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European Journal of Internal Medicine Apr 2021There is scarce evidence verifying the impact of neuraminidase inhibitors (NAIs) in reducing influenza complications. The aim was to evaluate the available evidence from...
BACKGROUND
There is scarce evidence verifying the impact of neuraminidase inhibitors (NAIs) in reducing influenza complications. The aim was to evaluate the available evidence from randomized-controlled trials (RCT) regarding the efficacy and safety of NAIs in reducing influenza complications.
METHODS
A systematic search of the literature was performed in the Cochrane Library, PubMed and Web of Science databases (2006-2019). Eligibility criteria were RCT that enrolled patients of any age or clinical severity with seasonal influenza (HN, HN or B) or influenza-like syndrome and receiving NAIs comparing to placebo therapy.
RESULTS
Eighteen RCTs (9004 patients) were included: nine focused on oral oseltamivir, six on inhaled zanamivir, and three on intravenous peramivir. Administration of NAIs therapy significantly decreased the time to clinical resolution (median difference: -17.7 hours; and total influenza-related complications (OR: 0.64, 95%CI: 0.51-0.82). In addition, NAIs significantly decreased acute otitis media complication (OR: 0.50, 95%CI: 0.31-0.82) and need for antibiotic treatment (OR: 0.64, 95%CI: 0.46-0.90); and showed a trend towards a reduced occurrence of pneumonia (OR: 0.44, 95%CI: 0.10-2.00), bronchitis (OR: 0.80, 95%CI: 0.43-1.48), sinusitis (OR: 0.73, 95%CI: 0.40-1.32), asthma exacerbations (OR: 0.57, 95%CI: 0.28-1.16), and hospitalizations (OR: 0.57, 95%CI: 0.24-1.38). The overall proportion of AEs tend to increase with NAIs treatment (OR: 1.16, 95%CI: 0.92-1.47). Use of NAIs was associated with a significant increase of nausea and vomiting (OR: 1.61, 95%CI: 1.04-2.50) and a decrease on diarrhea (OR: 0.81, 95%CI: 0.65-1.00).
CONCLUSIONS
NAIs are effective in reducing time to clinical resolution, total influenza-related complications, otitis media, and need of antibiotic administration. Reductions on mortality, pneumonia, asthma exacerbations or hospitalization rates only did demonstrate a trend benefit in favor of NAIs. The only significant AE is the increased occurrence of nausea and vomiting.
Topics: Antiviral Agents; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase; Oseltamivir; Randomized Controlled Trials as Topic; Zanamivir
PubMed: 33358065
DOI: 10.1016/j.ejim.2020.12.010 -
The Medical Journal of Malaysia Nov 2020Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate...
INTRODUCTION
Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19.
METHODS
An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included.
RESULTS
Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community.
DISCUSSION
In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.
Topics: Antiviral Agents; COVID-19; Humans; Pandemics; Ribavirin; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33219182
DOI: No ID Found -
The American Journal of Chinese Medicine 2020The aim of this research is to evaluate the clinical evidence of an herbal medicine (HM) treatment on influenza and describe the potential benefits and adverse events by... (Comparative Study)
Comparative Study Meta-Analysis
The aim of this research is to evaluate the clinical evidence of an herbal medicine (HM) treatment on influenza and describe the potential benefits and adverse events by reviewing all relevant randomized controlled trials. All papers published from 2010 to 2019 in all languages in six databases were searched, including all randomized controlled trials on adults and children, testing herbal medicine for treatment of influenza, alone or in combination with conventional antiviral therapy. The main outcome parameters of interest were total effective rate, time to resolution of fever, adverse events, complications, and duration of viral shedding. 25 trials of 3044 patients were included. Herbal medicine compared to placebo significantly reduced time to fever resolution by 4.96[Formula: see text]h (mean difference, [Formula: see text]4.96; 95% CI, [Formula: see text]7.11 to [Formula: see text]2.80; [Formula: see text]), herbal medicine compared to oseltamivir showed no significant difference (mean difference, [Formula: see text]1.82; 95% CI, [Formula: see text]6.08 to 2.44; [Formula: see text]), and herbal medicine plus oseltamivir combined treatment significantly reduced duration of fever by 7.84[Formula: see text]h compared to a single treatment with oseltamivir (mean difference, [Formula: see text]7.84; 95% CI, [Formula: see text]12.51 to [Formula: see text]3.17; [Formula: see text]). Herbal medicine compared to placebo showed a significantly better total effective rate (risk ratio, 1.90; 95% CI, 1.18 to 3.07; [Formula: see text]), herbal medicine compared to oseltamivir indicated significantly better effective rate (risk ratio, 1.15; 95% CI, 1.03 to 1.29; [Formula: see text]), and combined treatment showed a significantly better total effective rate compared to a single treatment with oseltamivir (risk ratio, 1.20; 95% CI, 1.06 to 1.36; [Formula: see text]). Regarding safety, no serious adverse events were reported in HM treatment. HM presented fewer adverse events compared to oseltamivir, but the difference was not significant (risk difference, [Formula: see text]0.04; 95% CI, [Formula: see text]0.09 to 0.00; [Formula: see text]), and the combined treatment did not increase adverse events compared to oseltamivir (risk difference, [Formula: see text]0.02; 95% CI, [Formula: see text]0.06 to 0.02; [Formula: see text]). Research findings show that herbal medicine treatments have beneficial therapeutic effects on influenza and could decrease duration of fever and improve total effective rate. In addition, herbal medicine plus oseltamivir combined therapy could increase the therapeutic effect compared to a single treatment with oseltamivir.
Topics: Antiviral Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Influenza, Human; Male; Oseltamivir; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33167671
DOI: 10.1142/S0192415X20500779 -
Drug Metabolism and Disposition: the... Oct 2020Carboxylesterase (CES) 1 is the predominant esterase expressed in the human liver and is capable of catalyzing the hydrolysis of a wide range of therapeutic agents,...
Carboxylesterase (CES) 1 is the predominant esterase expressed in the human liver and is capable of catalyzing the hydrolysis of a wide range of therapeutic agents, toxins, and endogenous compounds. Accumulating studies have demonstrated associations between the expression and activity of CES1 and the pharmacokinetics and/or pharmacodynamics of CES1 substrate medications (e.g., methylphenidate, clopidogrel, oseltamivir). Therefore, any perturbation of CES1 by coingested xenobiotics could potentially compromise treatment. Natural products are known to alter drug disposition by modulating cytochrome P450 and UDP-glucuronosyltransferase enzymes, but this issue is less thoroughly explored with CES1. We report the results of a systematic literature search and discuss natural products as potential modulators of CES1 activity. The majority of research reports reviewed were in vitro investigations that require further confirmation through clinical study. Cannabis products ( -tetrahydrocannabinol, cannabidiol, cannabinol); supplements from various plant sources containing naringenin, quercetin, luteolin, oleanolic acid, and asiatic acid; and certain traditional medicines (danshen and zhizhuwan) appear to pose the highest inhibition potential. In addition, ursolic acid, gambogic acid, and glycyrrhetic acid, if delivered intravenously, may attain high enough systemic concentrations to significantly inhibit CES1. The provision of a translational interpretation of in vitro assessments of natural product actions and interactions is limited by the dearth of basic pharmacokinetic data of the natural compounds exhibiting potent in vitro influences on CES1 activity. This is a major impediment to assigning even potential clinical significance. The modulatory effects on CES1 expression after chronic exposure to natural products warrants further investigation. SIGNIFICANCE STATEMENT: Modulation of CES1 activity by natural products may alter the course of treatment and clinical outcome. In this review, we have summarized the natural products that can potentially interact with CES1 substrate medications. We have also noted the limitations of existing reports and outlined challenges and future directions in this field.
Topics: Administration, Intravenous; Administration, Oral; Biological Products; Carboxylic Ester Hydrolases; Clopidogrel; Drug Evaluation, Preclinical; Drug Interactions; Humans; Methylphenidate; Oseltamivir
PubMed: 32591414
DOI: 10.1124/dmd.120.000065 -
Frontiers in Medicine 2020The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical,...
The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.
PubMed: 32574328
DOI: 10.3389/fmed.2020.00231 -
Journal of Clinical Pharmacy and... Oct 2020The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether... (Comparative Study)
Comparative Study Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether double-dose oseltamivir influences mortality in patients with influenza.
METHODS
PubMed, Excerpta Medica Database (Embase) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of double-dose oseltamivir on mortality in patients with influenza. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS AND DISCUSSION
Ten studies (four RCTs and six observational studies), involving 20 947 patients, were included. Pooled analysis suggested that double-dose oseltamivir was not associated with decreased mortality in patients with influenza, both in RCTs (OR, 1.29; 95% CI, 0.52-3.15; P = .58) and observational studies (OR, 1.59; 95% CI, 0.79-3.19; P = .20; I = 51%). Double-dose oseltamivir did not show statistical benefit on the virologic clearance rate (OR, 1.26; 95% CI, 0.85-1.88; P = .25; I = 0%) or the incidence of adverse events (AEs) (OR, 1.52; 95% CI, 0.85-2.72; P = .15; I = 59%).
WHAT IS NEW AND CONCLUSION
Current evidence indicates that double-dose oseltamivir does not decrease mortality or have advantages on the outcome of virologic clearance rate and incidence of AEs. However, the finding largely relied on the data from observational studies, which may potentially have led to selection bias. Therefore, high-quality and adequately powered RCTs are warranted.
Topics: Antiviral Agents; Dose-Response Relationship, Drug; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32497319
DOI: 10.1111/jcpt.13203 -
International Journal of Clinical... Sep 2020Since there is still no definitive conclusion regarding which non-steroidal anti-inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections,...
BACKGROUND
Since there is still no definitive conclusion regarding which non-steroidal anti-inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections, we decided to evaluate the efficacy and safety of various NSAIDs in viral respiratory infections so that we can reach a conclusion on which NSAID is best choice for coronavirus disease 2019 (COVID-19).
METHODS
A search was performed in Medline (via PubMed), Embase and CENTRAL databases until 23 March 2020. Clinical trials on application of NSAIDs in viral respiratory infections were included.
RESULTS
Six clinical trials were included. No clinical trial has been performed on COVID-19, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome infections. Studies show that ibuprofen and naproxen not only have positive effects in controlling cold symptoms, but also do not cause serious side effects in rhinovirus infections. In addition, it was found that clarithromycin, naproxen and oseltamivir combination leads to decrease in mortality rate and duration of hospitalisation in patients with pneumonia caused by influenza.
CONCLUSION
Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence. Naproxen may be a good choice for future clinical trials.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Survival Rate; COVID-19 Drug Treatment
PubMed: 32460369
DOI: 10.1111/ijcp.13557 -
Advances in Therapy Jun 2020Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A...
INTRODUCTION
Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza.
METHODS
The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009-2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events.
RESULTS
Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance.
CONCLUSION
Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit.
Topics: Adult; Antiviral Agents; Clinical Protocols; Critical Care; Humans; Influenza, Human; Neuraminidase; Randomized Controlled Trials as Topic; Respiratory Insufficiency
PubMed: 32347523
DOI: 10.1007/s12325-020-01347-5 -
Systematic Reviews Feb 2020To assess the benefits and harms of the human papillomavirus (HPV) vaccines. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of the human papillomavirus (HPV) vaccines.
DATA SOURCES
Clinical study reports obtained from the European Medicines Agency and GlaxoSmithKline from 2014 to 2017.
ELIGIBILITY CRITERIA
Randomised trials that compared an HPV vaccine with a placebo or active comparator in healthy participants of all ages.
APPRAISAL AND SYNTHESIS
Two researchers extracted data and judged risk of bias with the Cochrane tool (version 2011). Risk ratio (RR) estimates were pooled using random-effects meta-analysis.
OUTCOMES
Clinically relevant outcomes in intention to treat populations-including HPV-related cancer precursors irrespective of involved HPV types, treatment procedures and serious and general harms.
RESULTS
Twenty-four of 50 eligible clinical study reports were obtained with 58,412 pages of 22 trials and 2 follow-up studies including 95,670 participants: 79,102 females and 16,568 males age 8-72; 393,194 person-years; and 49 months mean weighted follow-up. We judged all 24 studies to be at high risk of bias. Serious harms were incompletely reported for 72% of participants (68,610/95,670). Nearly all control participants received active comparators (48,289/48,595, 99%). No clinical study report included complete case report forms. At 4 years follow-up, the HPV vaccines reduced HPV-related carcinoma in situ (367 in the HPV vaccine group vs. 490 in the comparator group, RR 0.73 [95% confidence interval, CI, 0.53 to 1.00], number needed to vaccinate [NNV] 387, P = 0.05, I = 67%) and HPV-related treatment procedures (1018 vs. 1416, RR 0.71 [95% CI 0.63 to 0.80], NNV 75, P < 0.00001, I = 45%). The HPV vaccines increased serious nervous system disorders (exploratory analysis: 72 vs. 46, RR 1.49 [1.02 to 2.16], number needed to harm [NNH] 1325, P = 0.040, I = 0%) and general harms (13,248 vs. 12,394, RR 1.07 [95% CI 1.03 to 1.11], NNH 51, P = 0.0002, I = 77%) but did not significantly increase fatal harms (45 vs. 38, RR 1.19 [95% CI 0.65 to 2.19], P = 0.58, I = 30%) or serious harms (1404 vs. 1357, RR 1.01 [95% CI 0.94 to 1.08], P = 0.79, I = 0%).
CONCLUSION
At 4 years follow-up, the HPV vaccines decreased HPV-related cancer precursors and treatment procedures but increased serious nervous system disorders (exploratory analysis) and general harms. As the included trials were primarily designed to assess benefits and were not adequately designed to assess harms, the extent to which the HPV vaccines' benefits outweigh their harms is unclear. Limited access to clinical study reports and trial data with case report forms prevented a thorough assessment.
SYSTEMATIC REVIEW REGISTRATION
CRD42017056093. Our systematic review protocol was registered on PROSPERO in January 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf. Two protocol amendments were registered on PROSPERO on November 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf. Our index of the HPV vaccine studies was published in Systematic Reviews in January 2018: https://doi.org/10.1186/s13643-018-0675-z. A description of the challenges obtaining the data was published in September 2018: https://doi.org/10.1136/bmj.k3694.
Topics: Adolescent; Adult; Aged; Alphapapillomavirus; Child; Female; Humans; Male; Middle Aged; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Young Adult
PubMed: 32106879
DOI: 10.1186/s13643-019-0983-y -
The Journal of International Medical... Jan 2020H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic...
H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic potential. We conducted a systemic review regarding virus-induced pathogenesis, vaccine development, and diagnosis of H7N9 AIV infection in humans. We followed PRISMA guidelines and searched PubMed, Web of Science, and Google Scholar to identify relevant articles published between January 2013 and December 2018. Pathogenesis data indicated that H7N9 AIV belongs to low pathogenic avian influenza, which is mostly asymptomatic in avian species; however, H7N9 induces high mortality in humans. Sporadic human infections have recently been reported, caused by highly pathogenic avian influenza viruses detected in poultry. H7N9 AIVs resistant to adamantine and oseltamivir cause severe human infection by rapidly inducing progressive acute community-acquired pneumonia, multiorgan dysfunction, and cytokine dysregulation; however, mechanisms via which the virus induces severe syndromes remain unclear. An H7N9 AIV vaccine is lacking; designs under evaluation include synthesized peptide, baculovirus-insect system, and virus-like particle vaccines. Molecular diagnosis of H7N9 AIVs is suggested over conventional assays, for biosafety reasons. Several advanced or modified diagnostic assays are under investigation and development. We summarized virus-induced pathogenesis, vaccine development, and current diagnostic assays in H7N9 AIVs.
Topics: Animals; Birds; Drug Resistance, Viral; Host-Pathogen Interactions; Humans; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Influenza in Birds; Influenza, Human
PubMed: 31068040
DOI: 10.1177/0300060519845488