The Role of Etravirine in the Management of Treatment-Experienced Pediatric Patients With HIV.

The role of etravirine in the management of treatment-experienced pediatric patients with HIV.

HIV AIDS (Auckl). 2013; 5: 67-73
Osterholzer D

Pediatric patients infected with human immunodeficiency virus (HIV) are now living longer, healthier lives due to the advent of combined antiretroviral (ARV) therapy, including regimens that often contain non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, first-generation NNRTIs such as nevirapine (NVP) and efavirenz (EFV) have a low genetic barrier to resistance, and both drugs can become ineffective with a single viral point mutation. New agents with activity against resistant viral strains must be available to salvage children and adolescents with virologic failure after NNRTI use. One such drug, etravirine, an oral second-generation NNRTI approved for use in the US in heavily treatment-experienced HIV-1-infected adults in 2008, is accumulating data in this younger population. Etravirine became approved by the US Food and Drug Administration in early 2012 to be used in combination with other ARV medications in HIV-1-infected children aged 6 years to <18 years who are failing their regimens with HIV-1 strains resistant to NNRTIs and other ARVs. This approval was largely based on data from a prospective, open-label, phase II clinical trial in this age group prescribed etravirine at 5.2 mg/kg twice daily (up to the adult dose of 200 mg twice daily) in combination with an investigator-selected optimized background regimen. Currently available 48-week follow-up data show complete viral suppression (<50 copies/mL) in 56% of the patients, with relatively few serious adverse events attributed to the drug. Additional studies and case reports from the field suggest its utility in clinical practice. This review is designed to increase the background understanding of this drug in pediatric HIV providers, to lay out the current pediatric data to support its use, and to define its practical role in the treatment of HIV-infected children now and in the future. HubMed – drug


Critical appraisal of the use of regorafenib in the management of colorectal cancer.

Cancer Manag Res. 2013; 5: 49-55
Festino L, Fabozzi A, Manzo A, Gambardella V, Martinelli E, Troiani T, De Vita F, Orditura M, Ciardiello F, Morgillo F

The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I-II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients. HubMed – drug


Atrial fibrillation in endurance athletes.

Eur J Prev Cardiol. 2013 Jan 30;
Wilhelm M

There is a growing population of veteran endurance athletes, regularly participating in training and competition. Although the graded benefit of exercise on cardiovascular health and mortality is well established, recent studies have raised concern that prolonged and strenuous endurance exercise may predispose to atrial and ventricular arrhythmias. Atrial fibrillation (AF) and atrial flutter are facilitated by atrial remodelling, atrial ectopy, and an imbalance of the autonomic nervous system. Endurance sports practice has an impact on all of these factors and may therefore act as a promoter of these arrhythmias. In an animal model, long-term intensive exercise training induced fibrosis in both atria and increased susceptibility to AF. While the prevalence of AF is low in young competitive athletes, it increases substantially in the aging athlete, which is possibly associated with an accumulation of lifetime training hours and participation in competitions. A recent meta-analysis revealed a 5-fold increased risk of AF in middle-aged endurance athletes with a striking male predominance. Beside physical activity, height and absolute left atrial size are independent risk factors for lone AF and the stature of men per se may explain part of their higher risk of AF. Furthermore, for a comparable amount of training volume and performance, male non-elite athletes exhibit a higher blood pressure at rest and peak exercise, a more concentric type of left ventricular remodelling, and an altered diastolic function, possibly contributing to a more pronounced atrial remodelling. The sports cardiologist should be aware of the distinctive features of AF in athletes. Therapeutic recommendations should be given in close cooperation with an electrophysiologist. Reduction of training volume is often not desired and drug therapy not well tolerated. An early ablation strategy may be appropriate for some athletes with an impaired physical performance, especially when continuation of competitive activity is intended. This review focuses on the prevalence, risk factors, and mechanisms of AF in endurance athletes, and possible therapeutic options. HubMed – drug


Renal denervation as therapy for hypertension: potentials and unanswered questions.

Eur J Prev Cardiol. 2012 Dec 19;
Vink EE, Bots ML, Blankestijn PJ

In 2005, cardiovascular diseases globally accounted for 30% of an estimated total of 58 million deaths. Hypertension is one of the major contributors to these events. Unfortunately, about two-thirds of all hypertensive patients do not reach treatment goals despite maximal drug treatment. Percutaneous catheter-based renal denervation as a therapy for uncontrolled hypertension is an intriguing idea, especially for patients with resistant hypertension. The first short-term results from a randomized trial are promising: 84% of the patients had a blood pressure (BP) reduction of ?10?mmHg and 39% had a systolic BP of ?140?mmHg 6 months after treatment. However, several questions remain unanswered. To gain more insight, initiatives should be started aiming at assessing safety of the treatment, sustainability of the BP-lowering effect, cost-effectiveness, and the effect on cardiovascular event rate. Many European centres have now started to perform renal denervation or are in the process of starting it up. Therefore, we call for an international collaboration effort to compose cohorts and conduct randomized trials to address the remaining issues at this point in time. HubMed – drug