Comparative effectiveness and safety of inhaled corticosteroid plus long-acting ß2-agonist fixed-dose combinations vs. long-acting muscarinic antagonist in bronchiectasis.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in bronchiectasis. RESEARCH DESIGN AND METHODS: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. RESULTS: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL. CONCLUSION: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.

Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and advanced kidney disease.

BACKGROUND: The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established. OBJECTIVES: To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD. METHODS: Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding. RESULTS: A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin. CONCLUSION: Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.

Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis.

BACKGROUND: An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive. OBJECTIVE: Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies. METHODS: We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated. RESULTS: Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73-0.99) and ICH (RR: 0.38; 95% CI: 0.28-0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results. CONCLUSIONS: In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.

Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.

BACKGROUND: Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results. METHODS: Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models. RESULTS: Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10). CONCLUSION: Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.

Statin use and incident erectile dysfunction--A nationwide propensity-matched cohort study in Taiwan.

BACKGROUND: Statins are commonly prescribed for cardiovascular diseases which have been reported to share many contributory underlying mechanisms with erectile dysfunction (ED). However, the correlation between statin use and incident ED is uncertain. METHODS: We conducted a population-based propensity-matched cohort study by identifying new statin users among male patients 40-79 years of age in the period 2000 to 2010. A statin nonuser control cohort matched for age, propensity score, and index year at a 3:1 ratio was selected for comparison. Cohorts were tracked for the occurrence of any type of incident ED according to the registry of ED diagnosis in the database. The association between statin use and the risk of ED was evaluated by Cox proportional hazard model and adjusted by age, PS, socioeconomic status, comorbidities, and medications. RESULTS: Compared with nonusers, statin users had a significantly lower risk of incident ED (HR, 0.75; 95% CI, 0.63-0.90, p=0.002). Further analysis demonstrated that statin users in the group of middle-aged (40-49 years old) or high-potency statin treated (i.e., rosuvastatin, atorvastatin, and simvastatin) had lower HR for incident ED. Analysis in the patterns of cumulative statin exposure also showed that high-potency statins could decrease the HR for incident ED in dose- and duration-dependent manners. CONCLUSIONS: Statin use was associated with a reduced risk of incident ED in the middle-aged men in Taiwan. The potency and the cumulative exposure of statin utilized played critical roles.

Statin use and incident dementia: a nationwide cohort study of Taiwan.

BACKGROUND: Statins are widely used in clinical treatment. However, an U.S. Food and Drug Administration issued health alert has raised concerns for the adverse effects of statin-associated confusion and memory loss in the elderly people. It is necessary to clarify the relationship between statin use and risk of incident dementia as well as whether class effects exist. METHODS: In this population-based retrospective cohort study, total 33,398 patients aged ≥ 60 years were selected from a subset of the Taiwan National Health Insurance Research Databases and followed up for tracking the occurrence of any type of dementia from 2000 to 2010. The Cox proportional hazards models were used. RESULTS: Compared to nonusers, statin users had a significantly lower risk of incident dementia (hazard ratio [HR], 0.78; 95% CI, 0.72-0.85, p<0.001). The potency and the cumulative duration of statin utilized were associated with the reducing risk of dementia. After stratifying by gender, the risk of incident dementia was lower in female statin users (HR, 0.76; 95% CI, 0.68-0.85, p<0.001) than in male statin users (HR, 0.86; 95% CI, 0.75-0.98, p=0.024). Higher potency and longer cumulative duration of statin use were required for reducing the risk of incident dementia in male patients than in female patients. CONCLUSION: Statin use was associated with a significantly lower risk of dementia in the elderly patients in Taiwan. The potency and the cumulative duration of statin utilized played critical roles.