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Intervirology 2015We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6... (Meta-Analysis)
Meta-Analysis Review
Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis.
OBJECTIVES
We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).
METHODS
Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11.
RESULTS
Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates.
CONCLUSIONS
Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.
Topics: Antiviral Agents; Coinfection; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Immunologic Factors; Interferon-alpha; Polyethylene Glycols; Polymorphism, Genetic; Ribavirin; Treatment Outcome
PubMed: 27010195
DOI: 10.1159/000444366 -
Translational Psychiatry Jun 2022It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive-compulsive and related disorders. Thus, in an attempt to answer... (Meta-Analysis)
Meta-Analysis
It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive-compulsive and related disorders. Thus, in an attempt to answer this clinical question, we performed a systematic review and a random-effects meta-analysis of double-blind, randomized, placebo-controlled trials. The primary outcome was change in overall symptoms as measured using standardized rating scales. Other outcomes were response to treatment; improvement in anxiety-related scales scores, depression-related scale scores, Clinical Global Impression Severity Scale (CGI-S) scores, and Sheehan Disability Scale (SDS) scores; all-cause discontinuation; and individual adverse events. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. We reviewed 17 studies (n = 629, 72.62% female; duration = 2-20 weeks; mean age = 30.47 years) of MMs: eicosapentaenoic acid (K = 1), folic acid (K = 1), lithium (K = 1), N-acetylcysteine (K = 10), inositol (K = 3), and silymarin (K = 1). MMs outperformed placebo in overall improvement in symptoms (p < 0.01) and in improving anxiety-related scale scores (p = 0.05). Subgroup analysis of individual MMs revealed that although overall symptoms were better improved by N-acetylcysteine (p < 0.01) and lithium (p = 0.04), no MMs outperformed placebo in terms of improving anxiety-related scale scores. Neither pooled nor individual MMs outperformed placebo in improving response to treatment, depression-related scale scores, CGI-S scores, SDS scores, or all-cause discontinuation. N-acetylcysteine was no more associated with a higher incidence of individual adverse events including gastrointestinal symptoms, than placebo. In conclusion, N-acetylcysteine was beneficial in the treatment of obsessive-compulsive and related disorders. However, further study with larger samples is necessary to confirm this finding.
Topics: Acetylcysteine; Adult; Double-Blind Method; Female; Humans; Inositol; Lithium; Male; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic
PubMed: 35764619
DOI: 10.1038/s41398-022-02026-5 -
Systematic Reviews May 2022In an unparalleled global response, during the COVID-19 pandemic, 90 countries asked 3.9 billion people to stay home. Yet other countries avoided lockdowns and focused... (Review)
Review
BACKGROUND
In an unparalleled global response, during the COVID-19 pandemic, 90 countries asked 3.9 billion people to stay home. Yet other countries avoided lockdowns and focused on other strategies, like contact tracing. How effective and cost-effective are these strategies? We aimed to provide a comprehensive summary of the evidence on past pandemic controls, with a focus on cost-effectiveness.
METHODS
Following PRISMA guidelines, MEDLINE (1946 to April week 2, 2020) and EMBASE (1974 to April 17, 2020) were searched using a range of terms related to pandemic control. Articles reporting on the effectiveness or cost-effectiveness of at least one intervention were included.
RESULTS
We found 1653 papers; 62 were included. The effectiveness of hand-washing and face masks was supported by randomized trials. These measures were highly cost-effective. For other interventions, only observational and modelling studies were found. They suggested that (1) the most cost-effective interventions are swift contact tracing and case isolation, surveillance networks, protective equipment for healthcare workers, and early vaccination (when available); (2) home quarantines and stockpiling antivirals are less cost-effective; (3) social distancing measures like workplace and school closures are effective but costly, making them the least cost-effective options; (4) combinations are more cost-effective than single interventions; and (5) interventions are more cost-effective when adopted early. For 2009 H1N1 influenza, contact tracing was estimated to be 4363 times more cost-effective than school closure ($2260 vs. $9,860,000 per death prevented).
CONCLUSIONS AND CONTRIBUTIONS
For COVID-19, a cautious interpretation suggests that (1) workplace and school closures are effective but costly, especially when adopted late, and (2) scaling up as early as possible a combination of interventions that includes hand-washing, face masks, ample protective equipment for healthcare workers, and swift contact tracing and case isolation is likely to be the most cost-effective strategy.
Topics: COVID-19; Communicable Disease Control; Cost-Benefit Analysis; Humans; Influenza A Virus, H1N1 Subtype; Pandemics; SARS-CoV-2
PubMed: 35550674
DOI: 10.1186/s13643-022-01958-9 -
Influenza and Other Respiratory Viruses Mar 2014Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a... (Meta-Analysis)
Meta-Analysis Review
Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.
Topics: Age Factors; Antiviral Agents; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Severity of Illness Index; Time Factors; Virus Shedding
PubMed: 24299099
DOI: 10.1111/irv.12216 -
PloS One 2022Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral... (Meta-Analysis)
Meta-Analysis
Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
Topics: Humans; Oseltamivir; Antiviral Agents; Influenza, Human; COVID-19 Drug Treatment
PubMed: 36454880
DOI: 10.1371/journal.pone.0277206 -
PLoS Pathogens May 2021Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response...
Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections.
Topics: Animals; Antiviral Agents; Coinfection; Humans; Immunity; Schistosoma; Schistosomiasis; Virus Diseases; Viruses
PubMed: 34015063
DOI: 10.1371/journal.ppat.1009555 -
Health Technology Assessment... Mar 2007To assess the clinical effectiveness and cost-effectiveness of pegylated interferon alpha (PEG) and non-pegylated interferon alpha (IFN) and ribavirin (RBV) for the... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of pegylated interferon alpha (PEG) and non-pegylated interferon alpha (IFN) and ribavirin (RBV) for the treatment of adults with histologically mild chronic hepatitis C (HCV) infection.
DATA SOURCES
Electronic bibliographic databases were searched up to July 2005.
REVIEW METHODS
A systematic review and an economic evaluation were carried out. A Markov state transition model was developed to estimate the cost-effectiveness of treatment strategies for adults with mild chronic HCV.
RESULTS
Among the included studies, eight randomised controlled trials (RCTs) of antiviral treatment in mild HCV were identified and included. In general these RCTs were of good quality. The results suggested that effectiveness, particularly with respect to sustained virological response was similar in patients with mild disease to the results obtained in patients with moderate/severe disease. This finding was supported by RCTs reporting the results for mild HCV sub-groups. The authors' cost-effectiveness analysis showed that early treatment compared with watchful waiting is associated with quality-adjusted life-year (QALY) gains but with increased treatment costs. The base-case incremental costs per QALY for 48 weeks of treatment are: watchful waiting with IFN + RBV versus best supportive care = pound 3097-6585; early treatment with IFN + RBV versus watchful waiting with IFN + RBV = pound 5043-8092; watchful waiting with PEG 2a + RBV versus best supportive care = pound 3052; early treatment with PEG 2a + RBV versus watchful waiting with PEG 2a + RBV = pound 5900; watchful waiting with PEG 2b + RBV versus best supportive care = pound 2534; and early treatment with PEG 2b + RBV versus watchful waiting with PEG 2b + RBV = pound 5774. These results were consistent with previous assessments of cost-effectiveness.
CONCLUSION
This systematic review and economic evaluation show that patients with histologically mild HCV can be successfully treated with both pegylated and non-pegylated interferon alpha. Early treatment and watchful waiting strategies are associated with acceptable cost-per-QALY estimates. Research needs to be directed towards newer, potentially more effective interventions, particularly those that improve treatment response in patients with genotype 1, with minimal adverse effects. Further research is required into the natural history of HCV to estimate better the rate of liver disease progression, and also into the effectiveness of non-invasive biochemical markers of liver disease, as an alternative to liver biopsy.
Topics: Antiviral Agents; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Male; Markov Chains; Multicenter Studies as Topic; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin
PubMed: 17346498
DOI: 10.3310/hta11110 -
Virology Journal Sep 2011Phylogenetic analysis has led to the classification of hepatitis C virus (HCV) into 1-6 major genotypes. HCV genotypes have different biological properties, clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Phylogenetic analysis has led to the classification of hepatitis C virus (HCV) into 1-6 major genotypes. HCV genotypes have different biological properties, clinical outcome and response to antiviral treatment and provide important clues for studying the epidemiology, transmission and pathogenesis. This article deepens the current molecular information about the geographical distribution of HCV genotypes and subgenotypes in population of four provinces of Pakistan. 34 published papers (1996-2011) related to prevalence of HCV genotypes/serotypes and subgenotypes in Pakistan were searched.
RESULT
HCV genotype/s distribution from all 34 studies was observed in 28,400 HCV infected individuals in the following pattern: 1,999 (7.03%) cases of genotype 1; 1,085 (3.81%) cases of genotype 2; 22,429 (78.96%) cases of genotype 3; 453 (1.59%) cases of genotype 4; 29 (0.10%) cases of genotype 5; 37 (0.13%) cases of genotype 6; 1,429 (5.03%) cases of mixed genotypes, and 939 (3.30%) cases of untypeable genotypes. Overall, genotype 3a was the predominant genotype with a rate of 55.10%, followed by genotype 1a, 3b and mixed genotype with a rate of 10.25%, 8.20%, and 5.08%, respectively; and genotypes 4, 5 and 6 were rare. Genotype 3 occurred predominately in all the provinces of Pakistan. Second more frequently genotype was genotype 1 in Punjab province and untypeable genotypes in Sindh, Khyber Pakhtunkhwa and Balochistan provinces.
Topics: Humans; Antiviral Agents; Databases, Bibliographic; Genotype; Hepacivirus; Hepatitis C; Molecular Typing; Pakistan; Phylogeny; Phylogeography; Prevalence; RNA, Viral
PubMed: 21902822
DOI: 10.1186/1743-422X-8-433 -
The World Allergy Organization Journal Feb 2023Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may... (Review)
Review
Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may shorten the duration of viral infections by enhancing the antiviral immunity. A systematic review was conducted to investigate whether previous anti-IgE treatment with omalizumab could protect against SARS-CoV-2 disease ("COVID-19") (infection, disease duration, and severity), and whether IFN-α upregulation could be involved. The research included articles published from March 2020 to January 2022. An accurate search was performed on bibliographic biomedical database (MEDLINE - Pubmed, SCOPUS, EMBASE, BIOMED CENTRAL, Google scholar, COCHRANE LIBRARY, ClinicalTrial.gov) including cohorts, case reports and reviews. Different methods were used, based on the study design, to assess the quality of eligible studies. Several authors link omalizumab to a possible protection against viruses, but they often refer to studies carried out before the pandemic and with viruses other than SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (eg, rhinoviruses -RV). Few cases of COVID-19 patients treated with omalizumab have been recorded, and, in most of them, no increased susceptibility to severe disease was observed. According to these data, the current indication is to continue omalizumab therapy during the pandemic. Moreover, although omalizumab may enhance the antiviral immune response even for SARS-CoV-2, further studies are needed to confirm this hypothesis. It would be helpful to establish a registry of omalizumab-treated (or in treatment) patients who have developed COVID-19. Finally, randomized controlled trials could be able to demonstrate the effect of omalizumab in protecting against severe SARS-CoV-2, through IFN-α upregulation or other immunological pathways.
PubMed: 36644451
DOI: 10.1016/j.waojou.2023.100741 -
Reviews in Medical Virology Jan 2022It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our... (Review)
Review
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Topics: Anti-Infective Agents; COVID-19; Humans; Lactoferrin; SARS-CoV-2; Virus Diseases
PubMed: 34133812
DOI: 10.1002/rmv.2261