scholarly journals Comparative efficacy of delafloxacin for complicated and acute bacterial skin and skin structure infections: results from a network meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ioanna Vlachaki ◽  
Matteo Vacchelli ◽  
Daniela Zinzi ◽  
Edel Falla ◽  
Yilin Jiang ◽  
...  

Abstract Background Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI. Methods A systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE®, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid. Results A feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation. Conclusions Delafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1020
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chih-Cheng Lai ◽  
Tzu-Ping Shih ◽  
Hung-Jen Tang

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90–1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40–0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07–1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.


2021 ◽  
Author(s):  
Vinícius Y Moraes ◽  
Alexandre R Marra ◽  
Leandro L Matos ◽  
Ary Serpa Neto ◽  
Luiz Vicente Rizzo ◽  
...  

Abstract Background: We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat coronavirus disease 2019 (COVID-19) patients. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine (HCQ) and the control group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. Results: Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with HCQ compared to standard of care or placebo (16.7% vs. 18.5%; pooled risk ratio 1.09; 95%CI: 0.99-1.19). Also, therate of serious adverse effects was similar between both groups, HCQ and control (3.7% vs. 2.9%; pooled risk ratio 1.22; 95%CI: 0.76-1.96). Conclusion: Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients.Systematic review registration: Prospero database, registration number: CRD42020197070.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lajos Szakó ◽  
Nelli Farkas ◽  
Szabolcs Kiss ◽  
Szilárd Váncsa ◽  
Noémi Zádori ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. Methods A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. Discussion Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040906
Author(s):  
Xinyu Zhao ◽  
Lihui Meng ◽  
Youxin Chen

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.


2020 ◽  
Vol 46 (08) ◽  
pp. 908-918
Author(s):  
Behnood Bikdeli ◽  
Saurav Chatterjee ◽  
Ajay J. Kirtane ◽  
Sahil A. Parikh ◽  
Giuseppe M. Andreozzi ◽  
...  

AbstractThrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52–0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22–0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51–0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45–1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24–0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26–0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40–2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47–2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sadayuki Kawai ◽  
Nozomi Takeshima ◽  
Yu Hayasaka ◽  
Akifumi Notsu ◽  
Mutsumi Yamazaki ◽  
...  

Abstract Background Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. Methods This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80–1.03, P = 0.15). Conclusion Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 785
Author(s):  
I-Chia Liang ◽  
Yun-Hsiang Chang ◽  
Adrián Hernández Hernández Martínez ◽  
Chi-Feng Hung

Background and Objectives: Iris-claw intraocular lens (ICIOL) could be implanted in the anterior chamber (AC) or retropupillary (RP) in eyes lacking capsular and/or zonular support. Several studies have focused on comparing the efficacy and complications of these two techniques and we designed this research to review the published literatures. Materials and Methods: Peer-reviewed studies were collected through network databases (PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and analyzed. The primary outcome was the standardized mean differences (SMDs) of pre- and post-operative corrected distant visual acuity (CDVA). The secondary outcome was the SMDs of pre- and post-operative intraocular pressure (IOP), endothelial cell counts (ECC), and the odds ratios (ORs) of post-operative IOP elevation and cystoid macular edema (CME). Comprehensive Meta-Analysis software was utilized to conduct statistical analysis. Results: Six studies (one randomized controlled trial and five retrospective case series) were relevant and included a total of 516 eyes (255 and 261 eyes in the AC ICIOL and RP ICIOL groups, respectively). The quantitative analysis showed no significant differences in CDVA (SMD: 0.164, 95% confidence interval (CI): −0.171 to 0.500), ECC (SMD: −0.011, 95% CI: −0.195 to 0.173), and IOP elevation events (OR: 0.797, 95% CI: 0.459 to 1.383). Lesser IOP reduction (SMD: 0.257, 95%CI: 0.023 to 0.490) and a relative increase in the incidence of CME (OR:2.315, 95% CI: 0.950 to 5.637) were observed in the AC ICIOL group compared with RP ICIOL group. Conclusions: Our meta-analysis indicated that AC and RP ICIOL seem to have equivalent visual outcomes. RP ICIOL may perform slightly better with more IOP reduction and lesser CME. More randomized controlled trials, which have higher patient participation and more outcomes are needed to confirm our conclusions.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028172
Author(s):  
Masahiro Kashiura ◽  
Noritaka Yada ◽  
Kazuma Yamakawa

IntroductionOver the past decades, the treatment for blunt splenic injuries has shifted from operative to non-operative management. Interventional radiology such as splenic arterial embolisation generally increases the success rate of non-operative management. However, the type of intervention, such as the first definitive treatment for haemostasis (interventional radiology or surgery) in blunt splenic injuries is unclear. Therefore, we aim to clarify whether interventional radiology improves mortality in patients with blunt splenic trauma compared with operative management by conducting a systematic review and meta-analysis.Methods and analysisWe will search the following electronic bibliographic databases to retrieve relevant articles for the literature review: Medline, Embase and the Cochrane Central Register of Controlled Trials. We will include controlled trials and observational studies published until September 2018. We will screen search results, assess the study population, extract data and assess the risk of bias. Two review authors will extract data independently, and discrepancies will be identified and resolved through a discussion with a third author where necessary. Data from eligible studies will be pooled using a random-effects meta-analysis. Statistical heterogeneity will be assessed by using the Mantel-Haenszel χ² test and the I² statistic, and any observed heterogeneity will be quantified using the I² statistic. We will conduct sensitivity analyses according to several factors relevant for the heterogeneity.Ethics and disseminationOur study does not require ethical approval as it is based on the findings of previously published articles. This systematic review will provide guidance on selecting a method for haemostasis of splenic injuries and may also identify knowledge gaps that could direct further research in the field. Results will be disseminated through publication in a peer-reviewed journal and presentations at relevant conferences.PROSPERO registration numberCRD42018108304.


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