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International Journal of Infectious... Jul 2022This study aimed to evaluate the efficacy and adverse events of favipiravir in patients with COVID-19. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to evaluate the efficacy and adverse events of favipiravir in patients with COVID-19.
METHODS
Our protocol was registered on PROSPERO (CRD42020206305). Fourteen databases were searched until February 8, 2021. An update search for new RCTs was done on March 2, 2022. Meta-analysis was done for randomized controlled trials (RCTs) and non-RCTs.
RESULTS
Overall, 157 studies (24 RCTs, 1 non-RCT, 21 observational studies, 2 case series, and 106 case reports) were included. On hospitalized patients, in comparison to standard of care, favipiravir showed a higher rate of viral clearance at day 5 (RR = 1.60, p = 0.02), defervescence at day 3-4 (RR = 1.99, p <0.01), chest radiological improvement (RR = 1.33, p <0.01), hospital discharge at day 10-11 (RR = 1.19, p <0.01), and shorter clinical improvement time (MD = -1.18, p = 0.05). Regarding adverse events, favipiravir groups had higher rates of hyperuricemia (RR = 9.42, p <0.01), increased alanine aminotransferase (RR = 1.35, p <0.01) but lower rates of nausea (RR = 0.42, p <0.01) and vomiting (R R= 0.19, p=0.02). There were no differences regarding mortality (RR=1.19, p=0.32), and increased aspartate aminotransferase (RR = 1.11, p = 0.25). On nonhospitalized patients, no significant differences were reported.
CONCLUSIONS
Adding favipiravir to the standard of care provides better outcomes for hospitalized patients with COVID-19. Pregnant, lactating women, and patients with a history of hyperuricemia should avoid using favipiravir.
Topics: Amides; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hyperuricemia; Pyrazines; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35470021
DOI: 10.1016/j.ijid.2022.04.035 -
Journal of Diabetes Investigation Sep 2022The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit... (Meta-Analysis)
Meta-Analysis
AIMS/INTRODUCTION
The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta-analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients.
MATERIALS AND METHODS
We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β-cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis.
RESULTS
Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference -0.36, 95% confidence interval -0.61 to -0.10, I = 91.6%), increased fasting C-peptide (weighted mean difference 0.08, 95% confidence interval -0.02 to 0.17, I = 88.8%) and had fewer adverse events compared with insulin alone. The inter-study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C-peptide, regardless of the duration of intervention and sample size.
CONCLUSIONS
Sitagliptin combined with insulin can achieve better glycemic control and improve islet β-cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well-designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.
Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Latent Autoimmune Diabetes in Adults; Randomized Controlled Trials as Topic; Sitagliptin Phosphate
PubMed: 35445591
DOI: 10.1111/jdi.13814 -
Advances in Therapy May 2022Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM.
METHODS
Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs.
RESULTS
A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis.
CONCLUSIONS
These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Treatment Outcome
PubMed: 35246820
DOI: 10.1007/s12325-022-02083-8 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
Clinical Microbiology and Infection :... Jan 2022Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed. (Review)
Review
BACKGROUND
Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed.
OBJECTIVES
To appraise existing evidence on efficacy and safety of pretomanid in tuberculosis.
DATA SOURCES
Pubmed, clinicaltrials.gov. and Cochrane library.
STUDY ELIGIBILITY CRITERIA
Quantitative studies presenting original data on clinical efficacy or safety of pretomanid.
PARTICIPANTS
Patients with tuberculosis.
INTERVENTIONS
Treatment with pretomanid or pretomanid-containing regimens in minimum one study group.
METHODS
Two authors independently extracted data and assessed risk of bias. Data on efficacy (early bactericidal activity, bactericidal activity, end-of-treatment outcomes and acquired resistance) and safety were summarized in tables. Mean differences in efficacy outcomes between regimens across studies were calculated.
RESULTS
Eight studies were included; four randomized controlled trials on 2-week early bactericidal activity in rifampicin-susceptible tuberculosis, three trials with randomized rifampicin-susceptible tuberculosis arms and a single rifampicin-resistant tuberculosis arm (two on 8-week bactericidal activity, one on end-of-treatment outcomes), one single-arm trial with end-of-treatment outcomes in highly resistant tuberculosis. Activity of pretomanid-moxifloxacin-pyrazinamide was superior to standard treatment on daily change in colony-forming units at days 0-2, 0-56 and 7-56 and time to culture conversion in rifampicin-susceptible tuberculosis (hazard ratio: 1.7; 95% CI 1.1-2.7), but not at end of treatment in one study. This study was stopped due to serious hepatotoxic adverse events, including three deaths, in 4% (95% CI 2-8) patients on pretomanid-moxifloxacin-pyrazinamide and none in controls. In patients with uncomplicated rifampicin-resistant tuberculosis on pretomanid-moxifloxacin-pyrazinamide treatment, 91% (95% CI 59-100) had favourable end-of-treatment outcomes. In patients with highly resistant tuberculosis, 90% (95% CI 83-95) on pretomanid-bedaquiline-linezolid had favourable outcomes six months after treatment, but linezolid-related toxicity was frequent. No acquired resistance to pretomanid was reported.
CONCLUSIONS
Evidence suggests an important role for pretomanid in rifampicin-resistant and highly resistant tuberculosis. Trials comparing pretomanid to existing core and companion drugs are needed to further define that role.
Topics: Antitubercular Agents; Humans; Linezolid; Moxifloxacin; Nitroimidazoles; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 34400340
DOI: 10.1016/j.cmi.2021.08.007 -
Vascular Medicine (London, England) Feb 2022Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management...
Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management relies exclusively on surgical repair as there is no effective medical therapy. A key element of AAA pathogenesis is the chronic inflammation mediated by inflammatory cells releasing proteases, including the enzyme dipeptidyl peptidase IV (DPP-IV). This review sought to recapitulate available evidence on the involvement of DPP-IV in AAA development. Further, we assessed the experimental use of currently available DPP-IV inhibitors for AAA management in murine models. Embase, Medline, PubMed, and Web of Science databases were utilised to access the relevant studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A narrative synthesis approach was used. Sixty-four studies were identified from the searched databases; a final 11 were included in the analysis. DPP-IV was reported to be significantly increased in both AAA tissue and plasma of patients and correlated with AAA growth. DPP-IV inhibitors (sitagliptin, vildagliptin, alogliptin, and teneligliptin) were all shown to attenuate AAA formation in murine models by reducing monocyte differentiation, the release of reactive oxygen species (ROS), and metalloproteinases (MMP-2 and MMP-9). DPP-IV seems to play a role in AAA pathogenesis by propagating the inflammatory microenvironment. This is supported by observations of decreased AAA formation and reduction in macrophage infiltration, ROS, matrix MMPs, and interleukins following the use of DPP-IV inhibitors in murine models. There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.
Topics: Animals; Aortic Aneurysm, Abdominal; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Macrophages; Mice; Sitagliptin Phosphate
PubMed: 34392748
DOI: 10.1177/1358863X211034574 -
European Journal of Clinical... Dec 2021We performed a systematic review and meta-analysis for the effectiveness of Favipiravir on the fatality and the requirement of mechanical ventilation for the... (Meta-Analysis)
Meta-Analysis
We performed a systematic review and meta-analysis for the effectiveness of Favipiravir on the fatality and the requirement of mechanical ventilation for the treatment of moderate to severe COVID-19 patients. We searched available literature and reported it by using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Until June 1, 2021, we searched PubMed, bioRxiv, medRxiv, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar by using the keywords "Favipiravir" and terms synonymous with COVID-19. Studies for Favipiravir treatment compared to standard of care among moderate and severe COVID-19 patients were included. Risk of bias assessment was performed using Revised Cochrane risk of bias tool for randomized trials (RoB 2) and ROBINS-I assessment tool for non-randomized studies. We defined the outcome measures as fatality and requirement for mechanical ventilation. A total of 2702 studies were identified and 12 clinical trials with 1636 patients were analyzed. Nine out of 12 studies were randomized controlled trials. Among the randomized studies, one study has low risk of bias, six studies have moderate risk of bias, and 2 studies have high risk of bias. Observational studies were identified as having moderate risk of bias and non-randomized study was found to have serious risk of bias. Our meta-analysis did not reveal any significant difference between the intervention and the comparator on fatality rate (OR 1.11, 95% CI 0.64-1.94) and mechanical ventilation requirement (OR 0.50, 95% CI 0.13-1.95). There is no significant difference in fatality rate and mechanical ventilation requirement between Favipiravir treatment and the standard of care in moderate and severe COVID-19 patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amides; Antiviral Agents; COVID-19; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Pyrazines; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Young Adult; COVID-19 Drug Treatment
PubMed: 34347191
DOI: 10.1007/s10096-021-04307-1 -
Journal of Microbiology, Immunology,... Oct 2021Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2... (Review)
Review
Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Carbamates; Cobicistat; Darunavir; Dibenzothiepins; Drug Combinations; Drug Therapy, Combination; Humans; Imidazoles; Indoles; Iran; Lopinavir; Morpholines; Pyrazines; Pyridones; Pyrrolidines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Sofosbuvir; Treatment Outcome; Triazines; Valine; COVID-19 Drug Treatment
PubMed: 34253490
DOI: 10.1016/j.jmii.2021.05.011 -
BMC Infectious Diseases May 2021Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited.
METHODS
We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes.
RESULTS
Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19-5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69-6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17-7.80) than on day 7 (OR = 1.60, 95% CI = 1.03-2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group.
CONCLUSIONS
Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amides; Antiviral Agents; Female; Humans; Male; Middle Aged; Pyrazines; SARS-CoV-2; Treatment Outcome; Viral Load; Young Adult; COVID-19 Drug Treatment
PubMed: 34044777
DOI: 10.1186/s12879-021-06164-x -
Scientific Reports May 2021The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and... (Meta-Analysis)
Meta-Analysis
The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid/PubMed, Scopus, Web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR = 1.24, 95% CI: 1.09-1.41; P = 0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR = 1.11, 95% CI: 0.98-1.25; P = 0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR = 0.93, 95% CI: 0.67-1.28; P = 0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.
Topics: Amides; Antiviral Agents; COVID-19; Clinical Trials as Topic; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Humans; Intensive Care Units; Pyrazines; SARS-CoV-2; Survival Analysis; Treatment Outcome; Viral Load; COVID-19 Drug Treatment
PubMed: 34040117
DOI: 10.1038/s41598-021-90551-6