This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 2 http://www.thecochranelibrary.com 0induced coagulopathy in adult trauma patients with bleeding Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding (Review)

Objective To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department.Design Systematic review and meta-analysis of diagnostic test accuracy studies.Data sources Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013.Study selection Studies were included if they evaluated the diagnostic accuracy of a single baseline measurement of Elecsys Troponin T high-sensitive assay for the diagnosis of acute myocardial infarction in patients presenting to the emergency department with suspected acute coronary syndrome. Study appraisal and data synthesisThe first author screened all titles and abstracts identified through the searches and selected all potentially relevant papers. The screening of the full texts, the data extraction, and the methodological quality assessment, using the adapted QUADAS-2 tool, were conducted independently by two reviewers with disagreements being resolved through discussion or arbitration. If appropriate, meta-analysis was conducted using the hierarchical bivariate model. ResultsTwenty three studies reported the performance of the evaluated assay at presentation. The results for 14 ng/L and 3-5 ng/L cut-off values were pooled separately. At 14 ng/L (20 papers), the summary sensitivity was 89.5% (95% confidence interval 86.3% to 92.1%) and the summary specificity was 77.1% (68.7% to 83.7%). At 3-5 ng/L (six papers), the summary sensitivity was 97.4% (94.9% to 98.7%) and the summary specificity was 42.4% (31.2% to 54.5%). This means that if 21 of 100 consecutive patients have the target condition (21%, the median prevalence across the studies), 2 (95% confidence interval 2 to 3) of 21 patients with acute myocardial infarction will be missed (false negatives) if 14 ng/L is used as a cut-off value and 18 (13 to 25) of 79 patients without acute myocardial infarction will test positive (false positives). If the 3-5 ng/L cut-off value is used, <1 (0 to 1) patient with acute myocardial infarction will be missed and 46 (36 to 54) patients without acute myocardial infarction will test positive. ConclusionsThe results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used. However, this method should be part of a comprehensive triage strategy and may not be appropriate for patients who present less than three hours after symptom onset. Care must also be exercised because of the higher imprecision of the evaluated assay and the greater effect of lot-to-lot reagent variation at low troponin concentrations.Systematic review registration PROSPERO registration number CRD42013003926.

BackgroundIdentification of permanent hearing impairment at the earliest possible age is crucial to maximise the development of speech and language. Universal newborn hearing screening identifies the majority of the 1 in 1000 children born with a hearing impairment, but later onset can occur at any time and there is no optimum time for further screening. A universal but non-standardised school entry screening (SES) programme is in place in many parts of the UK but its value is questioned.ObjectivesTo evaluate the diagnostic accuracy of hearing screening tests and the cost-effectiveness of the SES programme in the UK.DesignSystematic review, case–control diagnostic accuracy study, comparison of routinely collected data for services with and without a SES programme, parental questionnaires, observation of practical implementation and cost-effectiveness modelling.SettingSecond- and third-tier audiology services; community.ParticipantsChildren aged 4–6 years and their parents.Main outcome measuresDiagnostic accuracy of two hearing screening devices, referral rate and source, yield, age at referral and cost per quality-adjusted life-year.ResultsThe review of diagnostic accuracy studies concluded that research to date demonstrates marked variability in the design, methodological quality and results. The pure-tone screen (PTS) (Amplivox, Eynsham, UK) and HearCheck (HC) screener (Siemens, Frimley, UK) devices had high sensitivity (PTS ≥ 89%, HC ≥ 83%) and specificity (PTS ≥ 78%, HC ≥ 83%) for identifying hearing impairment. The rate of referral for hearing problems was 36% lower with SES (Nottingham) relative to no SES (Cambridge) [rate ratio 0.64, 95% confidence interval (CI) 0.59 to 0.69;p < 0.001]. The yield of confirmed cases did not differ between areas with and without SES (rate ratio 0.82, 95% CI 0.63 to 1.06;p = 0.12). The mean age of referral did not differ between areas with and without SES for all referrals but children with confirmed hearing impairment were older at referral in the site with SES (mean age difference 0.47 years, 95% CI 0.24 to 0.70 years;p < 0.001). Parental responses revealed that the consequences to the family of the referral process are minor. A SES programme is unlikely to be cost-effective and, using base-case assumptions, is dominated by a no screening strategy. A SES programme could be cost-effective if there are fewer referrals associated with SES programmes or if referrals occur more quickly with SES programmes.ConclusionsA SES programme using the PTS or HC screener is unlikely to be effective in increasing the identified number of cases with hearing impairment and lowering the average age at identification and is therefore unlikely to represent good value for money. This finding is, however, critically dependent on the results of the observational study comparing Nottingham and Cambridge, which has limitations. The following are suggested: systematic reviews of the accuracy of devices used to measure hearing at school entry; characterisation and measurement of the cost-effectiveness of different approaches to the ad-hoc referral system; examination of programme specificity as opposed to test specificity; further observational comparative studies of different programmes; and opportunistic trials of withdrawal of SES programmes.Trial registrationCurrent Controlled Trials ISRCTN61668996.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 36. See the NIHR Journals Library website for further project information.

ObjectivesTo evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests.DesignSystematic review.Data sourcesMEDLINE, EMBASE and the Cochrane Database up to May 2015.Eligibility criteria for selecting studiesWe included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions.Study appraisal and synthesis methods2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used.Results27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics.ConclusionsThe results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified.Trial registration numberCRD42014006192.

BackgroundCochrane reviews are one of the best known and most trusted sources of evidence-based information in health care. While steps have been taken to make Cochrane intervention reviews accessible to a diverse readership, little is known about the accessibility of the newcomer to the Cochrane library: diagnostic test accuracy reviews (DTARs). The current qualitative study explored how healthcare decision makers, who varied in their knowledge and experience with test accuracy research and systematic reviews, read and made sense of DTARs.MethodsA purposive sample of clinicians, researchers and policy makers (n = 21) took part in a series of think-aloud interviews, using as interview material the first three DTARs published in the Cochrane library. Thematic qualitative analysis of the transcripts was carried out to identify patterns in participants’ ‘reading’ and interpretation of the reviews and the difficulties they encountered.ResultsParticipants unfamiliar with the design and methodology of DTARs found the reviews largely inaccessible and experienced a range of difficulties stemming mainly from the mismatch between background knowledge and level of explanation provided in the text. Experience with systematic reviews of interventions did not guarantee better understanding and, in some cases, led to confusion and misinterpretation. These difficulties were further exacerbated by poor layout and presentation, which affected even those with relatively good knowledge of DTARs and had a negative impact not only on their understanding of the reviews but also on their motivation to engage with the text. Comparison between the readings of the three reviews showed that more accessible presentation, such as presenting the results as natural frequencies, significantly increased participants’ understanding.ConclusionsThe study demonstrates that authors and editors should pay more attention to the presentation as well as the content of Cochrane DTARs, especially if the reports are aimed at readers with various levels of background knowledge and experience. It also raises the question as to the anticipated target audience of the reports and suggests that different groups of healthcare decision-makers may require different modes of presentation.

Clinical studies in chronic myelogenous leukemia demonstrate that the overexpression of Bcr-Abl tyrosine kinase is usually accompanied by relatively low telomerase activity in the chronic phase, which reverts to a high activity in blast crisis. The present study was designed to investigate the cross-talk between both enzymes, using Bcr-Abl-positive K-562 and BcrAbl-negative Jurkat cell lines, treated with antisense oligodeoxyribonucleotides (ODNs) against Bcr-Abl/c-Abl mRNA. The decreased amount and enzyme activity of Bcr-Abl/c-Abl provoked telomerase activation in both cell lines. After shortterm treatment with anti-Bcr-Abl/c-Abl ODNs (6 days), no variations in hTERT and phospho-hTERT were detected. The decreased amount of Bcr-Abl/c-Abl was accompanied by: alterations in telomeric associated proteins^overexpression of tankyrase and decreased amount of TRF1/Tin2, cell growth arrest of K-562 cells, reaching a plateau after 6 days treatment, and increased proliferating activity of Jurkat cells. No changes in telomere length were detected after short-term treatment. In contrast, after long-term treatment with anti-Bcr-Abl/c-Abl ODNs (36 days), a signi¢cant elongation of telomeres and enhancement of hTERT were established, accompanied by an increased proliferating activity of both cell lines. These data provide evidence that the inhibition of Bcr-Abl or c-Abl synthesis keeps a potential to restore or induce cell proliferation through telomere lengthening control and telomerase activation.

BACKGROUND. Short, 21-mer, double-stranded/small interfering RNAs (ds/siRNAs)

Patients presenting with chest pain at an emergency department in the United Kingdom receive troponin tests to assess the likelihood of an acute myocardial infarction (AMI). Until recently, serial testing with two blood samples separated by at least six hours was necessary in order to analyse the change in troponin levels over time. New high-sensitivity troponin tests, however, allow the inter-test time to be shortened from six to three hours. Recent evidence also suggests that the new generation of troponin tests can be used to rule out AMI on the basis of a single test if patients at low risk of AMI present with very low cardiac troponin levels more than three hours after onset of worst pain. This paper presents a discrete event simulation model to assess the likely impact on the number of hospital admissions if emergency departments adopt strategies for serial and single testing based on the use of high-sensitivity troponin. Data sets from acute trusts in the South West of England are used to quantify the resulting benefits.