Medical and pharmacy coverage decision making at the population level.

Medicare is one of the largest health care payers in the United States. As a result, its decisions about coverage have profound implications for patient access to care. In this commentary, the authors describe how Medicare used evidence on heterogeneity of treatment effects to make population-based decisions on health care coverage for implantable cardiac defibrillators.

Clinical performance of the Nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety.

Background: Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system (SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection.

Objectives: To assess the effectiveness and safety of the Nevisense system in the distinction of benign lesions of the skin from melanoma with electrical impedance spectroscopy.

Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine inhibitors of Erk2.

The discovery and optimization of a series of tetrahydropyridopyrimidine based extracellular signal-regulated kinase (Erks) inhibitors discovered via HTS and structure based drug design is reported. The compounds demonstrate potent and selective inhibition of Erk2 and knockdown of phospho-RSK levels in HepG2 cells and tumor xenografts.

Motivations for avoiding wheat consumption in Australia: results from a population survey.

Objective: To assess the prevalence of and explanations for wheat avoidance, including reported symptoms, diagnoses and information sources influencing the decision to avoid wheat, and to investigate potential psychological predictors of this behaviour.

Design: Cross-sectional population survey.

Setting: The study was conducted in Australia, using a nationwide postal omnibus survey.

The efficacy of a self-managed Acceptance and Commitment Therapy intervention DVD for physical activity initiation.

Objectives: Initiating and maintaining physical activity presents the individual with challenges of inconvenience, discomfort, and counteractive energy. Addressing these challenges requires an intervention that elicits motivation to engage in this activity, minimizes the direct relationship between unwanted internal experiences and inaction, and is also in itself accessible and convenient. Accordingly, this study investigated the efficacy of a self-managed Acceptance and Commitment Therapy (ACT) intervention delivered via DVD and tailored for physical activity initiation.

A randomized, open-label clinical trial of tasisulam sodium versus paclitaxel as second-line treatment in patients with metastatic melanoma.

Background: Tasisulam sodium (hereafter referred to as tasisulam) is a novel, highly albumin-bound agent that demonstrated activity in a phase 2 melanoma study.

Methods: In this open-label phase 3 study, patients with AJCC stage IV melanoma received tasisulam (targeting an albumin-corrected exposure of 1200-6400 h (hour).μg/mL on day 1) or paclitaxel (80 mg/m(2) on days 1, 8, and 15) every 28 days as second-line treatment.

Difference of neuro- and immunomodulatory steroids and selected hormone and lipid concentrations between Toxoplasma-free and Toxoplasma-infected but not CMV-free and CMV-infected schizophrenia patients.

Objectives: Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. Toxoplasma is known to change levels of certain neurotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system.

Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study.

Background: In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma.

Patients And Methods: Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire.

Results: In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib.

Music-evoked incidental happiness modulates probability weighting during risky lottery choices.

We often make decisions with uncertain consequences. The outcomes of the choices we make are usually not perfectly predictable but probabilistic, and the probabilities can be known or unknown. Probability judgments, i.

Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: a multicenter phase II DeCOG trial with long-term follow-up.

Purpose: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. COL1A1-PDGFB gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRβ (platelet-derived growth factor receptor β) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up.

Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology].

Background: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP).

Methods: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012.

Methodological recommendations for comparative research on the treatment of chronic wounds.

Objective: To provide specific recommendations to product developers and clinical researchers on the design of comparative effectiveness studies for the treatment of chronic wounds, specifically those pertaining to arterial and venous-disease related ulcers, diabetic foot ulcers, pressure ulcers and burn wounds.

Method: The recommendations were developed based on a process defined by the Center for Medical Technology Policy (CMTP). After selecting the subject area, semi-structured phone interviews were conducted by one of the authors (SSS) with representatives of payers, manufacturers, clinicians, clinician/researchers and patient advocates.

Recommendations for the design of Phase 3 pharmaceutical trials that are more informative for patients, clinicians, and payers.

Background: Pharmaceutical pragmatic clinical trials (PCTs) are designed to provide the type of evidence that is desired by patients, clinicians and payers but too often missing from traditional regulatory trials.

Purpose: This paper presents framework for designing pragmatic trials incorporating evidence desired by post-regulatory decision makers while remaining within acceptable standards for regulatory approval.

Methods: Following a stakeholder meeting convened in May of 2009 to identify gaps in information collected in Phase 3 trials, CMTP staff and the authors drafted recommendations for Pragmatic Phase 3 Pharmaceutical Trials.

Performance-based risk-sharing arrangements-good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force.

There is a significant and growing interest among both payers and producers of medical products for agreements that involve a "pay-for-performance" or "risk-sharing" element. These payment schemes-called "performance-based risk-sharing arrangements" (PBRSAs)-involve a plan by which the performance of the product is tracked in a defined patient population over a specified period of time and the amount or level of reimbursement is based on the health and cost outcomes achieved. There has always been considerable uncertainty at product launch about the ultimate real-world clinical and economic performance of new products, but this appears to have increased in recent years.

I222 Neuraminidase mutations further reduce oseltamivir susceptibility of Indonesian Clade 2.1 highly pathogenic Avian Influenza A(H5N1) viruses.

We have tested the susceptibility to neuraminidase inhibitors of 155 clade 2.1 H5N1 viruses from Indonesia, isolated between 2006-2008 as well as 12 clade 1 isolates from Thailand and Cambodia from 2004-2007 using a fluorometric MUNANA-based enzyme inhibition assay. The Thailand and Cambodian clade 1 isolates tested here were all susceptible to oseltamivir and zanamivir, and sequence comparison indicated that reduced oseltamivir susceptibility we observed previously with clade 1 Cambodian isolates correlated with an S246G neuraminidase mutation.

Social and functional capacity of schizophrenia patients: A cross-sectional study.

Background: The chronic course of schizophrenia typically results in severe social, vocational and functional impairment, interferes with patients' autonomy, reduces quality of life and increases disability.

Aims: The aim of our study was: (1) to assess social and functional impairment in schizophrenia outpatients from the Czech Republic and Slovakia; and (2) to examine a relationship between functioning and antipsychotic treatment and demographic variables.

Methods: Schizophrenia outpatients in a stable phase of illness, treated with current antipsychotic medication for a minimum of one month, were enrolled for the study.

Reduced susceptibility to all neuraminidase inhibitors of influenza H1N1 viruses with haemagglutinin mutations and mutations in non-conserved residues of the neuraminidase.

Objectives: We characterized human H1N1 influenza isolate A/Hokkaido/15/02, which has haemagglutinin and neuraminidase mutations that reduce drug susceptibility to oseltamivir, zanamivir and peramivir.

Methods: One wild-type and three mutant viruses were isolated by plaque purification. Viruses were tested in MUNANA-based enzyme assays, cell culture and receptor binding assays.

A telephone-supported cardiovascular lifestyle programme (CLIP) for lipid reduction and weight loss in general practice patients: a randomised controlled pilot trial.

Objective: To evaluate a primary prevention care model using telephone support delivered through an existing health call centre to general practitioner-referred patients at risk of developing CVD, using objective measures of CVD risk reduction and weight loss.

Design: Participants were randomised into two groups: (i) those receiving a telephone-supported comprehensive lifestyle intervention programme (CLIP: written structured diet and exercise advice, plus seven telephone sessions with the Heart Foundation Health Information Service); and (ii) those receiving usual care from their general practitioner (control: written general lifestyle advice). Fasting plasma lipids, blood pressure, weight, waist circumference and height were assessed on general practice premises by a practice nurse at Weeks 0 and 12.

Design of libraries targeting protein-protein interfaces.

TARGETING PPIS: A novel strategy for designing libraries targeting protein-protein interfaces enabled us to identify diverse chemical entry points to interact with therapeutic targets for which conventional screening libraries delivered no or only few hit structures. The concept was experimentally validated by early hit evaluation in biochemical screens and early ADMET profiling.

Electrical impedance spectroscopy as a potential adjunct diagnostic tool for cutaneous melanoma.

Background: Previous studies have shown statistically significant differences in electrical impedance between various cutaneous lesions. Electrical impedance spectroscopy (EIS) may therefore be able to aid clinicians in differentiating between benign and malignant skin lesions.

Objectives: The aim of the study was to develop a classification algorithm to distinguish between melanoma and benign lesions of the skin with a sensitivity of at least 98% and a specificity approximately 20 per cent higher than the diagnostic accuracy of dermatologists.

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g.