{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:06:45Z","timestamp":1787026005007,"version":"build-2736575974"},"update-to":[{"DOI":"10.3310\/nihropenres.14059.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000}},{"DOI":"10.3310\/nihropenres.14059.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000}}],"reference-count":46,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR207256"],"award-info":[{"award-number":["NIHR207256"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alan Squirrell Artificial Kidney Unit Trust","award":["Charitynumber254317"],"award-info":[{"award-number":["Charitynumber254317"]}]},{"name":"National Institute for Health Research Applied Research Collaboration Kent Surrey Sussex","award":["NIHR200179"],"award-info":[{"award-number":["NIHR200179"]}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>Background High blood pressure (BP) affects more than one in four adults in England and only one in three patients are being treated effectively. Treatment of high BP includes changes to lifestyle such as more physical activity and\/or taking medication. However, low adoption and high attrition are common with the large amounts of exercise currently recommended (&gt;150\u00a0minutes moderate exercise per week plus 2 strength sessions). Evidence suggests that isometric exercise (IE), holding a fixed body position for a period of time, for example a wall squat, results in greater long term BP reductions, with less time and effort, than other recommended exercise. This ISOFITTER study aims to evaluate the effectiveness of IE to help reduce BP in hypertension in a real world setting. Methods A multi-centre, randomised, controlled trial of an isometric exercise wall squat intervention for hypertension employing an effectiveness-implementation hybrid type-1 design. Adults (n\u00a0=\u00a0542) with Stage 1 or Stage 2 hypertension, on no more than one antihypertensive, and no other medical contra-indications will be randomised to either a standard care plus IE intervention group or standard care control group. Blood pressure readings, fidelity measurements, medications, adverse events, quality of life, participant satisfaction and health service use will be collected at baseline, week 4, month 3 and month 6 with a subgroup (n\u00a0=\u00a050) of the IE arm invited to continue for 12\u00a0months. Qualitative participant focus groups and interviews with wider stakeholders will collect implementation data. Results The ISOFITTER study will establish effectiveness of a self-administered, home-based IE intervention in lowering blood pressure in people with uncomplicated stage 1 and 2 hypertension. Implementation evidence will support patient delivery, context for scaling up of the intervention and intervention cost. Conclusion Lifestyle changes for the treatment of hypertension in the absence of other risk factors should not be overlooked. For long term hypertension management, easily adopted, evidenced exercise interventions are needed. This study will help to address this evidence gap.<\/ns3:p>","DOI":"10.3310\/nihropenres.14059.3","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:04:08Z","timestamp":1776182648000},"page":"78","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Randomised controlled effectiveness study (RCT) of isometric exercise (IE) in adults with stage 1 and 2 hypertension \u2013 ISOFITTER study"],"prefix":"10.3310","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-0414","authenticated-orcid":false,"given":"Melanie","family":"Rees-Roberts","sequence":"first","affiliation":[{"name":"Centre for Health Services Studies Canterbury England CT2 7NZ University of Kent"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-0045","authenticated-orcid":false,"given":"Ellie","family":"Santer","sequence":"additional","affiliation":[{"name":"Centre for Health Services Studies Canterbury England CT2 7NZ University of Kent"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Borthwick","sequence":"additional","affiliation":[{"name":"Centre for Health Services Studies Canterbury England CT2 7NZ University of Kent"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Doulton","sequence":"additional","affiliation":[{"name":"Canterbury England CT1 3NG East Kent Hospitals University NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline A","family":"Swift","sequence":"additional","affiliation":[{"name":"Carshalton Surrey SM5 1AA Epsom and St Helier University Hospitals NHS 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Inform."},{"key":"ref51","article-title":"Medical Research Council"},{"key":"ref52","article-title":"Randomised controlled effectiveness study of isometric exercise (IE) in adults with stage 1 and 2 hypertension (ISOFITTER study) \u2013 external data repository.","author":"C Farmer","year":"2025"}],"container-title":["NIHR Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:04:10Z","timestamp":1776182650000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":46,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.14059.3","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.14059.2","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.14059.1","asserted-by":"subject"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15289.r37168, Giuseppe Caminiti, San Raffaele Open University, Rome; Cardiology Rehabilitation Unit, IRCCS San Raffaele, Rome, 07 Oct 2025, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v1#referee-response-37168","order":0,"name":"referee-response-37168","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Melanie Rees-Roberts<\/b>; \n<i>Posted: 08 Dec 2025<\/i>; Dear Reviewer,  Many thanks for taking the time to read and comment on this article. the authors would like to thank you for your helpful and constructive comments in reviewing this protocol paper. The following changes have been made in response to your comments:  \n<u>Reviewer 1 (7 Oct 2025)<\/u> &nbsp;  \n<i>Methods: Inclusion criteria: The sentence \u201c\u2026have no significant medical condition that would contraindicate their participation\u201d is not clear enough and needs further explanations<\/i>  \n<b>Response: <\/b>We have added the following to clarify a significant medical condition that would contraindicate participation: \u2018A significant medical condition that would contraindicate participation outside of the exclusion criteria below is any medical condition declared by the participant or identified by the recommending physician which may affect a participant\u2019s ability to undertake the intervention or their safety during the study (e.g. significant knee pain or weakness, epilepsy, narcolepsy, dementia etc).\u2019  \n<i>It is not clear to me why authors will exclude patients taking betablockers; this appears to be a major limitation: in fact, the exclusion of patients on \u03b2-blockers will limit applicability of the study results to a substantial hypertensive subgroup.<\/i>  \n<b>Response: <\/b>We have added the following text into the Participant Eligibility Criteria section to clarify this exclusion choice: \u2018We excluded potential participants who were taking beta adrenergic blocking agents (beta-blockers) because attenuated heart rate, blood pressure and haemodynamic responses would potentially undermine efficacy when prescribing this as well as other forms of exercise to lower resting blood pressure. Whilst this approach may exclude a proportion of people with treated hypertension, we think this would be relatively few. This is because our study only includes people on a single antihypertensive agent and beta-blockers are fourth line agents in the treatment of uncomplicated hypertension according to NICE guidelines (National Institute for Health and Care Excellence (2019) Hypertension in adults: diagnosis and management NG136. Available at:&nbsp;https:\/\/www.nice.org.uk\/guidance\/ng136).\u2019 Our approach is supported by a study by Jiao et al., demonstrating that the prescription of beta-blockers first-line for hypertension has fallen from 20.0% in 2001-2005 to 7.9% in the 2011+ era (Tianze Jiao, Robert W Platt, Antonios Douros, Kristian B Filion, Prescription Patterns for the Use of Antihypertensive Drugs for Primary Prevention Among Patients With Hypertension in the United Kingdom, American Journal of Hypertension, Volume 35, Issue 1, January 2022, Pages 42\u201353,&nbsp;https:\/\/doi.org\/10.1093\/ajh\/hpab137). A further study by Johnson et al., published in 2025 showed that beta-blockers are prescribed as first line therapy in 1.6% of cases (Johnson K, Beradid S, Brophy JM, Platt RW, Renoux C. Trends in first-line monotherapy and combination therapy for hypertension in UK primary care. Br J Clin Pharmacol. 2025; 1-11. doi:10.1002\/bcp.70271). Therefore, whilst selection criteria might exclude up to 20% of prevalent patients prescribed antihypertensives prior to 2005. We maintain that exclusion of people treated with beta-blockers because it has the potential to blunt the effect of isometric exercise, the prescription of beta-blockers as first (to third) line therapy for hypertension is not in line with NICE guidelines and in the recent era is very uncommonly used as a first line agent as a result.  \n<i>Authors should explain why the 12-months follow up will be restricted to only 50 subjects<\/i>  \n<b>Response: <\/b>The decision to restrict 12-month follow up to only 50 participants was purely pragmatic and would enable some exploration of longer term outcomes within the funding envelope and project timeline of 30 months whilst balancing overall value for money to the UK funder. We have added the following under the follow up assessments section to explain this: \u2018This longer term, 12-month follow up is restricted to 50 participants due to the funding envelope and duration of 30 months which allows the research to explore longer term outcomes within limited time and funding whilst maintaining value for money.\u2019","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3#referee-comment-3521","order":1,"name":"referee-comment-3521","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15289.r38469, Heriviyatno J Siagian, University of Sembilanbelas November Kolaka, Kolaka, 25 Nov 2025, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v1#referee-response-38469","order":2,"name":"referee-response-38469","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Melanie Rees-Roberts<\/b>; \n<i>Posted: 08 Dec 2025<\/i>; Dear reviewer,  Many thanks for taking the time to read and comment on this paper. The authors would like to thank the peer reviewers for their helpful and constructive comments in reviewing this protocol paper. The following changes have been made in response to these comments:  \n<u>Reviewer 2 (25 Nov 2025)<\/u>  \n<i>Clarification of Handling of Missing BP Data: The protocol relies heavily on participant-reported home BP readings. However, the procedures for handling missing or incomplete BP readings, particularly at multiple time points, are not fully described. Recommendation: Include a clear plan for missing data management (e.g., multiple imputation, last observation carried forward, complete case analysis, sensitivity analyses).<\/i>  \n<b>Response: <\/b>Thank you for this request, we have included the below short description in the Quantitative analysis section to clarify how we will handle missing data. \u2018To avoid loss of efficiency, missing outcome values (both primary systolic blood pressure and secondary diastolic blood pressure) will be imputed using multiple imputation, if the proportion of missing data is greater than 5% and less than 40% (41). Where there are less than 5% missing data, the proportion of missing data is considered negligible and missing observations will be excluded. Multiple imputation methods perform less well when the amount of missing data is substantial, if more than 40% of the primary outcome data are missing in the primary analysis the assumptions are less plausible. The interpretative limitations of the trial data will be discussed in the results section, where this is the case. An imputation model containing all potential prognostic baseline covariates, the primary outcome variable at 4 weeks follow-up, and the secondary outcome variable diastolic blood pressure at 4 weeks follow-up will be used (42). The number of imputations will be dependent on the amount of missing data, as a minimum the number of imputations will be derived to ensure at least 96% statistical efficiency (RE) according to the formula below, where l is the fraction of missing values and M is the number of repetitions (42). The statistical model and assumptions made in the analysis of the primary outcome will also be implemented in the multiple imputation procedures. If it is suspected data is missing not at random or the pattern of missing data is associated with trial allocation, sensitivity analysis will be performed using a pattern mixture approach with mixed modelling and multiple imputation [5] to compare the sensitivity of conclusions to varying assumptions about the missing value mechanism. All available data from baseline to the time of dropout will be included in the sensitivity analysis using a repeated measures mixed effects model.&nbsp;&nbsp; A full Data Analysis Plan can be found in our study Data Repository referenced at the end of this manuscript in the Data Availability section.\u2019 A full project Data Analysis Plan has also now been finalised and can be found open access in our data repository for the study for transparency.  \n<i>More Detail Needed on Adherence Monitoring. Although reminders and participant diaries are described, objective adherence monitoring for the intervention group is limited. Recommendation: Specify whether:<\/i>   \n<i>digital logs from the website will track video access or completion of training sessions,<\/i> \n<i>self-reported adherence will be validated by any secondary method,<\/i> \n<i>adherence thresholds will be defined for per-protocol analysis.<\/i>  \n<b>Response: <\/b>As this is a pragmatic study and due to funding constraints, digital logs of the website to track video access are not being collected. Qualitative focus groups with participants in the intervention arm will allow us to explore the usability and barriers\/facilitators to the study resources that enable isometric exercise programmes to be established by participants and how much they used them. To confirm fidelity of the intervention, the study has a planned early interim analysis consisting of RPE recorded at the last bout of the first 3 exercise sessions for the first 50 participants in the intervention arm to check whether participants are reporting within the target training zone. A sentence has been added to the Isometric exercise intervention section to clarify this as follows: \u2018To check fidelity of the intervention early on in the study an interim analysis of RPE recorded at the last bout of the first 3 exercise sessions for the first 50 participants in the intervention arm will be conducted.\u2019 At each follow up timepoint, participants are asked to confirm the number of sessions completed in the month prior to the timepoint to check completion of training sessions. This will be used to determine our per-protocol analysis. The per protocol data will contain all data for participants who complete the trial as planned \u2013 in intervention and standard care groups - without any major protocol violations or exclusions. Per protocol analyses essentially drop those individuals who have not complied with their allocated treatment \u2013 both those who only partially complied with their allocated treatment (less than 2\/3 sessions in the past month prior to the timepoint) and those who did not receive their allocated treatment. This means that per protocol analysis will represent a likely \u2018best case scenario\u2019 for treatment effect estimation. The study will also complete an intention to treat analysis containing all available data for participants who were randomised, regardless of whether or not they complied with allocation. This dataset will include participants who were withdrawn\/withdrew from the trial post-randomisation.&nbsp; These analyses are a lower bound estimate of treatment effects as they represent the effect of offering a programme, rather than the effect of receiving that programme. We also plan an exploratory analysis to see if our data may elucidate the minimum number of training sessions that elicit clinical benefit on blood pressure. We have detailed both these analysis approaches in the Quantitative data analysis section and we have now added reference to the study Data Analysis Plan which will be made available in the study data repository for transparency. &nbsp;  \n<i>Screening Process Needs Clearer Description. Participants perform 3-day home BP monitoring to determine eligibility, but the protocol does not specify:<\/i>   \n<i>what happens when morning and evening readings differ significantly,<\/i> \n<i>whether an average of all readings or a subset is used for eligibility confirmation,<\/i> \n<i>criteria for excluding participants with high variability.<\/i>  \n<i>Recommendation: Clarify the exact algorithm used to derive final eligibility BP and criteria for exclusion based on variability or measurement error.<\/i> \n<b>Response: <\/b>To determine eligibility, UK and European guidelines are used to determine the blood pressure at screening which acts as one key criteria for proceeding to randomisation and enrolment in the study. This is conducted for two reasons, firstly to exclude white coat hypertension and secondly to confirm blood pressure is within the range stated for inclusion criteria and classifies as Stage 1 or Stage 2 hypertension. At screening three sets of systolic and diastolic blood pressure measurements are requested morning and evening for 3 consecutive days (total of 18 measurements). To calculate eligibility, the first of each set is discarded, the remaining two from each day, morning and evening, are combined and averaged to provide the blood pressure used to assess against study eligibility criteria. As a stringent criterion are set at screening with multiple measurements to account for day to day and within day variability, all subsequent analyses will be conducted on the average of all blood pressure readings recorded at baseline and follow up timepoints. This is detailed in the Data Analysis Plan which is now available on our study data repository. We have added the following to the screening section to give more detail on this: \u2018The calculation of blood pressure for entry into the study is conducted using the 2\n<sup>nd<\/sup>&nbsp;and 3\n<sup>rd<\/sup>&nbsp;reading on the 3 consecutive days morning and evening (total of 12 readings used to calculate the average home blood pressure). The average of all readings for home blood pressure is conducted to ensure we aren't including people with either overtreated hypertension, white coat hypertension or people mis-diagnosed as hypertensive. Eligibility is then assessed against the full criteria.\u2019  \n<i>Implementation Outcomes Require Defined Framework. Implementation elements are mentioned (acceptability, adoption, feasibility), but the protocol could benefit from explicitly mapping these to established frameworks (e.g., CFIR, RE-AIM). Recommendation: Define which constructs will guide qualitative data analysis and how these map onto secondary objectives.<\/i>  \n<b>Response: <\/b>To refine our qualitative data collection instruments from our feasibility study, we have used the following frameworks:  Participant feasibility and acceptability \u2013 the COM-B behaviour change framework Stakeholder acceptability, adoption and feasibility \u2013 the Re-AIM framework.  These frameworks will be used to guide inductive thematic analysis of the qualitative data. To clarify this, we have added the following including new references for the frameworks into the qualitative data analysis section: \u2018To guide the thematic analysis of the participant, focus groups, a behaviour change framework (COM-B) has been used to refine the interview questions and will be used to guide analysis (45). For stakeholder interviews, the RE-AIM framework will be used to understand full implementation contexts (46).\u2019  \n<i>Flowchart (Figure 2). Consider simplifying the visual flow to improve readability for readers unfamiliar with hybrid designs.<\/i>  \n<b>Response: <\/b>We have used a standard flow chart template for the visual flow of the hybrid study design. We feel this is sufficient and has been reviewed during development of the protocol by the full research team including public members who did not raise any issues with readability of the visual flow. No changes made to this.  \n<i>Training Personalization Procedure. The description of wall-squat height adjustment is clear but could benefit from a brief rationale explaining how RPE correlates with physiological response.<\/i>  \n<b>Response: <\/b>To provide more detail on how the RPE correlates with physiological response, we have included the below paragraph in the Intervention section: \u2018The isometric wall squat prescription protocol employed on the ISOFITTER study uses rating of perceived exertion (RPE) to determine the correct individualised wall squat height \/ knee joint angle to elicit the necessary level of cardiovascular stress proven to result in longer term resting blood pressure reduction \/ adaptation (Lea et al. 2023). The progressive RPE training zones used to inform the four bouts that make up each isometric exercise session have been determined to replicate a warm up period and achieve a target heart rate and blood pressure previously documented when using the originally validated wall squat protocol based upon 95% HRpeak&nbsp;as measured during an incremental isometric exercise test (Wiles et al 2017, Taylor et al 2019).\u2019  \n<i>Diversity and Inclusion Plan. The recruitment strategy is commendably comprehensive; however, operational definitions of &quot;under-represented groups&quot; could be more explicit.<\/i>  \n<b>Response: <\/b>We have added particular demographics being monitored to support recruitment to a representative sample and identification in real-time of under-represented groups to operationally support recruitment strategy. The following has been added to the Participant Recruitment section to clarify this: \u2018Demographics of participants recruited will be closely monitored across age, sex, disability, ethnicity and socioeconomic status to identify any under-represented groups against an expected representative sample calculated from UK hypertension prevalence data and UK population data. This will help guide targeting of under-represented groups and achieving a representative sample as discussed below.\u2019  \n<i>Safety Considerations. The protocol rightly excludes individuals with contraindications. Including a brief summary of potential wall-squat-related risks (e.g., muscle strain, dizziness) would strengthen the safety section.<\/i>  \n<b>Response: <\/b>Wall squat related risks would not indicate a reason for exclusion from the study. This is because isometric exercise wall squats do not pose any risk to individuals over and above all forms of exercise recommended to maintain a healthy lifestyle (e.g. muscle strain, dizziness etc). Where there are risks to certain individuals with contraindications, for example those with pre-existing cardiovascular disease, these participants would be excluded under the current criteria. As per reviewer 1, we have given further detail about the exclusion criteria for any medical condition that may contraindicate participant inclusion but this does not include expected wall-squat risks \u2013 see response 1 to reviewer above. To detail expected wall squat related risks, we have added the following to the Adverse event monitoring section of the manuscript: \u2018Common wall squat related adverse events would be similar in nature to other forms of recommended exercise (e.g. aerobic exercise or strength training) and may include muscle soreness after exercise, stress on joints (particularly the knees and ankles), dizziness during or after exercise, blood pressure spikes if holding of breath occurs during exercise (instructions to breath normally is including in the instructions to participants) and potential post-exercise hypotension. These will be recorded throughout the study.\u2019  \n<i>Data Sharing Section: It may be helpful to specify whether anonymised qualitative data will also be available upon request.<\/i>  \n<b>Response: <\/b>This has been clarified in the data availability statement. Data that will be made available on request after the study includes quantitative study data and qualitative study data where the participants have opted in to the use of their anonymised data for future research during the consent process.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3#referee-comment-3522","order":3,"name":"referee-comment-3522","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15456.r38463, Gavin Devereux, University of Suffolk, Ipswich, 03 Feb 2026, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v2#referee-response-38463","order":4,"name":"referee-response-38463","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Melanie Rees-Roberts<\/b>; \n<i>Posted: 23 Mar 2026<\/i>; Dear reviewer, thank you for your comments and taking the time to peer review this article. We have updated the abstract to reflect your important points and to make it clearer to the read in relation to describing the study accurately.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-78\/v3#referee-comment-3558","order":5,"name":"referee-comment-3558","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study is funded by the National Institute for Health and Care Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number NIHR207256). The project is also supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration Kent Surrey Sussex (ARC KSS) (Grant Reference Number NIHR200179). 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 project is also supported by the Alan Squirrell Artificial Kidney Unit Trust (Charity number 254317). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}