The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data.

BACKGROUND: C-reactive protein (CRP) is increasingly being included in the diagnostic work-up for community-acquired pneumonia in primary care. Its added diagnostic value beyond signs and symptoms, however, remains unclear. We conducted a meta-analysis of individual patient data to quantify the added value of CRP measurement. METHODS: We included studies of the diagnostic accuracy of CRP in adult outpatients with suspected lower respiratory tract infection. We contacted authors of eligible studies for inclusion of data and for additional data as needed. The value of adding CRP measurement to a basic signs-and-symptoms prediction model was assessed. Outcome measures were improvement in discrimination between patients with and without pneumonia in primary care and improvement in risk classification, both within the individual studies and across studies. RESULTS: Authors of 8 eligible studies (n = 5308) provided their data sets. In all of the data sets, discrimination between patients with and without pneumonia improved after CRP measurement was added to the prediction model (extended model), with a mean improvement in the area under the curve of 0.075 (range 0.02-0.18). In a hypothetical cohort of 1000 patients, the proportion of patients without pneumonia correctly classified at low risk increased from 28% to 36% in the extended model, and the proportion with pneumonia correctly classified at high risk increased from 63% to 70%. The number of patients with pneumonia classified at low risk did not change (n = 4). Overall, the proportion of patients assigned to the intermediate-risk category decreased from 56% to 51%. INTERPRETATION: Adding CRP measurement to the diagnostic work-up for suspected pneumonia in primary care improved the discrimination and risk classification of patients. However, it still left a substantial group of patients classified at intermediate risk, in which clinical decision-making remains challenging.

C-reactive protein point-of-care testing and associated antibiotic prescribing.

BACKGROUND: In clinical trials, the potential of point-of-care (POC) C-reactive protein (CRP) tests was demonstrated in decreasing antibiotic prescribing in adults with acute cough in general practice, but effects of implementation are unknown. OBJECTIVE: To determine the overall effect of POC CRP testing on antibiotic prescribing rate in general practice. METHODS: In an observational study, GPs were instructed to use POC CRP in adults with acute cough following current guidelines. After routine history taking and physical examination, they reported whether they intended to prescribe antibiotics ('pre-test decision'). They reported their revised decision after receiving the POC CRP test result ('post-test decision'). Primary outcome was the percentage of patients in whom the GP changed his or her decision to prescribe antibiotics. Secondary outcome was the difference between 'pre-test' and 'post-test' antibiotic prescribing % at group level. RESULTS: A total of 40 GPs enrolled 939 patients, 78% of whom were tested for CRP. GPs changed their decision after POC CRP testing in 200 patients (27%). Antibiotic prescribing before and after CRP testing did not differ ('pre-test' 31%, 'post-test' 28%; 95% confidence interval of difference -7 to 1). In 41% of the tested patients, the indication for testing was in accordance with the guidelines. CONCLUSION: POC CRP influenced GPs to change their decision about antibiotic prescribing in patients with acute cough. POC CRP testing does not reduce overall antibiotic prescribing by GPs who already have a low antibiotic prescribing rate.

The added diagnostic value of five different C-reactive protein point-of-care test devices in detecting pneumonia in primary care: A nested case-control study.

BACKGROUND: The results obtained from various point-of-care (POC) test devices for estimating C-reactive protein (CRP) levels in a laboratory setting differ when compared to a laboratory reference test. We aimed to determine whether such differences meaningfully affect the accuracy and added diagnostic value in predicting radiographic pneumonia in adults presenting with acute cough in primary care. METHODS: A nested case control study of adult patients presenting with acute cough in 12 different European countries (the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe [GRACE] Network). Venous blood samples from 100 patients with and 100 patients without pneumonia were tested with five different POC CRP tests and a laboratory analyzer. Single test accuracy values and the added value of CRP to symptoms and signs were calculated. RESULTS: Single test accuracy values showed similar results for all five POC CRP tests and the laboratory analyzer. The area under the curve of the different POC CRP tests and the laboratory analyzer (range 0.79-0.80) were all comparable and higher than the clinical model without CRP (0.70). Multivariable odds ratios were the same (1.2) for all CRP tests. CONCLUSIONS: Five POC CRP test devices and the laboratory analyzer performed with similar accuracy in detecting pneumonia both as single test, and when used in addition to clinical findings. Variability in results obtained from standard CRP laboratory and POC test devices do not translate into clinically relevant differences when used for prediction of pneumonia in patients with acute cough in primary care.

Analytical performance, agreement and user-friendliness of five C-reactive protein point-of-care tests.

BACKGROUND: Point-of-care (POC) C-reactive protein (CRP) testing is increasingly used in primary care to assist general practitioners (GPs) in the diagnostic workup for various complaints. The present study compares analytical performance, agreement and user-friendliness of five of these POC CRP tests. METHODS: The following five POC CRP tests were evaluated: Afinion and NycoCard Reader II (both Alere), Eurolyser Smart 700/340 (Eurolyser), QuikRead go and QuikRead 101 (both Orion Diagnostica). Results were compared with those of a standard immunoturbidimetric method performed on a routine analyzer (Olympus AU 2700, Beckman Coulter). Analytical performance and agreement with the laboratory standard for the five different POC tests were analyzed. Subsequently, user-friendliness of the POC tests was assessed. RESULTS: Within-day CVs varied from 2.6% (QuikRead go) to 19.4% (Eurolyser Smart 700/340) for low CRP values (< 20 mg/L), and 1.1% (QuikRead go) to 17.5% (Eurolyser Smart 700/340) for high values (> 100 mg/L). Between-day CVs varied from 4.6% (Afinion) to 30.5% (Eurolyser Smart 700/340) for low values and 4.0% (QuikRead go) to 18.0% (Eurolyser Smart 700/340) for high values. With high CRP values (> 100 mg/L) agreement with the laboratory standard systematically decreased for all POC tests. Regarding user-friendliness Afinion and Eurolyser Smart 700/340 were judged easiest to operate. CONCLUSIONS: Analytical performance, agreement, and user-friendliness of the POC CRP tests varied considerably, yet overall four devices showed adequate analytical performance and agreement.

Analysis of recruitment in a pragmatic observational study on C-reactive protein point-of-care testing in primary care.

INTRODUCTION: Failure to recruit all eligible study patients can lead to biased results. Little is known on selective patient recruitment in studies on implementation of diagnostic devices. OBJECTIVES: The aim of this observational study was to measure recruitment of patients in an implementation study in primary care on use of point-of-care (POC) C-reactive protein (CRP) and to evaluate recruitment bias and its impact on the study endpoint. METHODS: In a cross-sectional observational study on POC CRP implementation and related antibiotics prescribing, we compared included patients with all eligible patients to assess the representativeness of the included subjects. Eligible patients were adults presenting with acute cough in primary care between March and September 2012. The frequency of POC CRP testing and the proportion of prescribed antibiotics were compared between recruited and non-recruited patients. As measure of bias, odds ratios (ORs) with accompanying 95% confidence intervals (CIs) for the association between CRP level (<20 mg/l or not) and antibiotic prescribing were computed. RESULTS: Of all 1473 eligible patients 348 (24%) were recruited. In recruited patients, POC CRP tests were conducted and antibiotics prescribed more frequently as compared to non-recruited patients (81% versus 6% and 44% versus 29%, respectively). The ORs were 18.2 (95%CI: 9.6-34.3), 30.5 (95%CI: 13.2-70.3) and 3.8 (95%CI: 0.9-14.8) respectively in all eligible patients, the recruited and the non-recruited patients. CONCLUSION: Selective recruitment resulted in an overestimation of POC CRP test use and antibiotic prescribing.

External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection: An Individual Patient Data Meta-Analysis.

BACKGROUND: Pneumonia remains difficult to diagnose in primary care. Prediction models based on signs and symptoms (S&S) serve to minimize the diagnostic uncertainty. External validation of these models is essential before implementation into routine practice. In this study all published S&S models for prediction of pneumonia in primary care were externally validated in the individual patient data (IPD) of previously performed diagnostic studies. METHODS AND FINDINGS: S&S models for diagnosing pneumonia in adults presenting to primary care with lower respiratory tract infection and IPD for validation were identified through a systematical search. Six prediction models and IPD of eight diagnostic studies (N total = 5308, prevalence pneumonia 12%) were included. Models were assessed on discrimination and calibration. Discrimination was measured using the pooled Area Under the Curve (AUC) and delta AUC, representing the performance of an individual model relative to the average dataset performance. Prediction models by van Vugt et al. and Heckerling et al. demonstrated the highest pooled AUC of 0.79 (95% CI 0.74-0.85) and 0.72 (0.68-0.76), respectively. Other models by Diehr et al., Singal et al., Melbye et al., and Hopstaken et al. demonstrated pooled AUCs of 0.65 (0.61-0.68), 0.64 (0.61-0.67), 0.56 (0.49-0.63) and 0.53 (0.5-0.56), respectively. A similar ranking was present based on the delta AUCs of the models. Calibration demonstrated close agreement of observed and predicted probabilities in the models by van Vugt et al. and Singal et al., other models lacked such correspondence. The absence of predictors in the IPD on dataset level hampered a systematical comparison of model performance and could be a limitation to the study. CONCLUSIONS: The model by van Vugt et al. demonstrated the highest discriminative accuracy coupled with reasonable to good calibration across the IPD of different study populations. This model is therefore the main candidate for primary care use.

Diagnostic properties of C-reactive protein for detecting pneumonia in children.

BACKGROUND: The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED). METHODS: In this cross-sectional study, data were retrospectively collected from children presenting with suspected pneumonia at the ED of Antonius Hospital Nieuwegein in The Netherlands between January 2007 and January 2012. Diagnostic outcome was pneumonia yes/no according to independent radiologist. (Un)adjusted association between CRP level and pneumonia and diagnostic value of CRP were calculated. RESULTS: Of 687 presenting children, 286 underwent both CRP measurement and chest radiography. 148 had pneumonia (52%). The proportion of pneumonia increased with CRP level. Negative predictive values declined, but positive predictive values increased with higher CRP thresholds. Univariable odds ratio for the association between CRP level and pneumonia was 1.2 (95% CI 1.11-1.21) per 10 mg/L increase. After adjustment for baseline characteristics CRP level remained associated with pneumonia. CONCLUSIONS: CRP level has independent diagnostic value for pneumonia in children presenting at the ED with suspected pneumonia, but low levels do not exclude pneumonia in this setting. These results prompt evaluation of CRP in primary care children with LRTI.