Early experiences with quality-assured HbA1c and professional glucose point-of-care testing in general practice: a cross-sectional observational study among patients, nurses and doctors.

BACKGROUND: Point-of-care testing (POCT) is increasingly used in primary care. The rapid availability of the test result during the patient encounter increases the potential for patients and care providers to make a direct and joint decision on disease management. Our aim was to get insight into the first experiences of patients and healthcare professionals after introducing quality-controlled HbA1c and professional glucose POCT in diabetes care in their own general practices. METHODS: A cross-sectional observational study using paper questionnaires for patients, nurses and general practitioners (GPs) in 13 general practices in the Netherlands. HbA1c and professional glucose POCT was introduced after training and under day-to-day quality control. Patients filled in the questionnaire immediately after the test; nurses and GPs after a minimum period of three months from the starting date. Descriptive data analyses were performed. RESULTS: A total of 1551 fingerstick blood POC tests were performed (1126 HbA1c; 425 Glucose). For HbA1c POCT, 84 patients, 29 nurses and 11 GPs filled in the questionnaires. For professional glucose POCT, 30 patients, 17 nurses and 8 GPs responded. Response rates varied between 24 and 56%. Patients, nurses and GPs were generally (very) satisfied with the novel POC tests. Patients were most positive about the location (in the GPs' office) and execution of the POC test (by their own nurse), and the speed of the test result. Almost all nurses indicated to have sufficient knowledge and skills to perform the test. Both nurses and GPs had confidence in the test results and indicated they experienced a higher patient satisfaction than with regular blood tests. Perceived disadvantages were the time required to regularly calibrate the devices and the extension of the consultation time because of the test. Patients, nurses and GPs generally expressed they wanted to continue performing these POC tests in routine diabetes care. CONCLUSIONS: Patients, nurses and GPs expressed (very) positive first experiences after introducing HbA1c and professional glucose testing on two high-quality POCT devices in their own general practices. Further research, with a random selection procedure of practices and patients and in other regions and countries, is recommended to confirm these findings.

Analytical performance and user-friendliness of five novel point-of-care D-dimer assays.

D-dimer testing combined with a clinical assessment has become a standard pathway for ruling-out venous thromboembolism (VTE). Recently, novel Point-of-Care (POC) D-dimer assays have been introduced, enabling low-volume blood sampling for rapid exclusion of VTE in a one-step procedure. We assessed the analytical validity and user-friendliness of a set of these novel POC D-dimer assays, and compared the results with a standard laboratory assay. Plasma samples were run on our reference assay (STA-Liatest D-di PLUS®) and five POC assays: Nano-Checker 710®, AFIAS-1®; iChroma-II®; Standard F200® and Hipro AFS/1®). After evaluating imprecision, Pearson Product-Moment correlation coefficients were calculated, Passing Bablok regression was performed and Bland-Altman plots were generated. User-friendliness was evaluated using the System Usability Scale (SUS). A set of 238 plasma samples of patients clinically suspected of VTE in general practice was available for analysis. Only one POC D-dimer assay (Nano-Checker 710) demonstrated an insufficient degree of imprecision. Pearson correlation coefficients and mean biases ranged from 0.68 to 0.93 and -165 to -53 µg/L respectively, and concordance with our reference assay varied from 71.8% to 89.5% using a 500 µg/L cut-off point. While we found considerable variation in overall user-friendliness, most devices were judged easy to use. In view of our findings regarding analytical performance and user-friendliness, we consider most of the novel POC D-dimer assays can be used in settings outside of the laboratory such as general practice, combining the possibility of multi-testing with low-volume capillary blood sampling and processing times of less than 15 min.

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.

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.

International definition of a point-of-care test in family practice: a modified e-Delphi procedure.

Background: The use of point-of-care tests (POCTs) in family practice is increasing, and the term POCT is often used in medical literature and clinical practice. Yet, no widely supported definition by several professional fields exists. Objective: To reach consensus on an international definition of a POCT in family practice. Methods: We performed a modified international e-Delphi procedure of four rounds among expert panel members from different professional backgrounds-family practitioners, laboratory specialists, policymakers, researchers and manufacturers. Results: Of 27 panel members from seven different countries, 26 participated in all rounds. Most panel members were active in POCT research or policymaking and 70% worked in family medicine. After choosing important components, structuring of answers and feedback, the following definition was chosen as the best or second best definition by 81% of panel members: a point-of-care test in family practice is a test to support clinical decision making, which is performed by a qualified member of the practice staff nearby the patient and on any part of the patient's body or its derivatives, during or very close to the time of consultation, to help the patient and physician to decide upon the best suited approach, and of which the results should be known at the time of the clinical decision making. Conclusion: The definition emerging from this study can inform family practitioners, laboratory specialists, policymakers and manufacturers on the most widely supported and recognized definition and could act as a clear starting point for the organization and execution of professional point-of-care testing in family practice worldwide.

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 and user-friendliness of four commercially available point-of-care devices for C-reactive protein.

INTRODUCTION: Proper implementation of Point-of-Care testing (POCT) for C-reactive protein (CRP) in primary care can decrease the inappropriate use of antibiotics, thereby tackling the problem of growing antimicrobial resistance. OBJECTIVE: The analytical performance and user-friendliness of four POCT-CRP assays were evaluated: QuikRead go easy, LumiraDx, cobas b 101 and Afinion 2. MATERIALS AND METHODS: Imprecision was evaluated using plasma pools in addition to manufacturer-specific control material. Trueness was assessed by verification of traceability to ERM-DA474/IFCC in parallel to method comparison towards the central laboratory CRP method (cobas c 503) using i) retrospectively selected plasma samples (n = 100) and ii) prospectively collected capillary whole blood samples (n = 50). User-friendliness was examined using a questionnaire. RESULTS: Between-day imprecision on plasma pools varied from 4.5 % (LumiraDx) to 11.5 % (QuikRead). Traceability verification revealed no significant difference between cobas c 503 CRP results and the ERM-DA474/IFCC certified value. cobas b 101 and Afinion achieved the best agreement with the central laboratory method. LumiraDx and QuikRead revealed a negative mean difference, with LumiraDx violating the criterion of > 95 % of POCT-CRP-results within ± 20 % of the comparison method. Regarding user-friendliness, Afinion obtained the highest Likert-scores. CONCLUSION: The analytical performance and user-friendliness of POCT-CRP devices varies among manufacturers, emphasizing the need for quality assurance supervised by a central laboratory.

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).

Enhanced communication skills and C-reactive protein point-of-care testing for respiratory tract infection: 3.5-year follow-up of a cluster randomized trial.

PURPOSE: The purpose of the study was to assess the long-term effect of family physicians' use of C-reactive protein (CRP) point-of-care testing and/or physician training in enhanced communication skills on office visit rates and antibiotic prescriptions for patients with respiratory tract infections. METHODS: We conducted a 3.5-year follow-up of a pragmatic, factorial, cluster-randomized controlled trial; 379 patients (20 family practices in the Netherlands) who visited their family physician for acute cough were enrolled in the trial and had follow-up data available (88% of original trial cohort). Main outcome measures were the average number of episodes of respiratory tract infections for which patients visited their family physician per patient per year (PPPY), and the percentage of the episodes for which patients were treated with antibiotics during follow-up. RESULTS: The mean number of episodes of respiratory tract infections during follow-up was 0.40 PPPY in the CRP test group and 0.56 PPPY in the no CRP test group (P = .12). In the communication skills training group, there was a mean of 0.36 PPPY episodes of respiratory tract infections, and in the no training group the mean was 0.57 PPPY (P = .09). During follow-up 30.7% of all episodes of respiratory tract infection were treated with antibiotics in the CRP test group compared with 35.7% in the no test group (P = .36). Family physicians trained in communication skills treated 26.3% of all episodes of respiratory tract infection with antibiotics compared with 39.1% treated by family physicians without training in communication skills (P = .02) CONCLUSIONS: Family physicians' use of CRP point-of-care testing and/or training in enhanced communication skills did not significantly affect office visit rates related to respiratory tract infections. Patients who saw a family physician trained in enhanced communication skills were prescribed significantly fewer antibiotics during episodes of respiratory tract infection in the subsequent 3.5 years.

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.

Clinical decision rules in primary care: necessary investments for sustainable healthcare.

Clinical judgement in primary care is more often decisive than in the hospital. Clinical decision rules (CDRs) can help general practitioners facilitating the work-through of differentials that follows an initial suspicion, resulting in a concrete 'course of action': a 'rule-out' without further testing, a need for further testing, or a specific treatment. However, in daily primary care, the use of CDRs is limited to only a few isolated rules. In this paper, we aimed to provide insight into the laborious path required to implement a viable CDR. At the same time, we noted that the limited use of CDRs in primary care cannot be explained by implementation barriers alone. Through the case study of the Oudega rule for the exclusion of deep vein thrombosis, we concluded that primary care CDRs come out best if they are tailor-made, taking into consideration the specific context of primary health care. Current CDRs should be evaluated frequently, and future decision rules should anticipate the latest developments such as the use of point-of-care (POC) tests. Hence, such new powerful diagnostic CDRs could improve and expand the possibilities for patient-oriented primary care.

The Role of CRP POC Testing in the Fight against Antibiotic Overuse in European Primary Care: Recommendations from a European Expert Panel.

Tackling antibiotic resistance represents one of the major challenges in modern medicine, and limiting antibiotics' overuse represents the first step in this fight. Most antibiotics are prescribed in primary care settings, and lower respiratory tract infections (LRTIs) are one of the most common indications for their prescription. An expert panel conducted an extensive report on C-reactive protein point-of-care (CRP POC) testing in the evaluation of LRTIs and its usefulness to limit antibiotic prescriptions. The expert panel stated that CRP POC testing is a potentially useful tool to limit antibiotic prescriptions for LRTI in a community setting. CRP POC must be used in conjunction with other strategies such as improved communication skills and the use of other molecular POC testing. Potential barriers to the adoption of CRP POC testing are financial and logistical issues. Moreover, the efficacy in limiting antibiotic prescriptions could be hampered by the fact that, in some countries, patients may gain access to antibiotics even without a prescription. Through the realization of a better reimbursement structure, the inclusion in standardized procedures in local guidelines, and better patient education, CRP point-of-care testing can represent a cornerstone in the fight against antimicrobial resistance.

Guidance on C-reactive protein point-of-care testing and complementary strategies to improve antibiotic prescribing for adults with lower respiratory tract infections in primary care.

The world faces the threat of increasing antimicrobial resistance, and there is growing consensus that swift action must be taken to improve the rational use of antibiotics and increase the stewardship of antibiotics to safeguard this key resource in modern healthcare. This paper provides the perspective of an international group of experts on the role of C-reactive protein point-of-care testing (CRP POCT) and other complementary strategies to improve antibiotic stewardship in primary care, with regards to the diagnosis and treatment of adult patients presenting symptoms of lower respiratory tract infections (LRTIs). It provides guidance regarding the clinical assessment of symptoms in combination with C-reactive protein (CRP) results, at the point of care, to support the management decision, and discusses enhanced patient communication and delayed prescribing as complementary strategies to decrease the inappropriate use of antibiotics. Recommendation: CRP POCT should be promoted to improve the identification of adults presenting with symptoms of LRTIs in primary care who might gain additional benefit from antibiotic treatment. Appropriateness of antibiotic use can be maximized when CRP POCT is used together with complementary strategies such as enhanced communication skills training and delayed prescribing in addition to routine safety netting.

C-reactive protein point-of-care testing and complementary strategies to improve antibiotic stewardship in children with acute respiratory infections in primary care.

This paper provides the perspective of an international group of experts on the role of C-reactive protein (CRP) point-of-care testing (POCT) and complementary strategies such as enhanced communication skills training and delayed prescribing to improve antibiotic stewardship in the primary care of children presenting with an acute illness episode due to an acute respiratory tract infection (ARTI). To improve antibiotics prescribing decisions, CRP POCT should be considered to complement the clinical assessment of children (6 months to 14 years) presenting with an ARTI in a primary care setting. CRP POCT can help decide whether a serious infection can be ruled out, before deciding on further treatments or management, when clinical assessment is unconclusive. Based on the evidence currently available, a CRP value can be a valuable support for clinical reasoning and facilitate communication with patients and parents, but the clinical assessment should prevail when making a therapy or referral decision. Nearly half of children tested in the primary care setting can be expected to have a CRP value below 20 mg/l, in which case it is strongly suggested to avoid prescribing antibiotics when the clinical assessment supports ruling out a severe infection. For children with CRP values greater than or equal to 20 mg/l, additional measures such as additional diagnostic tests, observation time, re-assessment by a senior decision-maker, and specialty referrals, should be considered.

[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.

Performance of C-Reactive Protein, Procalcitonin, TAT Complex, and Factor VIII in Addition to D-Dimer in the Exclusion of Venous Thromboembolism in Primary Care Patients.

BACKGROUND: In primary care, D-dimer-combined with a clinical assessment-is recommended for ruling-out venous thromboembolism (VTE). However, D-dimer testing frequently yields false-positive results, notably in the elderly, and the search for novel biomarkers thus continues. We assessed the added diagnostic value of 4 promising laboratory tests. METHODS: Plasma samples from 256 primary care patients suspected of VTE were collected. We explored added value (beyond D-dimer) of C-reactive protein (CRP), procalcitonin (PCT), thrombin-antithrombin III complex (TAT-c), and factor VIII (FVIII). Diagnostic performance of these biomarkers was assessed univariably and by estimating their area under the receiver operating curve (AUC). Added diagnostic potential beyond D-dimer testing was assessed using multivariable logistic regression. RESULTS: Plasma samples of 237 VTE-suspected patients were available for analysis-36 patients (25%) confirmed deep vein thrombosis, 11 patients (12%) pulmonary embolism. Apart from D-dimer, only CRP, and FVIII levels appeared to be higher in patients with VTE compared to patients without VTE. The AUCs for these 3 markers were 0.76 (95% CI: 0.69-0.84) and 0.75 (95% CI: 0.68-0.83), respectively, whereas the AUC for D-dimer was 0.90 (95% CI: 0.86-0.94). Combining these biomarkers in a multivariable logistic model with D-dimer did not improve these AUCs meaningfully. CONCLUSIONS: In our dataset, we were unable to demonstrate any added diagnostic performance beyond D-dimer testing of novel biomarkers in patients suspected of VTE in primary care. As such, D-dimer testing appears to remain the best choice in the exclusion of clinically suspected VTE in this setting. TRIAL REGISTRATION: Netherlands Trial Register NL5974. (METC protocol number: 16-356/M; NL56475.041.16.).

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.