Efficacy and Safety of Enoxaparin versus New Oral Anticoagulants to Prevent Venous Thromboembolism after Total Hip Replacement: A Systematic Review and Meta-Analysis

Prophylactic anticoagulant therapy is recommended for reducing the risk of venous thromboembolism (VTE) after a total hip replacement (THR). However, it is not clear which anticoagulant is preferable. Hence, a systematic review and meta-analysis of randomized double-blind controlled trials (RDBCTs) were conducted to investigate the clinical efficacy and safety of enoxaparin in comparison with newer oral anticoagulants for the prevention of VTE after THR. The Cochrane Library, Scopus, Web of Science, Embase, and PubMed/Medline databases were used for PICO search strategy. Relative risks (RR) of symptomatic VTE, clinically relevant bleeding, mortality, and a net clinical endpoint were estimated employing a random effect meta-analysis. ITC and RevMan software were used for indirect and direct comparisons, respectively. Nine RDBCTs comprising 24,584 patients were included. As compared to enoxaparin, a reduced risk for symptomatic VTE was observed with rivaroxaban (confidence interval [CI]: 0.32–0.77; RR: 0.46%) and comparable with apixaban (0.12–1.26; 0.42%) and dabigatran (0.22–2.20; 0.70%). Contrarily to enoxaparin, a greater risk for clinically relevant bleeding was observed with rivaroxaban (1.03–1.48; 1.23%), comparable with dabigatran (0.96–1.33; 1.10%) and reduced with apixaban (0.19–5.66; 0.96%). In indirect or direct comparisons, the interventions did not differ on the net clinical endpoint. In conclusion, the findings of this meta-analysis revealed no significant difference in the efficacy and safety of new oral anticoagulants as compared to enoxaparin for the prevention of VTE after total hip replacement surgery.

Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines

Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of two vaccine products. Estimates of rVE for enhanced influenza vaccines (eIV) vs. standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (e.g., all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (i.e., as compared with placebo) on the interpretation of rVE of eIV vs IIV. We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials.

Changes in Left atrial strain in patients with aortic stenosis after TAVI

Background Evaluation of left atrial (LA) function is an emerging biomarker of cardiovascular disease (CVD). LA strain by 2D speckle tracking echocardiography (LA strain, LAS) is feasible and reliable, and has been recently associated with adverse long-term outcomes in CVD, including aortic stenosis (AS). Purpose To evaluate the changes in left atrial strain (LAS) after correction of severe AS with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact. Methods One hundred consecutive patients with severe symptomatic AS who underwent TAVR at the Magna Graecia University of Catanzaro have been enrolled. Echocardiographic examination before and after TAVR was performed using Vivid E95 system and analysed using the EchoPAC 112.99 workstation (GE Healthcare). Patients underwent clinical follow up visits regularly. The primary study outcome was the difference in ΔLAS (postTAVR-preTAVR) between patients that met the main clinical endpoint (a composite of cardiovascular mortality and heart failure hospitalization) and those not meeting the endpoint. Statistical analyses were performed using JASP (version 0.14.1) and KMWin (version 1.52). Continuous variables were presented as mean and standard deviation and were compared through the unpaired Student's t test or the Mann-Whitney U test in case of a non-normal distribution. Differences between categorical variables were tested with the chi-square test. Multiple logistic regression analysis was performed to identify independent correlates of ΔLAS and to calculate Hazard Ratios (HR) with 95% CI. Kaplan-Meier was used to assess adverse event. Results During a median follow-up of 31 months, 35 patients (35%) met the composite clinical endpoint. The difference between LAS post-TAVR and LAS pre-TAVR (ΔLAS) was significantly larger in patients who met the combined endpoint (HR=0.76 [0.67–0.86]; p<0.001). Multivariate logistic regression analysis including ΔLAS, EuroSCORE II and left ventricular ejection fraction (LVEF) showed that ΔLAS (HR=0.80, p<0.001) was the only independent predictor of the combined clinical endpoint. Kaplan-Maier analysis showed that patients with a ΔLAS above its median value had a significantly better event-free survival compared to those below the median (p<0.001). Conclusions A lower reduction in ΔLAS after TAVR was an independent predictor of the primary composite outcome of cardiovascular death and hospitalization for HF. FUNDunding Acknowledgement Type of funding sources: None.

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19.Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment.Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151).Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments.Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Early reduction of left atrial function predicts adverse clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

AimsTo investigate the changes in left atrial strain (LAS) after correction of severe aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact.Methods and resultsOne hundred consecutive patients with severe symptomatic AS who underwent TAVR at the Magna Graecia University of Catanzaro underwent echocardiographic examination including assessment of LAS before and after TAVR. Independent investigators collected outcome data and information. The primary study outcome was the difference in ΔLAS (postTAVR–preTAVR) between patients those met the main clinical endpoint (a composite of cardiovascular mortality and heart failure hospitalisation) and those not meeting the endpoint.During a median follow-up of 31 months, 35 patients (35%) met the combined clinical endpoint. The difference between LAS post-TAVR and LAS pre-TAVR (ΔLAS) was significantly larger in patients who met the combined endpoint (HR=0.76 (0.67–0.86); p<0.001). Multivariate logistic regression analysis including ΔLAS, EuroSCORE II and left ventricular ejection fraction showed that ΔLAS (HR=0.80, p<0.001) was the only independent predictor of the combined clinical endpoint. Finally, a Kaplan-Maier analysis showed that patients with a ΔLAS above its median value had a significantly better event-free survival compared with those below the median (p<0.001).ConclusionsA lower reduction in ΔLAS after TAVR was an independent predictor of the primary composite outcome of cardiovascular death and hospitalisation for heart failure.

Analysis of the Responsiveness of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in the Treatment of OAG/OHT Patients

Aim. Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety. Methods. A literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation. Results. Eleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs. Conclusion. The existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.

Clinical, microbiological, and immunological effects of systemic probiotics in periodontal treatment: study protocol for a randomized controlled trial

Background The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for periodontitis stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological, and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. Methods Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6, and 12 months post-therapy and analyzed by checkerboard DNA–DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. Statistical analyses The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests and among groups (at each time point) using either ANOVA/ANCOVA or Kruskal-Wallis tests, depending on normality of the data. The chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤ 4 sites with PD ≥ 5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. Trial registration ClinicalTrials.gov NCT03733379. Registered on November 7, 2018.

Clinical, Microbiological And Immunological Effects Of Systemic Probiotics In Periodontal Treatment: Study Protocol For A Randomized Controlled Trial

Background: The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for Periodontitis Stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. Methods: Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6 and 12 months post-therapy, and analyzed by checkerboard DNA–DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. Statistical analyses: The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests; and among groups (at each time point) using either ANOVA /ANCOVA or Kruskal Wallis tests, depending on normality of the data. The Chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤4 sites with PD≥5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. Trial registration: ClinicalTrials.gov/NCT03733379/November 7, 2018.