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).

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.

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.

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.

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.

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.

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.

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.).

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.

Respiratory tract infections (RTIs) in primary care: narrative review of C reactive protein (CRP) point-of-care testing (POCT) and antibacterial use in patients who present with symptoms of RTI.

Antimicrobial resistance (AMR) continues to be a global problem and continues to be addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. Patients who attend general (ambulatory) practice with symptoms of respiratory tract infections (RTIs) are invariably assessed by some sort of clinical decision rule (CDR). However, CDRs rely on a cluster of non-specific clinical observations. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) point-of-care testing (POCT) to guide antibacterial prescribing in adult patients presenting to general practitioner (GP) practices with symptoms of RTI. Studies that were included were Cochrane reviews, systematic reviews, randomised controlled trials, cluster randomised trials, controlled before and after studies, cohort studies and economic evaluations. An overwhelming number of studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces index antibacterial prescribing. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. With the rapid development of artificial intelligence, patients will expect greater precision in diagnosing and managing their illnesses. Adopting systems that markedly reduce antibiotic consumption is a no-brainer for governments that are struggling to address the rise in AMR.

Development of a clinical prediction rule for sepsis in primary care: protocol for the TeSD-IT study.

BACKGROUND: Early recognition and treatment of sepsis is crucial to prevent detrimental outcomes. General practitioners (GPs) are often the first healthcare providers to encounter seriously ill patients. The aim of this study is to assess the value of clinical information and additional tests to develop a clinical prediction rule to support early diagnosis and management of sepsis by GPs. METHODS: We will perform a diagnostic study in the setting of out-of-hours home visits in four GP cooperatives in the Netherlands. Acutely ill adult patients suspected of a serious infection will be screened for eligibility by the GP. The following candidate predictors will be prospectively recorded: (1) age, (2) body temperature, (3) systolic blood pressure, (4) heart rate, (5) respiratory rate, (6) peripheral oxygen saturation, (7) mental status, (8) history of rigors, and (9) rate of progression. After clinical assessment by the GP, blood samples will be collected in all patients to measure C-reactive protein, lactate, and procalcitonin. All patients will receive care as usual. The primary outcome is the presence or absence of sepsis within 72 h after inclusion, according to an expert panel. The need for hospital treatment for any indication will be assessed by the expert panel as a secondary outcome. Multivariable logistic regression will be used to design an optimal prediction model first and subsequently derive a simplified clinical prediction rule that enhances feasibility of using the model in daily clinical practice. Bootstrapping will be performed for internal validation of both the optimal model and simplified prediction rule. Performance of both models will be compared to existing clinical prediction rules for sepsis. DISCUSSION: This study will enable us to develop a clinical prediction rule for the recognition of sepsis in a high-risk primary care setting to aid in the decision which patients have to be immediately referred to a hospital and who can be safely treated at home. As clinical signs and blood samples will be obtained prospectively, near-complete data will be available for analyses. External validation will be needed before implementation in routine care and to determine in which pre-hospital settings care can be improved using the prediction rule. TRIAL REGISTRATION: The study is registered in the Netherlands Trial Registry (registration number NTR7026).