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Journal of the International AIDS... Feb 2023Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a... (Review)
Review
INTRODUCTION
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
RESULTS AND DISCUSSION
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
CONCLUSIONS
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
Topics: Infant; Humans; Child; Adolescent; Tenofovir; HIV Infections; Anti-HIV Agents; HIV-1; Adenine; Emtricitabine
PubMed: 36823283
DOI: 10.1002/jia2.26037 -
European Annals of Otorhinolaryngology,... Dec 2020AQFThe authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding the management of Bell's palsy in adults. After a...
AQFThe authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding the management of Bell's palsy in adults. After a literature review by a multidisciplinary workgroup, guidelines were drawn up based on retrieved articles and group-members' experience, then read over by an independent group to edit the final version. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence. Thorough ENT and neurological clinical examination is recommended in all patients presenting with peripheral facial palsy to confirm diagnosis of Bell's palsy. MRI with gadolinium enhancement should explore the entire course of the facial nerve, if possible within the first month. ENMG should be performed to assess prognosis for recovery. In confirmed Bell's palsy, corticosteroid therapy should be implemented as early as possible (ideally within 72h) at a dose of 1mg/kg/day for 7-10 days. Antiviral therapy should be associated to steroids in patients with severe and early-onset disease and in Ramsay-Hunt syndrome. Isolated antiviral therapy is not recommended. To date, there is no evidence that surgical facial nerve decompression provides benefit.
Topics: Acute Disease; Adrenal Cortex Hormones; Antiviral Agents; Bell Palsy; Contrast Media; Decompression, Surgical; Drug Administration Schedule; Drug Therapy, Combination; Facial Nerve; Facial Paralysis; France; Gadolinium; Herpes Zoster Oticus; Humans; Hyperbaric Oxygenation; Magnetic Resonance Imaging; Neurologic Examination; Otolaryngology; Physical Therapy Modalities; Prognosis; Recovery of Function; Societies, Medical
PubMed: 32636146
DOI: 10.1016/j.anorl.2020.06.004 -
Immunity, Inflammation and Disease Dec 2021To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment.
METHODS
A literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of included studies. Meta-analysis was performed using RevMan 5.3.
RESULTS
Sixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non-antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR-PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78-1.14) and Day 14 (RR: 1.10; 95% CI: 0.96-1.25), and PCR negative conversion time (PCR-NCT; mean difference [MD]: 0.74; 95% CI: -0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06-4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p < .05). Adding arbidol to lopinavir/ritonavir also led to better efficacy in terms of NR-PCR on Day 7 and PCR-NCT (p < .05). There was no significant difference between arbidol and chloroquine in primary outcomes (p > .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05).
CONCLUSION
The present meta-analysis showed no significant benefit of using arbidol compared with non-antiviral treatment or other therapeutic agents against COVID-19 disease. High-quality studies are needed to establish the efficacy and safety of arbidol for COVID-19.
Topics: Antiviral Agents; Humans; Indoles; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34347937
DOI: 10.1002/iid3.502 -
Dermatologic Therapy Jun 2022Recent systematic reviews of plantar warts continue to consider cryotherapy as one of the treatments of choice, but this method appears to have lower cure rates than... (Meta-Analysis)
Meta-Analysis
Recent systematic reviews of plantar warts continue to consider cryotherapy as one of the treatments of choice, but this method appears to have lower cure rates than alternative treatments. A systematic review using meta-analyses of the efficacy of cryotherapy in plantar warts treatment was performed. Systematic electronic searches were conducted. The primary endpoint was complete clearance of plantar warts. Risk-of-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.4.1 software. Cryotherapy appears to have lower cure rates than other treatments (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.12-0.78) with substantial heterogeneity (I = 80%). A second subgroup analysis had low heterogeneity (I = 28.2%). Subgroup analysis showed that plantar wart cure rates were significantly lower with cryotherapy compared to the physical treatment group (OR 0.05, 95% CI 0.01-0.49) with substantial heterogeneity (I = 79%), and antiviral, chemotherapy, and retinoid group (OR 0.30, 95% CI 0.14-0.66) without heterogeneity (I = 0%). Intralesional versus spray-on cryotherapy appears to be more effective (OR 0.21, 95% CI 0.09-0.48). No difference in efficacy between two rounds of 10-s and four rounds of 5-s freeze-thaw cycles in cryotherapy was found. Evidence of the superiority of antivirals and chemotherapy over cryotherapy in the treatment of plantar warts was found. However, no evidence supports the superiority or inferiority of cryotherapy compared to other treatments.
Topics: Antiviral Agents; Cryotherapy; Dermatologic Agents; Humans; Treatment Outcome; Warts
PubMed: 35365922
DOI: 10.1111/dth.15480 -
The safety and efficacy of oral antiviral drug VV116 for treatment of COVID-19: A systematic review.Medicine Jul 2023Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the...
BACKGROUND
Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the safety and efficacy of VV116. Therefore, we conducted a systematic review to assess the safety and efficacy of VV116.
METHODS
A comprehensive search was conducted on PubMed, Scopus, and Google Scholar websites, with a cutoff date of March 23, to identify pertinent studies.
RESULTS
The results from the 3 included studies indicated that no serious adverse events were reported in the VV116 experimental groups, which exhibited a 2.57-day faster time to viral shedding than the control group and demonstrated non-inferiority to the nirmatrelvir-ritonavir control group in alleviating major symptoms.
DISCUSSION
Collectively, available studies suggest a reliable safety and efficacy profile for VV116. However, the limited number of trials was insufficient for meta-analysis, and the included population consisted of younger individuals with mild and moderate symptoms, not encompassing the elderly who are severely affected by COVID-19. We hope that more studies will be conducted in the future to ensure that VV116 has a more reliable safety and efficacy profile in the clinical setting, especially in severe or critical patients.
Topics: Aged; Humans; Antiviral Agents; COVID-19; Ritonavir
PubMed: 37417593
DOI: 10.1097/MD.0000000000034105 -
Clinical Pharmacology and Therapeutics Aug 2021Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral loads change rapidly following symptom onset, so to assess antivirals it is important to understand... (Meta-Analysis)
Meta-Analysis
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral loads change rapidly following symptom onset, so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient-level meta-analysis of SARS-CoV-2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to date. This systematic review identified case reports, case series, and clinical trial data from publications between January 1, 2020, and May 31, 2020, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A multivariable Cox proportional hazards (Cox-PH) regression model of time to viral clearance was fitted to respiratory and stool samples. A simplified four parameter nonlinear mixed-effects (NLME) model was fitted to viral load trajectories in all sampling sites and covariate modeling of respiratory viral dynamics was performed to quantify time-dependent drug effects. Patient-level data from 645 individuals (age 1 month to 100 years) with 6,316 viral loads were extracted. Model-based simulations of viral load trajectories in samples from the upper and lower respiratory tract, stool, blood, urine, ocular secretions, and breast milk were generated. Cox-PH modeling showed longer time to viral clearance in older patients, men, and those with more severe disease. Remdesivir was associated with faster viral clearance (adjusted hazard ratio (AHR) = 9.19, P < 0.001), as well as interferon, particularly when combined with ribavirin (AHR = 2.2, P = 0.015; AHR = 6.04, P = 0.006). Combination therapy should be further investigated. A viral dynamic dataset and NLME model for designing and analyzing antiviral trials has been established.
Topics: Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; COVID-19; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Interferons; Male; Middle Aged; Proportional Hazards Models; SARS-CoV-2; Viral Load; Virus Shedding; COVID-19 Drug Treatment
PubMed: 33641159
DOI: 10.1002/cpt.2223 -
European Journal of Clinical... Nov 2020Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.
METHODS
A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.
RESULTS
Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.
CONCLUSION
Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.
Topics: Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; COVID-19; Coronavirus Infections; Europe; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Prognosis; Ritonavir; Survival Analysis; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32810285
DOI: 10.1111/eci.13383 -
Virology Journal May 2022The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective?
MAIN BODY
The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software.
CONCLUSION
Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.
Topics: Alkaloids; Antiviral Agents; Humans; Plant Extracts; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35597998
DOI: 10.1186/s12985-022-01808-z -
Pain Physician Jul 2023The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to... (Meta-Analysis)
Meta-Analysis
A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.
BACKGROUND
The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain.
OBJECTIVES
The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020.
METHODS
Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events.
RESULTS
A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo.
LIMITATIONS
The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors.
CONCLUSIONS
For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated.
CLINICAL TRIAL REGISTRATION INFORMATION
PROSPERO under the identification CRD42020212834.
Topics: Humans; Antiviral Agents; Valacyclovir; Famciclovir; Network Meta-Analysis; Acute Pain; Randomized Controlled Trials as Topic; Acyclovir; Herpes Zoster; Neuralgia, Postherpetic
PubMed: 37535772
DOI: No ID Found -
European Cytokine Network Jun 2020Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.
METHODS
A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.
RESULTS
Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.
CONCLUSIONS
Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.
Topics: Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Cytokine Release Syndrome; Female; Gene Expression; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Pandemics; Pneumonia, Viral; Receptors, Interleukin-6; SARS-CoV-2; Severity of Illness Index; Survival Analysis; Treatment Outcome
PubMed: 32933891
DOI: 10.1684/ecn.2020.0448