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Original article
C-reactive protein point-of-care testing in acutely ill children: a mixed methods study in primary care
  1. Ann Van den Bruel1,
  2. Caroline Jones1,
  3. Matthew Thompson1,2,
  4. David Mant1
  1. 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  2. 2Department of Family Medicine, University of Washington, Seattle, Washington, USA
  1. Correspondence to Dr Ann Van den Bruel, Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK; ann.vandenbruel{at}phc.ox.ac.uk

Abstract

Background Point-of-care C-reactive protein (CRP) testing of adults with acute respiratory infection in primary care reduces antibiotic prescribing by 22%. The acceptability and impact of CRP testing in children is unknown

Objective To determine the acceptability and impact of CRP testing in acutely ill children.

Design Mixed methods study comprising an observational cohort with a nested randomised controlled trial and embedded qualitative study.

Subjects and setting Children presenting with an acute illness to general practice out-of-hours services; children with a temperature ≥38°C were randomised in the nested trial; parents and clinical staff were invited to the qualitative study.

Main outcomes Informed consent rates; parental and staff views on testing.

Results Consent to involvement in the study was obtained for 200/297 children (67.3%, 95% CI 61.7% to 72.6%); the finger-prick test might have been a contributory factor for 63 of the 97 children declining participation but it was cited as a definite factor in only 10 cases. None of the parents or staff raised concerns about the acceptability of testing, describing the pain caused as minor and transient. General practitioner views on the utility of the CRP test were inconsistent.

Conclusions CRP point-of-care testing in children is feasible in primary care and is likely to be acceptable. However, it will not reduce antibiotic prescribing and hospital referrals until general practitioners accept its diagnostic value in children.

Trial registration number ISRCTN 69736109.

  • General Paediatrics
  • Health Service
  • Infectious Diseases
  • Outcomes research
  • Technology
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What is already known on this topic

  • C-reactive protein (CRP) is an inflammatory marker which can help diagnose serious infections in children.

  • CRP has also been shown to reduce antibiotic prescribing in adults with acute respiratory tract infection.

  • A point-of-care test of CRP might influence diagnostic decision-making in primary care, including antibiotic prescribing and referral decisions.

What this study adds

  • Acceptability of a point-of-care test that involves a finger prick in children was high.

  • General practitioner (GP) views on the utility of the C-reactive protein (CRP) test were inconsistent.

  • There was no difference in referral rates or antibiotic prescriptions at the out-of-hours service in children who did or did not have the CRP test.

  • Parents, GPs and study nurses supported the idea of wider implementation of the tests.

Introduction

Acute illness is very common in children and mostly infectious, ranging from minor infections such as upper respiratory tract infections to serious infections such as pneumonia or meningitis.1

Timely recognition of serious infections is challenging because of their low incidence in general practice,2 children presenting at different stages of their illness and the limited diagnostic value of the presenting symptoms and signs.3 This diagnostic uncertainty is contributing to increasing hospital admissions rates4 and high levels of antibiotic prescribing.5 ,6

Studies in children in a hospital setting suggest that the inflammatory marker C-reactive protein (CRP) may be helpful in diagnosis.7 Moreover, a recent meta-analysis estimated that CRP point-of-care testing reduces antibiotic prescriptions by 22% in adults.8 However, there is no comparable evidence of the impact of CRP point-of-care testing in children in primary care, and there are doubts about the feasibility of routine finger-prick testing of children. We therefore report here the results of a study to assess the feasibility and acceptability of CRP point-of-care testing in an out-of-hours general-practice in Oxfordshire, UK.

Methods

Design

A cohort study of consecutive children presenting with an acute illness (maximum duration 5 days), with a nested randomised controlled trial of finger-prick blood CRP testing, was carried out; a qualitative interview study was embedded to explore acceptability of CRP testing. Children aged 1 month–16 years were eligible for inclusion. Children were excluded if they had consulted for acute trauma, were clinically unstable warranting immediate care, or had been included in this study before. The study was conducted at two out-of-hours services in Oxfordshire (UK), between July 2013 and April 2014.

Clinical assessment

After obtaining informed consent, children with a body temperature of at least 38°C (measured either by the study nurse or in the preceding 4 h by the parents) were eligible for 1:1 randomisation to CRP testing, using a computer generated web-based system. Children were subsequently assessed by the attending general practitioner (GP) who carried out a clinical examination according to their usual practice. GPs were informed that a serious infection was less likely when the CRP level was <20 mg/L and more likely when the level was >80 mg/L.7

Follow-up

Follow-up data for the 10 days after the index consultation were requested from the child's usual GP. Antibiotic prescriptions were defined as the prescription of any oral antibiotic agent included in section 5.1 of the British National Formulary. Referral was defined as a referral to any specialist service; additional testing was defined as the request of any laboratory or imaging test, including urine testing; hospital admission was defined as an admission to hospital for at least 24 h; re-consultation was defined as any consultation in daytime general practice, out-of-hours services or an emergency department. Explicit safety netting was defined as a statement in the medical record about when and how to re-consult. Outcome assessors were blinded to the group allocation.

Quantitative analysis

The primary outcome was recruitment rate. Secondary outcomes included antibiotic prescribing, hospital referral or admission, additional testing in primary care, or re-consultation in primary or secondary care. Analyses were done using STATA (V.11); where appropriate, descriptive results are reported with 95% CIs. The comparison between the two arms of the randomised controlled trial was tested for statistical significance by the χ2 test on the basis of intention-to-treat.

Embedded qualitative study

Qualitative semistructured interviews were conducted to explore the acceptability of the CRP test among a subset of parents/guardians, selected purposively to ensure variability in ethnicity, family composition, parent and child age, and randomisation to CRP or no testing. Additionally, all clinicians were invited to participate. Interviews took place within 1 month of inclusion (parents) or study end (clinicians), either face-to-face or by telephone using a flexible topic guide. Interviews were transcribed and analysed thematically. A coding scheme was devised after preliminary reading of the transcripts, and data were then coded and grouped into themes. Codes and themes were discussed and verified among the research team and with a public advisory panel.

Ethics

The study was approved by National Research Ethics Service Committee South Central, 13/SC/0045.

Results

Parental consent was not obtained for 97 of the 297 eligible children, corresponding to a consent rate of 67.3% (95% CI 61.7% to 72.6%). Of the refusals, 10 were specifically related to the potential finger-prick for the CRP test but a further 53 were possibly related (23 related to generic child upset and 30 for whom no reason was given).

The 200 children included had a mean age of 2.8 years (IQR 1.17–5.46 years), half were boys (51.5%) and from a range of ethnic backgrounds (white 80.5%; Asian 7.5%; other 12.0%). The most common reasons for attending were fever (n=91), cough (n=44) and vomiting (n=27).

Fifty-four children were included in the nested randomised controlled trial (based on fever at the time of assessment or in the preceding 4 h). The median value of the CRP levels for the 26 children tested was 21 mg/L, ranging from 0 to 154 mg/L. Three children had a CRP level above the 80 mg/L threshold: one child was referred to hospital by the out-of-hours GP and later diagnosed with appendicitis, the other two children were prescribed antibiotics at the index consultation and recovered uneventfully.

Table 1 shows the antibiotic prescribing and clinical outcomes for all 200 children in the study. Antibiotics were prescribed to 60 children (30%, 95% CI 23.6% to 36.4%) at the index consultation, 70 (35%) received explicit safety-netting advice and 11 (5.5%) were referred to hospital. There was no statistically significant difference in any outcome between those tested or not tested with CRP point-of-care. In the 10-day follow-up period, children randomised to CRP testing received significantly more antibiotic prescriptions. Five children were admitted to hospital, three with infection (pneumonia, appendicitis and a non-specified viral illness). The two non-infectious discharge diagnoses were nephrotic syndrome and angioedema.

Table 1

Clinical outcomes according to randomisation status

Acceptability and perception of clinical value

Twelve parents, five GPs and two study nurses participated in qualitative interviews. Parents reported no real concerns about the test (box 1); any minor concerns (delay in seeing the GP or discomfort) were offset by the recognition that any pain would be minor and short-lived, and the belief that the test would be beneficial. Those who had the CRP test mainly reported that the test caused little or no pain or discomfort, or their children even enjoyed it or were very interested. The study nurses also reported that children accepted the test, and there were no problems with pain or discomfort.

Box 1

Quotes from the qualitative interviews

1. Pain and discomfort

“kind of enjoyed it” (parent 134, child aged 5 years)“very interested” (parent 135, child aged 4 years)

2. How GPs applied the test results

“I had knowledge of the CRP sort of before I examined the child in detail, so in a way that I think was doubly helpful… I don't think it detracts from the consultation, I think it augments the consultation… because you know it takes the heat out of the whole encounter if you know that the CRP is normal.” (GP1)“[I looked at the result] at the end so that you wouldn't be biased” (GP4)“it's very important not to be caught either way by the potential problem of, you know, assuming yes, this particular patient has got a normal CRP therefore I'm going to send them home and the other way, sometimes you get people with abnormal CRPs who in fact are completely okay so it's just part of an overall assessment.” (GP3)“they should really say what they think is wrong with the patient first before looking into the results, and then see if they are right or not… Because I think they would start relying on that too much…I think they wouldn't put too much of attention on the actual patient.” (Parent 146, child aged 3 years)

3. GPs’ perceptions of the clinical value of the CRP test

“When I've got the CRP result available then I'm much more confident in my discussion with the patients, and I think that probably comes across to the patient as well… I think it just sort of enhances the whole clinical encounter” [GP1]“if I wasn't 100% sure it was a bacterial infection the CRP, if it's a high CRP it will be found more likely to prescribe than not” [GP4).“No, I wouldn't use it [CRP] as a criteria for prescribing antibiotics.” [GP5]“if you think they need to be admitted you probably should admit them and the CRP shouldn't really change your mind.” [GP4].“If a child's got a persistent high fever and a CRP of 30, 40 or 50, then I'd admit them for further investigation, even if I didn't know what the cause was… Interviewer: What would you do with that child without the CRP results? … They wouldn't actually require admission at that time.” [GP5]

CRP, C-reactive protein.

The GPs and some parents emphasised that a CRP result should be part of an overall assessment. The GPs perceptions ranged from believing that antibiotic prescriptions would be reduced to increased. Similarly, GPs suggested that either CRP should not influence the referral decision, or that a high CRP result would initiate referrals whereas a low CRP result might not reduce referrals.

However, with the exception of one parent, all interviewed parents, GPs and study nurses supported wider implementation. Potential positive impacts were better selection of referrals, avoiding unnecessary treatment, identification of serious illness, more rapid assessment, providing credibility to parents, reassuring parents and GPs, educating parents and safeguarding GPs. Although some potential problems were raised (cost, time, false reassurance, overtesting and parental expectations for testing), the overall view was there would be no major barriers to implementation.

Discussion

CRP point-of-care testing in acutely ill children in an out-of-hours service is feasible and acceptable to both parents/children and GPs. The recruitment rate of 67% for a study that involves a finger prick in a child was similar to that in other studies in children,9 and the finger prick seemed to be a minor factor in the parental decision to consent.

Although antibiotic prescription rates were not different at the index consultation, we found a statistically significant difference during the 10-day follow-up, but there is a substantial risk of a chance finding: of the six children who had a CRP test and antibiotics during follow-up, two were ultimately admitted to hospital and one was referred to the emergency department.

Implications for clinical practice

The results of the qualitative interviews suggest that in order for antibiotic prescribing to decrease, clinicians need very clear guidance on when to withhold antibiotics based on the CRP level. If antibiotics had been withheld from all feverish children with a CRP level <20 mg/L, antibiotic prescribing would have decreased from 38% to 23%. The safety of such a strategy should be assessed before widespread implementation, as studies suggest that serious infections can be present in children with CRP levels as low as 5 mg/L, especially in the early stages of the illness.10 ,11

Implications for research

Clinicians tend to err on the side of caution, which means that when a new diagnostic test is added to the diagnostic process they will use an abnormal test as a red flag, but not necessarily use a normal test result to rule out the need for referral or antibiotic prescribing. Future studies should investigate the most efficient ways of training clinicians in how to use and interpret new tests, and assess the impact of using this guidance on children's health outcomes and healthcare processes. In addition, we need to assess the incremental value of the test over and above existing clinical prediction rules such as the National Institute of Health and Care Excellence (NICE) traffic light system.

References

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Footnotes

  • Contributors AVdB conceived the study, was involved in the data collection, performed the analyses and wrote the manuscript. CJ conceived the qualitative strand of the study, performed all qualitative data collection, performed the qualitative analyses and contributed to the manuscript. MT and DM contributed to the conception of the study, contributed to the analyses and the writing of the manuscript. All authors approved the final version of the manuscript.

  • Funding The study was supported by a grant from the National School for Primary Care Research NSPCR no 154.

  • Competing interests After finalising this work, MT received funding from Alere to evaluate C-reactive protein point-of-care tests in a US-based research study.

  • Ethics approval National Research Ethics Service Committee South Central.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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