Efficacy of antimicrobial peptide P113 oral health care products on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment.

Background/purpose: Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. Materials and methods: This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. Results: In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. Conclusion: The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation.

Comparison of the prognosis among in-hospital survivors of cardiogenic shock based on etiology: AMI and Non-AMI.

BACKGROUND: Current data on post-discharge mortality and rehospitalization is still insufficient among in-hospital survivors of cardiogenic shock (CS), including acute myocardial infarction (AMI) and non-AMI survivors. METHODS: Patients with CS who survived after hospital discharge were selected from the Taiwan National Health Insurance Research Database. Each patient was followed up at 3-year intervals. Mortality and rehospitalization were analyzed using Kaplan-Meier curves and Cox regression models. RESULTS: There were 16,582 eligible patients. Of these, 42.4% and 57.6% were AMI-CS and non-AMI-CS survivors, respectively. The overall mortality and rehospitalization rates were considerably high, with reports of 7.0% and 22.1% at 30 days, 24.5% and 58.2% at 1 year, and 38.9% and 73.0% at 3 years, respectively, among in-hospital CS survivors. Cardiovascular (CV) problems caused approximately 40% mortality and 60% rehospitalization. Overall, the non-AMI-CS group had a higher mortality burden than the AMI-CS group owing to older age and a higher prevalence of comorbidities. In multivariable models, the non-AMI-CS group exhibited a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.60 to 0.78) and CV mortality (aHR 0.65, 95% CI 0.54 to 0.78) compared to the AMI-CS group. However, these risks diminished and even reversed after one year (aHR 1.13, 95% CI 1.03 to 1.25 for all-cause mortality; aHR 1.27, 95% CI 1.09 to 1.49 for CV mortality).This reversal was not observed in all-cause and CV rehospitalization. For rehospitalization, AMI-CS was associated with the risk of CV rehospitalization in the entire observation period (aHR:0.80, 95% CI:0.76-0.84). CONCLUSIONS: In-hospital AMI-CS survivors had an increased risk of CV rehospitalization and 30-day mortality, whereas those with non-AMI-CS had a greater mortality risk after 1-year follow-up.

Association between repeat imaging and readmission in patients with acute ischaemic stroke: a 16-year nationwide population-based study.

OBJECTIVES: This study aims to evaluate such usage patterns and identify factors that may contribute to the need for repeat imaging in acute ischaemic stroke patients and determine the association between repeat imaging and readmission in Taiwan. METHODS: We searched and analysed data from the Taiwan National Health Insurance Research Database for patients admitted for acute ischaemic stroke between 2002 and 2017. Cases where repeat brain imaging during the initial hospital admission occurred and where patients were readmitted within 30 days following discharge were documented. RESULTS: Of a total of 195 016 patients with new onset ischaemic stroke, 51 798 (26.6%) underwent repeat imaging during their initial admission. Factors associated with repeat brain imaging included younger age, longer hospital stay, use of recombinant tissue plasminogen activator (rt-PA) therapy (odds ratio = 2.10 [95% CI, 1.98-2.22]), more recent year of diagnosis, higher National Institutes of Health Stroke Scale (NIHSS) score, and admission to a hospital offering a higher level of care. Repeat imaging was also associated with an increased risk of ischaemic stroke and all types of stroke readmission. CONCLUSIONS: Repeat brain imaging of patients with stroke has increased in recent years, and it is associated with certain factors including age, length of stay, use of rt-PA, hospital level of care, and NIHSS score. It is also associated with increased readmission. ADVANCES IN KNOWLEDGE: Knowledge of the associations of repeat imaging may help clinicians use repeat imaging more carefully and efficaciously.

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

PURPOSE: The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). METHODS: This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. RESULTS: Statin users had significantly higher odds of DED (adjusted OR = 1.12; 95% confidence interval (CI) = 1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR = 1.04; 95% CI = 0.99-1.10, p = 0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR = 0.99, 95% CI = 0.93-1.06, p = 0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR = 1.00, p = 0.922; adjusted OR = 0.94, p = 0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. CONCLUSIONS: Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Mortality in anorexia nervosa and bulimia nervosa: A population-based cohort study in Taiwan, 2002-2017.

OBJECTIVE: To investigate natural- and unnatural-cause mortality at different follow-up time points in Taiwanese patients with anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: In this longitudinal cohort study, 330,393 patients, including 2143 patients with AN, 13,590 with BN, and 20 times as many respective non-AN and non-BN patients, were followed up for 16 years. We performed conditional Cox regression survival analysis to examine the risk of mortality in the AN and BN groups relative to the comparison group. RESULTS: A total of 1242 patients died, including 101 and 343 patients with AN and BN, respectively. Mortality rates for AN and BN were 5.42 and 2.90 deaths per 1000 person-years, respectively. Compared with the non-AN group, the AN group had a significantly higher risk of both natural- and unnatural-cause mortality, and the BN group had a significantly higher risk of unnatural-cause mortality. Suicide was the most common cause of death, and suicide risk was significantly higher in both the AN and BN groups. All-cause mortality risk was the highest at the beginning of follow-up and markedly declined in the AN group. In the BN group, all-cause mortality risk was lower but stable at follow-up. The risk of unnatural-cause mortality remained high throughout the follow-up period for both the groups. CONCLUSIONS: Early detection and treatment for associated physical problems in patients with AN are crucial. Regular monitoring for unnatural-cause mortality events (mainly suicide) in AN and BN over time is also crucial. PUBLIC SIGNIFICANCE: AN had a significantly higher risk of both natural- and unnatural-cause mortality and BN had a significantly higher risk of death from unnatural causes. All-cause mortality risk was highest at the beginning of follow-up in AN, but unnatural-cause mortality risk remained high throughout the follow-up period for both groups. Our findings imply that early detection and treatment in AN and regular monitoring for unnatural-cause mortality events in AN and BN are crucial.

Considerations for the Terminal Sterilization of Oligonucleotide Drug Products.

A primary function of the parenteral drug product manufacturing process is to ensure sterility of the final product. The two most common methods for sterilizing parenteral drug products are terminal sterilization (TS), whereby the drug product is sterilized in the final container following filling and finish, and membrane sterilization, whereby the product stream is sterilized by membrane filtration and filled into presterilized containers in an aseptic processing environment. Although TS provides greater sterility assurance than membrane sterilization and aseptic processing, not all drug products are amenable to TS processes, which typically involve heat treatment or exposure to ionizing radiation. Oligonucleotides represent an emerging class of therapeutics with great potential for treating a broad range of indications, including previously undruggable targets. Owing to their size, structural complexity, and relative lack of governing regulations, several challenges in drug development are unique to oligonucleotides. This exceptionality justifies a focused assessment of traditional chemistry, manufacturing, and control strategies before their adoption. In this article, we review the current state of sterile oligonucleotide drug product processing, highlight the key aspects to consider when assessing options for product sterilization, and provide recommendations to aid in the successful evaluation and development of TS processes. We also explore current regulatory expectations and provide our interpretation as it pertains to oligonucleotide drug products.

Risk of dialysis and renal diseases in patients with anorexia nervosa in Taiwan.

OBJECTIVE: To investigate the incidence and risk of renal-related complications in a nationwide cohort of Taiwanese patients with anorexia nervosa (AN). METHOD: This longitudinal cohort study analyzed the data of 43,951 individuals-comprising 2091 patients with AN and their controls matched (1:20) using propensity scores according to sex, age, degree of urbanization of residence, socioeconomic status, and year of diagnosis-from a population-based health insurance database; the study lasted 16 years. We used Kaplan-Meier curves to estimate the cumulative incidence of renal events. We also performed Cox proportional regression and constructed a risk model with death as a competing event (both adjusted for basic characteristics, renal diseases, and psychiatric comorbidities) to examine the risk of dialysis and renal outcomes in the AN group relative to the control group. RESULTS: In total, 204 and 10 patients with AN had renal-related outcomes and end-stage renal disease (ESRD), respectively. The cumulative incidence rates of all renal outcomes and ESRD in the AN group were 10.72% and .64%, respectively, at 10-year follow-up. Compared with the control group, the AN group had a significantly higher risk of acute dialysis (adjusted hazard ratio 2.10 [95% confidence interval 1.19-3.68]), hypokalemia, hypovolemia, nephritis, acute renal failure, and chronic renal failure. The AN group did not have a significantly higher risk of ESRD. DISCUSSION: The elevated risks of acute dialysis and some renal outcomes in AN highlight the importance of monitoring electrolyte imbalance and renal malfunctioning. PUBLIC SIGNIFICANCE: Malnutrition and purging behaviors may cause renal complications in patients with AN. In this longitudinal cohort study, we found that the 10-year cumulative incidence of all renal outcomes in AN was 10.72%, and that patients with AN had a two-fold higher risk of overall renal outcomes compared with those without AN. Our findings imply that weight restoration and ceasing purging behaviors are crucial for recovery from AN.

Epidemiology and survival outcomes of acute myeloid leukemia patients in Taiwan: A national population-based analysis from 2001 to 2015.

OBJECTIVES/BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with high mortality. To date, there is no comprehensive population-based analysis of patients with AML in Asia, including Taiwan. MATERIAL AND METHODS: This is a retrospective cohort study using three population-based databases, namely, the Taiwan Cancer Registry, Taiwanese National Health Insurance Research Database, and Taiwan Death Registry, between 2001 and 2015 to provide detailed information on patients with AML and relevant clinical variables, such as sex, age, year of diagnosis, socioeconomic status (SES) level, hospital level, treatment location, and Deyo-Charlson Comorbidity Index (Deyo-CCI) score. RESULTS: Patients with newly diagnosed AML (n = 9949) were included in the study. The median age was 60 years, and the overall age-adjusted AML incidence over 15 years was 2.44 per 100,000 person-years. The median overall survival (OS) of patients younger than 65 years was 18 months, whereas the OS of patients older than age 65 was only 5 months. AML patients with a prior cancer history had the worst outcomes, and the acute promyelocytic leukemia subtype predicted better survival. Patients who were older, male and a higher Deyo-CCI score had a significantly higher risk of death. In contrast, patients with a higher SES level and receiving treatment in a medical center had a lower risk of mortality than their respective counterparts. CONCLUSION: Our study results could enable clinicians to obtain a comprehensive picture of the epidemiology, survival outcomes and unmet medical needs of AML patients in Taiwan.

Trends in Diagnosed Dry Eye Disease Incidence, 2001 to 2015: A Nationwide Population-Based Study in Taiwan.

PURPOSE: The purpose of this study was to estimate the longitudinal trend in the incidence of diagnosed dry eye disease (DED) from 2001 to 2015 in Taiwan. METHODS: We obtained data from the Taiwan National Health Insurance Research Database that covers 99.9% of Taiwanese residents. The incident DED cases were identified according to diagnoses, drug codes, and procedure codes. We estimated age-specific and sex-specific incidence rates (IRs) between 2001 and 2015. RESULTS: The annual age-adjusted IRs of DED increased from 0.97 per 1000 in 2001 to 2.52 per 1000 in 2015 among male population and from 2.06 in 2001 per 1000 to 4.91 in 2015 per 1000 among female population. From 2001 to 2015, the annual IRs increased starting from age 20 to 39 years to age 70 to 79 years in both the male and female population. The men in both 20 to 39 and 50 to 59 age groups showed 3-fold higher IRs in 2015 than in 2001. However, the IRs were consistently lower in men than in women from 2001 to 2015. Overall, the IR was highest, between 10.3 (95% confidence interval, 10.1-10.5) and 13.8 (13.5-14.1) per 1000 population, in the population with the highest socioeconomic status. CONCLUSIONS: The IRs of DED increased from 2001 to 2015 for all demographics, particularly in the 20 to 39 and 50 to 59 years aged male population. These findings highlight the disease burden of DED and are expected to grow substantially.

Evaluation of risk adjustment performance of diagnosis-based and medication-based comorbidity indices in patients with chronic obstructive pulmonary disease.

OBJECTIVES: This study assessed risk adjustment performance of six comorbidity indices in two categories of comorbidity measures: diagnosis-based comorbidity indices and medication-based ones in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a population-based retrospective cohort study. Data used in this study were sourced from the Taiwan National Health Insurance Research Database. The study population comprised all patients who were hospitalized due to COPD for the first time in the target year of 2012. Each qualified patient was individually followed for one year starting from the index date to assess two outcomes of interest, medical expenditures within one year after discharge and in-hospital mortality of patients. To assess how well the added comorbidity measures would improve the fitted model, we calculated the log-likelihood ratio statistic G2. Subsequently, we compared risk adjustment performance of the comorbidity indices by using the Harrell c-statistic measure derived from multiple logistic regression models. RESULTS: Analytical results demonstrated that that comorbidity measures were significant predictors of medical expenditures and mortality of COPD patients. Specifically, in the category of diagnosis-based comorbidity indices the Elixhauser index was superior to other indices, while the RxRisk-V index was a stronger predictor in the framework of medication-based codes, for gauging both medical expenditures and in-hospital mortality by utilizing information from the index hospitalization only as well as the index and prior hospitalizations. CONCLUSIONS: In conclusion, this work has ascertained that comorbidity indices are significant predictors of medical expenditures and mortality of COPD patients. Based on the study findings, we propose that when designing the payment schemes for patients with chronic diseases, the health authority should make adjustments in accordance with the burden of health care caused by comorbid conditions.

Risk of Heart Failure in Patients with ST-Elevation Myocardial Infarction Receiving Drug-Eluting Stent Implantation and Undefined Duration of Antiplatelets.

It remains unknown as to whether the use of new-generation drug-eluting stent (NG-DES) in patients with ST-elevation myocardial infarction (STEMI) who receive an undefined duration of dual antiplatelet therapy (DAPT) reduces the risk of hospitalization for heart failure (HHF). In this population-based retrospective cohort study, we applied propensity score matching to select 6831 pairs of patients with STEMI who had similar baseline characteristics and received either NG-DES or bare-metal stent (BMS) implantation between 1 January 2007 and 31 December 2016. The risk of stent-associated HHF was evaluated, wherein death was considered a competing risk. Rates of cumulative incidence competing risk for HHF at the 1, 2, 3, 4, and 5 year follow-up were lower in the NG-DES group (3.79%, 5.21%, 6.15%, 7.01%, and 8.29%, respectively) than in the BMS group (4.51%, 6.21%, 7.32%, 8.33%, and 9.83%, respectively). NG-DES implantation was associated with a lower risk of HHF than BMS implantation after 5 years, with an adjusted subdistribution hazard ratio of 0.82 (95% confidence interval 0.72−0.92, p = 0.001). These results accord with those of patients who received DAPT for >6 months. Our findings highlight that NG-DESs may reduce HHF risk in patients with STEMI receiving an undefined duration of DAPT.

Effectiveness of induction regimens on survival outcome in acute myeloid leukemia patients: a real-world data from 2001 to 2015.

Since patients with acute myeloid leukemia (AML) in the real world have a much different clinical picture than patients recruited in the clinical trials, obtaining real-world evidence of medication adoption is important for therapeutic efficiency and safety. This study used three population-based data in Taiwan, the National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry, between 2001 and 2015, to investigate the effect of conventional chemotherapy (CCT) versus non-conventional chemotherapy (NCCT) on the overall survival (OS) of patients with AML (n = 7,763). Cox proportional hazard regression was used to estimate the hazard ratios (HR) of different treatments on the risk of mortality. To reduce the potential selection bias, we used the inverse probability of treatment weighting based on the propensity score to balance the baseline characteristics between patients receiving CCT and NCCT. The median survival time for CCT and NCCT arms was 10.2 months (95% confidence interval (95% CI): 9.7-10.9) and 4.1 months (95% CI: 3.8-4.5), respectively. Compared to the patients received NCCT, those receiving CCT had a lower risk of mortality (HR 0.63 (95% CI: 0.59-0.67, P < 0.001). Subgroup analysis showed that CCT did benefit patients in different gender, age, comorbidity, and socioeconomic status (SES) groups. In conclusion, the real-world population-based data exhibited CCT were more likely to be prescribed for patients with AML of younger age, fewer comorbidities, diagnosed recently (2011-2015), and higher SES. In fact, CCT had better treatment outcomes than NCCT in terms of OS for adult patients diagnosed with AML.

Cardiogenic shock in Taiwan from 2003 to 2017 (CSiT-15 study).

BACKGROUND: This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices. METHODS: Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan's National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels. RESULTS: In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22-25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years. CONCLUSIONS: In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.

Combination therapies with thiazolidinediones are associated with a lower risk of acute exacerbations in new-onset COPD patients with advanced diabetic mellitus: a cohort-based case-control study.

BACKGROUND: The effects of oral antihyperglycaemic drugs (OADs) for type 2 diabetes mellitus (T2DM) on the outcomes of co-existing chronic obstructive pulmonary disease (COPD) patients are not well studied. We examined the association of combinational OADs and the risk of acute exacerbations of COPD (AECOPD) in T2DM patients with co-existing COPD. METHODS: A cohort-based case-control study was conducted using data from the National Health Insurance Research Database of Taiwan. Among new-onset COPD-T2DM patients, 65,370 were prescribed metformin and 2nd-line OADs before the date of COPD onset. Each AECOPD case was matched to 4 randomly selected controls according to the propensity score estimated by the patient's baseline characteristics. Conditional logistic regression analysis was performed to estimate the association between AECOPD risk and OAD use. RESULTS: Among COPD-T2DM patients, 3355 AECOPD cases and 13,420 matched controls were selected. Of the patients treated with a double combination of oral OADs (n = 12,916), those treated with sulfonylurea (SU) and thiazolidinediones (TZD) had a lower AECOPD risk than the patients who received metformin (MET) and SU, with an adjusted odds ratio (OR) of 0.69 (95% confidence interval [CI] 0.51-0.94, P = 0.02). Of the patients with a triple combination of oral OADs (n = 3859), we found that those treated with MET, SU and TZD had a lower risk of AECOPD (adjusted OR 0.81 (0.68-0.96, P = 0.01) than a combination of MET, SU and α-glucosidase inhibitors (AGIs) regardless of the level of COPD complexity. CONCLUSION: Combination therapies with TZD were associated with a reduced risk of AECOPD in advanced T2DM patients with co-existing COPD.

Risk of heart failure following drug-eluting stent implantation in patients with non-ST-elevation myocardial infarction.

BACKGROUND AND AIMS: The association between implanted stent types and heart failure in patients with non-ST-elevation myocardial infarction (NSTEMI) remains unknown. The current study aimed to investigate whether the implantation of a newer-generation drug-eluting stent (NG-DES) compared with that of a bare-metal stent (BMS) in patients with NSTEMI who receive an undefined duration of dual antiplatelet therapy (DAPT) reduces the risk of hospitalization for heart failure (HHF). METHODS: In this nationwide, population-based retrospective cohort study, propensity score matching was used on the Taiwan's National Health Insurance Research Database to select 8,644 pairs of patients with NSTEMI and similar baseline characteristics receiving NG-DES or BMS implantation between January 1, 2007 and December 31, 2016. A competing risk model was constructed to evaluate the risk of HHF in the NG-DES and BMS groups. Death was considered a competing risk. RESULTS: Rates of cumulative incidence competing risk for HHF at 1, 2, 3, 4, and 5-year follow-ups were lower in the NG-DES group (4.11%, 5.63%, 6.72%, 7.65%, and 8.89%, respectively) than in the BMS group (5.89%, 7.81%, 9.25%, 10.8%, and 11.9%, respectively). After adjustment for all clinical variables, NG-DES implantation was associated with a lower risk of HHF than BMS implantation after 5 years, with an adjusted subdistribution hazard ratio of 0.71 (95% CI = 0.64-0.79, p < 0.001). These results are in agreement with those of patients who received DAPT for >6 months. CONCLUSIONS: NG-DESs may reduce HHF risk in patients with NSTEMI who receive an undefined duration of DAPT.

Association between Anemia and Stroke in Females: A Nationwide, Population-Based Cohort Study in Taiwan.

Optimal stroke prevention strategies for women should take into account specific sex-related stroke risk factors. Anemia is a common medical condition in females, particularly in women of reproductive age. This study investigated whether anemia is an independent risk factor for stroke in females in a population-based cohort study. We investigated newly diagnosed anemic female patients with no history of central nervous system disease, psychiatric disorders, traumatic brain injury, major operations or hemorrhagic diseases identified from the Taiwan National Health Insurance Research Database. Non-anemic matched controls (1:1) were selected based on a propensity score estimated using a logistic regression model that included demographic characteristics and comorbidities. A competing risk analysis was applied to estimate the stroke risk in anemic patients compared to that of their matched controls. In our study, the adjusted sub-distribution hazard ratios (aSHRs) of overall, hemorrhagic and ischemic stroke in anemic female patients aged <50 years were 1.35 (95% confidence interval (CI): 1.19-1.52, p < 0.001), 1.31 (95% CI, 1.09-1.56, p < 0.003), and 1.35 (95% CI, 1.15-1.58, p < 0.001), respectively, compared to non-anemic female controls. However, a positive association between anemia and stroke was not found for those aged ≥50 years. Similar results were observed when the follow-up age was limited to 50 years to reduce the potential effects of menopause on stroke. In conclusion, the present population-based cohort study found that anemia is a potential risk factor for overall, hemorrhagic and ischemic stroke in females of reproductive age.

Effect of drug-eluting stents on 1-year risk of new-onset atrial fibrillation in patients with acute myocardial infarction treated with percutaneous coronary intervention.

The use of a drug-eluting stent (DES) in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention is conventional. However, the effect of DES on new-onset atrial fibrillation (AF) after AMI still remains unclear.By using data from Taiwan's National Health Insurance Research Database, a total of 17,741 patients with ST-elevation myocardial infarction (STEMI) and 17,631 patients with non-ST-elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention were analyzed to investigate the risk of new-onset AF after index admission of AMI.There were 26.5% (N = 4696) of patients with STEMI and 39.5% (N = 6967) of patients with NSTEMI received DES implantation. Upon 1-year follow-up, we observed that DES placement was associated with a reduced 1-year risk of new-onset AF in the patients with NSTEMI (adjusted hazard ratio [aHR] = 0.74, 95% confidence interval [CI] = 0.59-0.93, P = .009) after adjustment for clinical relevant variables. This benefit was consistent with that in the patients with NSTEMI who were ≥75 years old, had a CHA2DS2-VASc score of ≥2, and did not receive intra-aortic balloon pump insertion (aHR = 0.72, 95% CI = 0.53-0.98, P = .039; aHR = 0.73, 95% CI = 0.586-0.92, P = .006; and aHR = 0.71, 95% CI = 0.56-0.90, P = .004; respectively). However, DES placement had a neutral effect on the risk of new-onset AF in the patients with STEMI.Compared with the use of BMS, the use of DES might reduce the risk of new-onset AF in patients with NSTEMI.

Efficacy and safety of clopidogrel and aspirin do not differ in patients with stable ischemic stroke.

BACKGROUND: The current study compared the efficacy and safety of clopidogrel vs aspirin in the secondary prevention of ischemic stroke (IS). METHODS: We included patients from the Taiwan National Health Insurance Research Database who were aged between 20 and 80 years, had their first ever IS, had no diagnosis of atrial fibrillation, and had not used an oral anticoagulant before the index IS between 2002 and 2010. We excluded patients who died or were admitted to a hospital due to acute myocardial infarction, recurrent IS, or major bleeding within 3 months of IS. Patients were then classified into clopidogrel as aspirin users. Propensity score matching was adopted to select clopidogrel and aspirin groups with similar baseline characteristics (n = 8457 vs 16,914, mean follow-up period of 2.1 years and 1.9 years, respectively). Conditional Cox proportional hazard regression was used to compare risks of all-cause death, cardiovascular death, recurrent stroke, acute myocardial infarction, and major bleeding in clopidogrel users and aspirin users. RESULTS: The risks of all-cause death, cardiovascular death, recurrent stroke, and acute myocardial infarction did not differ between clopidogrel and aspirin users. Subgroup analyses revealed that the results were consistent regardless of age, disease severity, or comorbidity. CONCLUSION: According to real-world data, the efficacy and safety of clopidogrel and aspirin for secondary prevention of stable IS did not differ.

Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan.

BACKGROUND: In addition to the traditional risk predictors, whether anemia is an early biomarker of dementia, needs to be confirmed. OBJECTIVE: This population-based cohort study aimed to investigate the dementia risk in patients with newly diagnosed anemia using data from the Taiwan National Health Insurance Research Database. METHODS: All newly diagnosed anemia patients (n = 26,343) with no history of stroke hospitalization, central nervous disease other than dementia, psychiatric disorders, traumatic brain injury, major operations, or blood loss diseases, were enrolled. A group of non-anemic controls, 1:4 matched with anemic patients on the basis of demographics and comorbidities, was also included. A competing risk analysis was used to evaluate the dementia risk in anemic patients compared to that of their matched controls. RESULTS: The adjusted subdistribution hazard ratio (SHR) of dementia risk in anemic patients was 1.14 (95% confidence interval [CI]: 1.08~1.21, p<0.001). Patients with iron supplements tended to exhibit a lower dementia risk (adjusted SHR: 0.84; 95% CI: 0.75~0.94, p=0.002) compared to patients without iron supplement. A subgroup analysis showed that a positive association between dementia and anemia existed in females, those aged 70 years and older, and patients without hypertension, diabetes, or hyperlipidemia. CONCLUSION: The present population-based cohort study identified that newly diagnosed anemia is a risk factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people with iron deficiency anemia.

Risk of new-onset atrial fibrillation after drug-eluting stent implantation in patients with stable coronary artery disease.

BACKGROUND: New-onset atrial fibrillation (NOAF) is associated with adverse outcomes in patients with coronary artery disease (CAD). Although newer generation drug-eluting stents (NG-DESs) are more beneficial than bare-metal stents (BMSs) in reducing the risk of in-stent restenosis and revascularization, whether NG-DES implantation in patients with stable CAD reduces NOAF risk compared with BMS implantation remains unknown. METHODS: This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching was used to select 18,423 pairs of patients with stable CAD receiving NG-DES implantation and BMS implantation with similar baseline characteristics for evaluation. A competing risk model was used to evaluate the risk of NOAF between the NG-DES and BMS groups in which death was considered a competing risk. RESULTS: After adjustment for patients' clinical variables, the use of NG-DESs was associated with a decreased risk of NOAF at 1-year follow-up (adjusted subdistribution hazard ratio [SHR] = 0.79, 95% confidence interval [CI] = 0.68-0.93, P = 0.005) compared with the use of BMSs. Similar results indicated that NG-DESs were beneficial for reducing the risk of NOAF (adjusted SHR = 0.81, 95% CI = 0.67-0.97, P = 0.020) in patients with a CHA2DS2-VASc score of ≥2. These findings were also consistent with those for patients who received dual antiplatelet therapy for an undefined duration of >1 month following stent implantation. CONCLUSIONS: Our findings suggest that NG-DESs might reduce the risk of NOAF in patients with stable CAD.