Dissociated Steroids

Glucocorticoids (GCs) are some of the most important drugs in clinical use today. They are mainly used to suppress disease-related inflammation and are widely used for the treatment of many inflammatory diseases including asthma and arthritis. However, GCs are also associated with debilitating side effects that place limitations on the long-term use of these drugs. The development of a GC with reduced side effects would allow more effective treatments for patients who require long-term suppression of inflammation. GCs exert their effects by binding and activating the GC receptor (GR). The activated receptor then binds GC response elements (GREs) in the promoter of genes, and activates transcription (transactivation) or interferes with the activation of transcription by inhibiting the transactivating function of other transcription factors, such as AP-1 and NF-ĸB (transrepression). Transrepression is believed to be responsible for the majority of the beneficial anti-inflammatory effects of GCs, whereas transactivation is believed to play a bigger role in the unwanted side effects of GCs. Compounds that can dissociate the transactivation function of GCs from the transrepression function may, therefore, have an improved therapeutic index. A number of these dissociated corticosteroids have been developed. In vitro assays using these compounds appear to show good dissociation. However, in vivo, the dissociation appears to be lost and these compounds still produce many of the side effects associated with conventional GCs. A better understanding of the molecular mechanisms behind GC-induced effects would allow the design of novel selective GR modulators with an improved therapeutic index

Transcutaneous Electrical Nerve Stimulation (TENS) for chronic pain - an overview of Cochrane reviews (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To provide an overview of evidence from Cochrane systematic reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine). To provide an overview of evidence from Cochrane systematic reviews of the safety of TENS to reduce pain in adults with chronic pain (excluding headache or migraine). To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency. To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty

The effectiveness of alcohol-based gel for hand sanitising in infection control

This article aims to evaluate the evidence relating to the effectiveness of alcohol-based gel in infection control in healthcare settings with particular reference to renal nursing, as this has become pertinent due to the increasing reliance on evidence-based practice. There is a need to implement better infection control strategies and education, to reinforce knowledge among the public, healthcare workers and those at high risk of infection not only in renal nursing, but in other areas of practice. Healthcare associated infections (HCAIs) put patients’ safety at risk, increase morbidity, mortality, extend the length of hospital admission and increase the cost to the National Health Service (NHS). There is evidence that the prevalence of HCAIs in England can be minimised through the use of different infection control measures. For example, alcohol-based gel has been found to be associated with minimising the spread of gastrointestinal infections not only in hospital settings, but also in child care centres. In addition, the UK national guidelines recommend regular hand washing (implementing the right technique) when hands are visibly dirty and hand disinfection with alcohol-based gel when hands are not visibly dirty. This should be before, in between and after different healthcare activities are performed

The close proximity of threat: Altered distance perception in the anticipation of pain

Pain is an experience that powerfully influences the way we interact with our environment. What is less clear is the influence that pain has on the way we perceive our environment. We investigated the effect that the anticipation of experimental pain (THREAT) and its relief (RELIEF) has on the visual perception of space. Eighteen (11F) healthy volunteers estimated the distance to alternating THREAT and RELIEF stimuli that were placed within reachable space. The results determined that the estimated distance to the THREAT stimulus was significantly underestimated in comparison to the RELIEF stimulus. We conclude that pain-evoking stimuli are perceived as closer to the body than otherwise identical pain-relieving stimuli, an important consideration when applied to our decisions and behaviors in relation to the experience of pain

Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews

Background Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS)is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain.ObjectivesTo provide an overview of evidence from Cochrane Reviews of theeffectiveness of TENS to reduce pain in adults with chronic pain(excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine)with a view to recommending strategies to reduce any uncertainty. Methods Search methods We searched the Cochrane Database of Systematic Reviews(CDSR), in the Cochrane Library, across all years up to Issue 11 of12, 2018. Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. Weincluded all Cochrane Reviews of randomised controlled trials(RCTs) assessing the effectiveness of TENS in people with chronic pain.We included reviews if they investigated the following: TENSversus sham; TENS versus usual care or no treatment/waiting list control;TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS deliveredusing different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judge-ments where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects;our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impressionof change.Main results We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achievedoverall high scores on the AMSTAR checklist. The evidence reportedwithin each review was consistently rated as very low quality.Using review authors’ assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD−1.58, 95%CI−2.08 to−1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants).However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD−0.85, 95% CI−1.36 to−0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham andno intervention data to be problematic since we would predict these different comparisons may be estimating different trueeffects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions.Authors’ conclusions We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were the reforeunable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability,health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic painNational Institute for Health Research,via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS

Surveillance strategies for Classical Swine Fever in wild boar – a comprehensive evaluation study to ensure powerful surveillance

Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar

The translation, validity and reliability of the German version of the Fremantle Back Awareness Questionnaire

Background: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess disrupted self-perception of the back. The aim of this study was to develop a German version of the Fre-BAQ (FreBAQ-G) and assess its test-retest reliability, its known-groups validity and its convergent validity with another purported measure of back perception. Methods: The FreBaQ-G was translated following international guidelines for the transcultural adaptation of questionnaires. Thirty-five patients with non-specific CLBP and 48 healthy participants were recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on two separate days to quantify intra-observer reliability. Assessor two administered the FreBaQ-G to each patient on day 1. The scores were compared to those obtained by assessor one on day 1 to assess inter-observer reliability. Known-groups validity was quantified by comparing the FreBAQ-G score between patients and healthy controls. To assess convergent validity, patient\u27s FreBAQ-G scores were correlated to their two-point discrimination (TPD) scores. Results: Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88 (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0±8.1) and 6.0 (4.8±7.8), respectively. The adjusted mean difference between patients and controls was 5.4 (95%CI: 3.0 to 7.8, p\u3c0.01). Patient\u27s FreBAQ-G scores were not associated with TPD thresholds (Pearson\u27s r = -0.05, p = 0.79). Conclusions: The FreBAQ-G demonstrated a degree of reliability and known-groups validity. Interpretation of patient level data should be performed with caution because the LoA were substantial. It did not demonstrate convergent validity against TPD. Floor effects of some items of the FreBAQ-G may have influenced the validity and reliability results. The clinimetric properties of the FreBAQ-G require further investigation as a simple measure of disrupted self-perception of the back before firm recommendations on its use can be made

Depicting the tree of life in museums: guiding principles from psychological research

The Tree of Life is revolutionizing our understanding of life on Earth, and, accordingly, evolutionary trees are increasingly important parts of exhibits on biodiversity and evolution. The authors argue that in using these trees to effectively communicate evolutionary principles, museums need to take into account research results from cognitive, developmental, and educational psychology while maintaining a focus on visitor engagement and enjoyment. Six guiding principles for depicting evolutionary trees in museum exhibits distilled from this research literature were used to evaluate five current or recent museum trees. One of the trees was then redesigned in light of the research while preserving the exhibit’s original learning goals. By attending both to traditional factors that influence museum exhibit design and to psychological research on how people understand diagrams in general and Tree of Life graphics in particular, museums can play a key role in fostering 21st century scientific literacy