scholarly journals Long term outcomes of Everolimus therapy in de novo liver transplantation: a systematic review and meta-analysis of randomized controlled trials

2019 ◽  
Author(s):  
Bzeizi Khalid ◽  
Smith Richard ◽  
Benmousa Ali ◽  
Dama Madhukar M.V.SC ◽  
Aba-Alkhail Faisal ◽  
...  

ABSTRACTBackgroundRisk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of Everolimus (EVR) in minimizing this risk when combined with a reduced CnIs dose.ObjectiveTo systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post liver transplantation.MethodsWe searched MEDLINE, Scopus and the Cochrane Library for randomized controlled trials (RCTs) comparing EVR and CnI based regimens post liver transplanation. Assessment of studies and data extraction was undertaken independently.ResultsEight studies were selected describing 769 patients. Cockcroft-Gault GFR (CG-GFR) was significantly higher at one (p=0.05), 3 & 5 years (p=0.030) in patients receiving EVR as compared to those receiving CnI therapy. The composite end point of efficacy failure was similar between the two arms after 1, 3 & 5 years of study. Higher number of patients discontinued EVR due to adverse effects in one year, however no difference was noted after 3 & 5 years. A higher rates of proteinuria, peripheral edema and incisional hernia were noted in patients on EVR.ConclusionThe analysis confirms non-inferiority of EVR and reduced CnI combination. Patients on the combination regimen had better renal function compared to standard CnI therapy.

2020 ◽  
Author(s):  
Ying Zhang ◽  
Yuting Wang ◽  
Youfa Zhou ◽  
Jian Li ◽  
Haiyan Zhou

Abstract Background: Despite widely use of recombinant factor VIIa (rFVIIa) for bleeding in patients without haemophilia, its efficiency and safety remain unclear. Therefore, we carried out a meta-analysis on this topic. Methods: We searched Cochrane Library, Web of Science, PubMed and Embase, from January 2008 to July 2019 for randomized controlled trials on the topic. The results of this work are synthesized and reported in accordance with the PRISMA statement. Results: Twelve trials met our inclusion criteria. rFVIIa over 200ug/kg reduced red blood cell (RBC) transfusions within 24 h by 232.34ml (95% confidence interval [CI]; -410.31 to -54.37). rFVIIa did not significantly reduce 30-day mortality (relative risk [RR], 1.00; 95%CI, 0.82-1.21), total thromboembolic events (RR, 1.13; 95%CI, 0.94-1.36), myocardial infarction (RR, 1.37; 95%CI, 0.92-2.05), deep vein thrombosis (RR, 0.83; 95%CI, 0.52–1.33), ICU staying (RR, 0.40; 95%CI, -1.28 to 2.07) and number of patients transfused RBC (RR, 0.94; 95%CI, 0.83-1.08). However, rFVIIa may increase the incidence of arterial thrombotic events (RR, 1.38; 95%CI, 1.08–1.77). Conclusion: rFVIIa over 200ug/kg reduced RBC transfusions for bleeding in patients without haemophilia. However, it may increase the risk of arterial thrombotic events.


2021 ◽  
pp. 1-8
Author(s):  
Lina Jakubauskiene ◽  
Matas Jakubauskas ◽  
Philipp Stiegler ◽  
Bettina Leber ◽  
Peter Schemmer ◽  
...  

<b><i>Background:</i></b> In recent decades, liver transplantation (LTx) has increased the survival and quality of life of patients with end-stage organ failure. Unfortunately, LTx is limited due to the shortage of donors. A lot of effort is put into finding new ways to reduce ischemia-reperfusion injury (IRI) in liver grafts to increase the number of suitable organs procured from expanded-criteria donors (ECD). The aim of this study was to systematically review the literature reporting LTx outcomes when using ischemic preconditioning (IPC) or remote ischemic preconditioning (RIPC) to reduce IRI in liver grafts. <b><i>Methods:</i></b> A literature search was performed in the MEDLINE, Web of Science, and EMBASE databases. The following combination was used: “Liver” OR “Liver Transplantation” AND “Ischemic preconditioning” OR “occlusion” OR “clamping” OR “Pringle.” The following outcome data were retrieved: the rates of graft primary nonfunction (PNF), retransplantation, graft loss, and mortality; stay in hospital and the intensive care unit; and postoperative serum liver damage parameters. <b><i>Results:</i></b> The initial search retrieved 4,522 potentially relevant studies. After evaluating 17 full-text articles, a total of 9 randomized controlled trials (RCTs) were included (7 IPC and 2 RIPC studies) in the qualitative synthesis; the meta-analysis was only performed on the data from the IPC studies. RIPC studies had considerable methodological differences. The meta-analysis revealed the beneficial effect of IPC when comparing postoperative aspartate aminotransferase (AST) corresponding to a statistically lower mortality rate in the IPC group (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27–0.98; <i>p</i> = 0.04). <b><i>Conclusion:</i></b> IPC lowers postoperative AST levels and reduces the mortality rate; however, data on the benefits of RIPC are lacking.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2984
Author(s):  
Stepan M. Esagian ◽  
Christos D. Kakos ◽  
Emmanouil Giorgakis ◽  
Lyle Burdine ◽  
J. Camilo Barreto ◽  
...  

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.


Author(s):  
Rahele Tavakoly ◽  
Amir Hadi ◽  
Nahid Rafie ◽  
Behrouz Talaei ◽  
Wolfgang Marx ◽  
...  

AbstractThe possible effect of probiotic interventions on immunological markers in athletes is inconclusive. Therefore, to synthesize and quantitatively analyze the existing evidence on this topic, systematic literature searches of online databases PubMed, Scopus, Cochrane Library, and ISI Web of Sciences was carried out up to February 2021 to find all randomized controlled trials (RCTs) concerning the immunological effects of probiotics in athletes. In the random-effects model, weighted mean difference (WMD) and 95% confidence interval (CI) explained the net effect. The authors assessed the likelihood of publication bias via Egger’s and Begg’s statistics. A total of 13 RCTs (836 participants) were retrieved. Probiotic consumption reduced lymphocyte T cytotoxic count significantly (WMD=−0.08 cells×109/L; 95% CI: −0.15 to −0.01; p=0.022) with evidence of moderate heterogeneity (I 2=59.1%, p=0.044) and monocyte count when intervention duration was ≤ 4 weeks (WMD=−0.08 cells×109/L; 95% CI: −0.16 to −0.001; I 2=0.0%). Furthermore, leukocyte count was significantly elevated (WMD=0.48 cells×109/L; 95% CI: 0.02 to 0.93; I 2=0.0%) when multi-strain probiotics were used. Probiotic supplements may improve immunological markers, including lymphocyte T cytotoxic, monocyte, and leukocyte in athletes. Further randomized controlled trials using diverse strains of probiotics and consistent outcome measures are necessary to allow for evidence-based recommendations.


2020 ◽  
Vol 27 (3) ◽  
pp. 291-298
Author(s):  
Yinyin Guo ◽  
Yanxin Luo ◽  
Hui Zhao ◽  
Liangliang Bai ◽  
Juan Li ◽  
...  

Background. A substantial proportion of patients undergoing colorectal surgery receive a temporary stoma, and the timing for stoma closure remains unclear. The aim of this study was to evaluate the safety and feasibility of early stoma closure (ESC) compared with routine stoma closure (RSC) after colorectal surgery. Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared ESC and RSC after colorectal surgery. Results. A total of 7 randomized controlled trials with 814 enrolled patients were identified for this meta-analysis. There were no significant differences between the ESC and RSC groups regarding the complications of stoma closure (26.8% and 16.6%, respectively; odds ratio [OR]: 1.30; 95% confidence interval [CI]: 0.89-1.90; P = .17). A subgroup analysis was conducted by Clavien-Dindo grade of complication, and no significant difference was observed in any subgroup ( P > .05). However, the ESC group had a significantly higher risk of wound complications than the RSC group (17.6% and 7.8%, respectively; OR: 2.61; 95% CI: 1.43-4.76; P = .002), and the RSC group had more cases of small bowel obstruction than the ESC group (3.1% and 8.4%, respectively; OR: 0.37; 95% CI: 0.15-0.87; P = .02). Conclusions. ESC is a safe and effective therapeutic approach in patients who have undergone colorectal surgery; it is associated with a reduced risk of bowel obstruction but a higher risk of wound complications.


2021 ◽  
Author(s):  
Seshadri Reddy Varikasuvu ◽  
Balachandar Thangappazham ◽  
Hemanth Raj

Background: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. Methods: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment. Results: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%). Conclusion: COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19.


2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P<0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.


2020 ◽  
Vol 2;23 (4;2) ◽  
pp. 135-148
Author(s):  
Zifeng Xu

Background: The pain control effect of ketamine versus control in women during cesarean operation is not well determined. Objectives: The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. Study Design: We used meta-analysis to address this concern. Setting: Meta-analysis-based study. Methods: The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. Results: A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], –1.10; 95% confidence interval [CI], –1.61, –0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, –6.11 mg; 95% CI, –9.93, –2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limitations: Limited patients were included with moderate strength. Conclusions: Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Key words: Ketamine, cesarean section, randomized controlled trials, meta-analysis


SLEEP ◽  
2021 ◽  
Author(s):  
Donghao Wang ◽  
Yongkang Tang ◽  
Yanghang Chen ◽  
Sun Zhang ◽  
Danjie Ma ◽  
...  

Abstract Study objectives This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA). Methods We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to 15 August 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity. Results Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for>4 h/night on>70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence. Conclusion CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.


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