Meta-analysis of safety and efficacy of rolapitant, NK-1 receptor antagonist for prevention of chemotherapy-induced nausea and vomiting.

Although chemotherapeutic agents represent a cornerstone of cancer treatment, chemotherapy-induced nausea and vomiting (CINV) affect the patients' quality of life and basic daily activities. Rolapitant is a novel selective neurokinin-1 receptor antagonist (NK-1 RA), which was clinically approved for prevention of CINV. The aim of the present study is to synthesize evidence about the safety and efficacy of rolapitant in combination with other antiemetic agents for prophylaxis against CINV. We performed a web-based literature search of six authentic databases to identify eligible studies. Safety and efficacy endpoints were extracted and pooled as odds ratios (ORs) in a fixed-effect meta-analysis model, using Comprehensive Meta-Analysis software for windows. Five randomized controlled trials (n = 2984) were pooled in the final analysis. Rolapitant (180mg) in combination with a serotonin-3 (5-HT3) receptor antagonist and dexamethasone was superior to placebo plus 5-HT3 receptor antagonist and dexamethasone in term of complete response rate in the acute (OR = 1.4, 95% CI [1.16, 1.7]) and the delayed phases (OR = 1.68, 95% CI [1.44, 1.96]). Moreover, rates of complete protection were significantly higher with rolapitant 180mg than with placebo in the overall, acute, and delayed phases (OR = 1.52, 95% CI [1.3, 1.76]), OR = 1.24, 95% CI [1.04, 1.49], and OR = 1.5, 95% CI [1.29, 1.75]), respectively. In conclusion, rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well tolerated and more effective than 5-HT3 receptor antagonist plus dexamethasone for the prevention of CINV.

Enhancement of neural regeneration after spinal cord injury using muscle graft in experimental dogs.

AIMS: Spinal cord injuries (SCIs) can cause severe disability or death. The principal treatments for traumatic SCI include surgical stabilization and decompression. Using muscle as a scaffold is a new approach. The aim of this work is to evaluate the clinical efficacy of muscle graft as a scaffold for the growing axons organizing their growth, preventing gliosis in the damaged area and enhancing neural recovery in canine model of traumatic spinal cord injury. METHODS: 14 dogs were divided into group I (Control group) 4 control dogs subjected to Sham operation, group II (Trauma control group) 5 dogs subjected to dorsal laminectomy with excision of 1 cm segment of the spinal cord and group III (Muscle graft group) 5 dogs subjected to dorsal laminectomy then muscle graft was taken from the longissimus thoraces and inserted into the spinal cord gap. The animals of all groups were euthanatized after 8 weeks. Olby and modified Tarlov scores were used to clinically evaluate the therapeutic effects. Spinal cord specimens were subjected to histological, morphometric and statistical studies. RESULTS: Olby and modified Tarlov scores revealed significant clinical improvement in the muscle graft group. Histological sections showed overgrowth of axons on the muscle graft and the sections started to organize as central gray matter and peripheral white matter. CD44 & CD105 stains were positive for endogenous stem cells. CONCLUSIONS: This study proved the clinical efficacy of muscle grafting as a tool for induction of neuroregeneration after traumatic spinal cord injury.

Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis.

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.