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Heliyon Oct 2022Since November 2019, the world has been grappling with the rapid spread of the Coronavirus disease 2019 (COVID-19). In response to this major health crisis, the first... (Review)
Review
INTRODUCTION
Since November 2019, the world has been grappling with the rapid spread of the Coronavirus disease 2019 (COVID-19). In response to this major health crisis, the first vaccination rollout was launched in December 2020. However, even fully vaccinated individuals are not completely immune to infection, albeit with less severe symptoms. Melatonin is known as an anti-oxidant, anti-inflammatory, and immunomodulatory agent whose anti-viral properties, cost-effectiveness, and relatively few side effects make it a potential adjuvant in the treatment of COVID-19. This systematic review aims to summarize the clinical studies on the effects of melatonin on COVID-19 patients.
METHODS
The search of articles was carried out in the Web of Science, PubMed/MEDLINE, Cochrane library, and Scopus databases up to January 2022.
RESULTS
Ten articles were included in our study. It seems melatonin can decrease inflammatory markers, inflammatory cytokines, and the expression of some genes, including the signal transducer and activator of transcription (STAT)4, STAT6, T-box expressed in T cell (T-bet), GATA binding protein 3 (GATA3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP1). In addition, melatonin appears to alleviate some clinical signs and symptoms and accelerate recovery. The use of melatonin in severe cases reduces thrombosis, sepsis, and mortality rate.
CONCLUSION
This systematic review highlights the probable role of melatonin as a potential adjuvant in the treatment of COVID-19 after about two weeks of consumption. However, further high-quality randomized clinical trials are required.
PubMed: 36254292
DOI: 10.1016/j.heliyon.2022.e10906 -
Experimental and Therapeutic Medicine Nov 2019Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin...
Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: 'HCV', 'hepatitis C', 'interferon', 'antiviral', 'treatment response' and 'insulin resistance'. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613-1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=-0.485; 95%CI=-0.713 to -0.256; P<0.001) and HOMA-β (difference in means=-15.448; 95%CI=-23.326 to -7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.
PubMed: 31602234
DOI: 10.3892/etm.2019.7995 -
Hepatobiliary & Pancreatic Diseases... Dec 2020Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term treatment. We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance.
DATA SOURCES
We searched PubMed, EMBASE and Web of Science for studies on nucleos(t)ide analogues (NAs) treatment [including tenofovir disoproxil fumarate (TDF)-based rescue therapies, adefovir (ADV)-based rescue therapies and double-dose ETV therapy] in CHB patients with ETV-resistance. The network meta-analysis was conducted for 1-year complete virological response (CVR) and biological response (BR) rates using GeMTC and ADDIS. A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate.
RESULTS
A total of 6 studies were finally included in this analysis. The antiviral efficacy was estimated. On network meta-analysis, the 1-year CVR rate in ETV-TDF [odds ratio (OR) = 22.30; 95 % confidence interval (CI): 2.78-241.93], LAM-TDF (OR = 70.67; 95 % CI: 5.16-1307.45) and TDF (OR = 16.90; 95 % CI: 2.28-186.30) groups were significantly higher than that in the ETV double-dose group; the 1-year CVR rate in the LAM-TDF group (OR = 14.82; 95 % CI: 1.03-220.31) was significantly higher than that in the LAM/LdT-ADV group. The 1-year BR rate of ETV-TDF (OR = 28.68; 95 % CI: 1.70-1505.08) and TDF (OR = 21.79; 95 % CI: 1.43-1070.09) therapies were significantly higher than that of ETV double-dose therapy. TDF-based therapies had the highest possibility to achieve the CVR and BR at 1 year, in which LAM-TDF combined therapy was the most effective regimen. The ratio of cost/effectiveness for 1-year treatment was 8 526, 17 649, 20 651 Yuan in the TDF group, TDF-ETV group, and ETV-ADV group, respectively.
CONCLUSIONS
TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Antiviral Agents; Cost-Benefit Analysis; Drug Costs; Drug Resistance, Viral; Drug Therapy, Combination; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Network Meta-Analysis; Treatment Outcome
PubMed: 33051132
DOI: 10.1016/j.hbpd.2020.09.007 -
Transboundary and Emerging Diseases Nov 2022Within-host model specified by viral dynamic parameters is a mainstream tool to understand SARS-CoV-2 replication cycle in infected patients. The parameter uncertainty... (Meta-Analysis)
Meta-Analysis
Within-host model specified by viral dynamic parameters is a mainstream tool to understand SARS-CoV-2 replication cycle in infected patients. The parameter uncertainty further affects the output of the model, such as the efficacy of potential antiviral drugs. However, gathering empirical data on these parameters is challenging. Here, we aim to conduct a systematic review of viral dynamic parameters used in within-host models by calibrating the model to the viral load data measured from upper respiratory specimens. We searched the PubMed, Embase and Web of Science databases (between 1 December 2019 and 10 February 2022) for within-host modelling studies. We identified seven independent within-host models from the above nine studies, including Type I interferon, innate response, humoral immune response or cell-mediated immune response. From these models, we extracted and analyse seven widely used viral dynamic parameters including the viral load at the point of infection or symptom onset, the rate of viral particles infecting susceptible cells, the rate of infected cells releasing virus, the rate of virus particles cleared, the rate of infected cells cleared and the rate of cells in the eclipse phase can become productively infected. We identified seven independent within-host models from nine eligible studies. The viral load at symptom onset is 4.78 (95% CI:2.93, 6.62) log(copies/ml), and the viral load at the point of infection is -1.00 (95% CI:-1.94, -0.05) log(copies/ml). The rate of viral particles infecting susceptible cells and the rate of infected cells cleared have the pooled estimates as -6.96 (95% CI:-7.66, -6.25) log([copies/ml] day ) and 0.92 (95% CI:-0.09, 1.93) day , respectively. We found that the rate of infected cells cleared was associated with the reported model in the meta-analysis by including the model type as a categorical variable (p < .01). Joint viral dynamic parameters estimates when parameterizing within-host models have been published for SARS-CoV-2. The reviewed viral dynamic parameters can be used in the same within-host model to understand SARS-CoV-2 replication cycle in infected patients and assess the impact of pharmaceutical interventions.
Topics: Animals; COVID-19; SARS-CoV-2; Antiviral Agents; Serologic Tests
PubMed: 35907777
DOI: 10.1111/tbed.14673 -
BMJ Open Apr 2021Respiratory infectious disease outbreaks pose a threat for loss of life, economic instability and social disruption. We conducted a systematic review of published...
OBJECTIVES
Respiratory infectious disease outbreaks pose a threat for loss of life, economic instability and social disruption. We conducted a systematic review of published econometric analyses to assess the direct and indirect costs of infectious respiratory disease outbreaks that occurred between 2003 and 2019.
SETTING
Respiratory infectious disease outbreaks or public health preparedness measures or interventions responding to respiratory outbreaks in OECD countries (excluding South Korea and Japan) so as to assess studies relevant to the European context. The cost-effectiveness of interventions was assessed through a dominance ranking matrix approach. All cost data were adjusted to the 2017 Euro, with interventions compared with the null. We included data from 17 econometric studies.
PRIMARY AND SECONDARY OUTCOME MEASURES
Direct and indirect costs for disease and preparedness and/or response or cost-benefit and cost-utility were measured.
RESULTS
Overall, the economic burden of infectious respiratory disease outbreaks was found to be significant to healthcare systems and society. Indirect costs were greater than direct costs mainly due to losses of productivity. With regard to non-pharmaceutical strategies, prehospitalisation screening and the use of protective masks were identified as both an effective strategy and cost-saving. Community contact reduction was effective but had ambiguous results for cost saving. School closure was an effective measure, but not cost-saving in the long term. Targeted antiviral prophylaxis was the most cost-saving and effective pharmaceutical intervention.
CONCLUSIONS
Our cost analysis results provide evidence to policymakers on the cost-effectiveness of pharmaceutical and non-pharmaceutical intervention strategies which may be applied to mitigate or respond to infectious respiratory disease outbreaks.
Topics: Civil Defense; Cost-Benefit Analysis; Disease Outbreaks; Humans; Japan; Republic of Korea
PubMed: 33926982
DOI: 10.1136/bmjopen-2020-045113 -
Systematic Reviews Aug 2019Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options.
METHODS
We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment.
RESULTS
Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes.
CONCLUSIONS
Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.
Topics: Antiviral Agents; Hepatitis B, Chronic; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31426837
DOI: 10.1186/s13643-019-1126-1 -
The Pediatric Infectious Disease Journal Nov 2023Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with...
BACKGROUND
Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB).
METHODS
A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies.
RESULTS
Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively.
CONCLUSION
Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.
PubMed: 37523508
DOI: 10.1097/INF.0000000000004057 -
Journal of Clinical Microbiology Feb 2022Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of... (Meta-Analysis)
Meta-Analysis
Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of the intensive phase of treatment. These methods either have suboptimal accuracy or a long turnaround time. There is a need to identify alternative biomarkers to monitor TB treatment response. We conducted a systematic review of active pulmonary TB treatment monitoring biomarkers. We screened 9,739 articles published between 1 January 2008 and 31 December 2020, of which 77 met the inclusion criteria. When studies quantitatively reported biomarker levels, we meta-analyzed the average fold change in biomarkers from pretreatment to week 8 of treatment. We also performed a meta-analysis pooling the fold change since the previous time point collected. A total of 81 biomarkers were identified from 77 studies. Overall, these studies exhibited extensive heterogeneity with regard to TB treatment monitoring study design and data reporting. Among the biomarkers identified, C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) had sufficient data to analyze fold changes. All four biomarker levels decreased during the first 8 weeks of treatment relative to baseline and relative to previous time points collected. Based on limited data available, CRP, IL-6, IP-10, and TNF-α have been identified as biomarkers that should be further explored in the context of TB treatment monitoring. The extensive heterogeneity in TB treatment monitoring study design and reporting is a major barrier to evaluating the performance of novel biomarkers and tools for this use case. Guidance for designing and reporting treatment monitoring studies is urgently needed.
Topics: Adult; Biomarkers; C-Reactive Protein; Humans; Interferon-gamma; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha
PubMed: 34911364
DOI: 10.1128/JCM.01859-21 -
The Journal of Infectious Diseases Aug 2023This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks.
METHODS
Five bibliographic databases were searched for studies reporting clinical features, management, and patient outcomes of mpox. Systematic review and meta-analysis were performed.
RESULTS
In total, 73 studies were included in the systematic review, of which 33 studies were subjected to meta-analysis. Previous outbreaks substantially affected children, whereas the 2022 outbreak primarily affected male adults, of which 94.66% (95% confidence interval [CI], 88.03-98.95) were men who have sex with men. Furthermore, 72.47% (95% CI, 51.04-89.71) reported high-risk sexual activity and the overall human immunodeficiency virus (HIV) prevalence was 37.65% (95% CI, 30.09-45.50). Skin lesions remain the typical symptom; however, their anatomic distribution differed. Systemic manifestations were common, but rectal pain was unique to the 2022 outbreak. The estimated overall fatality during past outbreaks in Africa was 4.61% (95% CI, 2.39%-7.35%), whereas 6.34% (95% CI, 3.35%-10.10%) of patients from the 2022 outbreak required hospitalization. Antiviral treatment, in particular tecovirimat, has been prescribed for a subset of patients, but the efficacy remains inconclusive.
CONCLUSIONS
These findings are important for better understanding the disease and guiding adequate response to mpox outbreaks.
Topics: Adult; Child; Humans; Male; Female; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Antiviral Agents; Disease Outbreaks; Pelvic Pain
PubMed: 36735342
DOI: 10.1093/infdis/jiad034 -
Clinical Gastroenterology and... Jul 2023Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity.
RESULTS
We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]).
CONCLUSION
Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.
Topics: Adult; Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Antiviral Agents; Incidence; Hepacivirus; Hepatitis C, Chronic; Hepatitis C; Liver Cirrhosis; Sustained Virologic Response
PubMed: 35525392
DOI: 10.1016/j.cgh.2022.04.013