A systematic review of outcome measures utilised in clinical research studies for surgical wounds healing by secondary intention: A study protocol

A systematic review of outcome measures utilised in clinical research studies for surgical wounds healing by secondary intention: A study protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol A systematic review of outcome measures utilised in clinical research studies for surgical wounds healing by secondary intention: A study protocol Misha Sidapra, Melanie Liu, Ross Lathan, Louise Hitchman, Judith Long, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8765851/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Management of surgical wounds healing by secondary intention is a costly and complex issue for patients, clinicians and researchers alike. They are often slow to heal, can require a high level of healthcare resource use, and constitute a large proportion of the £8.3 billion annual spend on wound care in the United Kingdom. Evidence-based innovations in care are desperately needed, but heterogeneity in research design and delivery is an obvious source of inefficiency and delay. Core Outcome Sets are evidence-based, consensually-derived minimum reporting guidelines that enable consistency in outcome reporting across studies in a research area. This systematic review identifies the primary and supporting outcomes currently and historically reported in trials in surgical wounds healing by secondary intention. Methods A structured, staged search of Medline, EMBASE, CINAHL, the Cochrane database and trial registries will be completed. Results will be screened to identify quantitative and qualitative studies in the population of participants with surgical wounds healing by secondary intention, and reported outcomes will be extracted verbatim from included studies, as well as definition, study type and method of outcome measurement, to produce a map of the current landscape of outcomes considered most relevant and salient in this research area. Discussion This descriptive systematic review will identify the historical and current outcomes reported in clinical studies about surgical wounds healing by secondary intention. Together with direct stakeholder input, this will form the basis of the consensus-building process in the development of a core outcome set in surgical wounds healing by secondary intention in the SWHSI-COS Study. Core outcomes set surgical wounds healing by secondary intention wound healing Background The National Health Service (NHS) provides approximately 10 million surgical operations annually (1). For those that involve an external wound, in most circumstances this wound will be closed primarily with stitches or staples. However, in many cases, this is not possible due to wound contamination, underlying infection or wound size. In these cases, patients are often supported to manage an open surgical wound at home while it heals from the bottom up, known as ‘healing by secondary intention’. Additionally, some surgical wounds that are initially closed primarily may open up due to underlying complications; this is known as ‘wound dehiscence’. In these cases, the decision may be made to not attempt to close the wound again, and instead allow it to heal by secondary intention. Open surgical wounds, referred to as ‘surgical wounds healing by secondary intention’ (SWHSI), can have a considerable impact on the quality of life, mental health and level of morbidity of a patient (2). Previous studies have estimated the incidence of SWHSIs to be around 4.1 per 10,000 population, with the highest incidences seen following colorectal and vascular operations (3). Most of these cases were also emergency procedures, and the majority were classed as ‘dirty’ wounds on the Centre for Disease Control and Prevention wound classification system (3, 4). Despite making up a small proportion of overall surgical wounds, SWHSIs accounted for 28% of wounds requiring ongoing inpatient or community care, making them disproportionately expensive to treat and impactful to patient’s lives due to the extended time to healing and increased resource requirement (nursing time, community review, etc.) compared to closed surgical wounds (5). Previous studies in this area have found that SWHSIs can take on average three months to heal, with this projected timeline increased to six months on average to heal if the wound is located on the lower limb (3). These findings are further supported by the recent multicentre randomised controlled SWHSI-2 trial which assessed the role of negative pressure wound therapy (NPWT) in the management of SWHSI, and found that the median time to wound healing was found to be approximately 6 months in this patient population regardless of NPWT use (6). Rationale SWHSIs can be a very complex clinical entity to manage, and are often very frustrating for the patients living with them for weeks, months or potentially even longer. Compounding this issue, the evidence base for their management remains sparse. Clinical trials aiming to tackle this issue include innovations in dressings, topical and systemic medications, medical devices and service-based therapies, and provide hope for improvement in outcomes for this patient group (6-10). However, clinical trials are often expensive and complex to run, can be underpowered due to recruitment difficulties and are often heterogenous in methodology and design. This can make it difficult to collate a cohesive body of evidence to aid clinicians or service commissioners designing and delivering care to make decisions about the best interventions to offer their patients. A core outcome set (COS) provides a potential solution to this issue by providing a common framework around which clinical trials can be developed. A COS is a consensually-derived group of outcomes that should be included as a minimum for all new trials in a given area. Use of a COS is strongly encouraged by regulatory bodies including the National Institute for Health and Care Excellence (NICE), and their use has been included in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist (11, 12). A total of 337 COS development projects have been published at the last update in 2019, with some of the longest running projects showing promising improvements in cohesive and collaborative trial design (13). At present there is no agreed COS for studies involving SWHSI; this systematic review is a fundamental first step to the production of this much needed guideline. Development of a COS follows guidance from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, and is a multi-stage process (14). This includes a systematic review of outcomes that have been previously utilised in the disease area. Together with additional input from key stakeholders (patients, clinicians, researchers etc.), these sources will form the basis for the outcome prioritisation Delphi process. This systematic review protocol has been developed and described in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidance. Methods Aims To identify primary and supplementary benefit and harm outcomes utilised in clinical trials in the population of adult patients with surgical wounds healing by secondary intention (which may be known by alternative terminology). Eligibility criteria Studies will be eligible for inclusion if they meet the following requirements: Population: Studies conducted in patients with SWHSI are eligible for inclusion. As terminology may vary for this clinical entity, we will define SWHSI as any externally-located wound resulting from a surgical procedure where the management strategy has been to allow for healing by secondary intention, or where a decision has been made to manage a previously primarily closed surgical wound by secondary intention (due to infection, dehiscence or other clinical reasoning). Studies in wounds that preceded a surgical procedure, e.g. a diabetic foot ulcer, pressure ulcers or traumatic wound will be eligible if the wounds have undergone formal surgical debridement in an operating theatre environment and are subsequently being managed by healing by secondary intention. Studies in surgical wounds where healing by secondary intention forms a subgroup of participants are eligible for inclusion, as the outcomes measured are likely to remain relevant to this population. Intervention / Comparator : As the goal of the systematic review is purely to identify outcomes used, any intervention or comparator used to manage SWHSIs in adult patients will be acceptable for inclusion into the review. However, studies focussing exclusively on delayed closure, skin grafts or flaps as treatments for open surgical wounds will be excluded as these wounds are no longer healing from the bottom up by secondary intention. Outcomes : all reported wound-related outcomes will be eligible for inclusion. Outcomes specific to the underlying disease process leading to the surgical operation only and unrelated to the wound will be excluded. Study Design : All quantitative study designs will be acceptable for inclusion. Studies for which only an abstract is available will still be eligible for inclusion if all data items for extraction are included in the abstract. We will also identify qualitative studies in this population for a complementary analysis to identify any outcomes that are considered salient to the patient group but have not been otherwise included in clinical trial design. Language : studies published in any language will be eligible for inclusion with use of translation services to be used as required. Reports published in languages other than English for which a translation cannot be obtained will be excluded. Information sources The COMET initiative describes the methodology for systematic reviews completed for the development of a COS (14). database will be searched to identify eligible papers. Trial registries will be searched for any ongoing or upcoming trials in this area. References of included papers will be hand-searched. Search strategy A staged approach as recommended by the COMET Initiative guidance will be used, with the initial search including all trials published in the last 10 years (15). A subsequent search will aim to find any additional trials published preceding this period until no new unique outcomes are found and data saturation can be assumed. A full search strategy will be designed with the input of an information specialist librarian. Data management and study selection References will be managed on EndNote and entered into the Covidence systematic review tool. Screening of search results and abstracts will be completed by a minimum of two independent reviewers, with discrepancies settled by a third reviewer. Full text screening and data extraction will be completed by the primary reviewer with a 10% random sample checked by an additional reviewer. In case of significant discrepancy (>10%), the entire data set will be extracted by two independent reviewers, with any further discrepancy settled by a third reviewer. Data extraction, outcomes and prioritisation Data items will be extracted into a pre-piloted spreadsheet. The following information will be extracted from each study in addition to baseline study information: Study design Outcome name Outcome type (primary / secondary; benefit / harm) Outcome definition Method of measurement Outcomes and definitions will be taken verbatim from their respective studies. Where a direct and complete definition is not given, the reviewers will independently extract a definition from the context of the paper, and following discussion, identify a definition for use in the review that is reflective of the contextual interpretation of the outcome. This will be done in conjunction with our patient and public involvement partners where appropriate to ensure that our interpretations remain true to the experiences of the target population. Similarly, included qualitative studies will be synthesised into a narrative analysis, and outcomes extracted through discussion and consensus from the reviewers as described previously. Risk of Bias Assessment As this is an unrestricted information gathering exercise, the quality of the trial from which the outcome is derived is not considered to be relevant to the study. Included studies will not undergo risk of bias analysis because their specific results are not relevant to this study. In the same context, meta-biases are not thought to be a particular source of concern within this study, except for where there is a high likelihood of patient voices and experiences being less prominent in the choice of outcome measures in historical clinical trials. The authors acknowledge that the choice of primary and supplementary outcomes is more reflective of the clinical conceptualisation of the disease state, and a bias may exist where what is included in clinical trial methodology is what is considered important or salient to the clinicians and researchers working in this area in preference to the concerns of the patient population this work aims to serve. This potential source of meta-bias is acknowledged with the understanding that this is a reality of the way that clinical trials have traditionally been designed; to counterbalance this potential meta-bias, direct accounts of patient experience are also included in other areas of this core outcome set development project. Data synthesis and dissemination Data items will be collated into domain-based groups as decided by a study advisory committee comprised of expert clinicians and patients, and condensed into tables to demonstrate the frequency of use in the scientific literature. Results will be made publicly available by publication. Confidence in cumulative evidence As this is an unrestricted data collection exercise, the quality of cumulative data is not relevant to the progression of the study, and therefore will not be addressed here. Discussion Living with surgical wounds healing by secondary intention can be highly impactful on the lives of patients dealing with them, and costly to treat for the health service. Improving treatments for these patients is reliant on the production of a high-quality evidence base which, to date, is lacking in this disease area. Development of a COS will help to streamline and optimise future research in this area, starting with a systematic review of previous trials in this area and the outcomes they have used. Abbreviations COMET Core Outcome Measures in Effectiveness Trials Initiative COS Core Outcomes Set NHS National Health Service NICE National Institute for Health and Care Excellence NPWT Negative pressure wound therapy PRISMA-P Preferred Reporting Items for Systematic review and Meta-Analysis Protocols SPIRIT Standard Protocol Items: Recommendations for Interventional Trials Checklist SWHSI Surgical wound healing by secondary intention Declarations Ethics approval and consent to participate This study forms one workstream of the larger SWHSI core outcome set development project (SWHSI-COS). The SWHSI-COS Study was reviewed and approved by HRA and Health and Care Research Wales (HCRW) and Leeds West Research Ethics Committee (23/YH/0253). Consent for publication Not applicable. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding This study is funded by a National Institute for Health and Care Research Doctoral Fellowship (NIHR303688). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder has no specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Authors' contributions All authors contributed substantially to the conception and design of this study; MS, ML, and JL produced the draft, with substantial review and revisions contributed by RL, LH, BR, CA, PT and IC leading to the development of the final manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable Sponsor: Hull University Teaching Hospitals NHS Trust, Kingston-Upon-Hull, United Kingdom Funder: This study is funded by a National Institute for Health and Care Research Doctoral Fellowship (NIHR303688). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. References Digital NHS. Hospital Admitted Patient Care Activity 2018-19 - NHS Digital. Sidapra M, Ramakrishnan P, Siracusa F, Walshaw J, Long J, Arundel C, et al. Patient-reported quality of life factors in vascular surgical wounds healing by secondary intention (SWHSI): a qualitative patient and public involvement (PPI) exploration. Journal of Vascular Societies of Great Britain and Ireland. 2023;2(3):154-9. Chetter I, Arundel C, Bell K, Buckley H, Claxton K, Corbacho Martin B, et al. The epidemiology, management and impact of surgical wounds healing by secondary intention: a research programme including the SWHSI feasibility RCT. Programme Grants for Applied Research. 2020;8(7):1-122. Chetter IC, Oswald AV, McGinnis E, Stubbs N, Arundel C, Buckley H, et al. Patients with surgical wounds healing by secondary intention: A prospective, cohort study. International Journal of Nursing Studies. 2019;89:62-71. Srinivasaiah N, Dugdall H, Barrett S, Drew PJ. A point prevalence survey of wounds in north-east England. Journal of Wound Care. 2007;16(10):413-9. Arundel C, Mandefield L, Fairhurst C, Baird K, Gkekas A, Saramago P, et al. Negative pressure wound therapy versus usual care in patients with surgical wound healing by secondary intention in the UK (SWHSI-2): an open-label, multicentre, parallel-group, randomised controlled trial. The Lancet. 2025;405(10490):1689-99. Norman G, Dumville JC, Mohapatra DP, Owens GL, Crosbie EJ. Antibiotics and antiseptics for surgical wounds healing by secondary intention. Cochrane Database of Systematic Reviews. 2016;2016(3). Dumville JC, Owens GL, Crosbie EJ, Peinemann F, Liu Z. Negative pressure wound therapy for treating surgical wounds healing by secondary intention. Cochrane Database Syst Rev. 2015;2015(6):Cd011278. Smith SR, Newton K, Smith JA, Dumville JC, Iheozor‐Ejiofor Z, Pearce LE, et al. Internal dressings for healing perianal abscess cavities. Cochrane Database of Systematic Reviews. 2016(8). Newton K, Dumville J, Briggs M, Law J, Martin J, Pearce L, et al. Postoperative Packing of Perianal Abscess Cavities (PPAC2): randomized clinical trial. Br J Surg. 2022;109(10):951-7. NICE. Support for developers of medicinal products for COVID-19 2020 [updated 2021. Available from: https://www.nice.org.uk/covid-19/support-for-developers-of-medicinal-products-for-covid-19. Calvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan A-W, King MT, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols. JAMA. 2018;319(5):483. Gargon E, Gorst SL, Williamson PR. Choosing important health outcomes for comparative effectiveness research: 5th annual update to a systematic review of core outcome sets for research. PLOS ONE. 2019;14(12):e0225980. Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. 2017. Kirkham JJ, Davis K, Altman DG, Blazeby JM, Clarke M, Tunis S, et al. Core Outcome Set-STAndards for Development: The COS-STAD recommendations. PLoS Medicine. 2017;14(11). Additional Declarations No competing interests reported. Supplementary Files PRISMAPchecklistBMCSR.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8765851","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":584653945,"identity":"f4600836-ef76-4546-afdb-064da276b4d4","order_by":0,"name":"Misha Sidapra","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYDACZgY2EMXDcABEGdgwGJCopSANqiUBryY2CAXW8uEwYS267ezPHvxgqJPhO3722IcfBufzzPkPsD34+AO3FrPDPOaGPQyHeSTP5CXP7DG4XWw5I4HdcAYeW4Ba2CSAHuExOJBjzMBjcDtxww0GNmkevFrYn0n+YajjMTj/xpjxj8G5xA3nD7BJ/8GrhcFMmoeBmcfgRo4xkDyQuOFAAps0Pu8DHWYmLWMA9MuNd8nMMgbJQIcltkn2pOHRcv74M8k3FXX2fOdzDzO++WMHdNjhYxI/bHBrgQBwXPDAeIwNhNTDAA9hJaNgFIyCUTAyAQD9k09KoE5TXgAAAABJRU5ErkJggg==","orcid":"","institution":"Hull York Medical School","correspondingAuthor":true,"prefix":"","firstName":"Misha","middleName":"","lastName":"Sidapra","suffix":""},{"id":584653949,"identity":"15652c26-34c4-4cbf-8187-6123205fbae7","order_by":1,"name":"Melanie Liu","email":"","orcid":"","institution":"Leeds Teaching Hospital Trust","correspondingAuthor":false,"prefix":"","firstName":"Melanie","middleName":"","lastName":"Liu","suffix":""},{"id":584653957,"identity":"9f5c1105-b44a-47b7-957c-ba6348f213ca","order_by":2,"name":"Ross Lathan","email":"","orcid":"","institution":"Hull York Medical School","correspondingAuthor":false,"prefix":"","firstName":"Ross","middleName":"","lastName":"Lathan","suffix":""},{"id":584653961,"identity":"d2625d7c-11e6-47c3-96c1-648ef3d167ae","order_by":3,"name":"Louise Hitchman","email":"","orcid":"","institution":"Hull York Medical School","correspondingAuthor":false,"prefix":"","firstName":"Louise","middleName":"","lastName":"Hitchman","suffix":""},{"id":584653964,"identity":"73c5cd3b-9e30-4fe9-a23b-0f47f8495cc1","order_by":4,"name":"Judith Long","email":"","orcid":"","institution":"Hull York Medical School","correspondingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Long","suffix":""},{"id":584653967,"identity":"8bac8b82-d95c-4e6d-8211-57cfdfb39461","order_by":5,"name":"Bharadhwaj Ravindhran","email":"","orcid":"","institution":"Hull York Medical School","correspondingAuthor":false,"prefix":"","firstName":"Bharadhwaj","middleName":"","lastName":"Ravindhran","suffix":""},{"id":584653971,"identity":"91d71b9a-3dd2-4003-b177-38d96f2a9c6b","order_by":6,"name":"Paul Tiffin","email":"","orcid":"","institution":"University of York","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Tiffin","suffix":""},{"id":584653972,"identity":"42ce1d66-c2bf-48cd-aec3-f89c5fea111e","order_by":7,"name":"Catherine Arundel","email":"","orcid":"","institution":"University of York","correspondingAuthor":false,"prefix":"","firstName":"Catherine","middleName":"","lastName":"Arundel","suffix":""},{"id":584653973,"identity":"0bd285a8-06dd-4247-84c4-25b94e124000","order_by":8,"name":"Ian Chetter","email":"","orcid":"","institution":"Hull York Medical School","correspondingAuthor":false,"prefix":"","firstName":"Ian","middleName":"","lastName":"Chetter","suffix":""}],"badges":[],"createdAt":"2026-02-02 13:56:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8765851/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8765851/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103215943,"identity":"60e8b27f-0d12-4b46-b73b-5d8f370bd5d1","added_by":"auto","created_at":"2026-02-23 09:28:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":563302,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8765851/v1/94e53947-f604-4fef-a7d5-5688339b21ee.pdf"},{"id":102473461,"identity":"14c01b05-366d-42f3-bdc9-ce579402f3e9","added_by":"auto","created_at":"2026-02-12 04:42:05","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":34303,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAPchecklistBMCSR.docx","url":"https://assets-eu.researchsquare.com/files/rs-8765851/v1/0514e9fb05ce79bd4f03b056.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A systematic review of outcome measures utilised in clinical research studies for surgical wounds healing by secondary intention: A study protocol","fulltext":[{"header":"Background","content":"\u003cp\u003eThe National Health Service (NHS) provides approximately 10 million surgical operations annually (1). For those that involve an external wound, in most circumstances this wound will be closed primarily with stitches or staples. However, in many cases, this is not possible due to wound contamination, underlying infection or wound size. In these cases, patients are often supported to manage an open surgical wound at home while it heals from the bottom up, known as ‘healing by secondary intention’. Additionally, some surgical wounds that are initially closed primarily may open up due to underlying complications; this is known as ‘wound dehiscence’. In these cases, the decision may be made to not attempt to close the wound again, and instead allow it to heal by secondary intention.\u003c/p\u003e\n\u003cp\u003eOpen surgical wounds, referred to as ‘surgical wounds healing by secondary intention’ (SWHSI), can have a considerable impact on the quality of life, mental health and level of morbidity of a patient (2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies have estimated the incidence of SWHSIs to be around 4.1 per 10,000 population, with the highest incidences seen following colorectal and vascular operations (3). Most of these cases were also emergency procedures, and the majority were classed as ‘dirty’ wounds on the Centre for Disease Control and Prevention wound classification system (3, 4). Despite making up a small proportion of overall surgical wounds, SWHSIs accounted for 28% of wounds requiring ongoing inpatient or community care, making them disproportionately expensive to treat and impactful to patient’s lives due to the extended time to healing and increased resource requirement (nursing time, community review, etc.) compared to closed surgical wounds (5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies in this area have found that SWHSIs can take on average three months to heal, with this projected timeline increased to six months on average to heal if the wound is located on the lower limb (3). These findings are further supported by the recent multicentre randomised controlled SWHSI-2 trial which assessed the role of negative pressure wound therapy (NPWT) in the management of SWHSI, and found that the median time to wound healing was found to be approximately 6 months in this patient population regardless of NPWT use (6). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRationale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSWHSIs can be a very complex clinical entity to manage, and are often very frustrating for the patients living with them for weeks, months or potentially even longer. Compounding this issue, the evidence base for their management remains sparse. Clinical trials aiming to tackle this issue include innovations in dressings, topical and systemic medications, medical devices and service-based therapies, and provide hope for improvement in outcomes for this patient group (6-10). However, clinical trials are often expensive and complex to run, can be underpowered due to recruitment difficulties and are often heterogenous in methodology and design. This can make it difficult to collate a cohesive body of evidence to aid clinicians or service commissioners designing and delivering care to make decisions about the best interventions to offer their patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA core outcome set (COS) provides a potential solution to this issue by providing a common framework around which clinical trials can be developed. A COS is a consensually-derived group of outcomes that should be included as a minimum for all new trials in a given area. Use of a COS is strongly encouraged by regulatory bodies including the National Institute for Health and Care Excellence (NICE), and their use has been included in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist (11, 12). A total of 337 COS development projects have been published at the last update in 2019, with some of the longest running projects showing promising improvements in cohesive and collaborative trial design (13). At present there is no agreed COS for studies involving SWHSI; this systematic review is a fundamental first step to the production of this much needed guideline. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDevelopment of a COS follows guidance from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, and is a multi-stage process (14). This includes a systematic review of outcomes that have been previously utilised in the disease area. Together with additional input from key stakeholders (patients, clinicians, researchers etc.), these sources will form the basis for the outcome prioritisation Delphi process. This systematic review protocol has been developed and described in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidance.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eAims\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo identify primary and supplementary benefit and harm outcomes utilised in clinical trials in the population of adult patients with surgical wounds healing by secondary intention (which may be known by alternative terminology).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudies will be eligible for inclusion if they meet the following requirements: \u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePopulation:\u003c/strong\u003e Studies conducted in patients with SWHSI are eligible for inclusion.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAs terminology may vary for this clinical entity, we will define SWHSI as any externally-located wound resulting from a surgical procedure where the management strategy has been to allow for healing by secondary intention, or where a decision has been made to manage a previously primarily closed surgical wound by secondary intention (due to infection, dehiscence or other clinical reasoning).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudies in wounds that preceded a surgical procedure, e.g. a diabetic foot ulcer, pressure ulcers or traumatic wound will be eligible if the wounds have undergone formal surgical debridement in an operating theatre environment and are subsequently being managed by healing by secondary intention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudies in surgical wounds where healing by secondary intention forms a subgroup of participants are eligible for inclusion, as the outcomes measured are likely to remain relevant to this population.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eIntervention / Comparator\u003c/strong\u003e: As the goal of the systematic review is purely to identify outcomes used, any intervention or comparator used to manage SWHSIs in adult patients will be acceptable for inclusion into the review. However, studies focussing exclusively on delayed closure, skin grafts or flaps as treatments for open surgical wounds will be excluded as these wounds are no longer healing from the bottom up by secondary intention. \u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e: all reported wound-related outcomes will be eligible for inclusion. Outcomes specific to the underlying disease process leading to the surgical operation only and unrelated to the wound will be excluded.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e: All quantitative study designs will be acceptable for inclusion. Studies for which only an abstract is available will still be eligible for inclusion if all data items for extraction are included in the abstract. We will also identify qualitative studies in this population for a complementary analysis to identify any outcomes that are considered salient to the patient group but have not been otherwise included in clinical trial design. \u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eLanguage\u003c/strong\u003e: studies published in any language will be eligible for inclusion with use of translation services to be used as required. Reports published in languages other than English for which a translation cannot be obtained will be excluded.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eInformation sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe COMET initiative describes the methodology for systematic reviews completed for the development of a COS (14). \u0026nbsp; database will be searched to identify eligible papers. Trial registries will be searched for any ongoing or upcoming trials in this area. References of included papers will be hand-searched.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA staged approach as recommended by the COMET Initiative guidance will be used, with the initial search including all trials published in the last 10 years (15). A subsequent search will aim to find any additional trials published preceding this period until no new unique outcomes are found and data saturation can be assumed. A full search strategy will be designed with the input of an information specialist librarian.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management and study selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReferences will be managed on EndNote and entered into the Covidence systematic review tool. Screening of search results and abstracts will be completed by a minimum of two independent reviewers, with discrepancies settled by a third reviewer. Full text screening and data extraction will be completed by the primary reviewer with a 10% random sample checked by an additional reviewer. In case of significant discrepancy (\u0026gt;10%), the entire data set will be extracted by two independent reviewers, with any further discrepancy settled by a third reviewer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction, outcomes and prioritisation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData items will be extracted into a pre-piloted spreadsheet. The following information will be extracted from each study in addition to baseline study information:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eStudy design\u003c/li\u003e\n \u003cli\u003eOutcome name \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOutcome type (primary / secondary; benefit / harm)\u003c/li\u003e\n \u003cli\u003eOutcome definition\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMethod of measurement\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eOutcomes and definitions will be taken verbatim from their respective studies. Where a direct and complete definition is not given, the reviewers will independently extract a definition from the context of the paper, and following discussion, identify a definition for use in the review that is reflective of the contextual interpretation of the outcome. This will be done in conjunction with our patient and public involvement partners where appropriate to ensure that our interpretations remain true to the experiences of the target population.\u003c/p\u003e\n\u003cp\u003eSimilarly, included qualitative studies will be synthesised into a narrative analysis, and outcomes extracted through discussion and consensus from the reviewers as described previously.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Bias Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this is an unrestricted information gathering exercise, the quality of the trial from which the outcome is derived is not considered to be relevant to the study. Included studies will not undergo risk of bias analysis because their specific results are not relevant to this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the same context, meta-biases are not thought to be a particular source of concern within this study, except for where there is a high likelihood of patient voices and experiences being less prominent in the choice of outcome measures in historical clinical trials. The authors acknowledge that the choice of primary and supplementary outcomes is more reflective of the clinical conceptualisation of the disease state, and a bias may exist where what is included in clinical trial methodology is what is considered important or salient to the clinicians and researchers working in this area in preference to the concerns of the patient population this work aims to serve.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis potential source of meta-bias is acknowledged with the understanding that this is a reality of the way that clinical trials have traditionally been designed; to counterbalance this potential meta-bias, direct accounts of patient experience are also included in other areas of this core outcome set development project.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData synthesis and dissemination\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData items will be collated into domain-based groups as decided by a study advisory committee comprised of expert clinicians and patients, and condensed into tables to demonstrate the frequency of use in the scientific literature. Results will be made publicly available by publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidence in cumulative evidence\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this is an unrestricted data collection exercise, the quality of cumulative data is not relevant to the progression of the study, and therefore will not be addressed here.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLiving with surgical wounds healing by secondary intention can be highly impactful on the lives of patients dealing with them, and costly to treat for the health service. Improving treatments for these patients is reliant on the production of a high-quality evidence base which, to date, is lacking in this disease area. Development of a COS will help to streamline and optimise future research in this area, starting with a systematic review of previous trials in this area and the outcomes they have used.\u003c/p\u003e"},{"header":" Abbreviations ","content":"\u003cp\u003e\u003cstrong\u003eCOMET \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eCore Outcome Measures in Effectiveness Trials Initiative\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/strong\u003eCore Outcomes Set\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNHS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eNational Health Service\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNICE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eNational Institute for Health and Care Excellence\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNPWT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eNegative pressure wound therapy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePRISMA-P \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003ePreferred Reporting Items for Systematic review and Meta-Analysis Protocols\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSPIRIT\u003c/strong\u003e\u0026nbsp; Standard Protocol Items: Recommendations for Interventional Trials Checklist\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSWHSI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eSurgical wound healing by secondary intention\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study forms one workstream of the larger SWHSI core outcome set development project (SWHSI-COS). The SWHSI-COS Study was reviewed and approved by HRA and Health and Care Research Wales (HCRW) and Leeds West Research Ethics Committee (23/YH/0253).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is funded by a National Institute for Health and Care Research Doctoral Fellowship (NIHR303688). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder has no specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed substantially to the conception and design of this study; MS, ML, and JL produced the draft, with substantial review and revisions contributed by RL, LH, BR, CA, PT and IC leading to the development of the final manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSponsor:\u0026nbsp;\u003c/strong\u003eHull University Teaching Hospitals NHS Trust, Kingston-Upon-Hull, United Kingdom\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunder:\u0026nbsp;\u003c/strong\u003eThis study is funded by a National Institute for Health and Care Research Doctoral Fellowship (NIHR303688). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDigital NHS. Hospital Admitted Patient Care Activity 2018-19 - NHS Digital.\u003c/li\u003e\n\u003cli\u003eSidapra M, Ramakrishnan P, Siracusa F, Walshaw J, Long J, Arundel C, et al. Patient-reported quality of life factors in vascular surgical wounds healing by secondary intention (SWHSI): a qualitative patient and public involvement (PPI) exploration. Journal of Vascular Societies of Great Britain and Ireland. 2023;2(3):154-9.\u003c/li\u003e\n\u003cli\u003eChetter I, Arundel C, Bell K, Buckley H, Claxton K, Corbacho Martin B, et al. The epidemiology, management and impact of surgical wounds healing by secondary intention: a research programme including the SWHSI feasibility RCT. Programme Grants for Applied Research. 2020;8(7):1-122.\u003c/li\u003e\n\u003cli\u003eChetter IC, Oswald AV, McGinnis E, Stubbs N, Arundel C, Buckley H, et al. Patients with surgical wounds healing by secondary intention: A prospective, cohort study. International Journal of Nursing Studies. 2019;89:62-71.\u003c/li\u003e\n\u003cli\u003eSrinivasaiah N, Dugdall H, Barrett S, Drew PJ. A point prevalence survey of wounds in north-east England. Journal of Wound Care. 2007;16(10):413-9.\u003c/li\u003e\n\u003cli\u003eArundel C, Mandefield L, Fairhurst C, Baird K, Gkekas A, Saramago P, et al. Negative pressure wound therapy versus usual care in patients with surgical wound healing by secondary intention in the UK (SWHSI-2): an open-label, multicentre, parallel-group, randomised controlled trial. The Lancet. 2025;405(10490):1689-99.\u003c/li\u003e\n\u003cli\u003eNorman G, Dumville JC, Mohapatra DP, Owens GL, Crosbie EJ. Antibiotics and antiseptics for surgical wounds healing by secondary intention. Cochrane Database of Systematic Reviews. 2016;2016(3).\u003c/li\u003e\n\u003cli\u003eDumville JC, Owens GL, Crosbie EJ, Peinemann F, Liu Z. Negative pressure wound therapy for treating surgical wounds healing by secondary intention. Cochrane Database Syst Rev. 2015;2015(6):Cd011278.\u003c/li\u003e\n\u003cli\u003eSmith SR, Newton K, Smith JA, Dumville JC, Iheozor‐Ejiofor Z, Pearce LE, et al. Internal dressings for healing perianal abscess cavities. Cochrane Database of Systematic Reviews. 2016(8).\u003c/li\u003e\n\u003cli\u003eNewton K, Dumville J, Briggs M, Law J, Martin J, Pearce L, et al. Postoperative Packing of Perianal Abscess Cavities (PPAC2): randomized clinical trial. Br J Surg. 2022;109(10):951-7.\u003c/li\u003e\n\u003cli\u003eNICE. Support for developers of medicinal products for COVID-19 2020 [updated 2021. Available from: https://www.nice.org.uk/covid-19/support-for-developers-of-medicinal-products-for-covid-19.\u003c/li\u003e\n\u003cli\u003eCalvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan A-W, King MT, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols. JAMA. 2018;319(5):483.\u003c/li\u003e\n\u003cli\u003eGargon E, Gorst SL, Williamson PR. Choosing important health outcomes for comparative effectiveness research: 5th annual update to a systematic review of core outcome sets for research. PLOS ONE. 2019;14(12):e0225980.\u003c/li\u003e\n\u003cli\u003eWilliamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. 2017.\u003c/li\u003e\n\u003cli\u003eKirkham JJ, Davis K, Altman DG, Blazeby JM, Clarke M, Tunis S, et al. Core Outcome Set-STAndards for Development: The COS-STAD recommendations. PLoS Medicine. 2017;14(11).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Core outcomes set, surgical wounds healing by secondary intention, wound healing","lastPublishedDoi":"10.21203/rs.3.rs-8765851/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8765851/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eManagement of surgical wounds healing by secondary intention is a costly and complex issue for patients, clinicians and researchers alike. They are often slow to heal, can require a high level of healthcare resource use, and constitute a large proportion of the \u0026pound;8.3\u0026nbsp;billion annual spend on wound care in the United Kingdom. Evidence-based innovations in care are desperately needed, but heterogeneity in research design and delivery is an obvious source of inefficiency and delay. Core Outcome Sets are evidence-based, consensually-derived minimum reporting guidelines that enable consistency in outcome reporting across studies in a research area. This systematic review identifies the primary and supporting outcomes currently and historically reported in trials in surgical wounds healing by secondary intention.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA structured, staged search of Medline, EMBASE, CINAHL, the Cochrane database and trial registries will be completed. Results will be screened to identify quantitative and qualitative studies in the population of participants with surgical wounds healing by secondary intention, and reported outcomes will be extracted verbatim from included studies, as well as definition, study type and method of outcome measurement, to produce a map of the current landscape of outcomes considered most relevant and salient in this research area.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis descriptive systematic review will identify the historical and current outcomes reported in clinical studies about surgical wounds healing by secondary intention. Together with direct stakeholder input, this will form the basis of the consensus-building process in the development of a core outcome set in surgical wounds healing by secondary intention in the SWHSI-COS Study.\u003c/p\u003e","manuscriptTitle":"A systematic review of outcome measures utilised in clinical research studies for surgical wounds healing by secondary intention: A study protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-12 04:42:00","doi":"10.21203/rs.3.rs-8765851/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4958985c-e156-4777-a6da-bb00ebb0255f","owner":[],"postedDate":"February 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T09:26:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-12 04:42:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8765851","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8765851","identity":"rs-8765851","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}