Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine

Objective. GFR-prediction equations based upon cystatin C and creatinine have better diagnostic performance in estimating GFR than equations based upon only one of the two markers. The present work concerns in what way a comparison between separate estimations of GFR based upon cystatin C (eGFR(cystatin C)) or creatinine (eGFR(creatinine)) can be used to evaluate the diagnostic performance of a combined cystatin C-and creatinine-based estimation of GFR. Methods. The difference between eGFR(cystatin C) and eGFR(creatinine) was compared with measured GFR (iohexol clearance) and a combined cystatin C- and creatinine-based estimation of GFR in a Swedish-Caucasian cohort of 857 adult patients. Results. A difference between eGFR(cystatin C) and eGFR(creatinine) of >= 40% indicated a markedly reduced diagnostic performance of the combined cystatin C- and creatinine-based estimation of GFR. Conclusion. Comparison of the agreement between eGFR(cystatin C) and eGFR(creatinine) can be used to evaluate the diagnostic performance of combined cystatin C-and creatinine-based estimations of GFR. If 'threshold values' for discordance are exceeded, it must be considered whether the clinical context requires the use of an invasive gold standard method to measure GFR. In some clinical contexts either creatinine or cystatin C are known to be invalidated as markers of GFR and in these situations the use of only the cystatin C-or the creatinine-based GFR estimate should be considered when the 'threshold values' are exceeded

Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids : a randomised trial in animals and humans

The aim of the present study was to investigate effects of the carotenoid-producing Bacillus indicus strain PD01 on intestinal barrier function and its ability to survive passage through the gastrointestinal tract and to assess systemic bioavailability of these carotenoids in vivo. As model for impaired barrier function, 16 early weaned piglets were randomly assigned to a control diet or control diet with PD01 for 23 days. In addition, 67 overweight/obese, otherwise healthy individuals were randomly assigned to groups receiving PD01 or placebo for 6 weeks. PD01 survived passage through the gastrointestinal tract in piglets and human subjects and resulted in significant accumulation of PD01 derived carotenoids (methyl-glycosyl-apo-8'-lycopenoate and glycosyl-apo-8'- lycopene) in human plasma after 3- and 6-weeks supplementation versus baseline (0.044 and 0.076 vs 0 mu M, respectively; p = 0.104). In summary, PD01 survived transit through the gastrointestinal tract, resulted in systemic carotenoid accumulation and improved compromised barrier function outcomes

Improving the use of research evidence in guideline development: 14. Reporting guidelines

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 14(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on reporting guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: There is little empirical evidence that addresses these questions. Our answers are based on logical arguments and standards put forward by other groups. What standard types of recommendations or reports should WHO use? • WHO should develop standard formats for reporting recommendations to facilitate recognition and use by decision makers for whom the recommendations are intended, and to ensure that all the information needed to judge the quality of a guideline, determine its applicability and, if needed, adapt it, is reported. • WHO should develop standard formats for full systematically developed guidelines that are sponsored by WHO, rapid assessments, and guidelines that are endorsed by WHO. • All three formats should include the same information as full guidelines, indicating explicitly what the group preparing the guideline did not do, as well as the methods that were used. • These formats should be used across clinical, public health and health systems recommendations. How should recommendations be formulated and reported? • Reports should be structured, using headings that correspond to those suggested by the Conference on Guideline Standardization or similar headings. • The quality of evidence and strength of recommendations should be reported explicitly using a standard approach. • The way in which recommendations are formulated should be adapted to the specific characteristics of a specific guideline. • Urgent attention should be given to developing a template that provides decision makers with the relevant global evidence that is needed to inform a decision and offers practical methods for incorporating the context specific evidence and judgements that are needed

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope

We present a new measurement of the kinematic Sunyaev-Zeldovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zeldovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.Comment: 15 pages, 8 figures, 2 table

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Improving the use of research evidence in guideline development: 8. Synthesis and presentation of evidence

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the eighth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on the synthesis and presentation of research evidence, focusing on four key questions. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We found two reviews of instruments for critically appraising systematic reviews, several studies of the importance of using extensive searches for reviews and determining when it is important to update reviews, and consensus statements about the reporting of reviews that informed our answers to the following questions. How should existing systematic reviews be critically appraised? • Because preparing systematic reviews can take over a year and require capacity and resources, existing reviews should be used when possible and updated, if needed. • Standard criteria, such as A MeaSurement Tool to Assess Reviews (AMSTAR), should be used to critically appraise existing systematic reviews, together with an assessment of the relevance of the review to the questions being asked. When and how should WHO undertake or commission new reviews? • Consideration should be given to undertaking or commissioning a new review whenever a relevant, up-to-date review of good quality is not available. • When time or resources are limited it may be necessary to undertake rapid assessments. The methods that are used to do these assessments should be reported, including important limitations and uncertainties and explicit consideration of the need and urgency of undertaking a full systematic review. • Because WHO has limited capacity for undertaking systematic reviews, reviews will often need to be commissioned when a new review is needed. Consideration should be given to establishing collaborating centres to undertake or support this work, similar to what some national organisations have done. How should the findings of systematic reviews be summarised and presented to committees responsible for making recommendations? • Concise summaries (evidence tables) of the best available evidence for each important outcome, including benefits, harms and costs, should be presented to the groups responsible for making recommendations. These should include an assessment of the quality of the evidence and a summary of the findings for each outcome. • The full systematic reviews, on which the summaries are based, should also be available to both those making recommendations and users of the recommendations. What additional information is needed to inform recommendations and how should this information be synthesised with information about effects and presented to committees? • Additional information that is needed to inform recommendations includes factors that might modify the expected effects, need (prevalence, baseline risk or status), values (the relative importance of key outcomes), costs and the availability of resources. • Any assumptions that are made about values or other factors that may vary from setting to setting should be made explicit. • For global guidelines that are intended to inform decisions in different settings, consideration should be given to using a template to assist the synthesis of information specific to a setting with the global evidence of the effects of the relevant interventions

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour