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International Journal of Infectious... Aug 2014Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis.
METHODS
A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile.
RESULTS
This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009).
CONCLUSIONS
Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.
Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; CD4 Lymphocyte Count; Clinical Trials as Topic; Coinfection; Cyclopropanes; HIV Infections; Humans; Nevirapine; Rifampin; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24911886
DOI: 10.1016/j.ijid.2014.04.020 -
Scientific Reports Mar 2023In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review... (Meta-Analysis)
Meta-Analysis
Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies.
In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33-0.43) for sustained virologic response (SVR) and 1.70 (1.61-1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19-0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19-0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.
Topics: Humans; Hepatitis C, Chronic; Carcinoma, Hepatocellular; Japan; Liver Neoplasms; Interferons; Antiviral Agents
PubMed: 36859564
DOI: 10.1038/s41598-023-30467-5 -
Journal of Microbiology, Immunology,... Oct 2021The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. (Meta-Analysis)
Meta-Analysis
PURPOSE
The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza.
METHODS
PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included.
RESULTS
Three RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], -1.29 h; 95% CI, -6.80 to 4.21; I = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, -26.32 h; 95% CI, -33.78 to -18.86; I = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69-0.98; I = 0%) and placebo (OR, 0.79; 95% CI, 0.66-0.96; I = 0%).
CONCLUSIONS
The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.
Topics: Adolescent; Adult; Antiviral Agents; Child; Dibenzothiepins; Female; Humans; Influenza, Human; Male; Middle Aged; Morpholines; Oseltamivir; Pyridones; Randomized Controlled Trials as Topic; Treatment Outcome; Triazines; Viral Load; Young Adult
PubMed: 34020891
DOI: 10.1016/j.jmii.2021.04.002 -
The Cochrane Database of Systematic... Feb 2016There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators.
OBJECTIVES
To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use.
AUTHORS' CONCLUSIONS
Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
Topics: Acetylcysteine; Allopurinol; Antioxidants; Antipsychotic Agents; Ascorbic Acid; Dehydroepiandrosterone; Drug Therapy, Combination; Free Radical Scavengers; Ginkgo biloba; Humans; Oxidative Stress; Randomized Controlled Trials as Topic; Schizophrenia; Selegiline; Vitamin E; Vitamins
PubMed: 26848926
DOI: 10.1002/14651858.CD008919.pub2 -
Leukemia Jun 2021Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% [51.5%-66.1%]) and 76.7% (67.4-84.0%; CHR: 48.5% [37.8-59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
Topics: Antiviral Agents; Humans; Interferon-alpha; Polycythemia Vera; Thrombocythemia, Essential
PubMed: 32868875
DOI: 10.1038/s41375-020-01020-4 -
Reviews in Medical Virology Jul 2021Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Patients can be asymptomatic...
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Patients can be asymptomatic or present respiratory and gastrointestinal symptoms, and even multiple-organ failure which can lead to death. The balance between an effective antiviral response and dysregulated immune response is the key factor determining the severity of COVID-19 progression. A systematic review was performed using the NCBI-PubMed database to find the articles related to COVID-19 immunity and inflammatory response published from 1 December 2019 to 15 April 2020. Haematological, immunological and biochemical parameters were extracted and correlated with disease severity, age and presence of comorbidities. Twelve articles were analysed comprising a total of 1042 hospitalized patients infected with SARS-CoV-2 and 95 different parameters. Total lymphocyte count and levels of CD3+ and CD4+ T cells were decreased in severe and critical cases. Neutrophilia was found in patients who progressed to acute respiratory distress syndrome (ARDS). Interleukin-six (IL-6) was high in mild and severe patients regardless of comorbidities. Erythrocyte sedimentation rate (ESR) and count and C-reactive protein (CRP) levels were increased regardless of disease severity or presence of comorbidities. High levels of D-dimer and lactate dehydrogenase were present in diabetic patients and patients who developed ARDS. Procalcitonin levels were elevated to varying degrees in severe and critical patients. We conclude that the total lymphocyte count, CD3+ and CD4+ T cells are low, especially in severe and critical COVID-19 patients; ESR, CRP and IL-6 were elevated, independent of the severity of disease. Understanding the inflammatory response of COVID-19 patients is essential for the development of better therapeutic and management strategies.
Topics: Biomarkers; COVID-19; Humans; Immunity; Inflammation
PubMed: 34260778
DOI: 10.1002/rmv.2199 -
Journal of Clinical Pharmacy and... Aug 2021Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as...
WHAT IS KNOWN AND OBJECTIVE
Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions.
METHODS
A systematic review of cases was carried out following the guidelines established by "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). The research was carried out using the PubMed-Medline and Embase databases, between July 1984 and March 2021.
RESULTS AND DISCUSSION
A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5-88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end-stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2-28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2-180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days.
WHAT IS NEW AND CONCLUSION
The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis.
Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Dose-Response Relationship, Drug; Female; Humans; Kidney Function Tests; Male; Middle Aged; Neurotoxicity Syndromes; Renal Insufficiency; Time Factors; Valacyclovir; Young Adult
PubMed: 34146428
DOI: 10.1111/jcpt.13464 -
Cancer Cell International Oct 2021Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about... (Review)
Review
BACKGROUND
Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection.
METHODS
Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15.
RESULTS
There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients.
CONCLUSIONS
The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
PubMed: 34627251
DOI: 10.1186/s12935-021-02230-1 -
Risk Management and Healthcare Policy 2021Vitamin D status is related to risks of influenza and respiratory tract infections. Vitamin D has direct antiviral effects primarily against enveloped viruses, and... (Review)
Review
INTRODUCTION
Vitamin D status is related to risks of influenza and respiratory tract infections. Vitamin D has direct antiviral effects primarily against enveloped viruses, and coronavirus is an enveloped virus. The 2019 coronavirus disease had a high mortality rate and impacted the whole population of the planet, with severe acute respiratory syndrome the principal cause of death. Vitamin D can adequately modulate and regulate the immune and oxidative response to infection with COVID-19. The goal of this systematic review was thus to summarize and decide if there were a link between vitamin D status and COVID-19 infection and prognosis.
METHODS
The protocol of this study is documented in the Prospero database and can be accessed with the protocol number CRD42020201283. PubMed and Google Scholar were used for a literature search from August 2020 to September 2020. We restricted the year of publication of reviewed articles to 2019-2020, and the selected language was English. Studies that used secondary data, feedback, or analysis of reviews were removed. To assess the standard of studies included, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used.
RESULTS
Of the nine studies reviewed, seven (77.8%) showed that COVID-19 infection, prognosis, and mortality were correlated with vitamin D status.
CONCLUSION
Most of the articles reviewed showed that blood vitamin D status can determine the risk of being infected with COVID-19, seriousness of COVID-19, and mortality from COVID-19. Therefore, maintaining appropriate levels of Vitamin D through supplementation or natural methods, eg, sunlight on the skin, is recommended for the public to be able to cope with the pandemic.
PubMed: 33447107
DOI: 10.2147/RMHP.S291584 -
Journal of Viral Hepatitis Dec 2015Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have... (Review)
Review
Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.
Topics: Adult; Antiviral Agents; Female; Graft Rejection; Hepatitis E; Hepatitis E virus; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Organ Transplantation; Polyethylene Glycols; RNA, Viral; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 25760481
DOI: 10.1111/jvh.12403