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Annals of Medicine Dec 2023The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.
AIM
To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection.
METHODS
We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109).
RESULTS
Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration.
CONCLUSION
Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.
Topics: Humans; Sofosbuvir; Hepacivirus; Sustained Virologic Response; Antiviral Agents; Hepatitis C; Drug Therapy, Combination; Hyperglycemia; Genotype; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36655629
DOI: 10.1080/07853890.2023.2168745 -
The Pan African Medical Journal 2019approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In...
INTRODUCTION
approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment.
METHODS
data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs).
RESULTS
the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds.
CONCLUSION
treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.
Topics: Antiviral Agents; Benzimidazoles; Cost-Benefit Analysis; Female; Fluorenes; Hepatitis C, Chronic; Humans; Male; Markov Chains; Quality-Adjusted Life Years; Sex Factors; Seychelles; Sofosbuvir; Substance Abuse, Intravenous; Uridine Monophosphate
PubMed: 31384341
DOI: 10.11604/pamj.2019.33.26.17742 -
Pharmacology & Therapeutics Jan 2014UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the... (Meta-Analysis)
Meta-Analysis Review
UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to clarify the potential for genotype-adjusted therapy recommendations. Data on UGT polymorphisms and dose-related pharmacokinetic parameters in man were retrieved by a systematic search in public databases. Mean estimates of pharmacokinetic parameters were extracted for each group of carriers of UGT variants to assess their effect size. Pooled estimates and relative confidence bounds were computed with a random-effects meta-analytic approach whenever multiple studies on the same variant, ethnic group, and substrate were available. Information was retrieved on 30 polymorphic metabolic pathways involving 10 UGT enzymes. For irinotecan and mycophenolic acid a wealth of data was available for assessing the impact of genetic polymorphisms on pharmacokinetics under different dosages, between ethnicities, under comedication, and under toxicity. Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size with the precision required to issue dose recommendations. In conclusion, compared to other drug metabolizing enzymes much less systematic research has been conducted on the polymorphisms of UGT enzymes. However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.
Topics: Analgesics; Anti-HIV Agents; Antihypertensive Agents; Antineoplastic Agents; Glucuronosyltransferase; Humans; Pharmaceutical Preparations; Pharmacokinetics; Polymorphism, Genetic; Psychotropic Drugs; Uridine Diphosphate
PubMed: 24076267
DOI: 10.1016/j.pharmthera.2013.09.002 -
BMC Infectious Diseases Nov 2017Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions... (Review)
Review
BACKGROUND
Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.
METHODS
According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).
RESULTS
Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.
CONCLUSIONS
On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Pyrrolidines; Ribavirin; Sofosbuvir; Treatment Outcome; Valine
PubMed: 29145802
DOI: 10.1186/s12879-017-2820-z -
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 -
Cornea Jun 2015To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. (Review)
Review
PURPOSE
To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye.
METHODS
Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events.
RESULTS
A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization.
CONCLUSIONS
Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.
Topics: Administration, Topical; Adult; Aged; Female; Fluorescein; Fluorescent Dyes; Humans; Keratoconjunctivitis Sicca; Male; Middle Aged; Ophthalmic Solutions; Polyphosphates; Purinergic P2Y Receptor Agonists; Randomized Controlled Trials as Topic; Rose Bengal; Tears; Treatment Outcome; Uracil Nucleotides
PubMed: 25909234
DOI: 10.1097/ICO.0000000000000429 -
The Cochrane Database of Systematic... 2000The prevalent use of this compound in the treatment of disorders of a cerebrovascular nature does not mean that a homogeneous and consistent application of this therapy... (Review)
Review
BACKGROUND
The prevalent use of this compound in the treatment of disorders of a cerebrovascular nature does not mean that a homogeneous and consistent application of this therapy has been applied. Dosage, method of administration, and selection criteria of patients have varied. The modalities of the studies, including length of observation, severity of disturbance, and methodology of the evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy, 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 of the elderly.
SEARCH STRATEGY
The CDCIG register of trials was searched for all relevant, non-animal randomised controlled trials using the terms CDP-choline/CDP, Citicoline, Cytidine Diphosphate Choline and Diphosphocholine. The Psychlit (1974-1996), Psychiatry (1980-1996) and MEDLINE electronic databases have been searched independently by the reviewers. The reviewers have also contacted manufacturers of CDP-choline.
SELECTION CRITERIA
All relevant, non-animal, unconfounded, double-blind, placebo-controlled, randomised trials of CDP-choline in cognitive impairment due to chronic cerebral disorders will be 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, 2 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 was no significant evidence of a beneficial effect of CDP-choline on attention. There were modest, but significant, beneficial effects of CDP-choline on memory function and behaviour. For the outcome of clinical global impression, the odds ratio for improvement in the subjects treated with CDP-Choline as opposed to the subjects treated with placebo was 8.89 [5.19, 15.22]. The drug was well tolerated.
REVIEWER'S CONCLUSIONS
There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder. Other studies with a more appropriate length of treatment are recommended owing to the chronic and irreversible nature of the disorders for which this treatment is indicated.
Topics: Aged; Cerebrovascular Disorders; Cognition Disorders; Cytidine Diphosphate Choline; Dementia; Humans; Mental Disorders; Nootropic Agents
PubMed: 10796523
DOI: 10.1002/14651858.CD000269 -
Expert Review of Gastroenterology &... Nov 2016Sofosbuvir (SOF) with simeprevir (SIM) combination was the first interferon-free regimen that reached optimal results in terms of sustained viral response (SVR). Areas... (Review)
Review
Sofosbuvir (SOF) with simeprevir (SIM) combination was the first interferon-free regimen that reached optimal results in terms of sustained viral response (SVR). Areas covered: A systematic review of the scientific literature concerning the effects that the SOF/SIM combination had on hepatitis C genotype 1 patients yielded 771 references. After the revision process, four clinical trials and 15 observational studies met the inclusion criteria; in total, these studies involved 5,766 patients. The SVR ranged from 67% to 100% depending on the patients' viral subtype and cirrhosis status. Adverse effects were common, but treatment discontinuation related to drug toxicity occurred in less than 5% of cases. Expert commentary: The SOF/SIM combination exhibits efficacy and tolerability profiles that are similar to those of the other available interferon-free combinations used for non-cirrhotic genotype 1b patients. Meanwhile, for patients with advanced cirrhosis or genotype 1a, this approach cannot be considered a routine treatment option due to the unsatisfactory results.
Topics: Antiviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Patient Selection; Risk Factors; Simeprevir; Sofosbuvir; Treatment Outcome
PubMed: 27626505
DOI: 10.1080/17474124.2016.1236682 -
Health Economic Evaluations of Sofosbuvir for Treatment of Chronic Hepatitis C: a Systematic Review.Applied Health Economics and Health... Oct 2016The approval of sofosbuvir offers new therapeutic options for patients suffering from chronic hepatitis C. In phase III trials, it has demonstrated significantly... (Review)
Review
BACKGROUND AND OBJECTIVE
The approval of sofosbuvir offers new therapeutic options for patients suffering from chronic hepatitis C. In phase III trials, it has demonstrated significantly greater efficacy and safety in comparison with the old standard of care. In addition, it provides the first interferon-free regimen allowing treatment of patients without previous therapeutic options. A current debate regarding pricing and affordability can be attributed to high treatment costs. The objective of this review was to compare health economic evaluations of sofosbuvir for the treatment of chronic hepatitis C in terms of models, patient populations, interventions and results.
METHODS
A systematic review was conducted using the data sources Medline (1946-09/2015), Embase (1974-09/2015), the Health Technology Assessment Database (September 2015) and the UK National Health Service Economic Evaluation Database (September 2015). We included health economic evaluations that measured the cost-effectiveness of sofosbuvir-based regimens compared with regimens without sofosbuvir for the treatment of adult patients infected with chronic hepatitis C. The articles were then critically appraised regarding the effectiveness data, cost data and models utilised.
RESULTS
Fourteen studies were included, which analysed the cost-effectiveness of sofosbuvir in seven different countries. Differences in study characteristics were found regarding study populations, modelling and willingness-to-pay thresholds. The study results demonstrated the cost-effectiveness of the treatment combination of sofosbuvir with pegylated interferon and ribavirin in comparison with the old standard of care. Dual therapy with sofosbuvir and ribavirin was considered cost effective only in comparison with no therapy.
CONCLUSION
Despite high costs, the included studies indicate that sofosbuvir-based regimens are cost effective in most patients. While the results are unequivocal with regard to sofosbuvir-based triple therapy, the cost-effectiveness of sofosbuvir-based dual therapy heavily depends on country-specific willingness to pay. Although interferon-containing triple therapy has now been replaced by newly approved direct-acting antivirals in most middle- and high-income countries, the availability of these oral treatment combinations is poor in low-income countries. Therefore, the findings of our review are still of relevance.
Topics: Antiviral Agents; Cost-Benefit Analysis; Drug Costs; Health Care Costs; Hepatitis C, Chronic; Humans; Sofosbuvir
PubMed: 27329481
DOI: 10.1007/s40258-016-0253-2 -
PloS One 2022Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for... (Meta-Analysis)
Meta-Analysis
Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for these conditions varies across populations. We tested whether UCP1 SNPs A-3826G, A-1766G, Ala64Thr and A-112C are associated with common CMP and their risk factors across Armenia, Greece, Poland, Russia and United Kingdom. This case-control study included genotyping of these SNPs, from 2,283 Caucasians. Results were extended via systematic review and meta-analysis. In Armenia, GA genotype and A allele of Ala64Thr displayed ~2-fold higher risk for CMP compared to GG genotype and G allele, respectively (p<0.05). In Greece, A allele of Ala64Thr decreased risk of CMP by 39%. Healthy individuals with A-3826G GG genotype and carriers of mutant allele of A-112C and Ala64Thr had higher body mass index compared to those carrying other alleles. In healthy Polish, higher waist-to-hip ratio (WHR) was observed in heterozygotes A-3826G compared to AA homozygotes. Heterozygosity of A-112C and Ala64Thr SNPs was related to lower WHR in CMP individuals compared to wild type homozygotes (p<0.05). Meta-analysis showed no statistically significant odds-ratios across our SNPs (p>0.05). Concluding, the studied SNPs could be associated with the most common CMP and their risk factors in some populations.
Topics: Cardiovascular Diseases; Case-Control Studies; Cytidine Monophosphate; Genetic Predisposition to Disease; Humans; Metabolic Diseases; Polymorphism, Single Nucleotide; Prevalence; Uncoupling Protein 1
PubMed: 35482655
DOI: 10.1371/journal.pone.0266386