-
Journal of Microbiology, Immunology,... Oct 2021Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2... (Review)
Review
Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Carbamates; Cobicistat; Darunavir; Dibenzothiepins; Drug Combinations; Drug Therapy, Combination; Humans; Imidazoles; Indoles; Iran; Lopinavir; Morpholines; Pyrazines; Pyridones; Pyrrolidines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Sofosbuvir; Treatment Outcome; Triazines; Valine; COVID-19 Drug Treatment
PubMed: 34253490
DOI: 10.1016/j.jmii.2021.05.011 -
PloS One 2021Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite... (Meta-Analysis)
Meta-Analysis
Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite adequate. The aim of this study was to evaluate the efficacy and safety of Sofosbuvir-based therapy without Ribavirin for all hepatitis C virus genotypes among patients with advanced CKD. We conducted an updated systematic literature search from the beginning of 2013 up to June 2020. Sustained virologic response (SVR) rate at 12 and/or 24 weeks after the end of treatment, and adverse events in HCV-infected patients with advanced CKD were pooled using random effects models. We included 27 published articles in our meta-analyses, totaling 1,464 HCV-infected patients with advanced CKD. We found a substantial heterogeneity based on the I2 index (P = 0.00, I2 = 56.1%). The pooled SVR rates at 12 and 24 weeks after the end of Sofosbuvir-based treatment were 97% (95% Confidence Interval: 95-99) and 95% (89-99) respectively. The pooled SVR12 rates were 98% (96-100) and 94% (90-97) in patients under 60 and over 60 years old respectively. The pooled incidence of severe adverse events was 0.11 (0.04-0.19). The pooled SVR12 rate after completion of the half dose regimen was as high as the full dose treatment but it was associated with less adverse events (0.06 versus 0.14). The pooled SVR12 rate was 98% (91-100) in cirrhotic patients and 100% (98-100) in non-cirrhotic patients. The endorsement of Sofosbuvir-based regimen can improve the treatment of hepatitis C virus infection in patients with advanced CKD.
Topics: Antiviral Agents; Hepatitis C; Hepatitis C, Chronic; Humans; Renal Insufficiency, Chronic; Sofosbuvir; Treatment Outcome
PubMed: 33566846
DOI: 10.1371/journal.pone.0246594 -
Theranostics 2021Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We...
Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of , , and clinical trials.
Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of , , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; COVID-19; Carbamates; Coronavirus Infections; Disease Models, Animal; Drug Combinations; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Imidazoles; Immunization, Passive; Pyrrolidines; Randomized Controlled Trials as Topic; Severe Acute Respiratory Syndrome; Sofosbuvir; Treatment Outcome; Valine; COVID-19 Serotherapy
PubMed: 33391531
DOI: 10.7150/thno.48342 -
Clinical Therapeutics Jan 2021Parkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic...
PURPOSE
Parkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic review aims to synthesize current existing evidence on the efficacy of citicoline adjunctive therapy in improving PD symptoms.
METHODS
An extensive literature search of Scopus, Embase, PubMed, Cochrane Library, and Google Scholar was conducted for articles published on or before December 31, 2019. The studies were screened and selected by 2 independent reviewers. We included all studies that explored the efficacy of citicoline as an adjunct therapy in PD.
FINDINGS
A total of 7 studies (2 crossover, 3 randomized controlled, and 2 open prospective studies) were included. Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy.
IMPLICATIONS
Citicoline adjuvant therapy has beneficial effects as an adjuvant therapy in patients with PD. However, due to the heterogeneity of the studies, there is a need for more high-quality studies.
Topics: Chemotherapy, Adjuvant; Cytidine Diphosphate Choline; Humans; Nootropic Agents; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 33279231
DOI: 10.1016/j.clinthera.2020.11.009 -
Annals of Hepatology 2021Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness... (Meta-Analysis)
Meta-Analysis
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Topics: Antiviral Agents; Benzimidazoles; Carbamates; Drug Combinations; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Macrocyclic Compounds; Pyrrolidines; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides; Valine
PubMed: 33059055
DOI: 10.1016/j.aohep.2020.09.012 -
Nutrients Oct 2020Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is...
Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Cytidine Diphosphate Choline; Dementia; Disease Models, Animal; Humans; Meta-Analysis as Topic; Nervous System Diseases; Neuralgia; Neurotransmitter Agents; Peripheral Nervous System; Stroke
PubMed: 33053828
DOI: 10.3390/nu12103113 -
Scientific Reports Aug 2020Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir... (Meta-Analysis)
Meta-Analysis
Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91-98%). The efficacy of the SOF-based regimen was 92% (95% CI 80-99%), 98% (95% CI 96-100%), and 100% (95% CI 95-100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5-29%), followed by anemia 15% (95% CI 3-31%), and nausea or vomiting 14% (95% CI 4-27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33-59%) compared to ribavirin-free regimens (3%, 95% CI 0-9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.
Topics: Antiviral Agents; Hepatitis C; Humans; Kidney Failure, Chronic; Sofosbuvir
PubMed: 32868869
DOI: 10.1038/s41598-020-71205-5 -
The Cochrane Database of Systematic... Aug 2020Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been proposed for the recovery from, and treatment of, ischemic stroke. One of them is citicoline. This review assessed the benefits and harms of citicoline for treating patients with acute ischemic stroke.
OBJECTIVES
To assess the clinical benefits and harms of citicoline compared with placebo or any other control for treating people with acute ischemic stroke.
SEARCH METHODS
We searched in the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS until 29 January 2020. We searched the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. Additionally, we also reviewed reference lists of the retrieved publications and review articles, and searched the websites of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in any setting including participants with acute ischemic stroke. Trials were eligible for inclusion if they compared citicoline versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
We selected RCTs, assessed the risk of bias in seven domains, and extracted data by duplicate. Our primary outcomes of interest were all-cause mortality and the degree of disability or dependence in daily activities at 90 days. We estimated risk ratios (RRs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed-effect and random-effects model meta-analyses. We assessed the overall quality of evidence for six pre-specified outcomes using the GRADE approach.
MAIN RESULTS
We identified 10 RCTs including 4281 participants. In all these trials, citicoline was given either orally, intravenously, or a combination of both compared with placebo or standard care therapy. Citicoline doses ranged between 500 mg and 2000 mg per day. We assessed all the included trials as having high risk of bias. Drug companies sponsored six trials. A pooled analysis of eight trials indicates there may be little or no difference in all-cause mortality comparing citicoline with placebo (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07; I² = 0%; low-quality evidence due to risk of bias). Four trials found no difference in the proportion of patients with disability or dependence in daily activities according to the Rankin scale comparing citicoline with placebo (21.72% versus 19.23%; RR 1.11, 95% CI 0.97 to 1.26; I² = 1%; low-quality evidence due to risk of bias). Meta-analysis of three trials indicates there may be little or no difference in serious cardiovascular adverse events comparing citicoline with placebo (8.83% versus 7.77%; RR 1.04, 95% CI 0.84 to 1.29; I² = 0%; low-quality evidence due to risk of bias). Overall, either serious or non-serious adverse events - central nervous system, gastrointestinal, musculoskeletal, etc. - were poorly reported and harms may have been underestimated. Four trials assessing functional recovery with the Barthel Index at a cut-off point of 95 points or more did not find differences comparing citicoline with placebo (32.78% versus 30.70%; RR 1.03, 95% CI 0.94 to 1.13; I² = 24%; low-quality evidence due to risk of bias). There were no differences in neurological function (National Institutes of Health Stroke Scale at a cut-off point of ≤ 1 points) comparing citicoline with placebo according to five trials (24.31% versus 22.44%; RR 1.08, 95% CI 0.96 to 1.21; I² = 27%, low-quality evidence due to risk of bias). A pre-planned Trial Sequential Analysis suggested that no more trials may be needed for the primary outcomes but no trial provided information on quality of life.
AUTHORS' CONCLUSIONS
This review assessed the clinical benefits and harms of citicoline compared with placebo or any other standard treatment for people with acute ischemic stroke. The findings of the review suggest there may be little to no difference between citicoline and its controls regarding all-cause mortality, disability or dependence in daily activities, severe adverse events, functional recovery and the assessment of the neurological function, based on low-certainty evidence. None of the included trials assessed quality of life and the safety profile of citicoline remains unknown. The available evidence is of low quality due to either limitations in the design or execution of the trials.
Topics: Activities of Daily Living; Acute Disease; Aged; Aged, 80 and over; Bias; Brain Ischemia; Cause of Death; Cytidine Diphosphate Choline; Humans; Middle Aged; Nootropic Agents; Randomized Controlled Trials as Topic; Recovery of Function; Stroke
PubMed: 32860632
DOI: 10.1002/14651858.CD013066.pub2 -
Journal of Alzheimer's Disease : JAD 2020A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
BACKGROUND
A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
OBJECTIVE
The purpose of this study was to determine the effects of CC as adjunct therapy to cholinesterase inhibitors (AChEI) in the treatment of AD.
METHODS
We identified relevant studies by electronic search until April 2020. We considered studies with a comparator group that enrolled elderly patients with a diagnosis of AD and employed CC as an adjunct therapy to AChEIs compared to AChEI monotherapy or comparisons of different AChEIs combined with CC. Methodological quality assessment was done using the Newcastle-Ottawa Scale.
RESULTS
Out of 149 articles identified, two retrospective cohort studies involving 563 elderly patients affected with AD were included. After 3 months and 9 months, better Mini-Mental Status Examination scores were observed in the "AChEIs + CC" group versus "AChEIs alone" group. CC combined with donepezil may be better in improving cognition than when combined with rivastigmine. No significant difference was noted in terms of activities of daily living (ADL) and instrumental-ADL. Neuropsychiatric Inventory and Geriatric Depression Scale-short form scores appeared to be lower in the combination treatment versus monotherapy. The adverse events of combined treatment were self-limiting and included occasional excitability, gastric intolerance, and headache.
CONCLUSION
Limited evidence from pooled data of two observational studies suggests that CC used in adjunct with AChEIs in the treatment of AD was well-tolerated and showed improvement in cognition, mood, and behavioral symptoms compared to treating with AChEIs alone.
Topics: Alzheimer Disease; Case-Control Studies; Cognition; Cytidine Diphosphate Choline; Drug Therapy, Combination; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32538854
DOI: 10.3233/JAD-200378 -
BioMed Research International 2019Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to... (Meta-Analysis)
Meta-Analysis
Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to 4. Therefore, the efficacy and safety of DAAs for genotypes 5 and 6 need to be analysed. Studies were identified from Medline, Scopus, and CENTRAL and a Chinese database CNKI, from inception until Dec 4, 2018. Clinical trials were included if they enrolled patients with genotypes 5 and/or 6 infection, any type of second-generation DAAs was studied, and sustained virological response was assessed at the 12 week after treatment (SVR12) as outcome measure. Meta-analysis using statistical program was applied for pooling proportions if data were sufficient (i.e., at least 2 studies). Thirteen studies were included in the analysis. Four studies assessed the efficacy of four DAA regimens in genotype 5 patients, which were mainly sofosbuvir (SOF) plus pegylated-interferon/ribavirin (PR) or other DAAs, with SVR12 ranging from 94.4% to 100%. Twelve studies assessed the efficacy of seven DAA regimens among genotype 6 patients, but only two DAA regimens (i.e., SOF + PR and SOF/ledipasvir) had sufficient data for pooling. The pooled SVR12 rates (95% CI) were 99.6% (92.2 to 100) for SOF + PR and 99.2% (96.5 to 100) for SOF/ledipasvir. No treatment-related serious adverse event was reported, while the nonserious adverse events were comparable to other genotypes. In conclusion, DAAs are effective and may be safe for the treatment of chronic hepatitis C genotypes 5 and 6. However, our evidence is based on noncomparative studies; hence, further larger-scale randomized controlled trials in these genotypes are still required.
Topics: Antiviral Agents; Benzimidazoles; Databases, Factual; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Ribavirin; Sofosbuvir; Uridine Monophosphate
PubMed: 31815126
DOI: 10.1155/2019/2301291