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The Cochrane Database of Systematic... Aug 2021Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to...
BACKGROUND
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
SELECTION CRITERIA
We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events.
MAIN RESULTS
We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Bias; COVID-19; Cause of Death; Confidence Intervals; Disease Progression; Humans; Middle Aged; Oxygen; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Ventilator Weaning; COVID-19 Drug Treatment
PubMed: 34350582
DOI: 10.1002/14651858.CD014962 -
Medicine Aug 2020To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an evidence-based medical strategy.
METHODS
Randomized controlled trials (RCTs) comparing the effect of pegylated interferon (Peginterferon) combined with ribavirin (PR) alone and its combination with TCM were manually retrieved from the Weipu Information Resources System (VIP), Wan Fang Database, PubMed, and the Chinese Journal Full Text Database (CNKI). Studies meeting the inclusion criteria were selected and analyzed using the Review Manager 5.3 software. Suitable tests were also performed to determine the quality, heterogeneity, and sensitivity of the studies included in the meta-analysis.
RESULTS
Twenty-eight RCTs met the inclusion criteria. The combination therapy or intervention group showed significantly greater HCV-RNA negative rate post-treatment compared to the monotherapy or the control group (P < .05). In addition, the serum levels of the liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were significantly improved after the combination therapy compared to PR alone (P < .05), while total bilirubin (TB) and r-glutamyltransferase (GGT) levels were not affected by TCM (P > .05). Finally, the parameters of liver fibrosis were also reduced by the combination therapy more effectively than the monotherapy.
CONCLUSION
The combination of TCM and PR can improve the Comprehensive Clinical Efficacy of hepatitis C and have a better negative rate of HCV-RNA with a better benefit in the liver function. The effect of TCM + PR is better than that of PR alone in treating hepatitis C.
Topics: Alanine Transaminase; Antiviral Agents; Aspartate Aminotransferases; Bilirubin; Combined Modality Therapy; Drug Therapy, Combination; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Liver Cirrhosis; Medicine, Chinese Traditional; Polyethylene Glycols; RNA, Viral; Recombinant Proteins; Ribavirin; Serum Albumin; gamma-Glutamyltransferase
PubMed: 32871904
DOI: 10.1097/MD.0000000000021825 -
Journal of Medical Virology Sep 2021The newborn coronaivus disease 2019 (COVID-19) pandemic has become the foremost concern of health system worldwide. Interferon typeI (IFN-I) are among the well-known... (Review)
Review
The newborn coronaivus disease 2019 (COVID-19) pandemic has become the foremost concern of health system worldwide. Interferon typeI (IFN-I) are among the well-known antiviruses. Hence IFN-α have gained much attention as a treatment for COVID-19 recently. To sum up the efficiency of IFN-α against COVID-19, we searched PubMed, SCOPUS, and EMBASE, from the date of genesis to the 1st of October 2020. Discharge from hospital and virus clearance considered as primary and secondary outcomes, respectively. We compared the aforementioned outcomes of patients treated with standard care protocol and the patients treated with IFN-α in addition to standard care protocol. Out of 356 identified records, 14 studies were subjected for full-text screening. Finally, a systematic review was performed with inclusion of five studies. Majority of the participants were males (ranged from 43.50% to 90.0%). We found that time of viral clearance and polymerase chain reaction negative (days) in most studies were decreased in the INF-α + standard care group. The mean days of virus's clearance in INF-α group and standard group reported 27.3 and 32.43. Likewise, the average days of hospitalization was found also lower in INF-α group (18.55 vs. 24.36). This study provides a stand to conclude that early administration of INF-α may be accounted as a promising treatment of COVID-19.
Topics: Adult; Antiviral Agents; Clinical Trials as Topic; Female; Humans; Interferon-alpha; Male; Middle Aged; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34101851
DOI: 10.1002/jmv.27072 -
International Journal of Infectious... Sep 2022Late treatment initiation threatens the clinical and public health benefits of antiretroviral therapy (ART). Quantitative synthesizes of the existing evidence related to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Late treatment initiation threatens the clinical and public health benefits of antiretroviral therapy (ART). Quantitative synthesizes of the existing evidence related to this are lacking in sub-Saharan Africa (SSA), which would help ascertain the best evidence-based interventions. This review aimed to systematically synthesize the available literature on factors affecting linkage to care and ART initiation among adults with HIV in SSA.
METHODS
Systematic searches were undertaken on four databases to identify observational studies investigating factors affecting both HIV care outcomes among adults (age ≥19 years) in SSA and were published between January 1, 2015 and June 1, 2021. RevMan-5 software was used to conduct meta-analyses and Mantel-Haenszel statistics to pool outcomes with a 95% confidence interval and <0.05 level of significance.
RESULTS
A total of 46 studies were included in the systematic review, of which 18 fulfilled requirements for the meta-analysis. In both narrative review and meta-analyses, factors related to health care delivery, individual perception, and sociodemographic circumstances were associated with late linkage to care and delays in ART initiation.
CONCLUSION
This review identified a range of risk factors for late linkage to care and delayed ART initiation among adults with HIV in SSA. We recommend implementation of patient-centered intervention approaches to alleviate these barriers.
Topics: Adult; Africa South of the Sahara; Anti-HIV Agents; Anti-Retroviral Agents; Delivery of Health Care; HIV Infections; Humans; Risk Factors; Young Adult
PubMed: 35843499
DOI: 10.1016/j.ijid.2022.07.037 -
European Respiratory Review : An... Mar 2021Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to...
Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively. In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.
Topics: Antiviral Agents; COVID-19; Clinical Trials as Topic; Hospitalization; Host-Pathogen Interactions; Humans; Immunization, Passive; Respiration, Artificial; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33731328
DOI: 10.1183/16000617.0384-2020 -
Medicine Jul 2020Coronavirus disease 2019 (COVID-19) is highly contagious, and the epidemic has spread to hundreds of countries around the world, and seriously threatens the life safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) is highly contagious, and the epidemic has spread to hundreds of countries around the world, and seriously threatens the life safety of people around the world. Arbidol is an antiviral drug with high potential against COVID-19, but evidence of effectiveness and safety is lacking. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of arbidol for COVID-19.
METHODS
The retrieval time will be from the database establishment to June 2020. The retrieval database will include the Cochrane Library, PubMed, Embase, OVID, CNKI, Wanfang, VIP, CBM, etc. The primary outcome will be clinical efficacy, and the secondary results will be accompanying symptoms, time for the temperature to return to normal, time of novel coronavirus nucleic acid turning negative, blood sample test, Computed Tomography examination, length of hospitalization, adverse reactions, and adverse events. RevManV.5.3 software will be used for meta-analysis, and fixed effects model, random-effects model, subgroup analysis, and descriptive analysis will be adopted according to the heterogeneity of the research results.
RESULTS
To provide the latest evidence of clinical efficacy and safety of arbidol in the treatment of COVID-19.
CONCLUSION
Our study will provide the latest evidence analysis of the efficacy and safety of arbidol for COVID-19, to provide evidence-based medicine for the prevention and control of this epidemic.
REGISTRATION DETAILS
PROSPERO CRD42020189203.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Indoles; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32791753
DOI: 10.1097/MD.0000000000021402 -
Biomedica : Revista Del Instituto... Oct 2020Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral...
Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral replication in vitro. Timely dissemination of scientific information is key in times of pandemic. A systematic review of the effect and safety of these drugs on COVID-19 is urgently needed. Objective: To map published studies until March 25, 2020, on the use of chloroquine and its derivates in patients with COVID-19. Materials and methods: We searched on PubMed, Embase, Lilacs, and 15 registries from the World Health Organization’s International Clinical Trials Registry Platform for theoretical and empirical research in English, Spanish, Italian, French, or Portuguese until March 25, 2020, and made a narrative synthesis of the results. Results: We included 19 records and 24 trial registries (n=43) including 18,059 patients. China registered 66% (16/24) of the trials. Nine trials evaluate chloroquine exclusively and eight hydroxychloroquine. The records are comments (n=9), in vitro studies (n=3), narrative reviews (n=2), clinical guidelines (n=2), as well as a systematic review, an expert consensus, and a clinical trial. Conclusions: One small (n=26), non-randomized, and flawed clinical trial supports hydroxychloroquine use in patients with COVID-19. There is an urgent need for more clinical trial results to determine the effect and safety of chloroquine and hydroxychloroquine on COVID-19.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Chloroquine; Clinical Trials as Topic; Compassionate Use Trials; Coronavirus Infections; Cytokine Release Syndrome; Drug Repositioning; Humans; Hydroxychloroquine; Multicenter Studies as Topic; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Registries; SARS-CoV-2; Treatment Outcome; Virus Replication; COVID-19 Drug Treatment
PubMed: 33152192
DOI: 10.7705/biomedica.5478 -
Medicine Aug 2020COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for COVID-19 is mainly based on symptomatic support therapy. Chinese herbal medicine has been used to prevent infectious diseases for thousands of years in China. Western medicine routine treatment combined with Chinese herbal medicine is an alternative clinical option but lacks evidence-based medical evidence. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19.
METHODS
We will search the following eight databases: Cochrane Library, PubMed, Embase, Medline, CNKI, Wanfang, VIP, and CBM. The search time is up to the end of July 2020. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. In case of disagreement, the third author will assist in the judgment. The primary outcome will be the clinical cure rate. The secondary outcome will be accounting symptoms, fever time, time of virus nucleic acid turning negative, check the condition by drawing blood, pneumonia absorption rate, patient hospitalization time, severe conversion rate and case fatality rate, adverse reactions, and adverse events. Revman 5.3 will be used for systematic reviews and meta-analysis. The report of the protocol will follow the PRISMA-P statement, and the report of the systematic review and meta-analysis will follow the PRISMA statement.
RESULTS
We will provide evidence-based medical evidence of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. The findings will be published in peer-reviewed journals.
REGISTRATION DETAILS
CRD42020190106.
Topics: Anti-Infective Agents; Antiviral Agents; COVID-19; China; Combined Modality Therapy; Coronavirus Infections; Drugs, Chinese Herbal; Female; Humans; Male; Medicine, Chinese Traditional; Pandemics; Patient Safety; Pneumonia, Viral; Severe Acute Respiratory Syndrome; Survival Analysis; Treatment Outcome; United States
PubMed: 32769922
DOI: 10.1097/MD.0000000000021616 -
Nutrients Jan 2022Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical... (Meta-Analysis)
Meta-Analysis Review
Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical challenge, it is necessary to monitor the therapeutic efficacy of ARV in people living with the human immunodeficiency virus (PLWH). A systematic review and meta-analysis were conducted to clarify the pharmacokinetic outcomes of the interaction between supplements such as food, dietary supplements, and nutrients, and ARV. Twenty-four articles in both healthy subjects and PLWH were included in the qualitative analysis, of which five studies were included in the meta-analysis. Food−drug coadministration significantly increased the time to reach maximum concentration (tmax) (p < 0.00001) of ARV including abacavir, amprenavir, darunavir, emtricitabine, lamivudine, zidovudine, ritonavir, and tenofovir alafenamide. In addition, the increased maximum plasma concentration (Cmax) of ARV, such as darunavir, under fed conditions was observed. Area under the curve and terminal half-life were not significantly affected. Evaluating the pharmacokinetic aspects, it is vital to clinically investigate ARV and particular supplement interaction in PLWH. Educating patients about any potential interactions would be one of the effective recommendations during this HIV epidemic.
Topics: Anti-Retroviral Agents; Darunavir; Dietary Supplements; Drug Interactions; Emtricitabine; Humans
PubMed: 35276881
DOI: 10.3390/nu14030520 -
Canadian Journal of Gastroenterology &... 2024People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting... (Review)
Review
BACKGROUND
People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting antivirals (DAAs) have the potential to alleviate this burden; however, the evidence on the impact of HCV infection and hospital outcomes is undetermined. This systematic review aims to assess this research gap, including how DAAs may modify the relationship between HCV infection and hospital-related outcomes.
METHODS
We searched five databases up to August 2022 to identify relevant studies evaluating the impact of HCV infection on hospital-related outcomes. We created an electronic database of potentially eligible articles, removed duplicates, and then independently screened titles, abstracts, and full-text articles.
RESULTS
A total of 57 studies were included. Analysis of the included studies found an association between HCV infection and increased number of hospitalizations, length of stay, and readmissions. There was less consistent evidence of a relationship between HCV and in-hospital mortality. Only four studies examined the impact of DAAs, which showed that DAAs were associated with a reduction in hospitalizations and mortality. In the 14 studies available among people living with HIV, HCV coinfection similarly increased hospitalization, but there was less evidence for the other hospital-related outcomes.
CONCLUSIONS
There is good to high-quality evidence that HCV negatively impacts hospital-related outcomes, primarily through increased hospitalizations, length of stay, and readmissions. Given the paucity of studies on the effect of DAAs on hospital outcomes, future research is needed to understand their impact on hospital-related outcomes.
Topics: Humans; Antiviral Agents; Hepacivirus; Hepatitis C, Chronic; Hepatitis C; Hospitals
PubMed: 38487594
DOI: 10.1155/2024/3325609