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

OBJECTIVES: To estimate the potential referral rate and cost impact at different cut-off points of a recently developed sepsis prediction model for general practitioners (GPs). DESIGN: Prospective observational study with decision tree modelling. SETTING: Four out-of-hours GP services in the Netherlands. PARTICIPANTS: 357 acutely ill adult patients assessed during home visits. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the cost per patient from a healthcare perspective in four scenarios based on different cut-off points for referral of the sepsis prediction model. Second, the number of hospital referrals for the different scenarios is estimated. The potential impact of referral of patients with sepsis on mortality and hospital admission was estimated by an expert panel. Using these study data, a decision tree with a time horizon of 1 month was built to estimate the referral rate and cost impact in case the model would be implemented. RESULTS: Referral rates at a low cut-off (score 2 or 3 on a scale from 0 to 6) of the prediction model were higher than observed for patients with sepsis (99% and 91%, respectively, compared with 88% observed). However, referral was also substantially higher for patients who did not need hospital assessment. As a consequence, cost-savings due to referral of patients with sepsis were offset by increased costs due to unnecessary referral for all cut-offs of the prediction model. CONCLUSIONS: Guidance for referral of adult patients with suspected sepsis in the primary care setting using any cut-off point of the sepsis prediction model is not likely to save costs. The model should only be incorporated in sepsis guidelines for GPs if improvement of care can be demonstrated in an implementation study. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7026).

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.

OBJECTIVES: C-reactive protein point-of-care testing (CRP POCT) is a promising diagnostic tool to guide antibiotic prescribing for lower respiratory tract infections (LRTI) in nursing home residents. This study aimed to evaluate cost-effectiveness and return-on-investment (ROI) of CRP POCT compared with usual care for nursing home residents with suspected LRTI from a healthcare perspective. DESIGN: Economic evaluation alongside a cluster randomised, controlled trial. SETTING: 11 Dutch nursing homes. PARTICIPANTS: 241 nursing home residents with a newly suspected LRTI. INTERVENTION: Nursing home access to CRP POCT (POCT-guided care) was compared with usual care without CRP POCT (usual care). MAIN OUTCOME MEASURES: The primary outcome measure for the cost-effectiveness analysis was antibiotic prescribing at initial consultation, and the secondary outcome was full recovery at 3 weeks. ROI analyses included intervention costs, and benefits related to antibiotic prescribing. Three ROI metrics were calculated: Net Benefits, Benefit-Cost-Ratio and Return-On-Investment. RESULTS: In POCT-guided care, total costs were on average €32 higher per patient, the proportion of avoided antibiotic prescribing was higher (0.47 vs 0.18; 0.30, 95% CI 0.17 to 0.42) and the proportion of fully recovered patients statistically non-significantly lower (0.86 vs 0.91; -0.05, 95% CI -0.14 to 0.05) compared with usual care. On average, an avoided antibiotic prescription was associated with an investment of €137 in POCT-guided care compared with usual care. Sensitivity analyses showed that results were relatively robust. Taking the ROI metrics together, the probability of financial return was 0.65. CONCLUSION: POCT-guided care effectively reduces antibiotic prescribing compared with usual care without significant effects on recovery rates, but requires an investment. Future studies should take into account potential beneficial effects of POCT-guided care on costs and health outcomes related to antibiotic resistance. TRIAL REGISTRATION NUMBER: NL5054.

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

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.

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

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.

[Antibiotics for non-severe, lower respiratory tract infections in children?] / Antibiotica bij hoestende kinderen?

Antibiotics are overprescribed for non-severe, lower respiratory tract infections (LRTI). A British general practice study shows that antibiotics do not shorten the duration of moderately bad symptoms in children presenting with presumed, uncomplicated LRTI. Important questions remain. The clinical diagnosis of pneumonia hampers badly. So who did the GPs dare to include for possible placebo treatment? The mean, normal body temperature, and the relatively high percentage of patients with an atopic background in the studied population may answer that question. Were antibiotics often prescribed for bronchial hyper reactivity instead of for actual infections? The low inclusion rate per GP suggests that this selected patient population has turned out to be different from the intended population. Tools that decrease diagnostic uncertainty and improve communication skills, combined with sincere compassion for the bothersome complaints probably help GPs, patients and their parents more to accept management without an antibiotic prescribed.

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

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.

Implementation and Use of Point-of-Care C-Reactive Protein Testing in Nursing Homes.

OBJECTIVES: This study evaluated logistics, process data, and barriers/facilitators for the implementation and use of C-reactive protein point-of-care testing (CRP POCT) for suspected lower respiratory tract infections (LRTIs) in nursing home (NH) residents. DESIGN: This process evaluation was performed alongside a cluster randomized, controlled trial (UPCARE study) to evaluate the effect of CRP POCT on antibiotic prescribing for suspected LRTIs in NH residents. SETTING AND PARTICIPANTS: Eleven NHs in the Netherlands. METHODS: Data sources for process data regarding intervention quality included a questionnaire among NH staff, logs, reports, and CRP POCT-analyzer records. Barriers and facilitators for implementation were assessed in focus group interviews with physicians and nurses from 3 NHs. RESULTS: Correct patient selection for CRP POCT and generally continued CRP POCT use indicated good fidelity. The initial training and training of new employees seemed to fit the need, but some POCT-user group sizes had increased over time, which could have impeded frequent use. Users were generally satisfied with CRP POCT and perceived its use feasible and relevant. Facilitators for implementation were initial commitment and active initiation, followed by continued attention and enthusiasm for building routine practice and trust. Short lines of communication between staff, short distance to the POCT-analyzer, 24/7 coverage of staff, and a clear task division facilitated continued attention and routine practice. CONCLUSIONS AND IMPLICATIONS: This process evaluation showed sufficient quality of providing CRP POCT in Dutch NHs. We processed findings of intervention quality and implementation knowledge into key recommendations for CRP POCT implementation in this setting. Future research could focus on CRP POCT use in countries with different organization of care in NHs.

Effect of C reactive protein point-of-care testing on antibiotic prescribing for lower respiratory tract infections in nursing home residents: cluster randomised controlled trial.

OBJECTIVE: To evaluate whether C reactive protein point-of-care testing (CRP POCT) safely reduces antibiotic prescribing for lower respiratory tract infections in nursing home residents. DESIGN: Pragmatic, cluster randomised controlled trial. SETTING: The UPCARE study included 11 nursing home organisations in the Netherlands. PARTICIPANTS: 84 physicians from 11 nursing home organisations included 241 participants with suspected lower respiratory tract infections from September 2018 to the end of March 2020. INTERVENTIONS: Nursing homes allocated to the intervention group had access to CRP POCT. The control group provided usual care without CRP POCT for patients with suspected lower respiratory tract infections. MAIN OUTCOME MEASURES: The primary outcome measure was antibiotic prescribing at initial consultation. Secondary outcome measures were full recovery at three weeks, changes in antibiotic management and additional diagnostics during follow-up at one week and three weeks, and hospital admission and all cause mortality at any point (initial consultation, one week, or three weeks). RESULTS: Antibiotics were prescribed at initial consultation for 84 (53.5%) patients in the intervention group and 65 (82.3%) in the control group. Patients in the intervention group had 4.93 higher odds (95% confidence interval 1.91 to 12.73) of not being prescribed antibiotics at initial consultation compared with the control group, irrespective of treating physician and baseline characteristics. The between group difference in antibiotic prescribing at any point from initial consultation to follow-up was 23.6%. Differences in secondary outcomes between the intervention and control groups were 4.4% in full recovery rates at three weeks (86.4% v 90.8%), 2.2% in all cause mortality rates (3.5% v 1.3%), and 0.7% in hospital admission rates (7.2% v 6.5%). The odds of full recovery at three weeks, and the odds of mortality and hospital admission at any point did not significantly differ between groups. CONCLUSIONS: CRP POCT for suspected lower respiratory tract infection safely reduced antibiotic prescribing compared with usual care in nursing home residents. The findings suggest that implementing CRP POCT in nursing homes might contribute to reduced antibiotic use in this setting and help to combat antibiotic resistance. TRIAL REGISTRATION: Netherlands Trial Register NL5054.

Vital signs of the systemic inflammatory response syndrome in adult patients with acute infections presenting in out-of-hours primary care: A cross-sectional study.

BACKGROUND: Signs of the systemic inflammatory response syndrome (SIRS) - fever (or hypothermia), tachycardia and tachypnoea - are used in the hospital setting to identify patients with possible sepsis. OBJECTIVES: To determine how frequently abnormalities in the vital signs of SIRS are present in adult out-of-hours (OOH) primary care patients with suspected infections and assess the association with acute hospital referral. METHODS: We conducted a cross-sectional study at the OOH GP cooperative in Nijmegen, the Netherlands, between August and October 2015. GPs were instructed to record the body temperature, heart rate and respiratory rate of all patients with suspected acute infections. Vital signs of SIRS, other relevant signs and symptoms, and referral state were extracted from the electronic registration system of the OOH GP cooperative retrospectively. Logistic regression analysis was used to evaluate the association between clinical signs and hospital referral. RESULTS: A total of 558 patients with suspected infections were included. At least two SIRS vital signs were abnormal in 35/409 (8.6%) of the clinic consultations and 60/149 (40.3%) of the home visits. Referral rate increased from 13% when no SIRS vital sign was abnormal to 68% when all three SIRS vital signs were abnormal. Independent associations for referral were found for decreased oxygen saturation, hypotension and rapid illness progression, but not for individual SIRS vital signs. CONCLUSION: Although patients with abnormal vital signs of SIRS were referred more often, decreased oxygen saturation, hypotension and rapid illness progression seem to be most important for GPs to guide further management.

Point-of-Care Testing for D-Dimer in the Diagnosis of Venous Thromboembolism in Primary Care: A Narrative Review.

Venous thromboembolism (VTE) is regarded as a significant cause of mortality and disability, affecting 1-2 per 1000 people annually, presenting with a relatively wide range of symptoms, which can pose a diagnostic challenge. Historically, people in whom VTE is suspected will have been taken to hospital for diagnosis and treatment; however, a high proportion of patients are found not to have VTE. Concerns have been expressed about potential delays in treatment, with the risk of additional morbidity and disability, and death. Diagnostic strategies are typically based on the use of a clinical prediction rule to determine the pre-test probability, complemented with a measurement of D-dimer, with confirmation by imaging assessment. This narrative review explores the literature on the use of point-of-care testing (POCT) for the measurement of D-dimer, as part of a clinical decision rule, for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the primary care setting. In the two main prospective management (validation) studies that included D-dimer POCT or similar technologies, with a total cohort of 1600 participants, DVT was ruled out in 49% of patients, with a false negative rate of 1.4%, whereas PE was ruled out in 45% of patients, with a false negative rate of 1.5%. This suggests that uptake of POCT D-dimer in primary care has the potential to reduce the number of referrals to hospitals for imaging confirmatory investigation, with consequent cost savings. Thus, adopting POCT for D-dimer in primary care can offer clinical and cost benefits, particularly when quantitative POCT assays are being used. Furthermore, POCT should be undertaken in collaboration with the local laboratories to ensure the harmonisation of D-dimer methods and quality assurance to improve the diagnosis of VTE.

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.

BACKGROUND: Antibiotics are over-prescribed for lower respiratory tract infections (LRTI) in nursing home residents due to diagnostic uncertainty. Inappropriate antibiotic use is undesirable both on patient level, considering their exposure to side effects and drug interactions, and on societal level, given the development of antibiotic resistance. C-reactive protein (CRP) point-of-care testing (POCT) may be a promising diagnostic tool to reduce antibiotic prescribing for LRTI in nursing homes. The UPCARE study will evaluate whether the use of CRP POCT for suspected LRTI is (cost-) effective in reducing antibiotic prescribing in the nursing home setting. METHODS/DESIGN: A cluster randomized controlled trial will be conducted in eleven nursing homes in the Netherlands, with the nursing home as the unit of randomization. Residents with suspected LRTI who reside at a psychogeriatric, somatic, or geriatric rehabilitation ward are eligible for study participation. Nursing homes in the intervention group will provide care as usual with the possibility to use CRP POCT, and the control group will provide care as usual without CRP POCT for residents with (suspected) LRTI. Data will be collected from September 2018 for approximately 1.5 year, using case report forms that are integrated in the electronic patient record system. The primary study outcome is antibiotic prescribing for suspected LRTI at index consultation (yes/no). DISCUSSION: This is the first randomised trial to evaluate the effect of nursing home access to and training in the use of CRP POCT on antibiotic prescribing for LRTI, yielding high-level evidence and contributing to antibiotic stewardship in the nursing home setting. The relatively broad inclusion criteria and the pragmatic study design add to the applicability and generalizability of the study results. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5054. Registered 29 August 2018.

[Lower respiratory tract infections unravelled]. / Onderste-luchtweginfecties uitgeplozen.

Global initiatives to tackle the rise of antimicrobial resistance highlight the need to invest in the development and use of new, rapid diagnostic tools in routine patient care to differentiate bacterial from viral infections. Selective use may enhance antibiotic stewardship, but should be based on evidence for the target populations. The landmark study of Ieven et al. in 11 European countries describes the role of bacteria, viruses and mixed bacterial-viral infections in adults presenting with mostly non-severe lower respiratory tract infections in primary care. Viruses, particularly rhinoviruses, were much more frequent than bacterial pathogens. The authors conclude that their new findings support a restrictive approach to antibiotic prescribing. Better diagnostics for aetiology are advocated for use in primary care. This article discusses the impact of these new data on the already broadly shared views on antibiotic stewardship, including restrictive use of antibiotics in non-severe infections. The question is raised whether the possible benefits of broad implementation of specific, diagnostic tests for aetiology outweigh the possible harm in primary care. Proper consultation skills are key for differentiating one patient with a severe infection from the many non-severe infections. Treating patients, not diagnoses prevails.

Understanding the adoption and use of point-of-care tests in Dutch general practices using multi-criteria decision analysis.

BACKGROUND: The increasing number of available point-of-care (POC) tests challenges clinicians regarding decisions on which tests to use, how to efficiently use them, and how to interpret the results. Although POC tests may offer benefits in terms of low turn-around-time, improved patient's satisfaction, and health outcomes, only few are actually used in clinical practice. Therefore, this study aims to identify which criteria are, in general, important in the decision to implement a POC test, and to determine their weight. Two POC tests available for use in Dutch general practices (i.e. the C-reactive protein (CRP) test and the glycated haemoglobin (HbA1c) test) serve as case studies. The information obtained from this study can be used to guide POC test development and their introduction in clinical practice. METHODS: Relevant criteria were identified based on a literature review and semi-structured interviews with twelve experts in the field. Subsequently, the criteria were clustered in four groups (i.e. user, organization, clinical value, and socio-political context) and the relative importance of each criterion was determined by calculating geometric means as implemented in the Analytic Hierarchy Process. Of these twelve experts, ten participated in a facilitated group session, in which their priorities regarding both POC tests (compared to central laboratory testing) were elicited. RESULTS: Of 20 criteria in four clusters, the test's clinical utility, its technical performance, and risks (associated with the treatment decision based on the test result) were considered most important for using a POC test, with relative weights of 22.2, 12.6 and 8.5%, respectively. Overall, the experts preferred the POC CRP test over its laboratory equivalent, whereas they did not prefer the POC HbA1c test. This difference was mainly explained by their strong preference for the POC CRP test with regard to the subcriterion 'clinical utility'. CONCLUSIONS: The list of identified criteria, and the insights in their relative impact on successful implementation of POC tests, may facilitate implementation and use of existing POC tests in clinical practice. In addition, having experts score new POC tests on these criteria, provides developers with specific recommendations on how to increase the probability of successful implementation and use.

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.

BACKGROUND: Overprescription of antibiotics for lower respiratory tract infections (LRTIs) in children is common, partly due to diagnostic uncertainty, in which case the addition of point-of-care (POC) C-reactive protein (CRP) testing can be of aid. AIM: To assess whether use of POC CRP by the GP reduces antibiotic prescriptions in children with suspected non-serious LRTI. DESIGN & SETTING: An open, pragmatic, randomised controlled trial in daytime general practice and out-of-hours services. METHOD: Children between 3 months and 12 years of age with acute cough and fever were included and randomised to either use of POC CRP or usual care. Antibiotic prescription rates were measured and compared between groups using generalising estimating equations. RESULTS: There was no statistically significant reduction in antibiotic prescriptions in the GP use of CRP group (30.9% versus 39.4%; odds ratio [OR] 0.6; 95% confidence interval [CI] = 0.29 to 1.23). Only the estimated severity of illness was related to antibiotic prescription. Forty-six per cent of children had POC CRP levels <10mg/L. CONCLUSION: It is still uncertain whether POC CRP measurement in children with non-serious respiratory tract infection presenting to general practice can reduce the prescription of antibiotics. Until new research provides further evidence, POC CRP measurement in these children is not recommended.

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

Identifying a child with pneumonia in the large group of children with acute respiratory tract infections can be challenging for primary care physicians. Knowledge on the diagnostic value of specific signs and symptoms may guide future decision rules and guidelines for clinicians. We aimed to identify and systematically review available evidence for the diagnostic value of signs, symptoms, and additional tests to diagnose pneumonia in children in an ambulatory setting in developed countries. We conducted a systematic review, searching in the electronic databases of PubMed and Embase. Quality assessment of studies was done using the QUADAS-2 criteria. After data extraction from selected studies, we calculated and summarized test characteristics (sensitivity, specificity, negative and positive predictive values) of all available signs, symptoms, additional laboratory tests, and chest ultrasonography. The original search yielded 4665 records, of which 17 articles were eligible for analysis: 12 studies on signs and symptoms, 4 on additional laboratory tests, and 6 on ultrasonography. All included studies were performed in a secondary care setting. Risk of bias was present in the majority of studies in the domain of patient selection. Prevalence of pneumonia varied from 3.4% to 71.7%. The diagnostic value of the available 27 individual signs and symptoms to identify pneumonia was low. In a low prevalence setting, (4 studies, pneumonia prevalence <10%) clinically ill appearance of the child and oxygen saturation <94% can aid a physician. In a high prevalence setting (10 studies, pneumonia >10%), additional diagnostic tests such as oxygen saturation, C-reactive protein, and white blood cell count are more promising. Chest ultrasonography showed high diagnostic value in settings with higher prevalence of pneumonia. Single signs and symptoms from medical history and physical examination or individual additional diagnostic tests are insufficient to diagnose pneumonia in ambulant children. Very few diagnostic studies are conducted in settings with low prevalence of pneumonia. Future research in low prevalence settings should focus on the diagnostic value of the combination of clinical features and additional testing possibly using meta-analysis of individual data.

Management of sepsis in out-of-hours primary care: a retrospective study of patients admitted to the intensive care unit.

OBJECTIVES: Timely recognition and treatment of sepsis is essential to reduce mortality and morbidity. Acutely ill patients often consult a general practitioner (GP) as the first healthcare provider. During out-of-hours, GP cooperatives deliver this care in the Netherlands. The aim of this study is to explore the role of these GP cooperatives in the care for patients with sepsis. DESIGN: Retrospective study of patient records from both the hospital and the GP cooperative. SETTING: An intensive care unit (ICU) of a general hospital in the Netherlands, and the colocated GP cooperative serving 260 000 inhabitants. PARTICIPANTS: We used data from 263 patients who were admitted to the ICU due to community-acquired sepsis between January 2011 and December 2015. MAIN OUTCOME MEASURES: Contact with the GP cooperative within 72 hours prior to hospital admission, type of contact, delay from the contact until hospital arrival, GP diagnosis, initial vital signs and laboratory values, and hospital mortality. RESULTS: Of 263 patients admitted to the ICU, 127 (48.3%) had prior GP cooperative contacts. These contacts concerned home visits (59.1%), clinic consultations (18.1%), direct ambulance deployment (12.6%) or telephone advice (10.2%). Patients assessed by a GP were referred in 64% after the first contact. The median delay to hospital arrival was 1.7 hours. The GP had not suspected an infection in 43% of the patients. In this group, the in-hospital mortality rate was significantly higher compared with patients with suspected infections (41.9% vs 17.6%). Mortality difference remained significant after correction for confounders. CONCLUSION: GP cooperatives play an important role in prehospital management of sepsis and recognition of sepsis in this setting proved difficult. Efforts to improve management of sepsis in out-of-hours primary care should not be limited to patients with a suspected infection, but also include severely ill patients without clear signs of infection.

Recognition of sepsis in primary care: a survey among GPs.

BACKGROUND: Early recognition and treatment of sepsis are important to reduce morbidity and mortality. Screening tools using vital signs are effective in emergency departments. It is not known how the decision to refer a patient to the hospital with a possible serious infection is made in primary care. AIM: To gain insight into the clinical decision-making process of GPs in patients with possible sepsis infections. DESIGN & SETTING: Survey among a random sample of 800 GPs in the Netherlands. METHOD: Quantitative questionnaire using Likert scales. RESULTS: One hundred and sixty (20.3%) of questionnaires were eligible for analysis. Based on self-reported cases of possible serious infections, the factors most often indicated as important for the decision to refer patients to the hospital were: general appearance (94.1%), gut feeling (92.1%), history (92.0%), and physical examination (89.3%). Temperature (88.7%), heart rate (88.7%), and blood pressure (82.1%), were the most frequently measured vital signs. In general, GPs more likely referred patients in case of: altered mental status (98.7%), systolic blood pressure <100 mmHg (93.7%), unable to stand (89.3%), insufficient effect of previous antibiotic treatment (87.4%), and respiratory rate ≥22/minute (86.1%). CONCLUSION: The GPs' assessment of patients with possible serious infection is a complex process, in which besides checking vital signs, many other aspects of the consultation guide the decision to refer a patient to the hospital. To improve care for patients with sepsis, the diagnostic and prognostic value of assessing the vital signs and symptoms, GPs' gut feeling, and additional diagnostic tests, should be prospectively studied in the primary care setting.

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.

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.

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.