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Systematic review with meta-analysis: impact of baseline resistance-associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients.
Singh, AD, Maitra, S, Singh, N, Tyagi, P, Ashraf, A, Kumar, R, Shalimar,
Alimentary pharmacology & therapeutics. 2020;(5):490-504
Abstract
BACKGROUND The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients receiving the second generation, pan-genotypic glecaprevir/pibrentasvir (G/P) regimen is unclear. AIM: To assess the effect of RAS on the SVR12 in CHC patients treated with G/P regimen. METHODS The EMBASE, MEDLINE and Cochrane central register of controlled trials databases were searched for relevant studies published before 1 March 2019. The principal outcome was to compare the SVR12 in CHC patients with and without baseline RAS, particularly in genotype-1, genotype-3 and direct-acting anti-virals (DAAs) failure patients. The outcomes were pooled using a random-effects model and odds ratio (OR) was calculated. The risk of bias was assessed using the Cochrane risk of bias tools for randomised and nonrandomised interventional studies. RESULTS After initially identifying 410 studies, 3302 patients from 17 studies were included. Among 50 cases of virologic failures, 48% had genotype-3 infection, 44% genotype-1 infection and 36% DAA-failure patients. Baseline RAS were present in 44(88%) patients. The most common NS5a and NS3 mutations were Y93H and A166S respectively. The odds of SVR12 were significantly reduced in patients with any baseline RAS (NS3 and/or NS5a) (OR 0.32, 95%C I[0.15, 0.65], I2 = 0%) and NS5a substitutions (OR 0.36, 95%CI [0.18,0.73]). The impact of RAS on SVR12 was significant among genotype-3 patients, but not among genotype-1 or DAA-failure cases. The presence of Y93H and A30K mutations significantly impacted SVR12 rates in genotype-3 patients. CONCLUSION Baseline NS3 or NS5a RAS, especially the NS5a substitutions-A30K, Y93H, decrease the odds of achieving SVR12 in genotype-3 CHC patients.
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Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis.
Ho Lee, Y, Gyu Song, G
Journal of clinical pharmacy and therapeutics. 2020;(4):674-681
Abstract
WHAT IS KNOWN AND OBJECTIVE Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head-to-head comparison trials. The relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for rheumatoid arthritis (RA) were assessed. METHODS We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) and examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy relative to placebo in patients with RA. RESULTS AND DISCUSSION Five RCTs comprising 1547 patients met the inclusion criteria. Compared with placebo, tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy showed a significantly higher American College of Rheumatology 20% (ACR20) response rate. Peficitinib 150 mg monotherapy showed the highest ACR20 response rate (odds ratio, 17.24.39; 95% credible interval, 6.57-51.80). The ranking probability based on the surface under the cumulative ranking curve indicated that peficitinib 150 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. However, the number of patients who experienced serious adverse events did not differ significantly between the JAK inhibitors, except for tofacitinib 5 mg, and placebo. WHAT IS NEW AND CONCLUSION All five JAK inhibitors-tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib-were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy.
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Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.
He, HS, Li, BY, Chen, QT, Song, CY, Shi, J, Shi, B
Medical science monitor : international medical journal of experimental and clinical research. 2019;:1169-1176
Abstract
BACKGROUND Currently, proton pump inhibitors (PPIs) are the first-line treatment for ulcers resulting from endoscopic submucosal dissection (ESD). Vonoprazan is a new oral potassium-competitive acid blocker (P-CAB). The aim of this systematic review and meta-analysis was to compare the efficacy, safety, and tolerance of vonoprazan with PPIs in the treatment of peptic ulcers resulting from ESD. MATERIAL AND METHODS Published results of randomized clinical trials (RCTs) comparing vonoprazan with PPIs in the treatment of ulcers resulting from ESD were identified up to March 2018. The main clinical endpoints evaluated were healing rate and adverse events. The meta-analysis included quality assessment of the studies, statistical analysis of endpoints, and sensitivity analysis using Revman version 5.3 meta-analysis software. RESULTS Systematic literature review identified seven published studies that included 548 patients. Five studies were published as full-text manuscripts, and two studies were published as abstracts. Meta-analysis of the vonoprazan treatment, compared with PPI treatment, for ESD showed that the pooled relative risk (RR) of healing rate was 0.64 (95% CI, 0.33-1.22) for the 4-week study group and 0.98 (95% CI, 0.84-1.15) for the 8-week study group. The RR for adverse events was 0.65 (95% CI, 0.31-1.38) (P>0.05). No statistical evidence of publication bias was found. CONCLUSIONS The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs.
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The efficacy of vonoprazan for management of post-endoscopic submucosal dissection ulcers compared with proton pump inhibitors: A meta-analysis.
Liu, C, Feng, BC, Zhang, Y, Li, LX, Zuo, XL, Li, YQ
Journal of digestive diseases. 2019;(10):503-511
Abstract
OBJECTIVE Artificial ulcers after endoscopic submucosal dissection (ESD) are usually treated by proton pump inhibitors (PPIs) in clinical setting. Vonoprazan, a newly developed potassium-competitive acid blocker, has recently been used to treat post-ESD ulcers. We aimed to evaluate the efficacy and safety of vonoprazan on the healing of post-ESD artificial ulcers compared with those of proton pump inhibitors (PPIs) using a meta-analysis. METHODS EMBASE, MEDLINE, Scopus and Cochrane Library databases were searched for all studies comparing the efficacy and safety of vonoprazan with those of PPIs in the treatment of post-ESD ulcers. RESULTS Fourteen articles with 1328 patients were included in this meta-analysis. When comparing ulcer shrinkage rate, vonoprazan showed a better efficacy than PPIs (mean difference 0.56, 95% confidence interval [CI] 0.18-0.93). Vonoprazan also led to a higher scar formation rate (odds ratio [OR] 1.58, 95% CI 1.00-2.47) and showed a potential superiority on reducing the risk of post-ESD bleeding compared with PPIs, with a pooled OR of 0.69, although there was no statistically significant difference. CONCLUSIONS Compared with PPIs, vonoprazan showed a better efficacy in ulcer shrinkage rate and achieved more complete healing in the treatment of post-ESD ulcers. Vonoprazan did not induce any incremental risk of post-ESD bleeding as well. It may be an appropriate choice in the management of artificial ulcers after ESD.
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Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.
Pu, S, Wang, D, Liu, D, Zhao, Y, Qi, D, He, J, Zhou, G
BMC pulmonary medicine. 2017;(1):148
Abstract
BACKGROUND Sivelestat is widely used in treating acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), although the clinical efficacy of sivelestat remains controversial. This study aimed to evaluate the impact of sivelestat in patients with ALI/ARDS. METHODS Electronic databases, PubMed, Embase, and the Cochrane Library, were searched to identify trials through April 2017. Randomized controlled trials (RCTs) were included irrespective of blinding or language that compared patients with and without sivelestat therapy in ALI/ARDS. A random-effects model was used to process the data, and the relative risk (RR) and standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to evaluate the effect of sivelestat. RESULTS Six RCTs reporting data on 804 patients with ALI/ARDS were included. Overall, no significant difference was found between sivelestat and control for the risk of 28-30 days mortality (RR: 0.94; 95% CI: 0.71-1.23; P = 0.718). Sivelestat therapy had no significant effect on ventilation days (SMD: 0.05; 95% CI: -0.27 to 0.38; P = 0.748), arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) level (SMD: 0.48; 95% CI: -0.45 to 1.41; P = 0.315), and intensive care unit (ICU) stays (SMD: -9.87; 95% CI: -24.30 to 4.56; P = 0.180). The results of sensitivity analysis indicated that sivelestat therapy might affect the PaO2/FiO2 level in patients with ALI/ARDS (SMD: 0.87; 95% CI: 0.39 to 1.35; P < 0.001). CONCLUSIONS Sivelestat therapy might increase the PaO2/FiO2 level, while it had little or no effect on 28-30 days mortality, ventilation days, and ICU stays. These findings need to be verified in large-scale trials.
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Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.
Abdul-Rahim, AH, Perez, AC, Fulton, RL, Jhund, PS, Latini, R, Tognoni, G, Wikstrand, J, Kjekshus, J, Lip, GY, Maggioni, AP, et al
Circulation. 2015;(17):1486-94; discussion 1494
Abstract
BACKGROUND Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). METHODS AND RESULTS We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. CONCLUSIONS A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.
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Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials.
Yang, Y, Wu, YX, Hu, YZ
Medicine. 2015;(30):e1226
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Abstract
We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of rosuvastatin on contrast-induced acute kidney injury (CI-AKI) and major adverse cardiovascular events (MACEs) in patients undergoing cardiac catherization.PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to May 2015, to compare rosuvastatin for preventing CI-AKI with placebo treatment in patients undergoing cardiac catherization.Five RCTs with a total of 4045 patients involving 2020 patients pretreated with rosuvastatin and 2025 control patients were identified and analyzed. Patients treated with rosuvastatin had a 51% lower risk of CI-AKI compared with the control group based on a fixed-effect model (OR = 0.49, 95% CI = 0.37-0.66, P < 0.001), and showed a trend toward a reduced risk of MACEs (OR = 0.62, 95% CI = 0.36-1.07, P = 0.08). A subgroup analysis showed that studies with Jadad score ≥3 showed a significant reduction of CI-AKI (OR = 0.53, 95% CI, 0.38-0.73, P < 0.001). However, the risk of CI-AKI did not significantly differ in the studies with Jadad score <3 (OR = 0.54, 95% CI, 0.13-2.24, P = 0.40). In addition, the rosuvastatin treatment showed no effect for preventing CI-AKI in patients with chronic kidney disease (CKD) undergoing elective cardiac catherization (I = 0%, OR = 0.81, 95% CI = 0.41-1.61, P = 0.55).This updated meta-analysis demonstrated that preprocedural rosuvastatin treatment could significantly reduce the incidence of CI-AKI, with a trend toward a reduced risk of MACEs in patients undergoing cardiac catheterization. However, rosuvastatin treatment did not seem to be effective for preventing CI-AKI in CKD patients undergoing elective cardiac catheterization.
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[Effect of sivelestat sodium on the prognosis of patients with acute lung injury and acute respiratory distress syndrome: a meta-analysis].
Xia, H, Sun, Z, Yang, Y, Shang, Y, Yao, S
Zhonghua wei zhong bing ji jiu yi xue. 2015;(10):800-4
Abstract
OBJECTIVE To investigate the effect of sivelestat sodium on the prognosis in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). METHODS Databases including PubMed, EBSCO, Springer, Ovid, Wanfang data, CNKI and China Biology Medicine (CBM) were searched to identify randomized controlled trials (RCTs) regarding sivelestat sodium treatment for ALI/ARDS published from 1985 to December 2014. The patients in treatment group received intravenous infusion of sivelestat sodium, and those in control group received normal saline. The items for analysis were 28-day mortality, duration of mechanical ventilation, length of intensive care unit (ICU) stay, and oxygenation index on day 3. According to the evaluation method of Cochrane system, data extraction and quality assessment from the literature were carried out. Meta-analysis was performed using RevMan 5.3. The publication bias was analyzed with funnel plot. RESULTS Five RCTs with a total of 780 participants were included, with 389 patients in sivelestat sodium group, and 391 in control group. Meta analysis showed: compared with control group, sivelestat sodium could not lower the 28-day mortality [odds ratio (OR) = 0.91, 95% confidence interval (95% CI) = 0.66-1.26, P = 0.58], or shorten the duration of mechanical ventilation or length of ICU stay [duration of mechanical ventilation: mean difference (MD) = -0.02, 95% CI = -0.29 to 0.24, P = 0.87; length of ICU stay: MD = -9.63, 95% CI = -23.34 to 4.08, P = 0.17], but it could improve oxygenation index on day 3 (MD = 0.88, 95% CI = 0.39 to 1.36, P = 0.000 4). Heterogeneity was not significant for the main analysis and no publication bias was shown on funnel plot. CONCLUSION Sivelestat sodium gave rise to a better oxygenation on day 3, but did not change the length of mechanical ventilation and ICU stay, and it did not improve 28-day mortality in ALI and ARDS.
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Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: a systematic review and meta-analysis of clinical trials.
Santoni, M, Conti, A, De Giorgi, U, Iacovelli, R, Pantano, F, Burattini, L, Muzzonigro, G, Berardi, R, Santini, D, Cascinu, S
International journal of cancer. 2014;(4):763-73
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Abstract
Gastrointestinal (GI) events have been described with sorafenib, sunitinib and pazopanib in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) in patients with cancer treated with these agents. PubMed databases were searched for articles published till May 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 6,447 patients were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and 4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066 breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When stratified by tumor type (RCC vs. non-RCC), the difference among the incidences of GI events was significant for diarrhea (p < 0.001) and vomiting (p = 0.006), that resulted higher in RCC patients. In RCC patients, sorafenib registered the lower incidence and RR of all grades GI events. The difference was statistically significant for sorafenib versus sunitinib-related all and high-grade events (p < 0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib and pazopanib is associated with a significant increase in the risk of GI events in patients with cancer, and frequent clinical monitoring should be emphasized when managing these three and newer VEGFR TKIs.
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Patients eligible for treatment with simeprevir in a French center.
Morel, V, Duverlie, G, Brochot, E
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2014;(1):149-51
Abstract
BACKGROUND Simeprevir (Olysio(®)), a second-wave protease inhibitor recently approved for the treatment of chronic hepatitis C, is not indicated in patients with genotype 1a strain harboring the Q80K protease mutation. Phase 2 and 3 studies on this molecule mainly focused on North American patients and the prevalence of Q80K is particularly high in the USA (around 50%). The prevalence of this mutation in other parts of the world is currently unknown. OBJECTIVES The purpose of our study was to perform a detection of this mutation in a single PCR technique and to study the prevalence of this Q80K mutation in a non U.S. population. We can thus estimate the proportion of HCV positive patients who can be treated with simeprevir. STUDY DESIGN We conducted a meta-analysis of response rates in the presence or absence of this mutation in randomized trials and then describe a simple and reliable method to detect this mutation. We also examined bilirubin levels in our cohort of 95 HCV genotype 1a patients. RESULTS Ten patients (10.5%) had a Q80K mutation and 12 patients exhibited bilirubin levels above the upper limit of normal at baseline. In our cohort, 21 patients (22%) were therefore ineligible for treatment with simeprevir. The prevalence of this mutation seems to be much lower in European patients. CONCLUSION In conclusion, before considering treatment with simeprevir, physicians must be able to screen for the Q80K mutation.