Indirect Comparison of Cryoablation and Radiofrequency Ablation as Initial Therapy for Symptomatic Paroxysmal Atrial Fibrillation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Data on first-line ablation treatment for patients with symptomatic atrial fibrillation (AF) are scarce. This study indirectly compared the efficacy and safety of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) as initial therapy for symptomatic AF. METHODS: We searched the EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) that compared CBA or RFA with antiarrhythmic drugs (AADs) as first-line treatment for AF from the time of database establishment up to December 2021. The odds ratio (OR) with a 95% confidence interval (CI) was used as a measure of the treatment effect. RESULTS: Six RCTs (3 CBA, 3 RFA) that enrolled a total of 1,215 patients were included in this analysis. There were no significant differences in atrial arrhythmia (AA) (OR 0.993, 95% CI: 0.602-1.638), symptomatic AA (OR 0.638, 95% CI: 0.344-1.182), or serious adverse events (OR 1.474, 95% CI: 0.404-5.376) between the two ablation techniques. The incidences of additional CBA therapy (OR 2.693, 95% CI: 1.277-5.681) and patients who crossed over to AAD therapy (OR 0.345, 95% CI: 0.179-0.664) in the CBA group were significantly lower than those in the RFA group. CONCLUSION: Among patients with paroxysmal AF receiving initial therapy, CBA and RFA share a similar efficacy and safety profile. When pulmonary vein isolation is performed by CBA, study crossover and the need for additional ablation are substantially lower.

Cell viability and drug evaluation biosensing system based on disposable AuNPs/MWCNT nanocomposite modified screen-printed electrode for exocytosis dopamine detection.

Cell viability, as an important index to evaluate drug effects, usually was measured by tetrazolium colorimetric assay, playing a key role in drug development and drug screening. Tedious operating procedures, unsatisfactory sensitivity and abominable environments perplex researchers to acquire more detailed in vivo-relevant biological information. Herein, a simple and low-cost cell viability and drug evaluation biosensing system-based on multiwalled carbon nanotubes, gold nanoparticles and Nafion modified screen-printed electrode (SPE) biosensor was constructed for detection of dopamine (DA) released from living cells to evaluate cytotoxicity of antineoplastic drugs such as cisplatin and resveratrol. The biosensing system was demonstrated to display exceptional selectivity, excellent flexibility and good stability toward DA measurement in complex bio-samples. Additionally, the satisfactory recoveries of DA in real samples revealed the reliability and accuracy of the biosensing system in practical application. The IC50 curves respectively obtained by the biosensing system and tetrazolium colorimetric assay provided similar IC50 value but distinctly different dose-effect relationship, which confirmed the enormous potential of the biosensor in cell viability and described drug efficacy profiles in cell function. In short, the cell viability and drug evaluation system using SPE biosensor paves a new way in drug screening and pharmaceutical application to measure bioactive molecule such as DA.

Using a simple preliminary screening tool to explore related factors of osteoporosis in the elderly of southern Taiwan.

ABSTRACT: The aims of this study were to use a simple screening tool to explore related factors with osteoporosis in the elderly in the community of southern Taiwan.This was an observational cross-sectional study using Osteoporosis Self-Assessment Tool for Asia (OSTA), Osteoporosis Self-Assessment Tool for Taiwanese (OSTAi), and the basic demographic information to identify osteoporosis in the participants. This study collected data from 200 participants aged 65 and above and living in southern Taiwan.The prevalence of osteoporosis among elders in the community was 30.5% (OSTA) and 58.0% (OSTAi), respectively. The prevalence of osteoporosis determined by OSTA and OSTAi in female (33.1% and 63.1%, respectively.) was higher than in male (25.7% and 48.6%, respectively.). Risk factors such as gender, age, and body mass index (BMI) were significantly associated with osteoporosis (P < .001). Using OSTA and OSTAi to assess the risk for osteoporosis, for every 1 year of age increase, the odds ratio (OR) value of osteoporosis increased by 1.84 and 1.50 times, respectively (P < .001); for every 1 kg/m2 increase in BMI, the OR of osteoporosis decreases by 0.36 and 0.44 times, respectively. The results of this study can be used a simple tool of OSTA and OSTAi self-examination to screen potential high-risk groups for osteoporosis in the community.OSTA and OSTAi can screen for possible high-risk groups early and without invasive examinations and self-examination tools in a hospital. Low BMI poses higher risks of osteoporosis for the elderly, so increasing functional ability, improving muscle strength, maintaining exercise habits and keeping proper weight could prevent osteoporosis in the seniors.

Meta-analysis of the safety and efficacy of using minimally interrupted novel oral anticoagulants in patients undergoing catheter ablation for atrial fibrillation.

PURPOSE: The ideal periprocedural anticoagulation strategy for patients being treated with a novel oral anticoagulant (NOAC) during catheter ablation (CA) for atrial fibrillation (AF) is unclear. We evaluated the safety and efficacy of using a minimally interrupted NOAC strategy versus an uninterrupted NOAC or vitamin K antagonist (VKA) strategy during AF ablation. METHODS: The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled or prospective observational studies that compared a minimally interrupted NOAC strategy with an uninterrupted NOAC or VKA strategy from the time of database establishment up to December 2019. The primary endpoints were major bleeding, minor bleeding, and symptomatic thromboembolism. The secondary endpoint was silent cerebral infarction (SCI) as detected by post-ablation brain magnetic resonance imaging (MRI). A measurement of treatment effect for the endpoint was reported as pooled odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 18 studies (6 randomized, 11 observational, and 1 randomized registry) with 6203 patients were included in the final analysis (47% of the patients received minimally interrupted NOAC). There was no significant difference between treatment groups regarding the risk for major bleeding (OR 1.04, 95% CI 0.69-1.57, P = 0.86, I2 = 27%). Different stratification methods did not yield significant difference regarding the risk for major bleeding. There was no difference between groups regarding the risk for minor bleeding (P = 1.00) or symptomatic thromboembolism (P = 0.26). Brain MRI results showed that both uninterrupted NOAC (OR 0.44, 95% CI 0.23-0.83, P = 0.01, I2 = 72%) and uninterrupted VKA (OR 0.48, 95% CI 0.24-0.97, P = 0.04, I2 = 36%) produced a significant reduction in the rate of SCI when compared with minimally interrupted NOAC. CONCLUSIONS: A periprocedural anticoagulation strategy of minimally interrupted NOAC is not superior to uninterrupted NOAC or VKA when used during AF ablation. There is evidence favoring the use of uninterrupted NOAC or VKA in terms of the risk for SCI.

The use of methylprednisolone in COVID-19 patients: A propensity score matched retrospective cohort study.

PURPOSE: To evaluate the efficacy and safety of methylprednisolone in treating the coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective cohort study was conducted, and all COVID-19 patients were recruited who were admitted to the Yichang Third People's Hospital from February 1st to March 31st, 2020. One-to-one propensity score matching (PSM) was used for minimizing confounding effects. The primary outcome was hospital mortality, with the secondary outcomes being the time needed for a positive SARS-CoV-2 nucleic acid test to turn negative and the length of hospital stay. RESULTS: Totaling 367 patients with COVID-19 hospitalized at the Yichang Third People's Hospital were identified, of whom 276 were mild or stable COVID-19, and 67 were serious or critically ill. Among them, 255 patients were treated using methylprednisolone, and 188 did not receive any corticosteroid-related treatment. After PSM, no statistically significant difference was found in the baseline characteristics between the two groups. Regarding the outcomes, there also were no statistically significant difference between the two groups. Patients without the use of methylprednisolone were more quickly to obtain negative results of their nasopharyngeal swab tests of SARS-CoV-2 nucleic acid after treatment, compared to those receiving methylprednisolone. CONCLUSION: Methylprednisolone could not improve the prognosis of patients with COVID-19, and the efficacy and safety of the use of methylprednisolone in patients with COVID-19 still remain uncertain, thus the use of corticosteroids clinically in patients with COVID-19 should be with cautions.

Meta-analysis of medical management versus catheter ablation for atrial fibrillation.

Several observational studies have shown a survival benefit for patients with atrial fibrillation (AF) who are treated with catheter ablation (CA) rather than medical management (MM). However, data from randomized controlled trials (RCTs) are uncertain. Therefore, we performed a meta-analysis of RCTs that compared the benefits of CA and MM in treatment of AF. We searched the Cochrane Library, PubMed, and EMBASE databases for RCTs that compared AF ablation with MM from the time of database establishment up to January 2020. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure treatment effect. Twenty-six RCTs that enrolled a total of 5788 patients were included in the meta-analysis. In this meta-analysis, the effect of AF ablation depended on the baseline level of left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. AF ablation appears to be of benefit to patients with a lesser degree of advanced HF and better LVEF by reducing mortality. Meanwhile, this mortality advantage was manifested in long-term follow-up. CA increased the risk for hospitalization when it was used as first-line therapy and decreased the risk when used as second-line therapy. CA reduced recurrence of atrial arrhythmia for different types of AF (paroxysmal or persistent AF) and CA-related complications were non-negligible. There was no convincing evidence for a reduction in long-term stroke risk after AF ablation, and additional high quality RCTs are needed to address that issue.

Peri-procedural novel oral anticoagulants dosing strategy during atrial fibrillation ablation: A meta-analysis.

BACKGROUND: This study aimed at determining whether uninterrupted novel oral anticoagulant (UI-NOAC) would have similar rates of bleeding and thromboembolic events as minimally interrupted NOAC (MI-NOAC) at the time of ablation for atrial fibrillation (AF) as relevant studies are scarce. METHODS: We searched through the PubMed, EMBASE, and Cochrane Library databases for prospective observational studies (POSs) or randomised controlled trials (RCTs) comparing UI-NOAC versus MI-NOAC from their establishment to January 2020. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to compare the pooled treatment effect. RESULTS: Nine studies (three POSs and six RCTs) with 2578 patients were included in the final analysis (55% patients received MI-NOAC). No significant difference was found regarding the risk of major bleeding (OR 0.92, 95% CI 0.43-2.00, P = .84, I2  = 0%). Both groups were comparable in all subgroups ([Asians: OR 1.00, 95% CI 0.43-2.36, P = .99, I2  = 0%], [non-Asians: OR 0.64, 95% CI 0.11-3.88, P = .63, I2  = 0%], [RCTs: OR 0.85, 95% CI 0.37-1.97, P = .71, I2  = 0%], and [POSs: OR 0.52, 95% CI 0.19-12.01, P = .69, I2  = 0%]). The risk of minor bleeding (P = .88) or stroke (P = .69) was comparable between the groups. UI-NOAC resulted in a significant reduction in silent stroke (SS) (OR 0.44, 95% CI 0.23-0.83, P = .01, I2  = 72%). No significant difference was found in SS between once-daily and twice-daily NOACs (OR 0.91, 95% CI 0.63-1.33, P = .64, I2  = 0%) in the MI-NOAC group. CONCLUSIONS: UI-NOAC, as a peri-procedural anticoagulation strategy for catheter ablation in AF, had similar safety compared with MI-NOAC, but was advantageous in terms of SS.

Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens.

PURPOSE: Vancomycin (VCM) is a first-line antibacterial drug used to treat post-craniotomy meningitis (PCM). VCM pharmacokinetic parameters are altered in PCM patients, compared to those in other patients. Although VCM population pharmacokinetics (PPK) has been reported, changes in VCM PPK in adult Chinese PCM patients remain unknown. We developed a VCM PPK model in adult Chinese PCM patients and proposed a new strategy for individualising VCM administration using this model. METHODS: Data was obtained from a prospective study of 100 adult PCM patients in the Neurosurgery Department of the First Affiliated Hospital of Fujian Medical University. The trough concentrations at steady state were determined by enzyme multiplied immunoassay. Nonlinear mixed-effect model software was employed to develop the PPK model. The final model was evaluated using the bootstrap method and normalised prediction error distribution and through the testing of 20 independent adult PCM patients. RESULTS: VCM clearance in PCM patients was higher than that observed in other patients. Creatinine clearance affected VCM clearance, whereas no co-administered drugs influenced VCM pharmacokinetics. Trough concentrations were accurately predicted by the final model, while the prediction errors were less than ±32 %. Moreover, a new strategy for individualising VCM regimens using the PPK model was proposed and validated. CONCLUSIONS: A PPK model was developed to estimate the individual clearance in inpatients receiving intravenously infused VCM and could be used to develop individualised dosing of adult Chinese PCM patients.

[Population pharmacokinetic/pharmacodynamic modeling of warfarin by nonlinear mixed effects model].

The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.

[Population pharmacokinetic modeling of flurbiprofen].

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.