Economic evaluations of pharmacogenetic and pharmacogenomic screening tests : a systematic review : second update of the literature

Objective : Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature. Methods : A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument. Results : We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing. Conclusions : Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance

Grapevine physiological response to row orientation-induced spatial radiation and microclimate changes

Terroir factors and vineyard practices largely determine canopy and root system functioning. In this study, changes in soil conditions, multi-level (vertical, horizontal) light interception (quantitative, photographic, schematic, 3D modelled), leaf water potential and photosynthetic activity were measured during the grape ripening period on NS, EW, NE-SW, and NW-SE orientated (Southern Hemisphere) vertically trellised Shiraz grapevine canopies. It was hypothesised that the spatial radiation interception angle and radiation distribution of differently orientated and vertically trained grapevine rows would affect soil conditions and vine physiological activity. Soil water content showed an increase and soil temperature a decreasing gradient with soil depth. In the afternoon, soil layers of EW orientated rows reached their highest temperature. This, along with measured photosynthetic active radiation received by canopies, complimented the diurnally-captured photographic, constructed and 3D modelled images (also schematically) of canopy and soil exposure patterns. The top, bottom and outside of NS canopies mainly received radiation from directly above, from the E and the W; during midday, high radiation was only received from above. The EW rows received the highest radiation component from above and from the N. The NE-SW rows received high levels of radiation from above, from the SE until 10:00, and from the NW from 13:00. A similar profile can be described for NW-SE rows, but with high radiation received from the NE up to 13:00 and from the SW from 16:00. Overall, lowest leaf water potential occurred for NE-SW canopies, followed by those orientated NW-SE, NS and EW. Photosynthetic activity reflected the positive radiation impact of the sun azimuth during the grape ripening period; best overall performance seemed to occur for E and N exposed canopy sides. This was largely driven by the responsiveness of the secondary leaves to radiation. Photosynthetic output decreased from apical to basal canopy zones with low, erratic values in the light-limited canopy centre. The NS and EW orientated canopies generally showed the highest average photosynthesis, while it was lower for the sides facing S, SE and SW. The results provide a better understanding of the physiological functioning of horizontal and vertical leaf layers in differently orientated grapevine canopies, as affected by climatic conditions. The study contributes to the longstanding challenges of capturing the complexity of parallel microclimatic and physiological output of grapevine canopies under open field conditions. The results can be directly applied to the selection of vineyard practices and seasonal management to ensure the attainment of yield, grape composition and wine quality objectives

An adaptive technique for content-based image retrieval

We discuss an adaptive approach towards Content-Based Image Retrieval. It is based on the Ostensive Model of developing information needs—a special kind of relevance feedback model that learns from implicit user feedback and adds a temporal notion to relevance. The ostensive approach supports content-assisted browsing through visualising the interaction by adding user-selected images to a browsing path, which ends with a set of system recommendations. The suggestions are based on an adaptive query learning scheme, in which the query is learnt from previously selected images. Our approach is an adaptation of the original Ostensive Model based on textual features only, to include content-based features to characterise images. In the proposed scheme textual and colour features are combined using the Dempster-Shafer theory of evidence combination. Results from a user-centred, work-task oriented evaluation show that the ostensive interface is preferred over a traditional interface with manual query facilities. This is due to its ability to adapt to the user's need, its intuitiveness and the fluid way in which it operates. Studying and comparing the nature of the underlying information need, it emerges that our approach elicits changes in the user's need based on the interaction, and is successful in adapting the retrieval to match the changes. In addition, a preliminary study of the retrieval performance of the ostensive relevance feedback scheme shows that it can outperform a standard relevance feedback strategy in terms of image recall in category search

Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Extended lymph node dissection for gastric cancer from a European perspective

Surgical oncolog

Laparoscopic versus small-incision cholecystectomy: Health status in a blind randomised trial

Contains fulltext : 69536.pdf (publisher's version ) (Open Access)BACKGROUND: Gallstones are a major cause of morbidity, and cholecystectomy is a commonly performed procedure. Minimal invasive procedures, laparoscopic cholecystectomy (LC) and small-incision cholecystectomy (SIC), have replaced the classical open cholecystectomy. No differences have been found in primary outcome measures between LC and SIC, therefore secondary outcome measures have to be considered to determine preferences. The aim of our study was to examine health status applying evidence-based guidelines in LC and SIC in a randomised trial. METHODS: Patients with symptomatic cholecystolithiasis were included in a blind randomised trial. Operative procedures, anaesthesia, analgesics and postoperative care were standardised in order to limit bias. Questionnaires were filled in preoperatively, the first day postoperatively, and at outpatients follow-up at 2, 6 and 12 weeks. In accordance with evidence-based guidelines, the generic short form (SF-36) and the disease-specific gastrointestinal quality-of-life index (GIQLI) questionnaires were used in addition to the body image questionnaire (BIQ). RESULTS: A total of 257 patients were randomised between LC (120) and SIC (137). Analyses were performed according to intention-to-treat (converted procedures included) and also distinguishing converted from minimal invasive (nonconverted) procedures. Questionnaires were obtained with a response rate varying from 87.5% preoperatively to 77.4% three months postoperatively. Except for two time-specific measurements in one SF-36 subscale, there were no differences between LC and SIC. There were significant differences in several subscales in all three questionnaires comparing minimal invasive versus converted procedures. CONCLUSIONS: Applying adequate methodological quality and evidence-based guidelines (by using SF-36 and GIQLI), there are no significant differences in health status between LC and SIC

Dysregulation of Ribosome Biogenesis and Translational Capacity Is Associated with Tumor Progression of Human Breast Cancer Cells

Protein synthesis is a fundamental cell process and ribosomes - particularly through the ribosomal RNA that display ribozyme activity - are the main effectors of this process. Ribosome biogenesis is a very complex process involving transcriptional a