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BackgroundBurn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells.MethodsWe will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy.DiscussionThis study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS.Trial registrationClinicalTrials.gov: NCT04736251.

BackgroundThe importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1-5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant.Methods and findingsMEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%-79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%-76%). A number of symptoms were significantly (p < 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5-45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3-35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5-66.6], p = 0.002; PCS 66.3 [95% CI 66.2-66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9-50.1], p = 0.002; PCS 48.0 [95% CI 47.9-48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation.ConclusionsThe main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD.Protocol registrationPROSPERO CRD42020164737.

Abstract Background Patient-reported outcomes (PROs) are increasingly collected in clinical trials as they provide unique information on the physical, functional and psychological impact of a treatment from the patient’s perspective. Recent research suggests that PRO trial data have the potential to inform shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. However, there remains limited evidence regarding the actual impact associated with PRO trial data and how to maximise PRO impact to benefit patients and society. Thus, our objective was to qualitatively explore international stakeholders’ perspectives surrounding: a) the impact of PRO trial data, b) impact measurement metrics, and c) barriers and facilitators to effectively maximise the impact of PRO trial data upon patients and society. Methods Semi-structured interviews with 24 international stakeholders were conducted between May and October 2018. Data were coded and analysed using reflexive thematic analysis. Results International stakeholders emphasised the impact of PRO trial data to benefit patients and society. Influence on policy-impact, including changes to clinical healthcare practice and guidelines, drug approval and promotional labelling claims were common types of PRO impact reported by interviewees. Interviewees suggested impact measurement metrics including: number of pharmaceutical labelling claims and interviews with healthcare practitioners to determine whether PRO data were incorporated in clinical decision-making. Key facilitators to PRO impact highlighted by stakeholders included: standardisation of PRO tools; consideration of health utilities when selecting PRO measures; adequate funding to support PRO research; improved reporting and dissemination of PRO trial data by key opinion leaders and patients; and development of legal enforcement of the collection of PRO data. Conclusions Determining the impact of PRO trial data is essential to better allocate funds, minimise research waste and to help maximise the impact of these data for patients and society. However, measuring the impact of PRO trial data through metrics is a challenging task, as current measures do not capture the total impact of PRO research. Broader international multi-stakeholder engagement and collaboration is needed to standardise PRO assessment and maximise the impact of PRO trial data to benefit patients and society.

Introduction The burden of atrial fibrillation (AF) in Thailand is high and associated with increased morbidity, mortality and healthcare costs. Vitamin K antagonists (eg, warfarin), commonly used for stroke prevention in patients with AF in Thailand, are effective but are often suboptimally controlled. We aim to evaluate the impact of an SAMe-TT2R2 score-guided strategy and educational intervention compared to usual care on anticoagulation control expressed by the time in therapeutic range (TTR) at 12 months, in anticoagulant-naïve Thai patients with AF.Methods and analysis Multicentre, open-label, parallel-group, randomised controlled trial conducted in Thailand among adult patients (age: 18 years) with AF who are anticoagulant naïve. Patients will be randomised to one of two groups; an SAMe-TT2R2 score-guided strategy with educational intervention and usual care versus usual care alone. The planned follow-up period is 12 months. The primary outcome is TTR at 12 months. Secondary outcomes include: (1) TTR at 6 months; (2) thromboembolic and bleeding events at 12 months; (3) composite major adverse cardiovascular events at 12 months; (4) change in patients’ knowledge of AF between baseline and 6 months and 12 months; (5) cost effectiveness; (6) quality of life at baseline, 6 months and 12 months using EQ-5D-5L (Thai version) and (7) patient satisfaction/perceptions of the TREAT intervention. An embedded qualitative study will assess patient perceptions of the TREAT intervention.Ethics and dissemination The study has been approved by the Ethical Review Committee, Ministry of Public Health of Thailand, and registered in the Thai Clinical Trials Registry. The results of this trial will be submitted for publication in a peer-reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided to all participants prior to publication.Trial registration number TCTR20180711003.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients’ symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item’s importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

Objectives (a) To adapt the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-patient-reported outcome (PRO) Extension guidance to a user-friendly format for patient partners and (b) to codesign a web-based tool to support the dissemination and uptake of the SPIRIT-PRO Extension by patient partners.Design A 1-day patient and public involvement session.Participants Seven patient partners.Methods A patient partner produced an initial lay summary of the SPIRIT-PRO guideline and a glossary. We held a 1-day PPI session in November 2019 at the University of Birmingham. Five patient partners discussed the draft lay summary, agreed on the final wording, codesigned and agreed the final content for both tools. Two additional patient partners were involved in writing the manuscript. The study compiled with INVOLVE guidelines and was reported according to the Guidance for Reporting Involvement of Patients and the Public 2 checklist.Results Two user-friendly tools were developed to help patients and members of the public be involved in the codesign of clinical trials collecting PROs. The first tool presents a lay version of the SPIRIT-PRO Extension guidance. The second depicts the most relevant points, identified by the patient partners, of the guidance through an interactive flow diagram.Conclusions These tools have the potential to support the involvement of patient partners in making informed contributions to the development of PRO aspects of clinical trial protocols, in accordance with the SPIRIT-PRO Extension guidelines. The involvement of patient partners ensured the tools focused on issues most relevant to them.

Background Patient-reported outcome measures (PROMs) can provide valuable insights on the impact of a disease or treatment on a patient’s health-related quality of life. In ophthalmology, particularly in dry eye disease (DED) and ocular surface disease (OSD), it is unclear whether the available PROMs were developed using comprehensive guidelines. To address this, we evaluated the methodological quality of studies assessing the psychometric properties of PROMs in DED and OSD [PROSPERO registration number CRD42019142328]. Methods Four databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the quality of the studies evaluating the psychometric properties of PROMs used in DED and OSD. Results The search strategy (S3 Table) retrieved 5,761 records, 573 duplicates were removed, 5,188 abstracts were screened and 127 full-text articles were retrieved for further review. Of these, 118 full-text articles did not meet the eligibility criteria and were excluded. Reference list and citation searching, identified an additional 8 articles bringing the total numbers of papers reviewed to 17. In general, psychometric properties such as content validity, measurement error and structural validity were not assessed by the studies included in this review. Studies reviewing The Impact of Dry Eye on Everyday Life (IDEEL) presented with the highest quality scores together with the Ocular Surface Disease Index (OSDI) questionnaire. Conclusions The quality of studies evaluating PROMs in DED and OSD was considered using the COSMIN standards. The majority of the studies evaluating PROMs included in this review did not meet the recommended COSMIN criteria and the quality of the PROMs evaluated is not assured. Further evaluation of their psychometric properties is required if these are going to be used in clinical practice or research.

BackgroundPatient-reported outcome measures (PROMs) can provide valuable insights on the impact of a disease or treatment on a patient's health-related quality of life. In ophthalmology, particularly in dry eye disease (DED) and ocular surface disease (OSD), it is unclear whether the available PROMs were developed using comprehensive guidelines. To address this, we evaluated the methodological quality of studies assessing the psychometric properties of PROMs in DED and OSD [PROSPERO registration number CRD42019142328].MethodsFour databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the quality of the studies evaluating the psychometric properties of PROMs used in DED and OSD.ResultsThe search strategy (S3 Table) retrieved 5,761 records, 573 duplicates were removed, 5,188 abstracts were screened and 127 full-text articles were retrieved for further review. Of these, 118 full-text articles did not meet the eligibility criteria and were excluded. Reference list and citation searching, identified an additional 8 articles bringing the total numbers of papers reviewed to 17. In general, psychometric properties such as content validity, measurement error and structural validity were not assessed by the studies included in this review. Studies reviewing The Impact of Dry Eye on Everyday Life (IDEEL) presented with the highest quality scores together with the Ocular Surface Disease Index (OSDI) questionnaire.ConclusionsThe quality of studies evaluating PROMs in DED and OSD was considered using the COSMIN standards. The majority of the studies evaluating PROMs included in this review did not meet the recommended COSMIN criteria and the quality of the PROMs evaluated is not assured. Further evaluation of their psychometric properties is required if these are going to be used in clinical practice or research.

Abstract Background Primary Sclerosing Cholangitis (PSC) is a rare chronic, cholestatic liver condition in which patients can experience a range of debilitating symptoms. Patient reported outcome measures (PROMs) could provide a valuable insight into the impact of PSC on patient quality of life and symptoms. A previous review has been conducted on the quality of life instruments used in liver transplant recipients. However, there has been no comprehensive review evaluating PROM use or measurement properties in PSC patients’ to-date. The aim of the systematic review was to: (a) To identify and categorise which PROMs are currently being used in research involving the PSC population (b) To investigate the measurement properties of PROMs used in PSC. Methods A systematic review of Medline, EMBASE and CINAHL, from inception to February 2018, was undertaken. The methodological quality of included studies was assessed using the Consensus-based Standards for selection of health Measurement Instruments (COSMIN) checklist. Results Thirty-seven studies were identified, which included 36 different PROMs. Seven PROMs were generic, 10 disease-specific, 17 symptom-specific measures and 2 measures on dietary intake. The most common PROMs were the Short form-36 (SF-36) (n = 15) and Chronic liver disease questionnaire (CLDQ) (n = 6). Only three studies evaluated measurement properties, two studies evaluated the National Institute of Diabetes Digestive and Kidney Diseases Liver Transplant (NIDDK-QA) and one study evaluated the PSC PRO; however, according to the COSMIN guidelines, methodological quality was poor for the NIDDK-QA studies and fair for the PSC PRO study. Conclusion A wide variety of PROMs have been used to assess health-related quality of life and symptom burden in patients with PSC; however only two measures (NIDDK-QA and PSC PRO) have been formally validated in this population. The newly developed PSC PRO requires further validation in PSC patients with diverse demographics, comorbidities and at different stages of disease; however this is a promising new measure with which to assess the impact of PSC on patient quality of life and symptoms.

Abstract Background Rare diseases can lead to a significant reduction in quality of life for patients and their families. Ensuring the patients voice is central to clinical decision making is key to delivering, evaluating and understanding the efficacy of therapeutic interventions. Patient reported outcome measures (PROMs) are used to capture the patient’s views about their health status and facilitate our understanding of the impact of these diseases and their treatments on patient’s quality of life and symptoms. Main text This review explores some of the current issues around the utilisation of PROMs in rare diseases, including small patient populations and dearth of valid PROMs. Difficulties in validating new or current PROMs for use in clinical trials and research are discussed. The review highlights potential solutions for some of the issues outlined in the review and the implementation of PROMs in research and clinical practice are discussed. Conclusion Patient input throughout the development of PROMs including qualitative research is essential to ensure that outcomes that matter to people living with rare disease are appropriately captured. Given the large number of rare diseases, small numbers of patients living with each condition and the cost of instrument development, creative and pragmatic solutions to PROM development and use may be necessary. Solutions include qualitative interviews, modern psychometrics and resources such as item banking and computer adaptive testing. Use of PROMs in rare disease research and clinical practice offers the potential to improve patient care and clinical outcomes.

BackgroundPatient-reported outcome measures (PROMs) can provide valuable information which may assist with the care of patients with chronic kidney disease (CKD). However, given the large number of measures available, it is unclear which PROMs are suitable for use in research or clinical practice. To address this we comprehensively evaluated studies that assessed the measurement properties of PROMs in adults with CKD.MethodsFour databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the methodological quality of the included studies and to inform a best evidence synthesis for each PROM.ResultsThe search strategy retrieved 3,702 titles/abstracts. After 288 duplicates were removed, 3,414 abstracts were screened and 71 full-text articles were retrieved for further review. Of these, 24 full-text articles were excluded as they did not meet the eligibility criteria. Following reference list and citation searching, 19 articles were retrieved bringing the total number of papers included in the final analysis to 66. There was strong evidence supporting internal consistency and moderate evidence supporting construct validity for the Kidney Disease Quality of Life-36 (KDQOL-36) in pre-dialysis patients. In the dialysis population, the KDQOL-Short Form (KDQOL-SF) had strong evidence for internal consistency and structural validity and moderate evidence for test-retest reliability and construct validity while the KDQOL-36 had moderate evidence of internal consistency, test-retest reliability and construct validity. The End Stage Renal Disease-Symptom Checklist Transplantation Module (ESRD-SCLTM) demonstrated strong evidence for internal consistency and moderate evidence for test-retest reliability, structural and construct validity in renal transplant recipients.ConclusionsWe suggest considering the KDQOL-36 for use in pre-dialysis patients; the KDQOL-SF or KDQOL-36 for dialysis patients and the ESRD-SCLTM for use in transplant recipients. However, further research is required to evaluate the measurement error, structural validity, responsiveness and patient acceptability of PROMs used in CKD.