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Antiviral Therapy 2017Ledipasvir and sofosbuvir are new direct-acting antiviral agents for patients with HCV infection. Ledipasvir inhibits the HCV non-structural 5A protein, while sofosbuvir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ledipasvir and sofosbuvir are new direct-acting antiviral agents for patients with HCV infection. Ledipasvir inhibits the HCV non-structural 5A protein, while sofosbuvir is a nucleotide polymerase inhibitor. Many studies have evaluated the safety and efficacy of ledipasvir and sofosbuvir combination with and without ribavirin for patients with chronic HCV genotype-1.
METHODS
A computer literature search of PubMed, SCOPUS, Web of Knowledge and Cochrane CENTRAL has been conducted. Studies were screened for eligibility and data were extracted. Sustained virological response (SVR) rate and commonly reported adverse events were pooled as risk ratio (RR) using Review Manager version 5.3 for windows and OpenMeta (Analyst) software.
RESULTS
Eight randomized controlled trials (n=1,892) were pooled in the final analysis. A 12-week ledipasvir and sofosbuvir regimen achieved SVR in 97.5% and 89% of non-cirrhotic and cirrhotic patients, respectively. A 24-week ledipasvir and sofosbuvir regimen achieved SVR in 99.6% and 92.6% in non-cirrhotic and cirrhotic patients, respectively. When ribavirin was added to the treatment regiment, the SVR did not differ significantly in either of the treatment regimens (12-week SVR: 93.9% versus 96.7%, RR=0.97, P=0.19 and 24-week SVR: 94.8% versus 97.2%, RR=0.98, P=0.24).
CONCLUSIONS
The combination of sofosbuvir and ledipasvir achieved high SVR rates (>90%) in both cirrhotic and non-cirrhotic patients with HCV genotype-1. The addition of ribavirin to this regimen did not significantly increase the SVR rates.
Topics: Animals; Antiviral Agents; Benzimidazoles; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatitis C; Humans; Male; Middle Aged; Publication Bias; RNA, Viral; Recurrence; Ribavirin; Sofosbuvir; Time Factors; Treatment Outcome; Viral Load
PubMed: 27588749
DOI: 10.3851/IMP3083 -
Postgraduate Medical Journal Jul 2022This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19.
METHODS
We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs).
RESULTS
There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000.
CONCLUSION
SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery.
PROTOCOL REGISTRATION
PROSPERO: CRD42021247510.
Topics: Humans; COVID-19; GRADE Approach; Imidazoles; Sofosbuvir; COVID-19 Drug Treatment; Controlled Clinical Trials as Topic
PubMed: 37066509
DOI: 10.1136/postgradmedj-2021-140287 -
Journal of Clinical Anesthesia Aug 2022To investigate the association of unintentional dural puncture (UDP) and postdural puncture headache (PDPH) with the risk of chronic headache, backache, neckache and... (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
To investigate the association of unintentional dural puncture (UDP) and postdural puncture headache (PDPH) with the risk of chronic headache, backache, neckache and depression. We also investigated if epidural blood patch (EBP) is associated with reduced risk of these morbidities.
DESIGN
Systematic review and meta-analysis.
PATIENTS
Pregnant women who experienced UDP and/or PDPH versus those who had uneventful neuraxial procedures, and women who received EBP versus those who did not.
INTERVENTIONS
None.
MEASUREMENTS
Primary outcomes were headache, backache, and neckache lasting ≥12 months, and depression ≥1 month. Secondary outcomes included chronic headache, backache, and neckache persisting ≥1 and ≥ 6 months, and the effects of EBP on those outcomes at ≥1 and ≥ 12 months. Subgroup analyses of prospective studies and sensitivity analyses of primary outcomes excluding poor quality studies were performed.
MAIN RESULTS
Twelve studies compared 6541 women with UDP and/or PDPH versus 1,004,510 with uncomplicated neuraxial procedures. Eight studies compared EBP (n = 3610) with no EBP (n = 3154). UDP and/or PDPH were associated with increased risk of headache (RR 3.95; 95%CI 2.13 to 7.34; I 42%), backache (RR 2.72; 95%CI 2.04 to 3.62; I 1%), and neckache (RR 8.09; 95%CI 1.03 to 63.35) persisting ≥12 months, and depression (RR 3.12; 95%CI 1.44 to 6.77; I 90%) lasting ≥1 month. Results were consistent in analyses at ≥1 and ≥ 6 months, subgroup analyses of prospective studies, and after exclusion of one poor-quality study from our primary outcome. EBP was not associated with significant reduction in the risk of long-term morbidities.
CONCLUSIONS
UDP and/or PDPH were associated with increased risk of chronic headache, backache, neckache, and depression. EBP was not associated with a significant reduction in those risks, but this conclusion is limited by the heterogeneity of current data and lack of information on the success of EBP in relieving acute PDPH symptoms.
Topics: Female; Humans; Pregnancy; Back Pain; Blood Patch, Epidural; Headache; Headache Disorders; Morbidity; Neck Pain; Post-Dural Puncture Headache; Prospective Studies; Punctures; Spinal Puncture; Uridine Diphosphate
PubMed: 35358942
DOI: 10.1016/j.jclinane.2022.110787 -
Canadian Journal of Gastroenterology &... 2017The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF),... (Meta-Analysis)
Meta-Analysis Review
The Efficacy and Safety of 12 Weeks of Sofosbuvir and Ledipasvir versus Sofosbuvir, Ledipasvir, and Ribavirin in Patients with Chronic Hepatitis C, Genotype 1, Who Have Cirrhosis and Have Failed Prior Therapy: A Systematic Review and Meta-Analysis.
The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF), ledipasvir (LDV), and ribavirin (RBV). This recommendation is based on expert opinion, and the efficacy of 12 weeks of SOF/LDV compared to SOF/LDV/RBV in this patient population has not yet been established. . We conducted a systematic review and meta-analysis. Two investigators independently searched electronic databases and relevant conference proceedings for randomized controlled trials comparing rates of sustained virologic response 12 weeks after therapy (SVR12) when using 12 weeks of SOF/LDV versus 12 weeks of SOF/LDV/RBV in patients with CHC, genotype 1, who have cirrhosis and failed previous therapy. Our search strategy yielded 596 studies of which four met criteria for inclusion. The pooled RR of not achieving SVR12 with SOF/LDV versus SOF/LDV/RBV was 1.21 (95% CI: 0.42-3.48). Adverse events were lower in the SOF/LDV compared to the SOF/LDV/RBV arms (pooled RR: 0.11, 95% CI: 0.04-0.29). Our findings suggest that 12 weeks of SOF/LDV cannot be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy.
Topics: Antiviral Agents; Benzimidazoles; Fluorenes; Genotype; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Ribavirin; Sofosbuvir
PubMed: 28367429
DOI: 10.1155/2017/6468309 -
Pain Medicine (Malden, Mass.) Apr 2022Chronic musculoskeletal pain (CMP) outcomes are affected by numerous variables, including the clinical conversation. When good therapeutic/working alliances are formed,...
Patient and Provider Attitudes, Beliefs, and Biases That Contribute to a Marginalized Process of Care and Outcomes in Chronic Musculoskeletal Pain: A Systematic Review-Part I: Clinical Care.
OBJECTIVE
Chronic musculoskeletal pain (CMP) outcomes are affected by numerous variables, including the clinical conversation. When good therapeutic/working alliances are formed, congruent clinical conversations can lead to improved CMP outcomes. Identifying patient/provider attitudes, beliefs, and biases in CMP that can influence the clinical conversation, and thus clinical management decisions, is foundationally important.
DESIGN
The aims of this systematic review were to 1) summarize the evidence of the attitudes and beliefs of patients and health care providers (HCPs) involved in the clinical conversation about CMP, and 2) examine whether and how these perceptions impacted the process of care.
METHODS
A systematic search of CINAHL, PubMed, Scopus, Sociology Database in ProQuest, and Web of Science used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Included studies were those investigating vulnerable adult populations with chronic pain. Study bias was examined with the Downs and Black tool.
RESULTS
Seven retrospective studies were included. When making pharmaceutical management decisions, HCPs demonstrated negative implicit biases toward minorities and women. When making referrals to multidisciplinary care, HCPs demonstrated negative implicit biases toward women with lower educational attainment. Unmet patient expectations resulted in higher dropout rates at multidisciplinary pain management programs. Patients' trust was influenced by the health care setting, and patients often had limited options secondary to health insurance type/status.
CONCLUSION
These findings suggest that patients with CMP may experience a marginalized process of care due to HCPs' negative implicit biases, unmet patient expectations, and the health care setting. Results suggest several factors may contribute to inequitable care and the recalcitrant nature of CMP, particularly in vulnerable populations with limited health care choices.
Topics: Adult; Attitude; Bias; Chronic Pain; Cytidine Monophosphate; Female; Humans; Musculoskeletal Pain; Retrospective Studies
PubMed: 34297104
DOI: 10.1093/pm/pnab195 -
Journal of Infection and Public Health 2018Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety... (Meta-Analysis)
Meta-Analysis Review
Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety and efficacy of velpatasvir plus sofosbuvir in the treatment of chronic HCV infection. A computerized literature search of PubMed, SCOPUS, EMBASE, EBSCO, Web of science, and Cochrane CENTRAL was conducted using relevant keywords. Data from eligible studies were pooled in a fixed effect meta-analysis model, using OpenMeta[Analyst] software. Pooled data from six randomized trials (n=1427 patients) showed that velpatasvir plus sofosbuvir achieved sustained virological response (SVR12) rates of 98.2% in genotype-1, 99.4% in genotype-2, 94.7% in genotype-3, 99.6% in genotype-4, 97.1% in genotype-5, and 98.8% in genotype-6 patients. The addition of ribavirin did not significantly increase the SVR12 (RR=0.95, 95%CI [0.88, 1.02]) or decrease relapse rates (RR=2.52, 95% CI [0.49, 12.87]) in HCV genotype-1 patients. However, adding ribavirin significantly increased SVR12 (RR=89.5, 95% CI [80.4, 99.5]) in genotype-3 patients. In conclusion, the 12-week regimen of sofosbuvir plus velpatasvir was highly effective in HCV patients, including those with cirrhosis and former treatment experience. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates. Further studies should investigate the effect of adding ribavirin to this regimen, especially in HCV genotype-3 patients.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Randomized Controlled Trials as Topic; Ribavirin; Sofosbuvir; Treatment Outcome; Viral Nonstructural Proteins
PubMed: 28970099
DOI: 10.1016/j.jiph.2017.09.004 -
Annals of Hepatology 2017
Meta-Analysis Review
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Chi-Square Distribution; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatitis C; Humans; Male; Middle Aged; Odds Ratio; Ribavirin; Sofosbuvir; Sustained Virologic Response; Time Factors; Treatment Outcome; Young Adult
PubMed: 28233739
DOI: 10.5604/16652681.1231562 -
Brain Injury Jul 2008There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper... (Review)
Review
PRIMARY OBJECTIVE
There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper aims to assess the evidence accumulated thus far.
METHODS
Studies are identified by searching MEDLINE, EMBASE and PsychINFO, contacting experts and pharmaceutical companies and hand searching bibliographies. All study designs are included.
MAIN OUTCOME AND RESULTS
This study identified 25 papers that studied cholinesterase inhibitors, physostigmine and choline in mild-to-severe traumatic brain injury. The outcome with cholinesterase inhibitors and choline is suggestive but not conclusive while physostigmine appears of little benefit. A lack of rigorous studies and a plethora of outcome measures preclude drawing definitive conclusions. Further randomized controlled trials are urgently required.
Topics: Brain Injuries; Cholinesterase Inhibitors; Cognition Disorders; Cytidine Diphosphate Choline; Humans; Lecithins; Neuropsychological Tests; Nootropic Agents; Physostigmine; Surface-Active Agents; Time Factors
PubMed: 18568705
DOI: 10.1080/02699050802132495 -
Daru : Journal of Faculty of Pharmacy,... Apr 2017Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis.
METHODS
In this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis.
RESULTS
After screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ = 5.29, P = 0.26 and I = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%).
CONCLUSIONS
Combination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Ribavirin; Sofosbuvir
PubMed: 28427463
DOI: 10.1186/s40199-017-0177-x -
Clinical Therapeutics Feb 2016Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and... (Comparative Study)
Comparative Study Review
PURPOSE
Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV).
METHODS
A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared.
FINDINGS
The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL.
IMPLICATIONS
After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.
Topics: Antiviral Agents; Carbamates; Clinical Trials, Phase III as Topic; Coinfection; Drug Therapy, Combination; Genotype; HIV Infections; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Pyrrolidines; Ribavirin; Sofosbuvir; Valine
PubMed: 26839044
DOI: 10.1016/j.clinthera.2015.12.017