Search results for "trials"

Efficacy of Low-Dose Paroxetine for the Treatment of Hot Flushes in Surgical and Physiological Postmenopausal Women: Systematic Review and Meta-Analy…

2019

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of v…

HCC therapies--lessons learned.

2014

The antiangiogenic multikinase inhibitor sorafenib was the first systemic agent to demonstrate a significant improvement in the overall survival of patients with advanced hepatocellular carcinoma (HCC), thereby introducing molecularly-targeted therapy in a therapeutic field of unmet needs. However, survival benefits for patients on sorafenib treatment are modest in clinical practice and advancing the field is far more challenging than initially anticipated. Molecular and clinical heterogeneity diminishes signals of potential activity in unselected populations, and underlying liver cirrhosis seals the fate of many novel targeted agents by causing relevant toxicity and mortality. The failure …

Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials

2019

Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…

Systemic therapy for intermediate and advanced hepatocellular carcinoma: Sorafenib and beyond.

2018

The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can b…

What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment

2015

The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolonga…

Effect of a common exercise programme with an individualised progression criterion based on the measurement of neuromuscular capacity versus current …

2021

IntroductionHigh-load resistance training has shown positive effects in pain and function in lower limb tendinopathies. However, some authors suggest that current exercise programmes produce an increase in tolerance to load and exercise in general but without fixing some existing issues in tendinopathy. This may indicate the need to include training aspects not currently taken into account in the current programmes. The main objective of this study will be to compare the effect of a common exercise protocol for the three predominant lower limb tendinopathies (Achilles, patellar and gluteal), based on an individualised control of the dose and training of specific aspects of the neuromuscular…

Statin therapy in patients with aortic stenosis after the ASTRONOMER trial: is there still any space?

2011

A Log-Rank Test for Equivalence of Two Survivor Functions

1993

We consider a hypothesis testing problem in which the alternative states that the vertical distance between the underlying survivor functions nowhere exceeds some prespecified bound delta0. Under the assumption of proportional hazards, this hypothesis is shown to be (logically) equivalent to the statement [beta[log(1 + epsilon), where beta denotes the regression coefficient associated with the treatment group indicator, and epsilon is a simple strictly increasing function of delta. The testing procedure proposed consists of carrying out in terms of beta (i.e., the standard Cox likelihood estimator of beta) the uniformly most powerful level alpha test for a suitable interval hypothesis about…

Marginal hazard ratio estimates in joint frailty models for heart failure trials

2019

Abstract This work is motivated by clinical trials in chronic heart failure disease, where treatment has effects both on morbidity (assessed as recurrent non‐fatal hospitalisations) and on mortality (assessed as cardiovascular death, CV death). Recently, a joint frailty proportional hazards model has been proposed for these kind of efficacy outcomes to account for a potential association between the risk rates for hospital admissions and CV death. However, more often clinical trial results are presented by treatment effect estimates that have been derived from marginal proportional hazards models, that is, a Cox model for mortality and an Andersen–Gill model for recurrent hospitalisations. …

Assessing the quality of studies in meta-research: Review/guidelines on the most important quality assessment tools

2020

Systematic reviews and meta-analyses pool data from individual studies to generate a higher level of evidence to be evaluated by guidelines. These reviews ultimately guide clinicians and stakeholders in health-related decisions. However, the informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Moreover, beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. Hence, quality of meta-research projects also affects evidence synthesis reliability. In this overview…