Evidence for using point-of-care diagnostics in the management of respiratory tract infections in primary care: a scoping review protocol

Background: Antimicrobial resistance (AmR) is widely considered a global health threat and is associated with significant morbidity, mortality and costs. Inappropriate antimicrobial use is the most important modifiable risk factor for AmR. Most human antimicrobial medicines use occurs in primary care [prescribed by general practitioners (GPs), dispensed by community pharmacists (CPs)]. However, up to 50% of use is deemed inappropriate. Point-of-care diagnostic tests are used as a basis for antimicrobial stewardship interventions to improve the diagnostic certainty of respiratory tract infections (RTIs), and therefore ensure prudent antimicrobial use. However, there is a lack of guidance on their use, and they are therefore not routinely used in clinical practice. Objective: A scoping review will be conducted to synthesise the available evidence to inform the development of best practice guidance for using point-of-care diagnostics in the management of RTIs in primary care. Methods: A scoping review will be conducted following guidance from the Joanna Briggs Institute (JBI) and reported using the PRISMA-ScR guidelines. Databases including Web of Science, MEDLINE, CINAHL, EMBASE, the International HTA database and the Cochrane Central Register of Controlled Trials, as well as grey literature, will be searched. Screening will be undertaken independently by two reviewers to identify studies and literature reporting the use of point-of-care diagnostics in the management of RTIs in primary care by GPs and/ or CPs. Findings will be described using narrative synthesis. Conclusion: The findings of this scoping review will be used to produce draft guidance on the use of point-of-care diagnostic tests in primary care, which will undergo further development using a Delphi consensus methodology involving experts in the field of RTIs, antimicrobial stewardship, point-of-care diagnostics and primary care.


Introduction
Antimicrobial resistance (AmR) is predicted to be the next global health pandemic and is expected to become the leading cause of death by 2050 1 .It has been projected by the Organisation for Economic Co-operation and Development (OECD) that over the next 30 years, 2.4 million people throughout Europe, North America and Australia will die because of AmR, and that this will cost up to USD 3.5 billion annually 2 .One of the main causative but modifiable risk factors associated with AmR is inappropriate antimicrobial use 3 .The majority (80-90%) of human antimicrobial medicines prescribing takes place in primary care, prescribed by general practitioners (GPs) and dispensed by community pharmacists (CPs).However, up to 50% of this prescribing is deemed inappropriate [3][4][5] .The inappropriate management (i.e.diagnosis and treatment) of respiratory tract infections (RTIs) is particularly problematic, with large variations reported between what is prescribed and what should be prescribed, when the viral aetiologies and self-limiting nature of most RTIs are considered 6 .
Improving the diagnostic certainly of RTIs in antimicrobial interventions is achieved by the use of point-of-care diagnostic tests (i.e.testing of patients at the time and place of care) 7 .
Point-of-care tests therefore help to ensure antimicrobials are only prescribed for those who have a bacterial infection, according to the outcomes of the test.Several point-of-care diagnostic tests can be used in the diagnosis of RTIs.Rapid antigen detection tests (RADT) can be used to detect group A Streptococcus, and report good sensitivity (86%; 95% CI 83-88) and specificity (96%; CI 94-97) 8,9 .A Cochrane review by Cohen and colleagues noted that their use in the management of sore throats in primary care results in reductions (25%) in antibiotic prescribing when compared to clinical management alone 10 .Point-of-care diagnostic tests involving the detection of inflammatory markers such as C-reactive protein (CRP) and procalcitonin are used in the diagnosis of lower RTI and sepsis, respectively 11,12 .A Cochrane review by Tonkin-Crine et al. found that point-of-care diagnostics using CRP testing and procalcitonin-guided management significantly reduced antibiotic prescribing for acute RTIs in primary care (RR 0.78 95% CI 0.66-0.92and OR 0.1 95% CI 0.07-0.14,respectively) 13 .
The value of using these tests in general practice has also been assessed in health economic evaluations.For example, a study published in 2022 on the cost-effectiveness of CRP point-of-care testing in primary care examined the use of the tests by GPs to guide antibiotic prescribing and found that such prescribing was reduced 14 .Using a decisionanalytic model and data from published studies, CRP POCT was compared to the usual practice of managing patients with RTI symptoms without CRP POCT over five years.The authors reported that CRP point-of-care testing helped to reduce antibiotic prescribing but that healthcare costs were greater, mainly due to the cost of CRP tests.However, they commented that further analysis of a potential CRP point-of-care testing programme over a longer time would be necessary to assess its clinical and cost-effectiveness impact.
Using point-of-care diagnostic tests in the management of RTIs could also have a positive impact on the workload of some primary care healthcare professionals.For example, a United Kingdom (UK) based service was provided by community pharmacists in Wales to test (using RADT to detect group A Streptococcus) and treat sore throats 15 .In total, 11,304 consultations were completed in pharmacies and 8256 (73.0%) of these met the threshold for RADT after a scoring system for sore throat symptoms was applied (FeverPAIN or Centor).Of the patients undertaking a RADT, 2449 (29.6%) tested positive and 2354 (28.5%) were given antibiotics.A total of 410 patients (3.6%) were given a RADT even though they did not meet the scoring criteria, and of these 54 (13.2%) tested positive and 52 (12.7%) were given antibiotics.The authors reported that, had this service not been available in pharmacies, 96% of the service users would have presented to their GP or the emergency setting.Overall, 2406/11,303 (21.3%) patients received antibiotics.This was lower than figures observed from consultations with GPs where rapid antigen detecting is not commonly used (90% of practices prescribe antibiotics for between 35% and 83% of sore throat consultations) 16 .
Point-of-care diagnostic testing has been found to be accurate.A recent systematic review identified studies which tested the accuracy of a biomarker among patients with acute cough or suspected community acquired pneumonia (CAP) and found that CRP was the most accurate for distinguishing CAP from other causes of lower RTI 17 .Further, in a cluster randomised controlled trial designed to assess whether point-of-care procalcitonin could reduce antibiotic prescribing in patients with lower RTIs in 60 Swiss general practices, the test was found to result in a 26% absolute reduction in the probability of prescription 18 .
Despite favourable evidence in support of their use, and the knowledge that point-of-care diagnostic tests are commonly used by patients themselves (e.g. to test for COVID-19), they are not routinely used by GPs or CPs in the management of RTIs in primary care.However, more research is needed to ascertain how such testing should be implemented.This was highlighted by a recent randomised controlled trial which tested the potential for point-of-care CRP testing in respiratory infections in a primary care setting in Vietnam 19 .The intervention group (24 health centres, n=18,621 patients) received point-of-care CRP testing plus routine care, while the control group (24 health centres, n=21,235) received routine care only.Intention to treat analysis showed that the proportion of patients prescribed antibiotics in the intervention group (93.1%) was lower than the control group (98.2%) (adjusted RR 0•83 [95% CI 0.66-0.93].While only 2606 patients (14%) in the intervention group had undergone CRP testing, prescriptions were shown to have reduced further in the per-protocol analysis with 1859 patients (73.1%) receiving an antibiotic prescription (adjusted RR vs control 0.64 [95% CI 0.60-0.70]).The authors noted that barriers to implementation of CRP testing should be explored and suggested that challenges include difficulties in patients accessing the test (because they were treated remotely), as patients often assumed and expected that they would be prescribed an antibiotic and many were uncertain about having the CRP test.
There is also considerable variation in the use of point-of-care testing and in antibiotic prescribing throughout Europe.A recently published prospective audit of the management of RTIs involving 18 European countries, reported that some countries (e.g.Croatia) did not use any point-of-care diagnostics in the management of RTIs and relied on clinical presentation and opinion alone, while other countries (e.g.Norway) tested for group A streptococcal and/or CRP at point-of-care 3 .The proportion of patients prescribed antibiotics ranged from 18% in Denmark and Belgium to >50% in Ireland and Hungary.While using point-of-care diagnostics was not associated with lower antibiotic prescribing in this study, the authors concluded that using point-of-care diagnostics may enhance the quality of prescribing decisions made based on clinical grounds alone.
A European expert panel recently published recommendations on the role of CRP point-of-care testing in combatting the overuse of antimicrobials.Recommendations endorse the use of CRP point-of-care testing as being a 'key tool' in addressing antimicrobial over-use, but identify that reimbursement structures and the lack of guidelines on the use of CRP point-of-care tests are major barriers to the use of CRP point-of-care testing at national and international levels 20 .Indeed, there is a lack of guidance on how any point-of-care diagnostic test should be used in the diagnosis of RTIs and the subsequent treatment of patients, either symptomatically or with antibiotics.This scoping review therefore aims to synthesise the available evidence on use of point-of-care diagnostics in the management of RTIs in the primary care context to inform the development of best practice guidance for using point-of-care diagnostics in the management (i.e.diagnosis and treatment) of RTIs in primary care.

Methods
A scoping review was deemed the most suitable methodological approach to ensure that all available evidence regarding the use of point-of-care diagnostics in the management of RTIs in primary care and the recommended treatment strategies based on the outcomes of the point-of-care diagnostic test is retrieved.The Joanna Briggs Institute's (JBI) approach to conducting scoping reviews has been adopted to ensure methodological rigour 21 .This approach is based on the framework originally developed by Arskey and O'Malley 22 , which was further refined by Levac and colleagues 23 .This framework proposes that the following nine steps should be employed: (1) defining and aligning the objective/s and question/s; (2) developing and aligning the inclusion criteria with the objective/s and question/s; (3) describing the planned approach to evidence searching, selection, data extraction, and presentation of the evidence; (4) searching for the evidence; (5) selecting the evidence; (6) extracting the evidence; (7) analysis of the evidence; (8) presentation of the results and ( 9) summarising the evidence in relation to the purpose of the review, making conclusions and noting any implications of findings.Steps 1-3 inclusive are described in detail in this protocol.Steps 4-9 will be followed in the reporting of the scoping review.The PRISMA-P checklist has been used in the reporting of this protocol 24 .The reporting of the review will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) checklist 25 .

Review question
The research question was developed in line with the Population-Concept-Context (PCC) framework as per JBI recommendations 21 : What is the available evidence regarding the use of point-of-care diagnostics (concept) in the management of RTIs (population) in primary care (context)?

Defining and aligning the objectives and research questions
The overall aim is to summarise the evidence to inform the development of best practice guidance for using point-of-care diagnostic tests in the management (i.e.diagnosis and treatment) of RTIs in primary care, i.e. by GPs and/or CPs.• Identify any gaps in the literature in order to inform the development of best practice guidance for using point-of-care diagnostic tests in the management of RTIs in primary care

Developing and aligning the inclusion criteria with the objective/s Eligibility criteria
The PCC framework 21 , as described above, will be employed to ensure appropriate study selection, in line with the research question.We will include published national, and international evidence-based guidelines, systematic reviews, quality indicators, grey literature and individual studies that provide guidance on the use of point-of-care diagnostic tests (concept) in the management of RTIs (population) in primary care (context).RCTs, pilot RCT studies and literature providing guidance on the treatment of a subsequently diagnosed RTI in primary care will also be included.Only studies published since January 1, 2010 will be included for pragmatic reasons (Table 1).

Population
The eligible population for this review includes patients presenting to GPs or CPs in primary care with a suspected RTI.No age restrictions apply.

Concept
This scoping review will consider any point-of-care diagnostic test used to diagnose any RTI.

Context
This review will include literature that provides guidance on the use of point-of-care diagnostic tests for the management of suspected RTIs in primary care, and the subsequent treatment of diagnosed RTIs in primary care.Literature that does not focus on the primary care healthcare setting will not be included.
The planned approach to evidence searching, selection, data extraction, and presentation of the evidence Searching the evidence An initial limited search of Web of Science was undertaken to identify relevant articles, using truncated keywords and MeSH terms provided in Table 2, based on the PCC framework, such as 'primary care, 'point-of-care', 'respiratory tract infection'.This was undertaken so that index terms used to describe these relevant articles and their abstracts could be used to develop the full search strategy.An initial search strategy has been completed for Web of Science, in conjunction with a specialist subject librarian (GS) and is provided in Table 3.This search strategy will be adapted for other databases including MEDLINE, CINAHL, EMBASE, the International HTA Database and the Cochrane Central Register of Controlled Trials.Grey literature searching will be undertaken, e.g., policy literature and government documents, using databases such as OpenGrey (www.opengrey.eu)and Scopus.

Selection of evidence
All titles and abstracts retrieved from searches will be transferred into the online platform, Covidence ®26 , to manage each step of the review process.All duplicates will be removed.All titles will be screened for eligibility based on inclusion and exclusion criteria (Table 1), followed by abstracts and then full texts.Two review authors (JC, CR) will undertake these reviews independently and resolve any disagreement by discussion with a third reviewer.Reasons for exclusion at full-text review will be noted.

Data extraction
Data extraction will be undertaken by two reviewers independently, using a data extraction form developed and piloted by both reviewers prior to commencement of this process.A draft data extraction table is provided in Table 4.
Any modifications made to this tool throughout data extraction will be detailed in the final scoping review report.Data relevant to the research questions will be extracted, including a description of the point-of-care diagnostic tests used in the management of RTIs in primary care, when they are used, which healthcare professional in primary care uses them, the communication amongst the primary care-based healthcare team and patients, for example, communication of diagnoses and prescribing decisions between GPs and pharmacists, how diagnosed RTIs are treated and what symptomatic management is provided to those who do not have a RTI.If necessary, authors of included literature will be contacted to request missing data.Disagreements between review authors will be resolved by discussions and will involve a third review author if necessary.

Assessment of the quality of included studies
As the aim of scoping reviews is to provide a broad overview of existing literature, assessment of methodological quality of included studies is not routinely undertaken 23 .However, for the current scoping review, we will critically appraise the included studies using the appropriate JBI Critical Appraisal Checklist 27 .This assessment will be completed independently by two reviewers (JC and CR).Disagreements will be resolved by discussion with a third reviewer, if necessary.The quality of evidence stemming from existing guidelines will be assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) assessment tool 28 .

Presentation of the evidence
The search results will be reported in the final scoping review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram (Figure 1).Key findings will be presented in tabular format, which will be developed and refined throughout the data extraction process.The findings will be synthesised in a narrative format according to scoping review guidelines.The narrative summaries will be presented along with the tables and provide an overview of the evidence for each point-of-care diagnostic test, the healthcare professional using the point-of-care diagnostic test and treatment strategies based on the outcomes of each test.
Gaps in the research evidence will also be identified.

Study status
The scoping review is currently at the full-text screening stage.A total of 13,201 studies were sourced from database searches.Of these, 3161 duplicates were removed leaving 10,040 titles for screening.After 9824 studies were deemed irrelevant, 216 full-text articles were passed to the full-text screening stage and when this is completed data extraction will begin.

Discussion
Using point-of-care diagnostic tests in the management of RTIs could serve as an important antimicrobial stewardship strategy to improve the appropriate management of RTIs and encourage more prudent use of antimicrobials in primary care.The lack of guidance to support their use has been identified as one of the barriers to their widespread use 20 .
The findings of this scoping review will be used to produce draft guidance on using point-of-care diagnostics tests in the management of RTIs in primary care.The content of the draft guidance will include details on what point-of-care diagnostic tests should be performed (depending on symptomatology), who should provide the test, i.e.GPs/CPs/both, where the test should be provided (general practice/community pharmacy/both) and how and when outcomes of tests should be communicated within the primary healthcare team, i.e. between GPs and CPs and with patients.Guidance on the appropriate management, including when antibiotics are indicated and guidance on patient self-management, will also be included.This initial draft guidance will undergo a Delphi validation 29 process, where experts in the field of RTIs, antimicrobial stewardship, point-of-care diagnostics and primary care, i.e.GPs and CPs, will be asked to agree on the content of the guidance.
Following agreement, views of GPs, CPs and patients will be sought to establish the perceived barriers and facilitators to using point-of-care diagnostic tests in the management of RTIs.

Open Peer Review
Current Peer Review Status:

Sara Haddad
American University of Beirut Medical Center, Beirut, Lebanon The article addresses the pressing issue of antimicrobial resistance and its association with inappropriate antimicrobial use, which is a significant global health concern.The majority of antimicrobial prescribing occurs in primary care settings, where general practitioners prescribe and community pharmacists dispense medications.However, up to 50% of this prescribing is deemed inappropriate, especially in cases of respiratory tract infections where antibiotics may be prescribed unnecessarily.To improve the appropriate use of antimicrobials, the article proposes the use of point-of-care diagnostic tests in primary care.These tests, which can be performed at the time and place of care, aim to enhance diagnostic certainty for RTIs and guide antibiotic prescriptions.Various point-of-care diagnostic tests, including Rapid Antigen Detection Tests, CRP, and procalcitonin, have shown promise in reducing antibiotic prescribing.Despite evidence supporting their effectiveness, point-of-care diagnostic tests are not routinely used.To address this gap, the article outlines a scoping review protocol.The scoping review aims to synthesize existing evidence on the use of point-of-care diagnostics in primary care settings to inform the development of best practice guidance.The study aims to identify evidence related to the use of point-of-care diagnostic tests, diagnostic criteria, treatment strategies based on test outcomes, and outcome measures used in primary care, and to produce draft guidance on the use of pointof-care diagnostic tests in primary care.
Is the rationale for, and objectives of, the study clearly described?Yes

Are sufficient details of the methods provided to allow replication by others? Yes
Are the datasets clearly presented in a useable and accessible format?

General comment:
We read with much attention and interest the article "Evidence for using point-of-care diagnostics in the management of respiratory tract infections in primary care: a scoping review protocol".This is a well written and comprehensive protocol for a scoping review on the evidence behind the use of point of care test for respiratory tract infection (RTI) in primary care.
We congratulate the authors for undertaking this meaningful work.They identified a gap between existing published evidence on the use and impact of POCT in primary care and their absence in the guidelines.Their work will provide an extensive overview of the evidence behind POCT use and impact in primary care.These data will be used to produce guidance on the use of POCT in primary care, further adapted using a Delphi consensus involving experts.This work participates in bridging the gap between evidence and implementation in primary care.

Rational and objectives:
The rational for the review is well described: point-of-care test are available to enhance the diagnostic accuracy of RTIs and thereby promote responsible use of antimicrobial drugs, but there is a current lack of guidance which is leading to a limited integration into primary care clinicalpractice.The objectives are therefore to summarize the existing evidence on the use of point-of-care test for the diagnosis and management of RTI in primary careand contribute to the establishment of guidelines.
The authors chose to include all respiratory tract infections: 1) sore throat (clinical suspicion of streptococcal pharyngitis) and 2) cough (clinical suspicion of pneumonia).Could the author justify why they include both clinical entities in the same work as the type of POCT will be very different?

Design
Regarding the design -a scoping review -the authors state that "it was deemed the most suitable methodological approach to ensure that all available evidence is retrieved".Could they explain more in details why they did not choose to do a systematic review?We understand it will provide a mapping of the available evidence with a broader scope than a systematic review.A paragraph detailing the reasons behind their choice would be useful.

Methods
We have a few comments on the methods: Could the author specify better why they chose only to include studies published from 2010, an whether this could lead to missing evidence?

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Have they thought about looking at ongoing or unpublished clinical trial in ClinicalTrials.gov, clinicaltrialsregister.eu and the International Clinical Trials Registry Platform of the World Health Organization?

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The authors will include different types of studies in the review (Systematic reviews, RCTs and pilot RCTs, Published guidelines, Grey literature, policy documents, government documents) that are highly heterogeneous in terms of population, methodology and objectives.How will they describe the strength of evidence in the review?(as systematic reviews often do using tools like the GRADE system).

Conclusion
We are looking forward to reading the future scoping review when it will be available Is the rationale for, and objectives of, the study clearly described?Yes

Are sufficient details of the methods provided to allow replication by others? Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable
Competing Interests: No competing interests were disclosed.
We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
-care diagnostic tests in the management of RTIs in primary care by GPs and/or CPs • Identify the evidence on diagnostic criteria and clinical prediction rules used in conjunction with individual point-of-care diagnostic tests • Identify the evidence on treatment strategies based on point-of-care diagnostic test outcomes • Describe the outcome measures used in studies investigating the effectiveness of point-of-care diagnostic tests for RTIs in primary care

Figure 1 .
Figure 1.PRISMA flow diagram for scoping review: Evidence for using point-of-care diagnostics in the management of respiratory tract infections in primary care.

Table 2 . Relevant Population Concept Context (PCC) search terms with truncated keywords and MeSH terms for Web of Science.
*RTI: Respiratory Tract Infection

Table 4 . Data extraction form.
*POC: Point-of-care § HCP: Healthcare professional This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
No competing interests were disclosed.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.