Trends in progression-free survival (PFS) and time to progression (TTP) over time within first-line aromatase inhibitors trials in hormone receptor-positive advanced breast cancer.

BACKGROUND: Over the last 20 years, aromatase inhibitors (AI) have been tested in clinical trials as first-line therapy for hormone receptor-positive (HR-positive) advanced breast cancer (ABC), firstly as experimental arms, when they proved to be effective, and recently as control arms. This analysis aims to evaluate trends in progression-free survival (PFS) and time to progression (TTP) over time. PATIENTS AND METHODS: A literature review was conducted using the MEDLINE database to identify randomized controlled phase II or III trials which reported PFS or TTP of at least one arm using first-line AI HR-positive ABC patients. A linear correlation was used to access the association between the year of the first patient enrolled and the observed PFS/TTP. RESULTS: The search retrieved 19 trials, accounting for 4552 postmenopausal patients divided into 21 separate AI treatment arms. The PFS/TTP increased from 6 to 9 months in the earlier trials to 13-16 months in the current era, representing an absolute gain of approximately 7 months, without the addition of any other drug. Our analysis showed a positive correlation between the year of the first patient enrolled in these trials and median PFS/TTP reported (R 2 = 0.34; p < 0.01). No correlation was found between the year of the first patient included in these trials and other potential prognostic factors such as visceral metastasis at baseline (R 2 = 0.26; p = 0.20) or exposure to adjuvant therapy (R 2 = 0.05; p = 0.18). CONCLUSION: Patients treated with first-line AIs in the more recently conducted trials have longer PFS/TTP when compared to their counterparts treated with the same drugs in older studies. These findings have important implications for the estimation of sample size and follow-up periods for the planning of future trials as well as in the translation of the results into clinical practice decisions.

Nerve conduits for treating peripheral nerve injuries: A systematic literature review.

Peripheral nerve injuries are a major public health problem. Nerve conduits have been developed in the recent years, although it is still not clear if they should replace nerve grafting and neurorrhaphy. This systematic review aims to gather evidence regarding the use of nerve conduits for peripheral nerve repair. The following electronic databases were searched: MEDLINE, Cochrane Library (CENTRAL) and Embase. Study selection and data extraction followed the PRISMA guidelines. The systematic review of the literature retrieved 6767 articles. Only 27 studies were retained accounting for 1022 patients: 10 randomized controlled trials, 15 case series and 2 cohort studies. Ten different types of tubes were described and a variety of evaluation methods were used to assess outcomes in terms of efficacy (motor and sensory recovery) and complications. The Semmes-Weinstein monofilament test and the static and moving 2-point discrimination test were the most commonly applied tests to evaluate nerve recovery. In general, outcomes showed no significant difference between groups. Synthetic conduits had more complications. Despite major methodological limitations in the studies, we can conclude that use of nerve conduits is preferable over suture repair and nerve grafting, as the functional recovery rates are above 80%. The choice of conduit is based on the surgeon's expertise, but use of synthetic conduits is discouraged due to their higher complication rates.

Nicotine activates and desensitizes midbrain dopamine neurons.

Tobacco use in developed countries is estimated to be the single largest cause of premature death. Nicotine is the primary component of tobacco that drives use, and like other addictive drugs, nicotine reinforces self-administration and place preference in animal studies. Midbrain dopamine neurons normally help to shape behaviour by reinforcing biologically rewarding events, but addictive drugs such as cocaine can inappropriately exert a reinforcing influence by acting upon the mesolimbic dopamine system. Here we show that the same concentration of nicotine achieved by smokers activates and desensitizes multiple nicotinic receptors thereby regulating the activity of mesolimbic dopamine neurons. Initial application of nicotine can increase the activity of the dopamine neurons, which could mediate the rewarding aspects of tobacco use. Prolonged exposure to even these low concentrations of nicotine, however, can cause desensitization of the nicotinic receptors, which helps to explain acute tolerance to nicotine's effects. The effects suggest a cellular basis for reports that the first cigarette of the day is the most pleasurable, whereas the effect of subsequent cigarettes may depend on the interplay between activation and desensitization of multiple nicotinic receptors.