 15 mg users had an increased risk of all-cause death (HR 1.25, 95% CI 1.05-1.50) in the secondary analysis. The risks of ischemic stroke, intracranial hemorrhage and gastrointestinal hemorrhage were similar between the 2 study groups in both the primary and secondary analyses. CONCLUSIONS: For non-valvular AF patients, rivaroxaban 15 mg seemed to be associated with an increased risk of all-cause death compared with dabigatran 110 mg. This was a retrospective data analysis and the results should not be over-interpreted to guide the choice of different NOACs.

Timely diagnosis and treatment of sleep apnea reduce cardiovascular sequelae in patients with myocardial infarction.

BACKGROUND: The present study aimed to test if the temporal sequence between sleep apnea (SA) diagnosis and incident myocardial infarction (MI) was associated with the long-term mortality and cardiovascular event in a community-based cohort. METHODS: We retrieved data from 9,453 incident MI patients between Jan. 1st 2000 and Dec. 31st 2012 from the Taiwan National Health Insurance Research Database. The study subjects included 207 MI patients with SA (SA-MI), further stratified into 110 with pre-existing SA before MI (SA-bMI) and 96 diagnosed with SA after MI (SA-pMI). The median follow-up period was 4.2 years. Propensity-score-matched controls were selected from 9,246 non-SA MI patients (non-SA-MI). The association of SA and outcomes including all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) were analyzed by a Cox proportional hazards model. RESULTS: The result showed that SA was not associated with mortality regardless of the timing of SA diagnosis. SA-pMI was associated with increased risk of MACCEs (Hazard ratio [HR]: 1.412, 95% confidence interval [CI]: 1.037~1.923, p = 0.029) including re-MI or revascularization and ischemic heart disease hospitalization. Such an association was most significant for SA diagnosed within one year after MI (HR: 2.029, 95% CI: 1.265~3.254, p = 0.003), which was not seen in patients treated with continuous positive airway pressure (CPAP). CONCLUSION: The temporal sequence and the time interval between SA diagnosis and incident MI was associated with the cardiovascular events after MI, especially within one year after MI. Early assessment for the presence of SA after incident MI and early CPAP intervention may reduce the risk of further adverse cardiovascular events.

Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan.

OBJECTIVES: To compare the effectiveness and safety of reduced-dose dabigatran, reduced-dose rivaroxaban, and warfarin in individuals aged 85 and older with atrial fibrillation (AF). DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance claims database, 2011∼2015. PARTICIPANTS: Individuals with AF aged 85 and older (mean 88.6) with incident use of oral anticoagulants between June 1, 2012 and May 31, 2015 (N=4,722; dabigatran 110 mg, n=1,489; rivaroxaban 15 mg/10 mg, n=1,736; warfarin, n=1,497). MEASUREMENTS: Clinical outcomes included all-cause death, cardiovascular death, ischemic stroke, acute myocardial infarction, arterial embolism or thrombosis, intracranial hemorrhage, and gastrointestinal hemorrhage needing transfusion. Propensity score-matched analysis was performed, and the marginal proportional hazards model was used to estimate the relative risk of various clinical outcomes in a matched dabigatran-warfarin cohort (n=1,180 in each group) and a rivaroxaban-warfarin cohort (n=1,207 in each group) RESULTS: Mean follow-up was 6.6 months for the overall population. Dabigatran group participants had lower risks of all-cause death (hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.45-0.77) and cardiovascular death (HR=0.45, 95% CI=0.30-0.68) than warfarin group participants. Rivaroxaban users also had lower risks of all-cause death (HR=0.61, 95% CI=0.47-0.79) and cardiovascular death (HR=0.52, 95% CI=0.35-0.75) than warfarin users. Dabigatran users also had a lower risk of intracranial hemorrhage than warfarin users (HR=0.31, 95% CI=0.10-0.97). CONCLUSION: Individuals with AF aged 85 and older who used reduced-dose dabigatran or reduced-dose rivaroxaban had statistically significantly lower all-cause mortality and cardiovascular mortality than those who used warfarin. Reduced-dose dabigatran was also associated with lower risk of intracranial hemorrhage than warfarin.