Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas.

Methods: We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries.

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials.

Background: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling.

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3.

Humanistic burden in schizophrenia: a literature review.

Objectives Of The Study And Background: Schizophrenia is a complex disease that affects 1% of the population. This disease has a considerable impact not only on patients' health and well-being but also on their surrounding environment. The costs of the disease's management remain large for individuals and society.

Dexamethasone (6 mg/m2/day) and prednisolone (60 mg/m2/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial.

Dexamethasone could be more effective than prednisolone at similar anti-inflammatory doses in the treatment of childhood acute lymphoblastic leukemia. In order to check if this "superiority" of dexamethasone might be dose-dependent, we conducted a randomized phase III trial comparing dexamethasone (6 mg/m(2)/day) to prednisolone (60 mg/m(2)/day) in induction therapy. All newly diagnosed children and adolescents with acute lymphoblastic leukemia in the 58951 EORTC trial were randomized on prephase day 1 or day 8.

Systematic review of appropriate cognitive assessment instruments used in clinical trials of schizophrenia, major depressive disorder and bipolar disorder.

Cognitive dysfunction is increasingly recognized as a symptom in mental conditions including schizophrenia, major depressive disorder (MDD), and bipolar disorder (BPD). Despite the many available cognitive assessment instruments, consensus is lacking on their appropriate use in clinical trials. We conducted a systematic literature review in Embase, PubMed/Medline and PsychINFO to identify appropriate cognitive function instruments for use in clinical trials of schizophrenia, MDD, and BPD.

Evaluation of renal function in patients with cirrhosis: where are we now?

In the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive.

Is it acceptable to destroy or include human embryos before day 5 in research programmes?

Day-3 poor-quality embryos (PQE) from IVF-embryo transfer cycles are usually destroyed or are included in research programmes. Knowing that these embryos have the ability to evolve to the blastocyst stage and yield embryonic stem cell lines, this study postulated that they could also give rise to live births. This is a prospective study including 186 IVF-embryo transfer candidates who had obtained at least one supernumerary PQE on day 3.

Difference of perceptions and evaluation of cognitive dysfunction in major depressive disorder patients across psychiatrists internationally.

Background: Many studies have suggested that major depressive disorder (MDD) is often associated with cognitive dysfunction. Despite this, guidance addressing assessment of cognitive dysfunction in MDD is lacking. The aim of this study was to examine psychiatrists' perceptions and evaluation of cognitive dysfunction in routine practice in MDD patients across different countries.

Costs and benefits of tool-use on the perception of reachable space.

Previous studies have shown that using a tool modifies in a short time-scale both near-body space perception and arm-length representation in the body schema. However, to date no research has specifically investigated the effect of tool-use on an action-related perceptual task. We report here a study assessing the effect of tool-use on the perception of reachable space for perceptual estimates made in reference to either the tool or the hand.

Drug reformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications.

Background: Repurposing has become a mainstream strategy in drug development, but it faces multiple challenges, amongst them the increasing and ever changing regulatory framework. This is the second study of a series of three-part publication project with the ultimate goal of understanding the market access rationale and conditions attributed to drug repurposing in the United States and in Europe. The aim of the current study to evaluate the regulatory path associated with each type of repurposing strategy according to the previously proposed nomenclature in the first article of this series.

Economic impact of new active substance status on EU payers' budgets: example of dimethyl fumarate (Tecfidera(®)) for multiple sclerosis.

Background: Recently, collaboration between regulators and payers was set up and was mainly focused on evidence generation along product clinical development. However, neither the regulatory path nor the new active substance status (NASs) was considered. Granting NASs will provide the product with 8 years of data protection and 2 years of market exclusivity during which no generic could enter the market.

Drug repurposing in pharmaceutical industry and its impact on market access: market access implications.

Background: Drug repurposing is a group of development strategies employed in order to overcome some of the hurdles innate to drug research and development. Drug repurposing includes drug repositioning, reformulation and combination.

Objective: This study aimed to identify the determinants of successful market access outcome for drug repurposing in the United States of America (USA) and in Europe.

Pharmaceutical expenditure forecast model to support health policy decision making.

Background And Objective: With constant incentives for healthcare payers to contain their pharmaceutical budgets, modelling policy decision impact became critical. The objective of this project was to test the impact of various policy decisions on pharmaceutical budget (developed for the European Commission for the project 'European Union (EU) Pharmaceutical expenditure forecast' - http://ec.europa.

Routine clinical assessment of cognitive functioning in schizophrenia, major depressive disorder, and bipolar disorder.

As more evidence points to the association of cognitive dysfunction with mental health disorders, the assessment of cognitive function in routine clinical care of these disorders is increasingly important. Despite this, it remains unknown how cognitive function is measured in routine clinical practice. The objective of this study was to assess psychiatrists' awareness of cognitive dysfunction in mental health disorders and their methods of cognitive assessment.

[Innovative medicines and market access agreements].

Market Access Agreements (MAA) for drugs have emerged in response to the need to control health expenditures, as well as to the uncertainty about the true benefit of a drug. It is possible to group MAA in two types of agreements: financial agreements and outcome-based agreements. MAA is a growing trend and is shifting towards conditional access.

Cryptogenic organizing pneumonia.

Organizing pneumonia (OP) is a pathological pattern defined by the characteristic presence of buds of granulation tissue within the lumen of distal pulmonary airspaces consisting of fibroblasts and myofibroblasts intermixed with loose connective matrix. This pattern is the hallmark of a clinical pathological entity, namely cryptogenic organizing pneumonia (COP) when no cause or etiologic context is found. The process of intraalveolar organization results from a sequence of alveolar injury, alveolar deposition of fibrin, and colonization of fibrin with proliferating fibroblasts.

Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients.

Unlabelled: Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only in non progressive patients.

Background: Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3-4 anaemia in 10% of patients.

Testing new regimens in patients with advanced soft tissue sarcoma: analysis of publications from the last 10 years.

Background: The prognosis of advanced soft tissue sarcoma remains poor. Many phase II trials investigating new regimens have been published in the last 10 years.

Materials And Methods: Full English-language reports of phase II clinical trials from January 1999 to October 2009 have been reviewed.

Regulatory environment and claims - limits and opportunities.

During the past decade, the use of claims became more and more important in many countries in relation to the increased awareness of consumer about the link between foods and health, offering to industry a valuable opportunity to differentiate and valorize their products and to promote innovation. However, more and more stringent regulations are developed, all based on the general principles adopted by the Codex Alimentarius Commission. In addition to the different regulatory processes and administrative requirements according to the country, the high level (and cost) of scientific substantiation of claims, the constraints introduced by nutrient profiles and the poor knowledge of the impact on consumer depending on the cultural contexts may limit these opportunities or, at least complicate their use.

Benefits of motor imagery training on muscle strength.

It is well established that motor imagery (MI) improves motor performance and motor learning efficiently. Previous studies provided evidence that muscle strength may benefit from MI training, mainly when movements are under the control of large cortical areas in the primary motor cortex. The purpose of this experiment is to assess whether MI might improve upper and lower limbs' strength through an ecological approach and validation, with complex and multijoint exercises.

Brain activity during visual versus kinesthetic imagery: an fMRI study.

Although there is ample evidence that motor imagery activates similar cerebral regions to those solicited during actual movements, it is still unknown whether visual (VI) and kinesthetic imagery (KI) recruit comparable or distinct neural networks. The present study was thus designed to identify, through functional magnetic resonance imaging at 3.0 Tesla in 13 skilled imagers, the cerebral structures implicated in VI and KI.

Management of tracheobronchial stenoses with endoprostheses: experience with 103 patients and 11 models.

Objective: To describe in a retrospective study our experience in endoscopic management of tracheobronchial stenosis with 145 stents (11 different models).

Methods: We analyzed the medical records of 103 patients (67 males and 36 females) who underwent the placement of prosthesis for any causes of tracheobronchial stenoses between 1990 and 2005.

Results: A total of 145 prostheses were placed.