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      Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial

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          Abstract

          Background

          Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment.

          Methods

          Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12–30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L.

          Results

          Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8–82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6–45.6 %) had a CRP < 5 mg/L.

          Conclusions

          CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals.

          Trial registration

          ClinicalTrials.gov Identifier: NCT02024282 (registered on 14 th September 2012).

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          Most cited references24

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          Variation of a test's sensitivity and specificity with disease prevalence.

          Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.
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            Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial

            Objective To assess the effect of general practitioner testing for C reactive protein (disease approach) and receiving training in enhanced communication skills (illness approach) on antibiotic prescribing for lower respiratory tract infection. Design Pragmatic, 2×2 factorial, cluster randomised controlled trial. Setting 20 general practices in the Netherlands. Participants 40 general practitioners from 20 practices recruited 431 patients with lower respiratory tract infection. Main outcome measures The primary outcome was antibiotic prescribing at the index consultation. Secondary outcomes were antibiotic prescribing during 28 days’ follow-up, reconsultation, clinical recovery, and patients’ satisfaction and enablement. Interventions General practitioners’ use of C reactive protein point of care testing and training in enhanced communication skills separately and combined, and usual care. Results General practitioners in the C reactive protein test group prescribed antibiotics to 31% of patients compared with 53% in the no test group (P=0.02). General practitioners trained in enhanced communication skills prescribed antibiotics to 27% of patients compared with 54% in the no training group (P<0.01). Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days’ follow-up. Clinicians in the combined intervention group prescribed antibiotics to 23% of patients (interaction term was non-significant). Patients’ recovery and satisfaction were similar in all study groups. Conclusion Both general practitioners’ use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients’ recovery and satisfaction with care. A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care. Trial registration Current Controlled Trials ISRCTN85154857.
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              Sources of variation and bias in studies of diagnostic accuracy: a systematic review.

              Studies of diagnostic accuracy are subject to different sources of bias and variation than studies that evaluate the effectiveness of an intervention. Little is known about the effects of these sources of bias and variation. To summarize the evidence on factors that can lead to bias or variation in the results of diagnostic accuracy studies. MEDLINE, EMBASE, and BIOSIS, and the methodologic databases of the Centre for Reviews and Dissemination and the Cochrane Collaboration. Methodologic experts in diagnostic tests were contacted. Studies that investigated the effects of bias and variation on measures of test performance were eligible for inclusion, which was assessed by one reviewer and checked by a second reviewer. Discrepancies were resolved through discussion. Data extraction was conducted by one reviewer and checked by a second reviewer. The best-documented effects of bias and variation were found for demographic features, disease prevalence and severity, partial verification bias, clinical review bias, and observer and instrument variation. For other sources, such as distorted selection of participants, absent or inappropriate reference standard, differential verification bias, and review bias, the amount of evidence was limited. Evidence was lacking for other features, including incorporation bias, treatment paradox, arbitrary choice of threshold value, and dropouts. Many issues in the design and conduct of diagnostic accuracy studies can lead to bias or variation; however, the empirical evidence about the size and effect of these issues is limited.
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                Author and article information

                Contributors
                +44(0)7477201379 , jan.verbakel@phc.ox.ac.uk
                marieke.lemiengre@ugent.be
                tine.deburghgraeve@kuleuven.be
                an.desutter@ugent.be
                bert.aertgeerts@kuleuven.be
                b.shinkins@leeds.ac.uk
                rafael.perera@phc.ox.ac.uk
                david.mant@phc.ox.ac.uk
                ann.vandenbruel@phc.ox.ac.uk
                frank.buntinx@kuleuven.be
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                6 October 2016
                6 October 2016
                2016
                : 14
                : 131
                Affiliations
                [1 ]Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care Building, Woodstock Road, Oxford, OX2 6GG UK
                [2 ]Department of Public Health and Primary Care, KU Leuven, Kapucijnenvoer 33J, 3000 Leuven, Belgium
                [3 ]Department of Family Medicine and Primary Health Care, Ghent University, De Pintelaan 185, Gent, 9000 Belgium
                [4 ]Leeds Institute of Health Sciences, University of Leeds, 101 Clarendon Road, Leeds, LS29LJ UK
                [5 ]Research Institute Caphri, Maastricht University, Universiteitssingel 40, Maastricht, 6229 ER The Netherlands
                Article
                679
                10.1186/s12916-016-0679-2
                5052874
                27716201
                a541b670-87fe-4dad-bba9-a17f10fcb2d4
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 May 2016
                : 24 August 2016
                Funding
                Funded by: Fonds Wetenschappelijk Onderzoek (BE)
                Award ID: G067509N
                Award Recipient :
                Funded by: National Institute for Health and Disability Insurance (RIZIV, Belgium)
                Award ID: CGV n° 2012/235
                Award Recipient :
                Funded by: NIHR Diagnostic Evidence Co­operative Oxford
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Medicine
                serious infection,child,c-reactive protein,point-of-care,primary care
                Medicine
                serious infection, child, c-reactive protein, point-of-care, primary care

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