Differences between European birthweight standards: impact on classification of ‘small for gestational age’

We describe a quantitative and comparative review of a selection of European birthweight standards for gestational age for singletons, to enable appropriate choices to be made for clinical and research use. Differences between median values at term across standards in 10 regions and misclassification of ‘small for gestational age’ (SGA), were studied. Sex and parity differences, exclusion criteria, and methods of construction were considered. There was wide variation between countries in exclusion criteria, methods of calculating standards, and median birthweight at term. The lightest standards (e.g. France's medians are 255g lower than Norway's medians) were associated with fewer exclusion criteria. Up to 20% of the population used in the construction of the Scottish standard would be classified as SGA using the Norwegian standard. Substantial misclassification of SGA is possible. Assumptions about variation used in the construction of some standards were not justified. It is not possible to conclude that there are real differences in birthweight standards between European countries. Country-based standards control for some population features but add misclassification due to the differing ways in which standards are derived. Standards should be chosen to reflect clinical or research need. If standards stratified by sex or parity are not available, adjustments should be made. In multinational studies, comparisons should be made between results using both a common standard and country-based standards

Hydrography and circulation west of Sardinia in June 2014

In the frame of the REP14-MED sea trial in June 2014, the hydrography and circulation west of Sardinia, observed by means of gliders, shipborne CTD (conductivity, temperature, depth) instruments, towed devices, and vessel-mounted ADCPs (acoustic doppler current profilers), are presented and compared with previous knowledge. So far, the circulation is not well-known in this area, and the hydrography is subject to long-term changes. Potential temperature, salinity, and potential density ranges as well as core values of the observed water masses were determined. Modified Atlantic Water (MAW), with potential density anomalies below 28.72 kg m−3, showed a salinity minimum of 37.93 at 50 dbar. Levantine Intermediate Water (LIW), with a salinity maximum of about 38.70 at 400 dbar, was observed within a range of 28.72<σΘ/(kg m−3) < 29.10. MAW and LIW showed slightly higher salinities than previous investigations. During the trial, LIW covered the whole area from the Sardinian shelf to 7°15′ E. Only north of 40° N was it tied to the continental slope. Within the MAW, a cold and saline anticyclonic eddy was observed in the southern trial area. The strongest variability in temperature and salinity appeared around this eddy, and in the southwestern part of the domain, where unusually low saline surface water entered the area towards the end of the experiment. An anticyclonic eddy of Winter Intermediate Water was recorded moving northward at 0.014 m s−1. Geostrophic currents and water mass transports calculated across zonal and meridional transects showed a good agreement with vessel-mounted ADCP measurements. Within the MAW, northward currents were observed over the shelf and offshore, while a southward transport of about 1.5 Sv occurred over the slope. A net northward transport of 0.38 Sv across the southern transect decreased to zero in the north. Within the LIW, northward transports of 0.6 Sv across the southern transects were mainly observed offshore, and decreased to 0.3 Sv in the north where they were primarily located over the slope. This presentation of the REP14-MED observations helps to further understand the long-term evolution of hydrography and circulation in the Western Mediterranean, where considerable changes occurred after the Eastern Mediterranean Transient and the Western Mediterranean Transition

Holographic Screening Length in a Hot Plasma of Two Sphere

We study the screening length of a quark-antiquark pair moving in a hot plasma living in two sphere $S^2$ manifold using AdS/CFT correspondence where the background metric is four dimensional Schwarzschild-AdS black hole. The geodesic solution of the string ends at the boundary is given by a stationary motion in the equatorial plane as such the separation length $L$ of quark-antiquark pair is parallel to the angular velocity $\omega$. The screening length and the bound energy are computed numerically using Mathematica. We find that the plots are bounded from below by some functions related to the momentum transfer $P_c$ of the drag force configuration. We compare the result by computing the screening length in the quark-antiquark reference frame where the gravity dual are "Boost-AdS" and Kerr-AdS black holes. Finding relations of the parameters of both black holes, we argue that the relation between mass parameters $M_{Sch}$ of the Schwarzschild-AdS black hole and $M_{Kerr}$ of the Kerr-AdS black hole in high temperature is given by $M_{Kerr}=M_{Sch}(1-a^2l^2)^{3/2}$, where $a$ is the angular momentum parameter.Comment: Major revision: title changed, adding authors, 13 pages, 8 figures, etc. Accepted for publication in European Physical Journal

Independent therapeutic advice: How achievable is it?

This supplement is likely to be of interest to anyone involved in the development of clinical guidelines and clinical research, including: • health professionals, trainees and students who use guidelines as a basis for their decision making • policy makers and others working to improve the quality of health care • people involved in university, college and hospital education. The supplement outlines the issues discussed at an Independence Forum hosted by Therapeutic Guidelines Limited in Melbourne, Australia, on 29 October 2012. It puts forward recommendations to overcome limitations of the evidence base and improve the trustworthiness of guidelines. Therapeutic Guidelines is an independent, not-forprofit organisation that was established to promote the quality use of medicines through the publication of clear, concise and ready to use guidelines. Therapeutic Guidelines convened the Independence Forum to discuss issues of independence and conflicts of interest in the context of the development of therapeutic guidelines for health professionals. Two eminent overseas speakers, Professor Silvio Garattini from the Mario Negri Institute, Italy, and Assistant Professor Barbara Mintzes from the University of British Columbia, Canada, gave keynote presentations on the complexity of the therapeutic environment and clinical evidence base. Key Australian commentators and health ethicists – Professor Paul Komesaroff from the Centre for the Study of Ethics in Medicine and Society at Monash University, and Associate Professor Ian Kerridge from the Centre for Values, Ethics and the Law in Medicine at the University of Sydney – focused on the influence of vested interests in clinical research trials and guideline development, citing high profile examples such as the case of hormone therapy after menopause. Panel discussions provided insights on these issues from a range of perspectives, including government, evidence-based medicine, clinical research, health professionals and community. During the last session, speakers and participants worked in small groups to formulate recommendations and strategies to improve the suitability of the evidence base and trustworthiness of therapeutic recommendations and guidelines.NP

Sample size determination for external pilot cluster randomised trials with binary feasibility outcomes:a tutorial

Abstract Justifying sample size for a pilot trial is a reporting requirement, but few pilot trials report a clear rationale for their chosen sample size. Unlike full-scale trials, pilot trials should not be designed to test effectiveness, and so, conventional sample size justification approaches do not apply. Rather, pilot trials typically specify a range of primary and secondary feasibility objectives. Often, these objectives relate to estimation of parameters that inform the sample size justification for the full-scale trial, many of which are binary. These binary outcomes are referred to as “feasibility outcomes” and include expected prevalence of the primary trial outcome, primary outcome availability, or recruitment or retention proportions. For pilot cluster trials, sample size calculations depend on the number of clusters, the cluster sizes, the anticipated intra-cluster correlation coefficient for the feasibility outcome and the anticipated proportion for that outcome. Of key importance is the intra-cluster correlation coefficient for the feasibility outcome. It has been suggested that correlations for feasibility outcomes are larger than for clinical outcomes measuring effectiveness. Yet, there is a dearth of information on realised values for these correlations. In this tutorial, we demonstrate how to justify sample size in external pilot cluster trials where the objective is to estimate a binary feasibility outcome. We provide sample size calculation formulae for a variety of scenarios, make available an R Shiny app for implementation, and compile a report of intra-cluster correlations for feasibility outcomes from a convenience sample. We demonstrate that unless correlations are very low, external pilot cluster trials can be made more efficient by including more clusters and fewer observations per cluster

Improving expert forecasts in reliability. Application and evidence for structured elicitation protocols

Quantitative expert judgementsare used in reliability assessmentsto informcritically important decisions. Structured elicitation protocols have been advocated to improveexpert judgements, yet their application in reliability ischallenged by a lack of examples or evidence that they improve judgements. This paper aims to overcome these barriers. We present a case study where two world-leading protocols, the IDEA protocol and the Classical Model were combined and applied by the Australian Department of Defence for a reliability assessment. We assess the practicality of the methods, and the extent to which they improve judgements. The average expert was extremely overconfident, with 90% credible intervals containing the true realisation 36% of the time. However,steps contained inthe protocols substantially improvedjudgements. In particular, an equal weighted aggregation of individual judgements, and the inclusion ofa discussion phase and revised estimate helped to improve calibration, statistical accuracy and the Classical Model score. Further improvements in precision and information were made via performance weighted aggregation. This paper provides useful insights into the application of structured elicitation protocols for reliability andthe extent to which judgements are improved. The findings raise concerns about existing practices for utilising experts in reliability assessments and suggest greater adoption of structured protocols is warranted. We encourage the reliability community to further develop examples and insights

Polypill for prevention of cardiovascular disease in an Urban Iranian population with special focus on nonalcoholic steatohepatitis: A pragmatic randomized controlled trial within a cohort (PolyIran - Liver) – Study protocol

Background: Cardiovascular disease (CVD) is among the most common causes of mortality in all populations. Nonalcoholic steatohepatitis is a common finding in patients with CVD. Prevention of CVD in individual patients typically requires periodic clinical evaluation, as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia. However, this is resource consuming and hard to implement, especially in developing countries. We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years. Design: The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. We randomly selected 2,400 cohort study participants aged above 50 years, randomly assigned them to intervention or usual care and invited them to participate in an additional measurement study (if they met the eligibility criteria) to measure liver related outcomes. Those agreeing and randomized to the intervention arm were offered a daily single dose of PolyPill. We will follow participants for 5 years. The primary outcome is major cardiovascular events, secondary outcomes include all-cause mortality and liver related outcomes: liver stiffness and liver enzyme levels. Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up. Analysis will be by allocated group. Trial Status: Between October and December 2011, 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study. For all these participants, the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study. In the intervention and control arms, 875 (66%) and 721 (67%) respectively, met the eligibility criteria and agreed to participate in the additional measurement study. Liver related outcomes will be measured in these participants. Of the 1,320 participants randomized to the intervention, 787 (60%) accepted the PolyPill. Conclusion: The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events, all-cause mortality and liver related outcomes. (ClinicalTrials.gov ID: NCT01245608). © 2015, Academy of Medical Sciences of I.R. Iran. All rights reserved

Independent therapeutic advice: How achievable is it?

This supplement is likely to be of interest to anyone involved in the development of clinical guidelines and clinical research, including: • health professionals, trainees and students who use guidelines as a basis for their decision making • policy makers and others working to improve the quality of health care • people involved in university, college and hospital education. The supplement outlines the issues discussed at an Independence Forum hosted by Therapeutic Guidelines Limited in Melbourne, Australia, on 29 October 2012. It puts forward recommendations to overcome limitations of the evidence base and improve the trustworthiness of guidelines. Therapeutic Guidelines is an independent, not-forprofit organisation that was established to promote the quality use of medicines through the publication of clear, concise and ready to use guidelines. Therapeutic Guidelines convened the Independence Forum to discuss issues of independence and conflicts of interest in the context of the development of therapeutic guidelines for health professionals. Two eminent overseas speakers, Professor Silvio Garattini from the Mario Negri Institute, Italy, and Assistant Professor Barbara Mintzes from the University of British Columbia, Canada, gave keynote presentations on the complexity of the therapeutic environment and clinical evidence base. Key Australian commentators and health ethicists – Professor Paul Komesaroff from the Centre for the Study of Ethics in Medicine and Society at Monash University, and Associate Professor Ian Kerridge from the Centre for Values, Ethics and the Law in Medicine at the University of Sydney – focused on the influence of vested interests in clinical research trials and guideline development, citing high profile examples such as the case of hormone therapy after menopause. Panel discussions provided insights on these issues from a range of perspectives, including government, evidence-based medicine, clinical research, health professionals and community. During the last session, speakers and participants worked in small groups to formulate recommendations and strategies to improve the suitability of the evidence base and trustworthiness of therapeutic recommendations and guidelines.NP

Accommodating quality and service improvement research within existing ethical principles

Funds were provided by a Canadian Institute of Health Research grant (Nominated PI: Monica Taljaard, PJT – 153045). Funds were also generously provided by Charles Weijer, who is funded by a Tier 1 Canadian Research Chair.Peer reviewedPublisher PD