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The Cochrane Database of Systematic... 2004CDP-choline is used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
CDP-choline is used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage, method of administration, and selection criteria of patients to which the treatments was given. Modalities of the clinical studies, including length of observation, severity of disturbance, and methodology of evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy due to these complexities, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review.
OBJECTIVES
The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders in the elderly.
SEARCH STRATEGY
The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 20 January 2004 using the terms CDP-choline, CDP, citicolone, cytidine diphosphate choline or diphosphocholine. This register contains records from all major health care databases and many ongoing trials databases and is updated regularly.
SELECTION CRITERIA
All relevant unconfounded, double-blind, placebo-controlled, randomized trials of CDP-choline for cognitive impairment due to chronic cerebral disorders are considered for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included.
MAIN RESULTS
Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 4 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There is no significant evidence of a beneficial effect of CDP-choline on attention. There are significant beneficial effects of CDP-choline on memory function and behaviour. The drug is well tolerated.
REVIEWERS' CONCLUSIONS
There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short/medium term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially vascular dementia.
Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Cognition Disorders; Cytidine Diphosphate Choline; Dementia; Humans; Mental Disorders; Nootropic Agents; Randomized Controlled Trials as Topic
PubMed: 15106147
DOI: 10.1002/14651858.CD000269.pub2 -
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 -
Current Drug Targets 2016Nowadays, a large number of people in the world are suffering from chronic Hepatitis C. HCV NS5B polymerase conserved across the identified 7 HCV genotypes is considered... (Review)
Review
Nowadays, a large number of people in the world are suffering from chronic Hepatitis C. HCV NS5B polymerase conserved across the identified 7 HCV genotypes is considered to be the most promising target in combating HCV. During the past decade, significant progress has been made in the discovery of novel nucleoside HCV NS5B polymerase inhibitors. A potent anti-HCV drug, sofosbuvir with high cure rates has been approved. Besides, quite a few nucleoside anti-HCV agents are being evaluated in clinical trials. The purpose of this review is to present recent progress in the development of nucleoside HCV NS5B polymerase inhibitors, focusing on lead compounds that hold great promise for medicinal use and their structure-activity relationships (SARs) in order to provide guidance for future drug design and discovery.
Topics: Animals; Antiviral Agents; Drug Design; Drug Discovery; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Sofosbuvir; Structure-Activity Relationship; Viral Nonstructural Proteins
PubMed: 26648061
DOI: 10.2174/1389450117666151209123751 -
Restorative Neurology and Neuroscience 2013Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is... (Review)
Review
Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is to systematically survey all adjuvant treatments after surgery investigated in rat and mouse models. Both PubMed and Embase were explored with a systematic bibliographic search algorithm. Inclusion criteria consisted of treatments applied to rats or mice after complete transection and microsurgical repair of lower-limb motor or mixed nerves. Effect size statistics enabled numerical comparison between outcomes of treated and untreated animals and ranked the best treatments. 1,553 articles were found according to our search strategies, and 22 of them corresponded to our pre-defined inclusion criteria. After data extraction and analysis, the top 3 adjuvant strategies in terms of combined average effect size were citicoline, neurotrophin-4, and nitric oxide synthesis inhibitor, with values of 5.52, 5.14 and 4.08, respectively. Definitive treatment comparison was difficult due to the lack of uniformity in outcome evaluation in the experiments performed. Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation.
Topics: Animals; Cytidine Diphosphate Choline; Disease Models, Animal; Humans; Lacerations; Nerve Growth Factors; Nitric Oxide Synthase; Peripheral Nerves; Rodentia; Treatment Outcome
PubMed: 23478341
DOI: 10.3233/RNN-120253 -
Expert Review of Clinical Pharmacology Aug 2022This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19.
RESEARCH DESIGN AND METHODS
PubMed, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 6, 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of SOF-DCV (study group) with alternative treatments (control group) in patients with COVID-19 were included.
RESULTS
A total of 9 RCTs were included. The all-cause mortality rate in the study group was 10.7% (96/898), which was lower than that in the control group (12.3%, 108/871). However, this difference was not statistically significant (odds ratio [OR] = 0.83; 95% CI, 0.62-1.12; = 49%). The overall clinical recovery rate was significantly higher in the study group than in the control group (OR = 2.34; 95% CI, 1.47-3.72; = 20%). Furthermore, the average length of hospital stay was shorter in the study group than in the control group (mean deviation = -1.84; 95% CI, -3.42 to -0.26, = 68%).
CONCLUSIONS
Although SOF-DCV did not confer a survival benefit in patients with COVID-19, it may increase a patient's odds of clinical recovery, and shorten the length of their hospital stay.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Humans; Imidazoles; Pyrrolidines; Randomized Controlled Trials as Topic; Sofosbuvir; Treatment Outcome; Valine; COVID-19 Drug Treatment
PubMed: 35852099
DOI: 10.1080/17512433.2022.2103539 -
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 -
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 -
The Cochrane Database of Systematic... Apr 2007Delirium is a common mental disorder with serious adverse outcomes in hospitalised patients. It is associated with increases in mortality, physical morbidity, length of... (Review)
Review
BACKGROUND
Delirium is a common mental disorder with serious adverse outcomes in hospitalised patients. It is associated with increases in mortality, physical morbidity, length of hospital stay, institutionalisation and costs to healthcare providers. A range of risk factors has been implicated in its aetiology, including aspects of the routine care and environment in hospitals. Prevention of delirium is clearly desirable from patients' and carers' perspectives, and to reduce hospital costs. Yet it is currently unclear whether interventions for prevention of delirium are effective, whether they can be successfully delivered in all environments, and whether different interventions are necessary for different groups of patients.
OBJECTIVES
Our primary objective was to determine the effectiveness of interventions designed to prevent delirium in hospitalised patients. We also aimed to highlight the quality and quantity of research evidence to prevent delirium in these settings.
SEARCH STRATEGY
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 28th September, 2005. As the searches in MEDLINE, EMBASE, CINAHL and PsycINFO for the Specialized Register would not necessarily have picked up all delirium prevention trials, these databases were searched again on 28th October, 2005. We also examined reference lists of retrieved articles, reviews and books. Experts in this field were contacted and the Internet searched for further references and to locate unpublished trials.
SELECTION CRITERIA
Randomised controlled trials evaluating any interventions to prevent delirium in hospitalised patients.
DATA COLLECTION AND ANALYSIS
Data collection and quality assessment were performed by three reviewers independently and agreement reached by consensus.
MAIN RESULTS
Six studies with a total of 833 participants were identified for inclusion. All were conducted in surgical settings, five in orthopaedic surgery and one in patients undergoing resection for gastric or colon cancer. Only one study of 126 hip fracture patients comparing proactive geriatric consultation with usual care was sufficiently powered to detect a difference in the primary outcome, incident delirium. Total cumulative delirium incidence during admission was reduced in the intervention group (OR 0.48 [95% CI 0.23, 0.98]; RR 0.64 [95% CI 0.37, 0.98]), suggesting a 'number needed to treat' of 5.6 patients to prevent one case. The intervention was particularly effective in preventing severe delirium. In logistic regression analyses adjusting for pre fracture dementia and Activities of Daily Living impairment, there was no reduction in effect size, OR 0.6, but this no longer remained significant [95% CI 0.3,1.3]. There was no effect on the duration of delirium episodes, length of hospital stay, and cognitive status or institutionalisation at discharge. There was also no significant difference in cumulative delirium incidence between treatment and control groups in a sub-group of 50 patients with dementia (RR 0.9 [95% CI 0.59, 1.36]). In another trial of low dose haloperidol prophylaxis, there was no difference in delirium incidence but the severity and duration of a delirium episode, and length of hospital stay were all reduced. We identified no completed studies in hospitalised medical, care of the elderly, general surgery, cancer or intensive care patients. In outcomes, no studies examined for death, use of psychotropic medication, activities of daily living, psychological morbidity, quality of life, carers or staff psychological morbidity, cost of intervention and cost to health care services. Outcomes were only reported up to discharge, with no studies reporting medium or longer-term effects.
AUTHORS' CONCLUSIONS
Research evidence on effectiveness of interventions to prevent delirium is sparse. Based on a single study, a programme of proactive geriatric consultation may reduce delirium incidence and severity in patients undergoing surgery for hip fracture. Prophylactic low dose haloperidol may reduce severity and duration of delirium episodes and shorten length of hospital admission in hip surgery. Further studies of delirium prevention are needed.
Topics: Anesthesia, Epidural; Anesthetics, Inhalation; Cytidine Diphosphate Choline; Delirium; Donepezil; Halothane; Hospitalization; Humans; Indans; Nootropic Agents; Piperidines
PubMed: 17443600
DOI: 10.1002/14651858.CD005563.pub2 -
Journal of Neurochemistry Oct 2012The neuroprotective actions of citicoline have been documented for experimental stroke therapy. We used a systematic review and meta-analysis to assess this evidence.... (Meta-Analysis)
Meta-Analysis Review
Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial.
The neuroprotective actions of citicoline have been documented for experimental stroke therapy. We used a systematic review and meta-analysis to assess this evidence. From 64 identified studies using citicoline in stroke animal models, only those describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included (14 studies, 522 animals). Overall, the quality of the studies was modest (5, 4-6), while the absence of studies involving animals with co-morbidities, females, old animals or strain differences indicated that studies did not fulfill the STAIR recommendations. Weighted mean difference meta-analysis showed citicoline to reduce infarct volume by 27.8% [(19.9%, 35.6%); p < 0.001]. In the stratified analysis, citicoline effect on reducing infarct volume was higher in proximal occlusive models of middle cerebral artery (MCA) compared with distal occlusion. Moreover, the efficacy was superior using multiple doses than single dose and when a co-treatment was administered compared with citicoline monotherapy, the only independent factor identified in the meta-regression. Citicoline improved neurological deficit by 20.2% [(6.8%, 33.7%); p = 0.015], but only four studies including 176 animals reported these data. In conclusion, this meta-analysis provides evidence of citicoline efficacy in stroke animal models and shows the optimal neuroprotective profile and the missing experimental requirements before jumping into clinical trials.
Topics: Animals; Clinical Trials as Topic; Cytidine Diphosphate Choline; Disease Models, Animal; Humans; Neuroprotective Agents; Nootropic Agents; Stroke
PubMed: 22845688
DOI: 10.1111/j.1471-4159.2012.07891.x -
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