Low-dose aspirin for prevention of cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease: A real-world nationwide cohort study.

AIMS/INTRODUCTION: Cardiovascular mortality risk is elevated among patients with diabetes and concurrent chronic kidney disease. However, controversy surrounds the use of aspirin for primary prevention within this population. This study aims to assess the effectiveness and safety of low-dose aspirin for primary prevention in patients with diabetes and pre-end-stage renal disease. MATERIALS AND METHODS: This was a retrospective population-based cohort study using the National Health Insurance Research Database in Taiwan. The study included adults with type 2 diabetes who were enrolled in the pre-end-stage renal disease pay-for-performance program and had no atherosclerotic cardiovascular disease. We used propensity score analysis to control baseline characteristics between the two groups. Clinical outcomes including cardiovascular mortality, all-cause mortality, major bleeding, and renal disease progression were compared between patients who first received aspirin and those who did not. RESULTS: Between January 2012 and December 2015, a total of 2,155 low-dose aspirin users and 6,737 nonaspirin users were identified. Following propensity score adjustment, aspirin use exhibited a comparable risk of cardiovascular death compared with nonaspirin users (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.65-1.95; P = 0.681). The risk of all-cause mortality was similar between the two groups (aHR 1.07; 95% CI 0.92-1.24; P = 0.385). Similar risks were observed in terms of major bleeding and renal disease progression. CONCLUSIONS: In patients with diabetes and pre-end-stage renal disease who lacked atherosclerotic cardiovascular disease, low-dose aspirin did not demonstrate a reduction in mortality. These findings do not support the use of aspirin for primary prevention in this high-risk population.

Correlation between antibiotic consumption and resistance of Pseudomonas aeruginosa in a teaching hospital implementing an antimicrobial stewardship program: A longitudinal observational study.

BACKGROUND/PURPOSE: The rapid emergence of Pseudomonas aeruginosa resistance made selecting antibiotics more challenge. Antimicrobial stewardship programs (ASPs) are urging to implant to control the P. aeruginosa resistance. The purpose of this study is to evaluate the relationship between antimicrobial consumption and P. aeruginosa resistance, the impact of ASPs implemented during the 14-year study period. METHODS: A total 14,852 P. aeruginosa isolates were included in our study. The resistant rate and antimicrobial consumption were investigated every six months. Linear regression analysis was conducted to examine the trends in antibiotics consumption and antimicrobial resistance over time. The relationship between P. aeruginosa resistance and antimicrobial consumption were using Pearson correlation coefficient to analysis. The trend of resistance before and after ASPs implanted is evaluated by segment regression analysis. RESULTS: P. aeruginosa resistance to ceftazidime, gentamicin, amikacin, ciprofloxacin and levofloxacin significantly decreased during the study period; piperacillin/tazobactam (PTZ), cefepime, imipenem/cilastatin and meropenem remained stable. The P. aeruginosa resistance to ciprofloxacin and levofloxacin increasing initial then decreased after strictly controlled the use of levofloxacin since 2007. As the first choice antibiotic to treat P. aeruginosa, the consumption and resistance to PTZ increase yearly and resistance became stable since extended-infusion therapy policy implant in 2009. CONCLUSION: Our ASP intervention strategy, which included extended infusion of PTZ and restrict use of levofloxacin, may be used to control antimicrobial resistance of P. aeruginosa in medical practice.

Development of a combination antibiogram for empirical treatments of Pseudomonas aeruginosa at a university-affiliated teaching hospital.

INTRODUCTION: The significantly higher mortality rate in the critical illness patients with Pseudomonas aeruginosa (PA) infection is linked to inappropriate selecting of empirical treatment. Traditional local antibiogram provides clinicians the resistant rate of a single antimicrobial agent to the pathogen in the specific setting. The information is valuable to the clinicians in selecting suitable empirical antibiotic therapy. However, traditional local antibiogram can only provide information for single agent empirical antibiotic not combination regimens. The combination antibiogram should be developed to facilitate the selection of appropriate antibiotics to broader the coverage rate of resistant PA. METHODS: The susceptibility to the ß-lactam antibiotics (piperacillin/tazobactam (PTZ), ceftazidime, cefepime, imipenem, or meropenem) or to those administered in combination with an aminoglycoside (gentamicin or amikacin) or fluoroquinolone (ciprofloxacin or levofloxacin) was calculated. The chi-square test was used to compare the differences of combination coverage rates between non-ICU and ICU isolates. RESULTS: 880 PA isolates were isolated during study period. The susceptibility of single agents ranged from 83.1% to 89.7%. The combination regimens containing amikacin provide the highest cover rate (98.9%-99.1%) and those containing levofloxacin provide less coverage rate (92.3%-93.9%). The susceptibility to five ß-lactam single agents in ICU isolates significantly lower than non-ICU isolates. The non-ICU isolates exhibited significantly higher susceptibility to the PTZ-gentamicin (p = 0.002) and ceftazidime-gentamicin (p = 0.025) than ICU isolates. CONCLUSION: Our results support the use of aminoglycosides instead of fluoroquinolones as additive agents in empirical combination treatments for patients with critical infections caused by PA.

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.

Effects of various statins on depressive symptoms: A network meta-analysis.

BACKGROUND: Previous studies have indicated that statins can reduce the severity of depressive symptoms. However, the optimal choice of statin remains unclear. Therefore, we conducted a network meta-analysis to determine the optimal statin for treating depression. METHOD: We performed a pairwise and network meta-analysis by searching the PubMed, Embase, and Cochrane Library databases on October 29th, 2020. Eligible studies were randomized controlled trials that reported on changes in depressive symptoms. The Cochrane Collaboration tool was used to assess risk of bias. We tested for possible inconsistency globally by using a χ2-test and locally by calculating inconsistency factors for each comparison in closed loops. The ranking probabilities of being at each possible rank for each intervention were estimated. Comparison-adjusted funnel plots were obtained to assess publication bias. Sensitivity analysis was also performed. RESULTS: We identified 13 studies that matched our inclusion criteria. The risks of bias were mostly low. None of the global or local tests found significance. Compared with placebo, atorvastatin significantly reduced the severity of depressive symptoms (mean difference -3.46, 95% confidence interval -5.26 to -1.67). Atorvastatin had the first and second rank with probabilities of 44.9% and 39.0%, respectively. Comparison-adjusted funnel plots revealed no significant publication bias. LIMITATIONS: Low similarity of included studies and a relative large treatment effect of a single study were observed. CONCLUSIONS: In this first network meta-analysis, atorvastatin, with high intensity and a lipophilic effect, was identified as the optimal choice of statin for treating depression.

Effectiveness and safety of rivaroxaban versus warfarin in Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation: A real-world nationwide cohort study.

BACKGROUND: The optimal anticoagulant for end-stage renal disease patients for stroke prophylaxis is unknown. The efficacy and safety of warfarin in this population are debatable. In addition, real-world evidence of direct oral anticoagulants in patients with end-stage renal disease is limited. The aim of this study was to evaluate the clinical outcomes of rivaroxaban compared with warfarin in Taiwanese patients with end-stage renal disease with nonvalvular atrial fibrillation in a real-world setting. METHODS AND RESULTS: This was a retrospective population-based cohort study conducted using Taiwan's National Health Insurance Research Database. Patients with nonvalvular atrial fibrillation and end-stage renal disease who started on rivaroxaban or warfarin between February 2013 and September 2017 were eligible to participate in the study. The inverse probability of treatment weighting approach was used to balance baseline characteristics. Bleeding and thromboembolic outcomes were compared using competing risk analyses. The study population consisted of 3358 patients (173 and 3185 patients on rivaroxaban and warfarin, respectively). In the rivaroxaban group, 50.8%, 38.7%, and 10.4% of the patients received 10, 15, and 20 mg of the drug, respectively. The cumulative incidence of major bleeding was similar between the two groups; however, the gastrointestinal bleeding rate was lower in the rivaroxaban group (adjusted subdistribution hazard ratio [SHR]: 0.56, 95% confidence interval [CI]: 0.34-0.91) than in the warfarin group. Furthermore, the composite risk of ischemic stroke or systemic embolism was significantly lower in the rivaroxaban group (adjusted SHR: 0.36, 95% CI: 0.17-0.79). Similar findings were observed for patients who received 10 mg of rivaroxaban. CONCLUSIONS: In Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation, rivaroxaban may be associated with a similar risk of major bleeding but a lower risk of thromboembolism compared with warfarin. The potential benefit of 10 mg of rivaroxaban in this population requires further investigation.

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis.

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 µg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 µmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.

Interactions between traditional Chinese medicine and western drugs in Taiwan: A population-based study.

BACKGROUND: Drug-drug interactions have long been an active research area in clinical medicine. In Taiwan, however, the widespread use of traditional Chinese medicines (TCM) presents additional complexity to the topic. Therefore, it is important to see the interaction between traditional Chinese and western medicine. OBJECTIVE: (1) To create a comprehensive database of multi-herb/western drug interactions indexed according to the ways in which physicians actually practice and (2) to measure this database's impact on the detection of adverse effects between traditional Chinese medicine compounds and western medicines. METHODS: First, a multi-herb/western medicine drug interactions database was created by separating each TCM compound into its constituent herbs. Each individual herb was then checked against an existing single-herb/western drug interactions database. The data source comes from the National Health Insurance research database, which spans the years 1998-2011. This study estimated the interaction prevalence rate and further separated the rates according to patient characteristics, distribution by county, and hospital accreditation levels. Finally, this new database was integrated into a computer order entry module of the electronic medical records system of a regional teaching hospital. The effects it had were measured for two months. RESULTS: The most commonly interacting Chinese herbs were Ephedrae Herba and Angelicae Sinensis Radix/Angelicae Dahuricae Radix. Ephedrae Herba contains active ingredients similar to in ephedrine. 15 kinds of traditional Chinese medicine compounds contain Ephedrae Herba. Angelicae Sinensis Radix and Angelicae Dahuricae Radix contain ingredients similar to coumarin, a blood thinner. 9 kinds of traditional Chinese medicine compounds contained Angelicae Sinensis Radix/Angelicae Dahuricae Radix. In the period from 1998 to 2011, the prevalence of herb-drug interactions related to Ephedrae Herba was 0.18%. The most commonly prescribed traditional Chinese compounds were MA SHING GAN SHYR TANG (23.1%), followed by SHEAU CHING LONG TANG (15.5%) and DINQ CHUAN TANG (13.2%). The prevalence of herb-drug interactions related to Angelicae Sinensis Radix, Angelicae Dahuricae Radix was 4.59%. The most common traditional Chinese compound formula were TSANG EEL SAAN (32%), followed by HUOH SHIANG JENQ CHIH SAAN (31.4%) and SHY WUH TANG (10.7%). Once the multi-herb drug interaction database was deployed in a hospital system, there were 480 prescriptions that indicated a TCM-western drug interaction. Physicians were alerted 24 times during two months. These alerts resulted in a prescription change four times (16.7%). CONCLUSION: Due to the unique cultural factors that have resulted in widespread acceptance of both western and traditional Chinese medicine, Taiwan stands well positioned to report on the prevalence of interactions between western drugs and traditional Chinese medicine and devise ways to reduce their incidence. This study built a multi-herb/western drug interactions database, embedded inside a hospital clinical information system, and then examined the effects that drug interaction alerts had on clinician prescribing behaviour. The results demonstrated that western drug/traditional Chinese medicine interactions are prevalent and that western-trained physicians tend to change their prescribing behaviour more than traditional Chinese medicine physicians in their response to medication interaction alerts.