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

Author

Minnaard, Margaretha C, de Groot, Joris AH, Hopstaken, Rogier M, Schierenberg, Alwin, de Wit, Niek J, Reitsma, Johannes B, Broekhuizen, Berna DL, van Vugt, Saskia F, Neven, Arie Knuistingh, Graffelman, Aleida W, Melbye, Hasse, Rainer, Timothy H, Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert-Jan, van de Pol, Alma C, and Verheij, Theo JM

Subjects
Infectious Diseases, Pneumonia, Lung, Clinical Research, Pneumonia & Influenza, 4.2 Evaluation of markers and technologies, 7.3 Management and decision making, Detection, screening and diagnosis, Management of diseases and conditions, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundC-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.MethodsWe 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.ResultsAuthors 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%.InterpretationAdding 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.

Published
2017

4. Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort

Author

Infection & Immunity, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, UMC Utrecht Holding, HEE, MS Interne Geneeskunde, Child Health, JC onderzoeksprogramma Methodologie, Loots, Feike J., van der Meulen, Miriam P., Smits, Marleen, Hopstaken, Rogier M., de Bont, Eefje Gpm, van Bussel, Bas Ct, Latten, Gideon Hp, Oosterheert, Jan Jelrik, van Zanten, Arthur Rh, Verheij, Theo Jm, Frederix, Geert Wj, Infection & Immunity, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, UMC Utrecht Holding, HEE, MS Interne Geneeskunde, Child Health, JC onderzoeksprogramma Methodologie, Loots, Feike J., van der Meulen, Miriam P., Smits, Marleen, Hopstaken, Rogier M., de Bont, Eefje Gpm, van Bussel, Bas Ct, Latten, Gideon Hp, Oosterheert, Jan Jelrik, van Zanten, Arthur Rh, Verheij, Theo Jm, and Frederix, Geert Wj

Published
2024

5. Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort

Author

Loots, Feike J, primary, van der Meulen, Miriam P, additional, Smits, Marleen, additional, Hopstaken, Rogier M, additional, de Bont, Eefje GPM, additional, van Bussel, Bas CT, additional, Latten, Gideon HP, additional, Oosterheert, Jan Jelrik, additional, van Zanten, Arthur RH, additional, Verheij, Theo JM, additional, and Frederix, Geert WJ, additional

Published
2024
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6. External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection: An Individual Patient Data Meta-Analysis

Author

Schierenberg, Alwin, Minnaard, Margaretha C, Hopstaken, Rogier M, van de Pol, Alma C, Broekhuizen, Berna DL, de Wit, Niek J, Reitsma, Johannes B, van Vugt, Saskia F, Graffelman, Aleida W, Melbye, Hasse, Rainer, Timothy H, Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert-Jan, de Groot, Joris AH, and Verheij, Theo JM

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pneumonia, Clinical Research, Lung, Pneumonia & Influenza, Management of diseases and conditions, 7.3 Management and decision making, Area Under Curve, Calibration, Databases as Topic, Humans, Models, Biological, Primary Health Care, Probability, ROC Curve, Reproducibility of Results, General Science & Technology
Abstract

BackgroundPneumonia 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 findingsS&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.ConclusionsThe 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.

Published
2016

9. Cost-effectiveness and return-on-investment of C-reactive protein point-of-care testing in comparison with usual care to reduce antibiotic prescribing for lower respiratory tract infections in nursing homes: a cluster randomised trial

Author

Boere, Tjarda M, primary, El Alili, Mohamed, additional, van Buul, Laura W, additional, Hopstaken, Rogier M, additional, Verheij, Theo J M, additional, Hertogh, Cees M P M, additional, van Tulder, Maurits W, additional, and Bosmans, Judith E, additional

Published
2022
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11. New clinical prediction model for early recognition of sepsis in adult primary care patients: a prospective diagnostic cohort study of development and external validation

Author

Loots, Feike J, Smits, Marleen, Hopstaken, Rogier M, Jenniskens, Kevin, Schroeten, Fleur H, van den Bruel, Ann, van de Pol, Alma C, Oosterheert, Jan Jelrik, Bouma, Hjalmar, Little, Paul, Moore, Michael, van Delft, Sanne, Rijpsma, Douwe, Holkenborg, Joris, van Bussel, Bas CT, Laven, Ralph, Bergmans, Dennis CJJ, Hoogerwerf, Jacobien J, Latten, Gideon HP, de Bont, Eefje GPM, Giesen, Paul, den Harder, Annemarie, Kusters, Ron, van Zanten, Arthur RH, Verheij, Theo JM, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), MUMC+: MA Medische Staf IC (9), RS: CAPHRI - R5 - Optimising Patient Care, Intensive Care, MUMC+: MA Arts Assistenten IC (9), RS: NUTRIM - R2 - Liver and digestive health, and Family Medicine

Subjects
general practice, Aquacultuur en Visserij, diagnosis, INTERNATIONAL CONSENSUS DEFINITIONS, PERFORMANCE, GUIDELINES, clinical decision rule, Nutritional Biology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], vital signs, sepsis, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Aquaculture and Fisheries, after-hours care, SCORE, Life Science, CAMPAIGN, ORGAN FAILURE
Abstract

BACKGROUND: Recognising patients who need immediate hospital treatment for sepsis while simultaneously limiting unnecessary referrals is challenging for GPs. AIM: To develop and validate a sepsis prediction model for adult patients in primary care. DESIGN AND SETTING: This was a prospective cohort study in four out-of-hours primary care services in the Netherlands, conducted between June 2018 and March 2020. METHOD: Adult patients who were acutely ill and received home visits were included. A total of nine clinical variables were selected as candidate predictors, next to the biomarkers C-reactive protein, procalcitonin, and lactate. The primary endpoint was sepsis within 72 hours of inclusion, as established by an expert panel. Multivariable logistic regression with backwards selection was used to design an optimal model with continuous clinical variables. The added value of the biomarkers was evaluated. Subsequently, a simple model using single cut-off points of continuous variables was developed and externally validated in two emergency department populations. RESULTS: A total of 357 patients were included with a median age of 80 years (interquartile range 71-86), of which 151 (42%) were diagnosed with sepsis. A model based on a simple count of one point for each of six variables (aged >65 years; temperature >38°C; systolic blood pressure ≤110 mmHg; heart rate >110/min; saturation ≤95%; and altered mental status) had good discrimination and calibration (C-statistic of 0.80 [95% confidence interval = 0.75 to 0.84]; Brier score 0.175). Biomarkers did not improve the performance of the model and were therefore not included. The model was robust during external validation. CONCLUSION: Based on this study's GP out-of-hours population, a simple model can accurately predict sepsis in acutely ill adult patients using readily available clinical parameters. ispartof: BRITISH JOURNAL OF GENERAL PRACTICE vol:72 issue:719 pages:E437-E445 ispartof: location:England status: published

Published
2022

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

Author

Minnaard, Margaretha C., de Groot, Joris A.H., Hopstaken, Rogier M., Schierenberg, Alwin, de Wit, Niek J., Reitsma, Johannes B., Broekhuizen, Berna D.L., van Vugt, Saskia F., Neven, Arie Knuistingh, Graffelman, Aleida W., Melbye, Hasse, Rainer, Timothy H., Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert-Jan, van de Pol, Alma C., and Verheij, Theo J.M.

Subjects
Bacterial pneumonia -- Analysis -- Diagnosis, Decision-making -- Analysis -- Health aspects, Pneumonia -- Analysis -- Diagnosis, C-reactive protein -- Analysis -- Health aspects, Health
Abstract

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 (CRP) is an acute phase protein synthesized by hepatocytes. Serum concentrations rise above 5 mg/L about 6 hours after a stimulus, with a peak after 48 hours. (1) [...]

Published
2017
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15. The accuracy and feasibility of respiratory rate measurements in acutely ill adult patients by GPs : a mixed-methods study

Author

Loots, Feike J., Dekker, Irma, Wang, Ruo Chen, van Zanten, Arthur R.H., Hopstaken, Rogier M., Verheij, Theo J.M., Giesen, Paul, Smits, Marleen, Loots, Feike J., Dekker, Irma, Wang, Ruo Chen, van Zanten, Arthur R.H., Hopstaken, Rogier M., Verheij, Theo J.M., Giesen, Paul, and Smits, Marleen

Abstract

Background: Tachypnoea in acutely ill patients can be an early sign of a life-threatening condition such as sepsis. Routine measurement of the respiratory rate by GPs might improve the recognition of sepsis. Aim: To assess the accuracy and feasibility of respiratory rate measurements by GPs. Design & setting: Observational cross-sectional mixed-methods study in the setting of out-of-hours (OOH) home visits at three GP cooperatives in The Netherlands. Method: GPs were observed during the assessment of acutely ill patients, and semi-structured interviews were performed. The GP-assessed respiratory rate was compared with a reference measurement. In the event that the respiratory rate was not counted, GPs were asked to estimate the rate (dichotomised as ≥22 breaths per minute or <22 breaths per minute). Results: Observations of 130 acutely ill patients were included, and 14 GPs were interviewed. In 33 patients (25%), the GP counted the respiratory rate. A mean difference of 0.27 breaths per minute (95% confidence interval [CI] = -5.7 to 6.3) with the reference measurement was found. At a cut-off point of ≥22 breaths per minute, a sensitivity of 86% (95% CI = 57% to 98%) was found when the GP counted the rate, and a sensitivity of 43% (95% CI = 22% to 66%) when GPs estimated respiratory rates. GPs reported both medical and practical reasons for not routinely measuring the respiratory rate. Conclusion: GPs are aware of the importance of assessing the respiratory rate of acutely ill adult patients, and counted measurements are accurate. However, in most patients the respiratory rate was not counted, and the rate was often underestimated when estimated.

Published
2022

16. Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis : A Prospective Cohort Study in Out-Of-Hours Primary Care

Author

Loots, Feike J., Smits, Marleen, Jenniskens, Kevin, van Zanten, Arthur R.H., Kusters, Ron, Verheij, Theo J.M., Hopstaken, Rogier M., Loots, Feike J., Smits, Marleen, Jenniskens, Kevin, van Zanten, Arthur R.H., Kusters, Ron, Verheij, Theo J.M., and Hopstaken, Rogier M.

Abstract

BACKGROUND: Point-of-care testing (POCT) has shown promising results in the primary care setting to improve antibiotic therapy in respiratory tract infections and it might also aid general practitioners (GPs) to decide if patients should be referred to a hospital in cases of suspected sepsis. We aimed to assess whether biomarkers with possible POCT use can improve the recognition of sepsis in adults in the primary care setting. METHODS: We prospectively included adult patients with suspected severe infections during out-of-hours home visits. Relevant clinical signs and symptoms were recorded, as well as the biomarkers C-reactive protein, lactate, procalcitonin, high-sensitive troponin I, N-terminal pro b-type natriuretic peptide, creatinine, urea, and pancreatic stone protein. We used a POCT device for lactate only, and the remaining biomarkers were measured in a laboratory from stored blood samples. The primary outcome was sepsis within 72 h of inclusion. The potential of biomarkers to either rule in or rule out sepsis was tested for individual biomarkers combined with a model consisting of signs and symptoms. Net reclassification indices were also calculated. RESULTS: In total, 336 patients, with a median age of 80 years, were included. One hundred forty-one patients (42%) were diagnosed with sepsis. The C statistic for the model with clinical symptoms and signs was 0.84 (95% CI 0.79-0.88). Both lactate and procalcitonin increased the C statistic to 0.85, but none of the biomarkers significantly changed the net reclassification index. CONCLUSIONS: We do not advocate the routine use of POCT in general practice for any of the tested biomarkers of suspected sepsis.

Published
2022

17. Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis: A Prospective Cohort Study in Out-Of-Hours Primary Care

Author

HAG Infectieziekten, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Methoden Team 5, Loots, Feike J., Smits, Marleen, Jenniskens, Kevin, van Zanten, Arthur R.H., Kusters, Ron, Verheij, Theo J.M., Hopstaken, Rogier M., HAG Infectieziekten, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Methoden Team 5, Loots, Feike J., Smits, Marleen, Jenniskens, Kevin, van Zanten, Arthur R.H., Kusters, Ron, Verheij, Theo J.M., and Hopstaken, Rogier M.

Published
2022

18. New clinical prediction model for early recognition of sepsis in adult primary care patients: a prospective diagnostic cohort study of development and external validation

Author

Infection & Immunity, JC onderzoeksprogramma Infectieziekten, HAG Infectieziekten, Epi Methoden Team 5, Huisartsopleiding, MS Interne Geneeskunde, Onderzoek Beeld, Loots, Feike J., Smits, Marleen, Hopstaken, Rogier M., Jenniskens, Kevin, Schroeten, Fleur H., Van Den Bruel, Ann, Van De Pol, Alma C., Oosterheert, Jan Jelrik, Bouma, Hjalmar, Little, Paul, Moore, Michael, Van Delft, Sanne, Rijpsma, Douwe, Holkenborg, Joris, Van Bussel, Bas C.T., Laven, Ralph, Bergmans, Dennis C.J.J., Hoogerwerf, Jacobien J., Latten, Gideon H.P., De Bont, Eefje G.P.M., Giesen, Paul, Den Harder, Annemarie, Kusters, Ron, Van Zanten, Arthur R.H., Verheij, Theo J.M., Infection & Immunity, JC onderzoeksprogramma Infectieziekten, HAG Infectieziekten, Epi Methoden Team 5, Huisartsopleiding, MS Interne Geneeskunde, Onderzoek Beeld, Loots, Feike J., Smits, Marleen, Hopstaken, Rogier M., Jenniskens, Kevin, Schroeten, Fleur H., Van Den Bruel, Ann, Van De Pol, Alma C., Oosterheert, Jan Jelrik, Bouma, Hjalmar, Little, Paul, Moore, Michael, Van Delft, Sanne, Rijpsma, Douwe, Holkenborg, Joris, Van Bussel, Bas C.T., Laven, Ralph, Bergmans, Dennis C.J.J., Hoogerwerf, Jacobien J., Latten, Gideon H.P., De Bont, Eefje G.P.M., Giesen, Paul, Den Harder, Annemarie, Kusters, Ron, Van Zanten, Arthur R.H., and Verheij, Theo J.M.

Published
2022

22. Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis: A Prospective Cohort Study in Out-Of-Hours Primary Care .

Author

Loots, Feike J, Smits, Marleen, Jenniskens, Kevin, van Zanten, Arthur R H, Kusters, Ron, Verheij, Theo J M, and Hopstaken, Rogier M

Subjects
SEPSIS, TROPONIN I, RESPIRATORY infections, COHORT analysis, PEPTIDES, LONGITUDINAL method
Abstract

Background: Point-of-care testing (POCT) has shown promising results in the primary care setting to improve antibiotic therapy in respiratory tract infections and it might also aid general practitioners (GPs) to decide if patients should be referred to a hospital in cases of suspected sepsis. We aimed to assess whether biomarkers with possible POCT use can improve the recognition of sepsis in adults in the primary care setting. Methods: We prospectively included adult patients with suspected severe infections during out-of-hours home visits. Relevant clinical signs and symptoms were recorded, as well as the biomarkers C-reactive protein, lactate, procalcitonin, high-sensitive troponin I, N-terminal pro b-type natriuretic peptide, creatinine, urea, and pancreatic stone protein. We used a POCT device for lactate only, and the remaining biomarkers were measured in a laboratory from stored blood samples. The primary outcome was sepsis within 72 h of inclusion. The potential of biomarkers to either rule in or rule out sepsis was tested for individual biomarkers combined with a model consisting of signs and symptoms. Net reclassification indices were also calculated. Results: In total, 336 patients, with a median age of 80 years, were included. One hundred forty-one patients (42%) were diagnosed with sepsis. The C statistic for the model with clinical symptoms and signs was 0.84 (95% CI 0.79–0.88). Both lactate and procalcitonin increased the C statistic to 0.85, but none of the biomarkers significantly changed the net reclassification index. Conclusions: We do not advocate the routine use of POCT in general practice for any of the tested biomarkers of suspected sepsis. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial

Author

Postgraduate Huisartsgeneeskunde, HAG Infectieziekten, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Boere, Tjarda M., Van Buul, Laura W., Hopstaken, Rogier M., Veenhuizen, Ruth B., Van Tulder, Maurits W., Cals, Jochen W.L., Verheij, Theo J.M., Hertogh, Cees M.P.M., Postgraduate Huisartsgeneeskunde, HAG Infectieziekten, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Boere, Tjarda M., Van Buul, Laura W., Hopstaken, Rogier M., Veenhuizen, Ruth B., Van Tulder, Maurits W., Cals, Jochen W.L., Verheij, Theo J.M., and Hertogh, Cees M.P.M.

Published
2020

32. Improving management of patients with acute cough by C-reactive protein point of care testing and communication training (IMPAC3T): study protocol of a cluster randomised controlled trial

Author

Severens Johan L, Hood Kerenza, Butler Christopher C, Hopstaken Rogier M, Cals Jochen WL, and Dinant Geert-Jan

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Most antibiotic prescriptions for acute cough due to lower respiratory tract infections (LRTI) in primary care are not warranted. Diagnostic uncertainty and patient expectations and worries are major drivers of unnecessary antibiotic prescribing. A C-reactive protein (CRP) point of care test may help GPs to better guide antibiotic treatment by ruling out pneumonia in cases of low test results. Alternatively, enhanced communication skills training to help clinicians address patients' expectations and worries could lead to a decrease in antibiotic prescribing, without compromising clinical recovery, while enhancing patient enablement. The aim of this paper is to describe the design and methods of a study to assess two interventions for improving LRTI management in general practice. Methods/Design This cluster randomised controlled, factorial trial will introduce two interventions in general practice; point of care CRP testing and enhanced communication skills training for LRTI. Twenty general practices with two participating GPs per practice will recruit 400 patients with LRTI during two winter periods. Patients will be followed up for at least 28 days. The primary outcome measure is the antibiotic prescribing rate. Secondary outcomes are clinical recovery, cost-effectiveness, use of other diagnostic tests and medical services (including reconsultation), and patient enablement. Discussion This trial is the first cluster randomised trial to evaluate the influence of point of care CRP testing in the hands of the general practitioner and enhanced communication skills, on the management of LRTI in primary care. The pragmatic nature of the study, which leaves treatment decisions up to the responsible clinicians, will enhance the applicability and generalisability of findings. The factorial design will allow conclusion to be made about the value of CRP testing on its own, communication skills training on its own, and the two combined. Evaluating a biomedical and communication based intervention ('hard' and 'soft' technologies) together in this way makes this trial unique in its field.

Published
2007
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33. Point-of-care C-reactive protein to assist in primary care management of children with suspected non-serious lower respiratory tract infection : a randomised controlled trial

Author

Schot, Marjolein Jc, Van den Bruel, Ann, Broekhuizen, Berna Dl, Cals, Jochen Wl, Noteboom, Eveline A, Balemans, Walter, Hopstaken, Rogier M, van Delft, Sanne, de Wit, Niek J, Verheij, Theo Jm, Schot, Marjolein Jc, Van den Bruel, Ann, Broekhuizen, Berna Dl, Cals, Jochen Wl, Noteboom, Eveline A, Balemans, Walter, Hopstaken, Rogier M, van Delft, Sanne, de Wit, Niek J, and Verheij, Theo Jm

Published
2018

35. Point-of-care C-reactive protein to assist in primary care management of children with suspected non-serious lower respiratory tract infection: a randomised controlled trial

Author

HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, HAG Oncologie, General Practice & Nursing Science, Child Health, Cancer, JC Overig onderzoek, Infection & Immunity, Schot, Marjolein Jc, Van den Bruel, Ann, Broekhuizen, Berna Dl, Cals, Jochen Wl, Noteboom, Eveline A, Balemans, Walter, Hopstaken, Rogier M, van Delft, Sanne, de Wit, Niek J, Verheij, Theo Jm, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, HAG Oncologie, General Practice & Nursing Science, Child Health, Cancer, JC Overig onderzoek, Infection & Immunity, Schot, Marjolein Jc, Van den Bruel, Ann, Broekhuizen, Berna Dl, Cals, Jochen Wl, Noteboom, Eveline A, Balemans, Walter, Hopstaken, Rogier M, van Delft, Sanne, de Wit, Niek J, and Verheij, Theo Jm

Published
2018

36. Diagnostic value of signs, symptoms and diagnostic tests for diagnosing pneumonia in ambulant children in developed countries: a systematic review

Author

HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, General Practice & Nursing Science, Child Health, Cancer, JC Overig onderzoek, Schot, Marjolein J C, Dekker, Anne R J, Giorgi, Wesley G, Hopstaken, Rogier M, de Wit, Niek J, Verheij, Theo J M, Cals, Jochen W L, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, General Practice & Nursing Science, Child Health, Cancer, JC Overig onderzoek, Schot, Marjolein J C, Dekker, Anne R J, Giorgi, Wesley G, Hopstaken, Rogier M, de Wit, Niek J, Verheij, Theo J M, and Cals, Jochen W L

Published
2018

38. Point-of-care C-reactive protein to assist in primary care management of children with suspected non-serious lower respiratory tract infection: a randomised controlled trial

Author

Schot, Marjolein JC, primary, Van den Bruel, Ann, additional, Broekhuizen, Berna DL, additional, Cals, Jochen WL, additional, Noteboom, Eveline A, additional, Balemans, Walter, additional, Hopstaken, Rogier M, additional, van Delft, Sanne, additional, de Wit, Niek J, additional, and Verheij, Theo JM, additional

Published
2018
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39. The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data

Author

HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, Epi Methoden Team 1, Circulatory Health, HAG Zorginnovatieonderzoek, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Epi Methoden Team 4, JC onderzoeksprogramma Methodologie, HAG Infectieziekten, Minnaard, Margaretha C., de Groot, Joris A H, Hopstaken, Rogier M, Schierenberg, Alwin, de Wit, Niek J, Reitsma, Johannes B, Broekhuizen, Berna D. L., de Vries-van Vugt, Saskia F., Knuistingh Neven, Arie, Graffelman, Aleida W, Melbye, Hasse, Rainer, Timothy H, Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert-Jan, van de Pol, Alma C, Verheij, Theo J M, HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, Epi Methoden Team 1, Circulatory Health, HAG Zorginnovatieonderzoek, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Epi Methoden Team 4, JC onderzoeksprogramma Methodologie, HAG Infectieziekten, Minnaard, Margaretha C., de Groot, Joris A H, Hopstaken, Rogier M, Schierenberg, Alwin, de Wit, Niek J, Reitsma, Johannes B, Broekhuizen, Berna D. L., de Vries-van Vugt, Saskia F., Knuistingh Neven, Arie, Graffelman, Aleida W, Melbye, Hasse, Rainer, Timothy H, Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert-Jan, van de Pol, Alma C, and Verheij, Theo J M

Published
2017

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

Author

Minnaard, Margaretha C., van de Pol, Alma C., Hopstaken, Rogier M., van Delft, Sanne, Broekhuizen, Berna D. L., Verheij, Theo J. M., de Wit, Niek J., Minnaard, Margaretha C., van de Pol, Alma C., Hopstaken, Rogier M., van Delft, Sanne, Broekhuizen, Berna D. L., Verheij, Theo J. M., and de Wit, Niek J.

Published
2016

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

Author

Minnaard, Margaretha C., van der Zand, Janna, van de Pol, Alma C., de Wit, Niek J., Schierenberg, Alwin, Hopstaken, Rogier M., van Delft, Sanne, Verheij, Theo J M, Broekhuizen, Berna D L, Minnaard, Margaretha C., van der Zand, Janna, van de Pol, Alma C., de Wit, Niek J., Schierenberg, Alwin, Hopstaken, Rogier M., van Delft, Sanne, Verheij, Theo J M, and Broekhuizen, Berna D L

Published
2016

43. External validation of prediction models for pneumonia in primary care patients with lower respiratory tract infection: An individual patient data meta-analysis

Author

HAG Zorginnovatieonderzoek, HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, HAG Infectieziekten, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Epi Methoden Team 4, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Methoden Team 1, Schierenberg, Alwin, Minnaard, Margaretha C., Hopstaken, Rogier M., van de Pol, Alma C, Broekhuizen, Berna D. L., De Wit, Niek J., Reitsma, Johannes B., de Vries-van Vugt, Saskia F., Graffelman, Aleida W., Melbye, Hasse, Rainer, Timothy H., Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert Jan, de Groot, Joris A H, Verheij, Theo J M, HAG Zorginnovatieonderzoek, HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, HAG Infectieziekten, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Epi Methoden Team 4, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Methoden Team 1, Schierenberg, Alwin, Minnaard, Margaretha C., Hopstaken, Rogier M., van de Pol, Alma C, Broekhuizen, Berna D. L., De Wit, Niek J., Reitsma, Johannes B., de Vries-van Vugt, Saskia F., Graffelman, Aleida W., Melbye, Hasse, Rainer, Timothy H., Steurer, Johann, Holm, Anette, Gonzales, Ralph, Dinant, Geert Jan, de Groot, Joris A H, and Verheij, Theo J M

Published
2016

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

Author

HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, HAG Infectieziekten, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Minnaard, Margaretha C., van de Pol, Alma C., Hopstaken, Rogier M., van Delft, Sanne, Broekhuizen, Berna D. L., Verheij, Theo J. M., de Wit, Niek J., HAG Onderzoek, HAG Child Health, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, HAG Infectieziekten, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, Child Health, Minnaard, Margaretha C., van de Pol, Alma C., Hopstaken, Rogier M., van Delft, Sanne, Broekhuizen, Berna D. L., Verheij, Theo J. M., and de Wit, Niek J.

Published
2016

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

Author

HAG Onderzoek, HAG Child Health, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, HAG Zorginnovatieonderzoek, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, Minnaard, Margaretha C., van der Zand, Janna, van de Pol, Alma C., de Wit, Niek J., Schierenberg, Alwin, Hopstaken, Rogier M., van Delft, Sanne, Verheij, Theo J M, Broekhuizen, Berna D L, HAG Onderzoek, HAG Child Health, General Practice & Nursing Science, Cancer, Brain, JC Overig onderzoek, HAG Zorginnovatieonderzoek, HAG Infectieziekten, JC onderzoeksprogramma Infectieziekten, Infection & Immunity, Minnaard, Margaretha C., van der Zand, Janna, van de Pol, Alma C., de Wit, Niek J., Schierenberg, Alwin, Hopstaken, Rogier M., van Delft, Sanne, Verheij, Theo J M, and Broekhuizen, Berna D L

Published
2016

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

Author

Minnaard, Margaretha C., primary, de Groot, Joris A.H., additional, Hopstaken, Rogier M., additional, Schierenberg, Alwin, additional, de Wit, Niek J., additional, Reitsma, Johannes B., additional, Broekhuizen, Berna D.L., additional, van Vugt, Saskia F., additional, Neven, Arie Knuistingh, additional, Graffelman, Aleida W., additional, Melbye, Hasse, additional, Rainer, Timothy H., additional, Steurer, Johann, additional, Holm, Anette, additional, Gonzales, Ralph, additional, Dinant, Geert-Jan, additional, van de Pol, Alma C., additional, and Verheij, Theo J.M., additional

Published
2016
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49. 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

Author

Minnaard, Margaretha C, van de Pol, AC, de Groot, JAH, de Wit, Niek J., Hopstaken, Rogier M, van Delft, Sanne, Goossens, Herman, Ieven, Margareta, Lammens, Christine, Little, Paul, Butler, Chris C, Broekhuizen, Berna D. L., Verheij, Theo J M, Minnaard, Margaretha C, van de Pol, AC, de Groot, JAH, de Wit, Niek J., Hopstaken, Rogier M, van Delft, Sanne, Goossens, Herman, Ieven, Margareta, Lammens, Christine, Little, Paul, Butler, Chris C, Broekhuizen, Berna D. L., and Verheij, Theo J M

Published
2015

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