Excision of fascia in melanoma thicker than 2 mm: no evidence for improved clinical outcome.

BACKGROUND Lack of evidence-based data causes significant variation among surgeons concerning the depth of wide excision for primary cutaneous melanomas. OBJECTIVES To evaluate the clinical effect of excision of the deep fascia in melanomas thicker than 2 mm on patient outcome. METHODS We performed a retrospective cohort review (1996-2012) of patients with melanomas thicker than 2 mm. Included patients underwent excision with a 1-cm margin. Data collected included the patients' sex, age, tumour location, tumour type, Breslow depth and presence of ulceration. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were compared between the fascia-excised and the fascia-preserved groups. RESULTS Out of 2182 patients with malignant melanomas, 213 melanomas thicker than 2 mm, with a median follow-up of 1547 days, were included. The mean age of the patients was 62·6 years and the mean Breslow depth was 4·2 mm. Analysis of data for death attributable to melanoma (P = 0·72), local recurrence (P = 0·71), and locoregional (P = 0·87) and distant metastases (P = 0·34) were not significantly different between the study groups. Furthermore, Kaplan-Meier and Cox regression analysis of both groups showed no evidence of significant difference regarding disease-free [P = 0·35; hazard ratio (HR) 1·25; 95% confidence interval (CI) 0·79-1·97] and overall survival (P = 0·63; HR 1·18; 95% CI 0·61-2·27). CONCLUSIONS We believe that excision of the deep fascia does not improve the outcome of melanomas thicker than 2 mm.

Using Bayes' rule to define the value of evidence from syndromic surveillance

In this work we propose the adoption of a statistical framework used in the evaluation of forensic evidence as a tool for evaluating and presenting circumstantial "evidence" of a disease outbreak from syndromic surveillance. The basic idea is to exploit the predicted distributions of reported cases to calculate the ratio of the likelihood of observing n cases given an ongoing outbreak over the likelihood of observing n cases given no outbreak. The likelihood ratio defines the Value of Evidence (V). Using Bayes' rule, the prior odds for an ongoing outbreak are multiplied by V to obtain the posterior odds. This approach was applied to time series on the number of horses showing clinical respiratory symptoms or neurological symptoms. The separation between prior beliefs about the probability of an outbreak and the strength of evidence from syndromic surveillance offers a transparent reasoning process suitable for supporting decision makers. The value of evidence can be translated into a verbal statement, as often done in forensics or used for the production of risk maps. Furthermore, a Bayesian approach offers seamless integration of data from syndromic surveillance with results from predictive modeling and with information from other sources such as disease introduction risk assessments.

Brief Communication: "An inventory of permafrost evidence for the European Alps"

The investigation and modelling of permafrost distribution, particularly in areas of discontinuous permafrost, is challenging due to spatial heterogeneity, remoteness of measurement sites and data scarcity. We have designed a strategy for standardizing different local data sets containing evidence of the presence or absence of permafrost into an inventory for the entire European Alps. With this brief communication, we present the structure and contents of this inventory. This collection of permafrost evidence not only highlights existing data and allows new analyses based on larger data sets, but also provides complementary information for an improved interpretation of monitoring results.

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies.

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

A critical evaluation of the clinical evidence for pomegranate preparations in the prevention and treatment of cardiovascular diseases

This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit.