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Abstract Background Outcome measures in clinical practice assist in establishing progress for effective quality of care. Physiotherapists in the intensive care unit (ICU) promote lung function and facilitate early mobilization to prevent ICU-related complications. Objectives To determine the physical functional outcomes in critically ill patients in the trauma and medical critical care units at three hospitals in the Tshwane District. Method This was a quantitative prospective observational cohort study. Adult patients admitted in the trauma, medical ICU, and high care (HC) units were recruited. Ethical clearance was obtained from the [Masked for blind review], the National Department of Health Research (NHRD), and the Chief Executive Officers (CEOs) of the hospitals. Written consent was obtained from the recruited patients. Assessments were done on Mondays, Wednesdays, and Fridays using the Chelsea Critical Care Physical Assessment (CPAx) Tool until discharge from the units. Data were analyzed using SPSS version 28. Results Functional outcomes that improved quicker were respiratory function, cough reflex, rolling in the bed, and grip strength. An increase in CPAx scores correlated with improvement in the Glasgow coma scale (GCS) in both groups. Median and inter-quartile CPAx scores in the medical ICU for the initial assessments were 3(2–8) with an increase to 8(3.75–28.25) in the final assessment (p = 0.003). The median and interquartile CPAxs scores for initial assessments in the trauma ICU were 2(1–11.75) and 5(3.25–14) for the final assessments, with a p-value of 0.005 which showed statistical significance. Conclusion CPAx mean scores in the trauma ICU were higher than in the medical ICU. There were significant positive changes in the scoring of both populations but this was slightly better in the trauma ICU. Using the CPAx tool in a HC setting seemed feasible and patients showed higher scores compared to both trauma and medical ICU. Clinical implications The CPAX tool assists in the development of rehabilitation goals in the ICU and HC by physiotherapists. The tool can be adapted in the medical and trauma critical care units to assess functional outcomes. Trial registration Pan African Clinical Trials Registry, PACTR202305860988637, Registered 7 May 2023-Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25542 .

Resumen: Introducción: La atrofia muscular espinal 5q (AME) es una enfermedad genética neurodegenerativa que afecta a las motoneuronas alfa produciendo debilidad progresiva. Actualmente se precisan nuevas herramientas que permitan medir y caracterizar con precisión la progresión de la enfermedad y la eficacia de los nuevos tratamientos. El objetivo del presente trabajo es realizar la validación preliminar de un nuevo teclado inteligente (Neuromyotype) capaz de medir la fuerza y la velocidad de tecleo en pacientes con AME. Material y métodos: Se incluyeron 22 pacientes mayores de 15 años con AME y 26 controles sanos. En ellos se realizaron tres mediciones con el teclado (fuerza máxima, tiempo de ejecución de una tarea aleatoria de tecleo, tiempo de ejecución de una tarea secuencial de tecleo) y el tiempo para completar el Nine-Hole Peg Test (9HPT). A los pacientes se les administraron además unas escalas motoras (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb Module [RULM]) y funcionales (Egen Klassification [EK2] y la versión revisada de Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]). Se analizaron la viabilidad y la validez de constructo de Neuromyotype, midiendo el poder discriminativo entre pacientes y controles (mediante curvas ROC y el estadístico de Bangdiwala) y entre los distintos tipos funcionales de AME (walker, sitter y non-sitter) y su correlación con el resto de escalas motoras. Resultados: Las mediciones del teclado se pudieron realizar en todos los pacientes, al contrario que el resto de las escalas. Su administración fue rápida y sencilla. Las tres variables del teclado discriminaron muy bien entre pacientes y controles, siendo la fuerza (ROC = 0,963) la que mejor diferencia de las tres, igualando al 9HPT (ROC = 0,966). También mostraron una buena capacidad para diferenciar por tipo funcional (especialmente a los non-sitter de los sitter y walker), siendo el tiempo secuencial (B = 0,83) la herramienta que mejor discriminaba entre los tres grupos por encima del resto de escalas motoras. Todas las escalas motoras y funcionales mostraron correlaciones fuertes o muy fuertes entre sí (rs = 0,71-0,99), con la fuerza correlacionando mejor con escalas motoras y las variables de tiempo con las escalas funcionales. Conclusión: Este estudio demuestra la viabilidad y la validez de Neuromyotype para la valoración de pacientes adolescentes y adultos con AME. Los datos obtenidos con esta herramienta podrían ser de gran relevancia clínica, ahorrando tiempo y recursos en comparación con el resto de las escalas. Abstract: Introduction: Spinal muscular atrophy 5q (SMA) is a genetic neurodegenerative disease that affects alpha motor neurons producing progressive weakness. New outcome measures are currently required to accurately characterize the disease progression and the efficacy of new available treatments. The objective of this work is to preliminarily validate a new intelligent keyboard (Neuromyotype) measuring typing strength and speed in patients with SMA. Material and methods: Twenty two SMA patients older than 15 years, and 26 healthy controls were included. Three measurements were obtained with the keyboard (maximum strength, execution time of a random typing task, execution time of a sequential typing task) together with the time to complete the Nine-Hole Peg Test (9HPT). Patients were also administered motor (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb Module [RULM]), and functional scales (Egen Klassification [EK2] and the revised version of Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]). The viability and construct validity of the Neuromyotype were analyzed, measuring the discriminative power between patients and controls (using ROC curves and the Bangdiwala statistic), between the different functional types of SMA (walker, sitter and non-sitter) and their correlation with the rest of motor scales. Results: Neuromyotype measurements could be performed in all patients, unlike the rest of the scales. Its administration was quick and easy. The 3 variables on the keyboard discriminated very well between patients and controls, with strength (ROC = 0.963) being the one that best differentiates from the 3, equaling 9HPT (ROC = 0.966). They also showed a good ability to differentiate by functional type (especially non-sitters from sitters and walkers), with sequential time (B = 0.83) being the tool that best discriminates between the three groups above the rest of motor scales. All motor and functional scales showed strong or very strong correlations with each other (rs = 0.71-0.99), with strength correlating better with motor scales and timed variables with functional scales. Conclusion: This study shows the feasibility and validity of Neuromyotype for the evaluation of adolescent and adult patients with SMA. Data obtained with this tool could be of great clinical relevance, saving time and resources compared to the rest of the scales.

Abstract Background The commonly used (‘legacy’) PROMs evaluating outcomes of total hip arthroplasty (THA), have several limitations regarding their measurement properties and interpretation of scores. One innovation in PROMs is the use of Computerized Adaptive Testing (CAT). The Patient-Reported Outcomes Measurement Information System (PROMIS®) is a validated system of CATs. The aim of this study was to assess the measurement properties of PROMIS and legacy instruments in patients undergoing THA. Methodology Patients in this multicenter study filled out a questionnaire twice, including Dutch-Flemish PROMIS v1.2 Physical Function (PROMIS-PF) and v1.1 Pain Interference (PROMIS-PI) CATs and short forms, PROMIS v1.0 Pain Intensity, and legacy PROMs (Hip disability and Osteoarthritis Outcome Score (HOOS), HOOS-Physical function Shortform (HOOS-PS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Hip Score (OHS), and two numeric rating scales measuring pain). The reliability, measurement precision (Standard Error of Measurement (SEM)), smallest detectable change (SDC), and burden of PROMIS instruments were presented head-to-head to legacy PROMs. Furthermore, construct validity was assessed. Results 208 patients were included. All instruments had a sufficient test-retest reliability (range ICC: 0.83–0.96). The SEM of PROMIS CATs and short forms ranged from 1.8 to 2.2 T-score points, the SEM of legacy instruments 2.6–11.1. The SDC of PROMIS instruments ranged from 2.1 to 7.3 T-score points, the SDC of legacy instruments 7.2–30.9. The construct validity of PROMIS CAT and short forms were found sufficient, except for the PROMIS-PI short form. The burden of PROMIS CATs was smaller than PROMIS short forms (range 4.8–5.2 versus 8–20 items, respectively). The burden of legacy instruments measuring physical functioning ranged from 5 to 40 items. Conclusions The PROMIS-PF is less burdensome, with high measurement precision, and almost no minimal or maximal scores, and an equal reliability compared to legacy instruments measuring physical functioning in patients undergoing THA. The PROMIS Pain Intensity 1a is comparable to the legacy pain instruments in terms of burden, reliability and SDC. Measuring the construct Pain Interference may not have additional value in this population because of its high correlation with instruments measuring physical functioning. The SDC values presented in this study can be used for individual patient monitoring.

Abstract Background Oral function tests have been shown to reliably detect impaired bulbar function in adults with spinal muscular atrophy (SMA). Although not routinely recorded, it is known that persons with SMA are affected to varying degrees. Detecting differences in bite and tongue force, endurance, and maximum mouth opening has become particularly promising since the introduction of causal therapy for SMA. This study aimed to compare oral function among adult persons with SMA with different SMA types, walking abilities, and treatment status to a healthy control group. Methods Data from oral function tests conducted on 58 persons with SMA and 45 healthy individuals were analyzed. Differences in oral function between SMA subgroups were pairwise tested and compared to the healthy control group using Wilcoxon rank sum tests. Results In an overall comparison, three out of five oral function tests revealed lower values for the SMA group compared to the control group. Subgroup analyses indicated lower scores for most oral function tests in non-ambulatory, untreated patients with SMA type 2 compared to controls. Ambulatory, treated patients with SMA type 3 achieved strength and endurance values comparable to those of healthy individuals. Conclusions The impairment of oral function varies across persons with SMA. Routine measurement of oral function is warranted to determine individual bulbar involvement stages. Further evaluation should be scheduled if indicators such as restricted maximum mouth opening arise. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/register/de/trial/DRKS00015842/preview .

William Blake LeMaster,1 Corey J Witenko,2 Melinda K Lacy,2 Ann W Olmsted,2 Edmund J Moran,2 Donald A Mahler3,4 1Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; 2Theravance Biopharma US, Inc, South San Francisco, CA, USA; 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 4Respiratory Services, Valley Regional Hospital, Claremont, NH, USACorrespondence: Edmund J Moran, Theravance Biopharma US, Inc, 901 Gateway Boulevard, South San Francisco, CA, 94080, USA, Tel +1 650 892 9229, Email emoran@theravance.comPurpose: Several lung function endpoints are utilized in clinical trials of inhaled bronchodilators for chronic obstructive pulmonary disease (COPD). Trough forced expiratory volume in 1 second (FEV1) is a commonly reported endpoint in COPD trials and can be complemented by area under the FEV1 vs time curve (FEV1 AUC), which provides information on duration and consistency of bronchodilation over a dosing interval. Revefenacin, a once-daily bronchodilator, significantly improved lung function in patients with COPD when measured by trough FEV1 in two replicate Phase 3 trials. Here, we report an FEV1 AUC substudy using data from these trials.Patients and Methods: This post hoc analysis examined substudy data from 12-week replicate Phase 3 trials (NCT02459080/NCT02512510); patients with moderate to very severe COPD were randomized 1:1 to revefenacin 175 μg or placebo once daily. The substudy patients had FEV1 AUC0– 2h assessed on Day 1, and those who continued to Day 84 also underwent 24-hour serial spirometry postdose where FEV1 AUC0– 2h, AUC0– 12h, AUC12-24h, and AUC0– 24h were evaluated.Results: Fifty and 47 patients who received revefenacin and placebo underwent 24-hour serial spirometry; most baseline characteristics were aligned between groups. At Day 84 postdose, revefenacin demonstrated sustained improvements in bronchodilation over 24 hours; differences in least squares mean vs placebo were 282, 220, 205, and 212 mL for FEV1 AUC0– 2h, AUC0– 12h, AUC12– 24h, and AUC0– 24h (all P < 0.001), respectively.Conclusion: This substudy analysis supplements previous findings that revefenacin provides sustained bronchodilation over 24 hours. Assessing additional complementary COPD clinical trial endpoints can help clinicians make treatment decisions.Keywords: Bronchodilators, long-acting muscarinic antagonist, outcome measures, spirometry, forced expiratory volume in 1 second

Introduction: Few studies have assessed the minimum clinically important difference (MCID) of each Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) domain. This study assessed MCIDs of JOABPEQ in patients with lumbar spine disease by generation. Methods: We evaluated the JOABPEQ score of 805 consecutive patients with lumbar spine disease undergoing posterior surgery preoperatively and 1 year postoperatively. MCIDs of each JOABPEQ domain were determined using anchor- and distribution-based methods according to age. A question based on the concept of a health transition item was used as the anchor for the MCID decision. Results: Overall, MCIDs of the JOABPEQ were 28.6 and 27.3 points for pain-related disorder and gait disturbance, respectively. The MCID for the lumbar spine dysfunction domain did not reach 0.6 over the area under the curve. Regarding the differences among generations, MCIDs of pain-related disorder and gait disturbance domains differed slightly between the elderly and middle-aged. The psychological disorder domain did not reflect clinically meaningful changes in the elderly. MCIDs of the social life disturbance domain decreased with age. Conclusions: Focusing on achieving the ideal responsiveness of patient-reported outcomes across generations, MCIDs of the pain-related disorder and gait disturbance domains may be valuable for patients, regardless of age, when adopting the JOABPEQ for patients with lumbar spine disease undergoing surgery. This study only evaluated cases that underwent posterior lumbar surgery. Future research will necessitate conducting surveys concerning the outcomes of various treatments for lumbar spine disease.

Abstract Background The prevalence of Occupational Burnout is high among healthcare professionals (HCP). Hence, it is crucial to have robust measures for ascertaining burnout in this population. The Shirom-Melamed Burnout Measure is a prevalent tool used in the diagnosis of burnout, and in the delivery planning of mental health services. The 14-item Shirom-Melamed Burnout Measure (SMBM) was developed after a methodological revision of the 22-item Shirom-Melamed Burnout Questionnaire (SMBQ). Studies on the psychometric properties of the SMBM and SMBQ exist, but there remains a need for thorough evaluation to assess the methodological quality of individual studies. To address this gap, this systematic review aimed to critically appraise the measurement properties of the different versions of the Shirom-Melamed Burnout Measure/Questionnaire (SMBM/Q) used among healthcare professionals. Methodology Four databases (PubMed, CINAHL, PsychINFO, and Scopus) were searched for studies on the psychometric properties of all versions of the SMBM/Q among HCP. The methodological quality of the studies was evaluated using the COSMIN Risk of Bias checklist. Evidence supporting the measurement properties (EMP) of the SMBM was synthesized using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results Our final pool consisted of five research articles. One study on the 12-item SMBM was included to estimate content validity, two studies reported on the 14-item SMBM, while the other two employed the 22-item version. Interestingly, each study used the SMBM in a different language, namely English/Hebrew, Chinese, French, Serbian, and Swedish. Structural validity, internal consistency, and construct validity are the SMBM’s most assessed measurement properties. The Hebrew and French versions demonstrated high levels of structural validity and internal consistency, and the remaining reports on validity demonstrated low levels due to methodological flaws. Conclusions Per COSMIN guidelines, the SMBM should not be utilized for clinical purposes due to insufficient content validity, but has promising potential with ongoing research. Engaging critical stakeholders for concept elicitation will ensure the relevance, comprehensiveness, and comprehensibility of the PRO items. Likewise, establishing an MIC will allow capturing change over time, which will benefit longitudinal experimental studies. Plain English summary Occupational burnout is a significant problem among healthcare professionals, and it is crucial to have a reliable tool to measure it. The Shirom-Melamed Burnout Measure (SMBM) is commonly used to diagnose burnout and plan mental health services. Studies on the psychometric properties of the SMBM exist, but there remains a need for thorough evaluation to assess the methodological quality of individual studies. To address this gap, this systematic review critically appraised the measurement properties of the different versions of the Shirom-Melamed Burnout Measure (SMBM) used among healthcare professionals. Our findings indicate that only a few studies have examined the SMBM, and they have used the tool in different languages. Structural validity, internal consistency, and construct validity are the SMBM’s most assessed measurement properties. We recommend that more research is needed to assess the content validity of the SMBM. We also suggest that critical stakeholders should be involved in the development of the SMBM to ensure that it is relevant, comprehensive, and understandable.

Abstract Maladaptive coping such as fear avoidance behavior can prolong recovery from mild traumatic brain injury (mTBI). Routine assessment of fear avoidance may improve management of mTBI. This study aimed to validate a single-item measure of fear avoidance to make its assessment more pragmatic. The present study is a secondary analysis of a clinical trial that involved adults with persistent post-concussion symptoms (N = 90, 63% female). Participants completed the single-item fear avoidance rating, a validated legacy measure of fear avoidance (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and measures of anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), post-concussion symptoms (Rivermead Postconcussion Symptoms Questionnaire), and disability (World Health Organization Disability Assessment Schedule 12.0). Questionnaires were completed twice, at baseline (mean 18.1 weeks post injury) and again 12–16 weeks later following study-delivered rehabilitation in addition to usual care. We analyzed the associations (Spearman’s correlations) and agreement (weighted Kappa) between the single-item and FAB-TBI at baseline, posttreatment, individual FAB-TBI item scores, and the change in scores between baseline and posttreatment. In addition, we examined correlations between the single-item fear avoidance measure and related constructs, including anxiety, depression, post-concussion symptoms, and disability. The single-item fear avoidance measure correlated strongly with the FAB-TBI both at baseline and following treatment (ρ = 0.63 − 0.67, p

Abstract Background Co-design with consumers and healthcare professionals is widely used in applied health research. While this approach appears to be ethically the right thing to do, a rigorous evaluation of its process and impact is frequently missing. Evaluation of research co-design is important to identify areas of improvement in the methods and processes, as well as to determine whether research co-design leads to better outcomes. We aimed to build on current literature to develop a framework to assist researchers with the evaluation of co-design processes and impacts. Methods A multifaceted, iterative approach, including three steps, was undertaken to develop a Co-design Evaluation Framework: 1) A systematic overview of reviews; 2) Stakeholder panel meetings to discuss and debate findings from the overview of reviews and 3) Consensus meeting with stakeholder panel. The systematic overview of reviews included relevant papers published between 2000 and 2022. OVID (Medline, Embase, PsycINFO), EBSCOhost (Cinahl) and the Cochrane Database of Systematic reviews were searched for papers that reported co-design evaluation or outcomes in health research. Extracted data was inductively analysed and evaluation themes were identified. Review findings were presented to a stakeholder panel, including consumers, healthcare professionals and researchers, to interpret and critique. A consensus meeting, including a nominal group technique, was applied to agree upon the Co-design Evaluation Framework. Results A total of 51 reviews were included in the systematic overview of reviews. Fifteen evaluation themes were identified and grouped into the following seven clusters: People (within co-design group), group processes, research processes, co-design context, people (outside co-design group), system and sustainment. If evaluation methods were mentioned, they mainly included qualitative data, informal consumer feedback and researchers’ reflections. The Co-Design Evaluation Framework used a tree metaphor to represent the processes and people in the co-design group (below-ground), underpinning system- and people-level outcomes beyond the co-design group (above-ground). To evaluate research co-design, researchers may wish to consider any or all components in the tree. Conclusions The Co-Design Evaluation Framework has been collaboratively developed with various stakeholders to be used prospectively (planning for evaluation), concurrently (making adjustments during the co-design process) and retrospectively (reviewing past co-design efforts to inform future activities).

Abstract Background The Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE). Methods The study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements. Results Content validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items’ response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels. Conclusion The Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Abstract Background Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders of varying severity characterized by bone fragility. The primary objective of this international multidisciplinary collaboration initiative was to reach a consensus for a standardized set of clinician and patient-reported outcome measures, as well as associated measuring instruments for dental care of individuals with OI, based on the aspects considered important by both experts and patients. This project is a subsequent to the Key4OI project initiated by the Care4BrittleBones foundation which aims to develop a standard set of outcome measures covering a large domain of factors affecting quality of life for people with OI. An international team of experts comprising orthodontists, pediatric dentists, oral and maxillofacial surgeons, and prosthetic dentists used a modified Delphi consensus process to select clinician-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs) to evaluate oral health in individuals with OI. Important domains were identified through a literature review and by professional expertise (both CROMs and PROMs). In three focus groups of individuals with OI, important and relevant issues regarding dental health were identified. The input from the focus groups was used as the basis for the final set of outcome measures: the selected issues were attributed to relevant CROMs and, when appropriate, matched with validated questionnaires to establish the final PROMs which represented best the specific oral health-related concerns of individuals with OI. Results Consensus was reached on selected CROMs and PROMs for a standard set of outcome measures and measuring instruments of oral health in individuals with OI. Conclusions Our project resulted in consensus statements for standardization oral health PROMs and CROMs in individuals with OI. This outcome set can improve the standard of care by incorporating recommendations of professionals involved in dental care of individuals with OI. Further, it can facilitate research and international research co-operation. In addition, the significant contribution of the focus groups highlights the relevance of dental and oral health-related problems of individuals with OI.

Abstract Background SMA is a hereditary neuromuscular disease that causes progressive muscle weakness and atrophy. Several studies have shown that the burden of SMA is very high at many levels. Functional assessment tools currently used do not completely address the impact of the disease in patients’ life. The objective of this qualitative study was to identify aspects of SMA that are relevant to patients and to design items useful for assessment purposes. Results Five focus group sessions were run during an annual SMA families meeting in Madrid, Spain. Focus groups were composed by parents of SMA type I children, sitter children type II-III, parents of sitter children type II-III, adult patients, and parents of walker children. Two trained facilitators conducted the focus groups using a semi-structured guideline to cover previously agreed topics based on the input of a Scientific and Patient Advisory Committee. The guideline was adapted for the different groups. According to what was communicated by participants, SMA entails a high burden of disease for both patients and their parents. Burden was perceived in physical, psychological, and social areas. Patient’s physical domain was the most relevant for participants, especially for parents of non-ambulant children, followed by limitations of motor scales to capture all changes, parents psychological burden, treatment expectations and patient’s psychological burden. Ten domains were the main areas identified as impacted by the disease: mobility and independence, fatigue and fatigability, infections and hospital consultations, scoliosis and contractures, vulnerability, pain, feeding, time spent in care, breathing, and sleep and rest. Conclusions This study confirms the necessity of evaluating other aspects of the disease that are not assessed in the functional motor scale. Measures of other aspects of the disease, such as pain, fatigue, feeding, should be also considered. A patient-reported outcomes instrument measuring such aspects in a valid and reliable way would be very useful. This study generated a list of new items relevant to be systematically measured in the assessment of the impact of SMA on the patients’ everyday life.

Abstract Background Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies. Methods Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative. Discussion It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes. Systematic review registration PROSPERO CRD42022357644

The National Psoriasis Foundation surveyed a random, stratified sample of individuals with psoriatic disease in the United States to determine the prevalence of an unacceptable psoriatic arthritis (PsA) symptom state and its effect on depression and social participation. Acceptable and unacceptable levels of PsA were defined using established cutoff points (acceptable ≤4 vs unacceptable >4) on the Psoriatic Arthritis Impact of Disease 9. Psoriasis severity was defined by body surface area: mild < 3%, moderate–severe ≥ 3%. Depression was assessed utilizing the Patient Health Questionnaire 2. Social participation was assessed by the Patient Reported Outcome Information Measurement System Ability to Participate in Social Role and Activities-SF4a. The analysis cohort comprised 801 patients with PsA. Unacceptable disease activity level (Psoriatic Arthritis Impact of Disease >4) was reported by 59.6% of participants. After adjusting for age, sex, and psoriasis severity, individuals with likely depression (OR = 0.014, P < .001) and those with limited ability to participate in social roles and activities (OR = 0.05, P < .001) were less likely to experience acceptable levels of PsA activity. Ultimately, the results demonstrated that most United States patients with PsA have unacceptable levels of disease activity, which is associated with increased prevalence of depression and limitations in social participation.

Alhanouf Yousef Alnafisah,1 Ahmed Fawaz Alkhalidi,1 Hanin Aljohani,1 Manal Almutairi,1 Adel Alharf,2 Hadeel Alkofide3 1Efficacy and Safety Evaluation Department, Benefit and Risk Evaluation Directorate, Saudi Food and Drug Authority (SFDA), Riyadh, Saudi Arabia; 2Drug Sector, Saudi Food and Drug Authority (SFDA), Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Ahmed Fawaz Alkhalidi, Efficacy and Safety Evaluation Department, Benefit and Risk Evaluation Directorate, SFDA, Riyadh, 5163, Saudi Arabia, Tel +966555546169, Email afkhaldi@sfda.gov.saPurpose: In response to the COVID-19 pandemic, the World Health Organization (WHO) developed a set of outcome measures for trials primarily aimed at hospitalised patients. However, a gap exists in defining outcome standards for non-hospitalised patients. Therefore, this study aims to discuss hospitalisation as a primary outcome in outpatient trials and its potential pitfalls, specifically focusing on trials related to anti-SARS-COV-2 therapy.Methods: In this narrative review, researchers thoroughly searched MEDLINE and ClinicalTrials.gov from January 2020 to December 2022, targeting Phase III randomized controlled trials involving outpatients with mild-to-moderate COVID-19. The trials were specifically related to anti-SARS-COV-2 monoclonal antibodies or antiviral agents. The study collected essential data, including the type of intervention, comparator, primary objective, primary endpoint, and the use of estimands in the trial.Results: The search identified 12 trials that evaluated the efficacy of anti-SARS COV-2 therapies in a predefined population. Three studies used hospitalisation and death as primary endpoints in high-risk patients receiving monoclonal antibodies. Nine studies assessed the efficacy of several antiviral agents: four trials used hospitalisation and death as the main endpoints, while others used different measures such as virologic measures using the Reverse Transcription-Polymerase Chain Reaction test (RT-PCR), the eight-point WHO ordinal scale, symptom alleviation by Day 7 and time to clinical response.Conclusion: Choosing hospitalization as an endpoint may provide meaningful data such as the cost-effectiveness ratio of a drug. However, different hospital utilisation patterns and investigator decisions could bias clinical outcomes if no specific criteria are considered. Therefore, investigators should have clear criteria for determining variables that influence this measure.Keywords: COVID-19, outcome measures, non-hospitalized patients, monoclonal antibodies, antiviral agents

Ahmed S Alhowimel,1 Collins Ogbeivor,2 Ahmad Dalli Alruwaili,3 Omar M Morizn,1 Abdulaziz Aljamaan,1 Aqeel M Alenazi,1 Norah A Alhwoaimel,1 Mohammed M Alshehri,4 Bader A Alqahtani,1 Faris A Alodaibi5 1Department of Health and Rehabilitation Sciences, College of Applied Medical Science, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; 2Department of Physical Rehabilitation, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 3Joint Clinic, Riyadh, Saudi Arabia; 4Physical Therapy Department, Jazan University, Jazan, Saudi Arabia; 5Department of Rehabilitation Science, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Ahmed S Alhowimel, Department of Health and Rehabilitation Sciences, College of Applied Medical Science, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia, Tel +96611558888, Email a.a; howimel@psau.edu.saPurpose: This cross-sectional study aimed to validate the Arabic version of the Attitude toward Education and Advice for Low Back Pain (AxEL) Questionnaire.Patients and Methods: This study was conducted in two phases. First, the AxEL questionnaire was translated into Arabic and cross-culturally adapted. Second, the psychometric properties (such as validity) of the translated AxEL were evaluated.Results: The results showed that back translators and language specialists had no trouble translating the AxEL. The translators’ agreement was very high (88.2%), and the questionnaire items were logically and clearly translated from English into Arabic.Conclusion: The Arabic version of AxEL is a valid tool that can assess individuals’ beliefs and attitudes towards low back pain (LBP). It fills a significant void in cross-cultural research and can help healthcare providers understand the attitudes and beliefs influencing individuals’ management of LBP within the Arabic context.Keywords: education, low back pain, outcome measures

Abstract Introduction The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA. Methods Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe. Results We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P

Abstract Background Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. Methods A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman’s multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. Results Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of ‘accessible and timely’, ‘person-centred’, and values of ‘dignity and respect’ and ‘kindness with compassion’ were most prevalent. Among the three patient experience surveys identified, ‘accessible and timely’ and ‘person-centred’ were the most frequent domains. The least frequently highlighted domains and values were ‘equitable’ and ‘holistic’. No questions addressed the ‘safety’ domain. Conclusions The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of ‘Kindness and compassion’ require further emphasis when seeking feedback on healthcare experiences and the domains of ‘safety’, ‘equitable’, and ‘efficiency’ are not adequately represented in existing patient experience surveys.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).

Background Traditional Chinese acupuncture has been widely applied for the treatment of knee osteoarthritis (KOA) with outstanding efficacy. However, recognized and unified outcome indicators remain to be absent, which impedes the translation of research into high-quality clinical evidence. Therefore, the establishment of core outcome indicators for acupuncture in KOA is conducive to enhance the scientific rigor, rationality, and feasibility of clinical research programs in traditional Chinese medicine (TCM) , provide higher quality evidence-based basis for clinical research. Objective To analyze the current status of the application of outcome indicators in randomized controlled trials (RCTs) of acupuncture for KOA, so as to provide a basis for the assessment method of clinical efficacy. Methods PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP and SinoMed were searched for clinical RCTs of acupuncture in the treatment of KOA from 2003 to 2022. Two researchers screened and extracted the characteristics of literature. The indicator domain, measurement tools and the time point of measurement of RCTs of acupuncture for KOA were analyzed. Results A total of 131 papers were included, with a sample size of 22 726 cases and 89 outcome indicators, which were classified into 40 (44.9%) items for symptoms and signs, 22 (24.7%) items for physical and chemical examinations, 5 (5.6%) items for quality of life, 5 (5.6%) items for psychological state, 3 (3.4%) items for satisfaction evaluation, 2 (2.2%) items for safety indicators, and 12 (13.5%) items for other indicators. Among the 131 articles, 23 measurement time points were included in the 131 articles, ranging from 1 hour to 3 years after treatment, 106 (80.9%) articles used "clinical efficacy" as the outcome indicator, 23 (17.6%) articles used safety evaluation and adverse event reports. Conclusion There are some problems in the use of outcome indicators in the RCTs of acupuncture for KOA, such as large variation in the use of outcome indicators, confounding of primary and secondary indicators, abuse of index combination, irregular use of composite indexes, inadequate safety evaluation, irregular measurement time points, insufficient evaluation of long-term prognosis, and failing to reflect the characteristics of TCM intervention of acupuncture. Future research should combine treatment based on syndrome differentiation characteristics of TCM, to evaluate the efficacy of acupuncture in the treatment of KOA by using scientific and reasonable outcome indicators. It is urgent to establish the core indicators set of TCM in the treatment of KOA, and to construct a standardized and recognized COS-TCM.

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Aim Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. Methods The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Results Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Conclusions Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Trial registration Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075

Tibial hemimelia is a rare condition with a reported incidence of approximately one in one million live births. Although tibial hemimelia can vary its presentation, it often presents a shortened lower limb associated with deformities in the knee and ankle. The objective of this study is to present a case of tibial hemimelia and the surgical technique performed to correct the deformity and bone lengthening using a circular external fixator in several stages. A 15-year-old male patient was evaluated, presenting Jones type 3 tibial hemimelia (visible distal part, but no proximal) in the right lower limb associated with congenital clubfoot and ankle deformity. Studying and planning the patient’s case was essential to classify and define the best treatment. These treatments can be flawed and often reach amputation. In the case described, several surgical approaches were performed with the objective of reconstructions and deformity correction, followed by limb lengthening, presenting excellent results. Level of evidence IV; Therapeutic studies; Case Report.

ABSTRACT Introduction Outcome measurement instruments (OMIs) are used to gauge the effects of treatment. In post‐stroke aphasia rehabilitation, benchmarks for meaningful change are needed to support the interpretation of patient outcomes. This study is part of a research programme to establish minimal important change (MIC) values (the smallest change above which patients perceive themselves as importantly changed) for core OMIs. As a first step in this process, the views of people with aphasia and clinicians were explored, and consensus was sought on a threshold for clinically meaningful change. Methods Sequential mixed‐methods design was employed. Participants included people with post‐stroke aphasia and speech pathologists. People with aphasia were purposively sampled based on time post‐stroke, age and gender, whereas speech pathologists were sampled according to their work setting (hospital or community). Each participant attended a focus group followed by a consensus workshop with a survey component. Within the focus groups, experiences and methods for measuring meaningful change during aphasia recovery were explored. Qualitative data were transcribed and analysed using reflexive thematic analysis. In the consensus workshop, participants voted on thresholds for meaningful change in core outcome constructs of language, communication, emotional well‐being and quality of life, using a six‐point rating scale (much worse, slightly worse, no change, slightly improved, much improved and completely recovered). Consensus was defined a priori as 70% agreement. Voting results were reported using descriptive statistics. Results Five people with aphasia (n = 4, > 6 months after stroke; n = 5,

IntroductionStroke-induced upper limb disabilities can be characterized by both motor impairments and activity limitations, commonly assessed using Fugl-Meyer Motor Assessment for Upper Extremity (FMMA-UE) and Action Research Arm Test (ARAT), respectively. The relationship between the two assessments during recovery is largely unstudied. Expectedly they diverge over time when recovery of impairment (restitution) plateaus, but compensation-driven improvements still occur. The objective of this study is to evaluate the alignment between FMMA-UE and ARAT in defining upper limb functional recovery categories by ARAT scores. We aimed to establish cut-off scores for both measures from the acute/early subacute, subacute and chronic stages of stroke recovery.MethodsSecondary analysis of four prospective cohort studies (acute/early subacute: n = 133, subacute: n = 113, chronic: n = 92) stages post-stroke. Receiver operating characteristic curves calculated the area under the curve (AUC) to establish optimal FMMA-UE cut-offs based on predefined ARAT thresholds distinguishing five activity levels from no activity to full activity. Weighted kappa was used to determine agreement between the two assessments. We used minimally clinically important difference (MCID) and minimal detectable change (MDC95) for comparison.ResultsFMMA-UE and ARAT scores showed no relevant divergence across all recovery stages. Results indicated similar cut-off scores in all recovery stages with variability below MCID and MDC95 levels. Cut-off scores demonstrated robust AUC values from 0.77 to 0.86 at every recovery stage. Only in highly functional patients at the chronic stage, we found a reduced specificity of 0.55. At all other times sensitivity ranged between 0.68 and 0.99 and specificity between 0.71 and 0.99. Weighted kappa at the acute/early subacute, subacute and chronic stages was 0.76, 0.83, and 0.81, respectively.DiscussionOur research shows a strong alignment between FMMA-UE and ARAT cut-off scores throughout stroke recovery, except among the subgroup of highly recovered patients at the chronic stage. Discrepancies in specificity potentially stem from fine motor deficits affecting dexterity outcomes that are not captured by FMMA-UE. Additionally, the high congruence of both measures suggests they are not suited to distinguish between restitution and compensation. Calling for more comprehensive assessment methods to better understand upper limb functionality in rehabilitation.

IntroductionTo investigate the feasibility, discriminative and convergent validity, and reliability of a lower limb sensor-based proprioception measure in children with upper motor neuron (UMN) lesions.MethodWe assessed three proprioception modalities (joint movement, joint position, and dynamic position sense) of the lower limbs in 49 children with UMN lesions and 50 typically developing (TD) peers (5–19 years). Forty-three children with UMN lesion had a congenital and six an acquired brain lesion and 82% were able to walk without a walking aid. We evaluated the feasibility, compared the test results between children with UMN lesions and TD peers, and calculated Spearman correlations (rs) between the modalities. We quantified relative reliability with Intra-Class Correlation Coefficients (ICC) and absolute reliability with Smallest Detectable Changes (SDC).ResultsMost children with UMN lesions (>88%) found the tests easy to perform. The children with UMN lesions had significantly (p

IntroductionThe Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023.MethodsTwenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care.ResultsFive outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6.ConclusionsPR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

Abstract Social connection is important for long‐term care (LTC) residents' quality of life and care. However, there is a lack of consensus on how to measure it and this limits ability to find what improves and impairs social connection in LTC homes. We therefore aimed to systematically review and evaluate the measurement properties of existing measures of social connection for LTC residents, to identify which, if any, measures can be recommended. We searched eight electronic databases from inception to April 2022 for studies which reported on psychometric properties of a measure of any aspect(s) of social connection (including social networks, interaction, engagement, support, isolation, connectedness, and loneliness) for LTC residents. We used COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to evaluate the measurement properties reported for each identified measure and make recommendations. We identified 62 studies reporting on 38 measures; 21 measured quality of life, well‐being or life satisfaction and included a social connection subscale or standalone items and 17 measures specifically targeted social connection. We found there was little high‐quality evidence on psychometric properties such as sufficient content validity (n = 0), structural validity (n = 3), internal consistency (n = 3), reliability (n = 1), measurement error (n = 0), construct validity (n = 4), criterion validity (n = 0) and responsiveness (n = 0). No measures demonstrated satisfactory psychometric properties on all these aspects, so none could be recommended for use. Thirty‐four measures have the potential to be recommended but require further research to assess their quality and the remaining four are not recommended for use. Our review therefore found that no existing measures have sufficient evidence to be recommended for assessment of social connection in residents of LTC homes. Further validation and reliability studies of existing instruments or the development of new measures are needed to enable accurate measurement of social connection in LTC residents for future observational and interventional studies. Highlights Social connection is fundamental to person‐centered care in long‐term care homes. There is insufficient evidence for the reliability and validity of existing measures. No current measures can be recommended for use based on existing evidence. A reliable and valid measure of social connection is needed for future research.

Abstract Introduction Person‐centered goals capture individual priorities in personal contexts. Goal Attainment Scaling (GAS) has been used in drug trials involving people living with dementia (PLWD) but GAS has been characterized as difficult to incorporate into trials and clinical practice. We used GAS in a trial of New Interventions for Independence in Dementia Study (NIDUS)‐family, a manualized care and support intervention, as the primary outcome and to tailor the interventions to goals set. We aimed to assess the feasibility and content of baseline goal‐setting. Methods We developed training for nonclinical facilitators to set individualized GAS goals remotely with PLWD and family carer dyads, or carers alone, in the intervention trial, during the COVID‐19 pandemic. A qualitative content analysis of the goals set explored participants’ priorities and unmet needs, to consider how existing GAS goal domains might be extended in a psychosocial intervention trial context. Results Eleven facilitators were successfully trained to set and score GAS goals. A total of 313/328 (95%) participants were able to collaboratively set three to five goals with the facilitators. Of these, 302 randomized participating dyads set 1043 (mean 3.5, range 3 to 5) goals. We deductively coded 719 (69%) goals into five existing GAS domains (mood, behavior, self‐care, cognition, and instrumental activities of daily living); 324 (31%) goals were inductively coded into four new domains: carer break, carer mood, carer behavior, and carer sleep. The most frequently set goals pertained to social support. There was little variation in types of goals set based on the context of who set them or level of pandemic restrictions in place. Discussion It is feasible for people without clinical training to set GAS holistic goals for PLWD and family carers in the community. GAS has potential to facilitate personalization of care and support interventions, such as NIDUS‐family, and facilitate the roll out of more personalized care. Highlights Goal Attainment Scaling (GAS) can capture meaningful priorities of people with dementia and their family carers. A psychosocial intervention RCT used GAS as the primary outcome measure and goals were set collaboratively by non‐clinically trained facilitators. The findings underscore the feasibility of using GAS as an outcome measure with this population. The content analysis findings unveiled the diversity in experiences and priorities of the study participants. GAS has the potential to support the implementation of more person‐centred approaches to dementia care.

Abstract Background Patient‐reported outcomes measures (PROMs) are increasingly being collected within cancer clinical trials, yet limited literature on the feasibility and acceptability of doing so. Methods We collected parent‐proxy and adolescent (≥12 years old) PROMs through a longitudinal, psychosocial sub‐study (‘PRISM‐Impact’) embedded in a precision medicine trial for children with poor prognosis cancer (‘PRISM’). We report on feasibility (response, participation, and attrition rates; follow‐up and responding to elevated distress) and acceptability (parents’ perceived benefit/burden of participation; and impact on decision to participate in PRISM) of PRISM‐Impact. Results Over the reporting period, 462 families were eligible for PRISM‐Impact. Family and adolescent response rates were 53% and 45%, respectively. Parents whose child had relapsed were more likely to participate in PRISM‐Impact than parents whose child had not (p

Background: In the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson's disease on QoL of affected individuals. The Short Parkinson's Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson's disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale. Methods: Translation and cultural adaptation were performed. Included patients had diagnosis of Parkinson's disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach's Alpha and construct validity using Pearson's correlation between SPES-SCOPA and the gold standard PDQ-39. Results: 101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach's Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements. Conclusion: This research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

Incorporating person-centered outcomes into clinical trials for neurodegenerative diseases has been challenging due to a deficiency in quantitative measures. Meanwhile, the integration of personally meaningful treatment targets in clinical practice remains qualitative, failing to truly inform evaluations, therapeutic interventions and longitudinal monitoring and support. We discuss the current advances and future directions in capturing individualized brain health outcomes and present an approach to integrate person-centered outcome in a scalable manner. Our approach stems from the evidence-based electronic Person-Specific Outcome Measure (ePSOM) program which prompts an individual to define personally meaningful treatment priorities and report level of confidence in managing items that matter to the individual the most (e.g., “Do I feel confident in my ability to contribute to a conversation?”). Deployed either as a single version (person only) or a dyad version (person and care partner), our proposed tool could be used as an endpoint in clinical trials, offering proof of meaningful intervention benefits and in clinical practice, by establishing an anchor for the therapeutic objectives sought by the individual.

Introduction: Spinal surgical procedures became very frequent in the last decades with fusion techniques being widely used for several indications. Many of these surgeries imply a significant tissue disruption and muscle atrophy with subsequent pain and functional impairment. Research question: How to prepare and manage patients according to a rapid/enhanced recovery (RR/ERAS) protocol in a private setting while improving patient’s peri-operative experience and minimizing surgical footprint? Material and methods: All patients suffering from a thoracolumbar degenerative disease and with an indication for fusion between January 2018 and October 2021 were screened. Pain control, functional recovery, complication rate and patient’ satisfaction were recorded for at least one-year of follow-up (FU). Results: 100 patients were prospectively followed for at least one year after surgery. More than two thirds (n = 69, 69.0 %) had a trans-psoas extreme lateral interbody fusion (X-LIF) or anterior approach with posterior instrumentation and direct decompression when needed, 14 (14.0 %) had an anterior lumbar interbody fusion (ALIF) and 17 (17.0 %) patients had a posterior approach only (posterior LIF or transforaminal LIF). Most patients had multi-level surgery (n = 56, 56.0 %). All patients improved their quality of life and back and leg pain at one year FU with those having an antero-lateral approach improving significantly more. Overall satisfaction rate was higher than 90 %. Discussion and Conclusion: The application of RR/ERAS protocols to fusion surgery in degenerative spine proves to feasible and beneficial in a private care setting. Patients having anterolateral approaches tend to improve more than those with posterior only approaches.

Abstract Background Protein phosphatase 2 regulatory subunit B’ Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. As this disorder was recognized within the last decade, there are only 103 people published diagnoses to date. A thorough understanding of the motor manifestations of this disorder has not yet been established. Knowledge of the natural history of PPP2R5D related neurodevelopmental disorder will lead to improved standard of care treatments as well as serve as a baseline foundation for future clinical trials. Appropriate outcome measures are necessary for use in clinical trials to uniformly measure function and monitor potential for change. The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder. Results Thirty-eight individuals with PPP2R5D pathogenic variants, median age 8.0 years (range 1–27) were evaluated. Gross motor, upper limb and ambulatory function were assessed using the GMFM-66, six-minute walk test (6MWT), 10-meter walk run (10MWR), timed up and go (TUG), and revised upper limb module (RULM). The pediatric disability inventory computer adapted test (PEDI-CAT) captured caregiver reported assessment. Median GMFM-66 score was 60.6 (SD = 17.3, range 21.1–96.0). There were strong associations between the GMFM-66 and related mobility measures, 10MWR (rs = −0.733; p < 0.001), TUG (rs= −0.747; p = 0.003), 6MWT (r = 0.633; p = 0.006), RULM (r = 0.763; p < 0.001), PEDICAT-mobility (r = 0.855; p < 0.001), and daily activities (r = 0.822; p < 0.001) domains. Conclusions The GMFM is a valid measure for characterizing motor function in individuals with PPP2R5D related neurodevelopmental disorder. The GMFM-66 had strong associations with the RULM and timed function tests which characterized gross motor, upper limb and ambulatory function demonstrating concurrent validity. The GMFM-66 was also able to differentiate between functional levels in PPP2R5D related neurodevelopmental disorder demonstrating discriminant validity. Future studies should examine its sensitivity to change over time, ability to identify sub-phenotypes, and suitability as an outcome measure in future clinical trials in individuals with PPP2R5D variants.

Background Coronary microvascular disease (CMVD) is currently a research hotspot in the field of cardiovascular disease, traditional Chinese medicine (TCM) has unique advantages and significant efficacy in the treatment of CMVD, but there are problems in relevant clinical trials, such as inconsistencies in the diagnostic and efficacy criteria, exploring the core outcome set of TCM in the treatment of CMVD is conducive to the development of high-quality evidence in the future. Objective To analyze the application of outcomes measures in randomized controlled trials (RCTs) of CMVD treated with TCM, and propose corresponding questions and recommendations. Methods CNKI, SinoMed, VIP, Wanfang, PubMed, Embase and Cochrane Library were systematically searched for RCTs of CMVD treated with TCM from inception to February 09, 2023. The basic information, interventions and outcome measures in RCTs of CMVD treated with TCM were extracted, the Cochrane systematic review manual bias risk assessment tool was used to evaluate the bias risk of the included literature and the Excel software was used to statistically analyze the outcome measures. Results A total of 88 articles were included, involving 2 clinical trial registration protocols and 1 English literature. Cochrane systematic review manual bias risk assessment showed that the included literature were evaluated as unclear in terms of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, and other bias; mostly low risk in terms of outcome data completeness and selective reporting. A total of 18 RCTs were analyzed for TCM syndromes of patients diagnosed with CMVD, involving 6 RCTs related to blood stasis due to qi deficiency, 3 RCTs related to intermingled phlegm and blood stasis. A total of 115 outcome measures were obtained by statistical analysis, the total frequency was 571 times, which can be divided into 7 categories, including clinical efficacy, physicochemical testing, signs and symptoms, TCM syndrome points, quality of life, long-term prognosis, and safety testing. The frequency of total clinical efficacy rate was the highest (46 times), 3 months was the most commonly used intervention node. and the highest frequency of composite outcome measures was the clinical efficacy combined with physicochemical testing. Conclusion It was found that the overall quality of RCTs of TCM in the treatment of CMVD was generally low, and there are some problems in the outcome measures, such as the lack of standardized TCM syndrome diagnosis criteria and efficacy criteria, and the lack of long-term prognosis monitoring. In the future, it is also necessary to conduct high-quality RCTs, combined with the characteristics of TCM treatment, to construct a standardized core outcome set of TCM in the treatment of CMVD.

Whilst existing quantitative research identifies outcomes believed to be important by researchers and clinicians, it may neglect outcomes that are meaningful to patients. This study aimed to explore the outcomes of exercise that are important to people with lung cancer and their carers. Data collection involved a qualitative methodology including semi-structured interviews and focus groups. Question guide development was informed by the International Classification of Functioning (ICF) framework. Data were analyzed by two researchers with NVivo (v12) software using a conventional content analysis process, followed by directed content analysis to map outcomes to the ICF. Conduct and reporting adhered to COREQ guidelines. Fifteen participants provided data. Most participants had received their diagnoses 24 months prior to study involvement (n = 9), and one-third had completed treatment (n = 5). Important outcomes were reported by participants across all domains of the ICF: activity and participation (n = 24), body function (n = 19), body structure (n = 5), environmental factors (n = 5), and personal factors (n = 1). Additional code categories pertained to the impacts of non-cancer factors such as age, frailty, and comorbidities; identifying barriers to exercise; and individualizing outcome measures. Clinicians and researchers should consider selecting outcomes from all relevant domains of the ICF, with a focus on the activity and participation domain, in addition to non-cancer factors such as ageing, frailty, and co-morbidities. Feedback should be provided to patients following outcome measures collection and reassessment.

Abstract Introduction The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation. Methods This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients’ association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12 months and 24 months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests. Results The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test). Conclusions The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

Introduction Patients with Parkinson’s disease are often prescribed physical therapy. Physiotherapists often assist Parkinson’s disease patients with assessment and treatment, but little is known about the assessment tools and interventions they use. Additionally, physical therapists do not consistently integrate standard outcome measures and treatment procedures into their practices. Consequently, this study was carried out to determine physical therapists’ preferences for assessment and treatment of Parkinson’s disease. Methods Five hundred questionnaires were distributed to physiotherapists working in clinical settings. Overall, 446 physiotherapists responded to the survey and returned the questionnaires. Questionnaires with incomplete information were excluded from the survey. In total, 418 physiotherapists participated in the study, of whom 324 saw PD patients in their clinical practice. Results Overall, 446 physiotherapists responded to the survey and returned the questionnaires. Questionnaires with incomplete information were excluded from the survey. In total, 418 physiotherapists participated in the study, of whom 324 saw PD patients in their clinical practice. Study participants included 43.8% male PTs and 56.2% female PTs with an average age of 30.02 ± 5.38 years. The Berg balance scale for balance assessment was preferred by 220 (67.9%), the Mini Mental State Examination for cognitive assessment was preferred by 317 (97.8%), and the Unified Parkinson’s Disease Rating Scale was preferred by 168 (51.85%) PTs. Neurological PTs employed PNF (proprioceptive neuromuscular facilitation) to decrease stiffness, and exercise and task-focused training for functional training. Virtual Reality and Motor Imagery were also known by 56.6% and 62.4% of PTs, respectively, although only 4.8% and 1.85% used them. Conclusions Study results revealed that most physiotherapists follow routine assessment and treatment protocols and do not implement innovative technology in the physical rehabilitation of patients with Parkinson’s disease.

Background and Study Aim. In the context of the growing importance of strength training, the analysis of the impact of strength loads on muscle hypertrophy becomes increasingly significant. Therefore, it is critical to comprehend both the effects of strength training on stimulating muscle growth and the potential ramifications. This study aimed to systematically analyze and collate the existing scientific evidence on the effects of weight training on muscle hypertrophy. Material and Methods. The research method involved the source selection of relevant studies from various databases, with predefined inclusion criteria. A thorough literature search was conducted, followed by data extraction focusing on study design, subject population, type of weight training, duration, and outcome measures of muscle hypertrophy. Databases such as PubMed, Google Scholar and Scopus were the primary sources of literature searches. Results. The results of this systematic review indicated evidence supporting the positive effect of weight training on muscle hypertrophy in most of the studies included. However, some studies produced controversial findings or even showed no significant impact. Factors such as variations in exercise type, intensity, and frequency also influence the outcome of weight training on muscle growth. Conclusions. While weight training has the potential to stimulate muscle hypertrophy, its effects may vary based on various factors. Therefore, selecting the correct type of exercise, setting the appropriate intensity, and planning the frequency of activity is essential in achieving optimal results. This study has strong relevance in fostering effective and safe exercise programs.It can also serve as a basis for further research in exploring other factors that may influence weight training-induced muscle hypertrophy outcomes.

Background Flexor tendon injury zone V is a multicomponent soft tissue injury involving tendons, nerves, and vessels. Outcome assessment of repair thus requires evaluation of the hand as a whole rather than solely evaluating tendon function. The purpose of this Preferred Reporting Items for Systematic Reviews and Meta-Analyses -compliant systematic review was to identify and assess the components of outcome measures used in flexor zone V.

Background: This study aimed to translate, culturally adapt, and psychometrically validate the PROMIS Anxiety Short Form 8a item bank into Arabic for the general population of Saudi Arabia. Methods: The PROMIS Anxiety Short Form was translated according to the FACIT group method. Second, psychometric validation was conducted on a convenience sample of 322 participants (mean age, 26 ± 10.4 years; predominantly female) from the general population in Saudi Arabia. Rasch analysis (Winsteps® version 5.6.1) was used to examine category functioning, item fit, the person separation index, item difficulty, unidimensionality, and local dependency. Results: Translation and cultural adaptation demonstrated that most of the items were culturally suitable and conveyed the same underlying concepts as the original scale. The five response categories of the scale satisfied the category functioning criteria, and all items fit the underlying construct, with the exception of one item that demonstrated a misfit. The item difficulty demonstrated poor targeting for the sample population; however, the person separation index and reliability were good (2.67 and 0.88, respectively) and no local dependency was noted. Conclusions: The Arabic translation of PROMIS-A SF8a demonstrated good structural validity and psychometrics, making it a valuable tool for screening anxiety in Arabic-speaking populations. The application of this outcome measure shows promise for healthcare professionals and patients alike, as it contributes to the provision of high-quality care and formulation of appropriate treatment plans.

L-cone opsin expression by gene therapy is a promising treatment for blue cone monochromacy (BCM) caused by congenital lack of long- and middle-wavelength-sensitive (L/M) cone function. Eight patients with BCM and confirmed pathogenic variants at the OPN1LW/OPN1MW gene cluster participated. Optical coherence tomography (OCT), chromatic perimetry, chromatic microperimetry, chromatic visual acuity (VA), and chromaticity thresholds were performed with unmodified commercial equipment and/or methods available in the public domain. Adaptive optics scanning laser ophthalmoscope (AOSLO) imaging was performed in a subset of patients. Outer retinal changes were detectable by OCT with an age-related effect on the foveal disease stage. Rod and short-wavelength-sensitive (S) cone functions were relatively retained by perimetry, although likely impacted by age-related increases in the pre-retinal absorption of short-wavelength lights. The central macula showed a large loss of red sensitivity on dark-adapted microperimetry. Chromatic VAs with high-contrast red gratings on a blue background were not detectable. Color vision was severely deficient. AOSLO imaging showed reduced total cone density with majority of the population being non-waveguiding. This study developed and evaluated specialized outcomes that will be needed for the determination of efficacy and safety in human clinical trials. Dark-adapted microperimetry with a red stimulus sampling the central macula would be a key endpoint to evaluate the light sensitivity improvements. VA changes specific to L-opsin can be measured with red gratings on a bright blue background and should also be considered as outcome measures in future interventional trials.

Background Choroideremia is an X-linked inherited retinal degeneration that begins in childhood with nyctalopia and loss of peripheral vision, and gradually progresses to blindness in adulthood. Choroideremia is caused by null mutations in the CHM gene, which encodes Rab escort protein 1. Objective Assessment of the efficacy and safety of a single subretinal injection of an adeno-associated virus serotype 2 vector encoding Rab escort protein 1 in patients with choroideremia. Design Multicentre open-label clinical trial of a gene therapy for choroideremia using an adeno-associated virus serotype 2-Rab escort protein 1 vector. Setting This study (NCT02407678) was conducted at two NHS eye hospitals in the UK. Participants Males aged 18 years or above, having a clinical diagnosis of choroideremia with genetic confirmation of CHM gene mutation or molecular confirmation of Rab escort protein 1 protein deficiency and having best corrected visual acuity better than or equal to 6/60 (20/200; LogMAR 1.0). Intervention Adeno-associated virus serotype 2-Rab escort protein 1 vector suspension (1 × 1012 vector particles per ml) was supplied by Nightstar Therapeutics (London, UK), now part of Biogen Inc. (Cambridge, MA, USA). Up to 0.1 ml of adeno-associated virus serotype 2-Rab escort protein 1 vector suspension, corresponding to a dose of up to 1 × 1011 vector particles, was administered to the treated eye by subretinal injection. Selection of treated eyes was randomised in participants having relatively symmetrical retinal degeneration. Main outcome measures The primary safety-related outcome was change from baseline in best corrected visual acuity in treated eyes at 24 months post treatment, with prospective efficacy evaluated by comparative change from baseline in best corrected visual acuity in treated and untreated contralateral (control) eyes. Secondary outcomes included comparative change from baseline in mean retinal sensitivity (microperimetry) and retinal anatomy (area of autofluorescence) in treated and control eyes. Visual assessments were conducted by masked assessors. Results The primary efficacy-related outcome (comparative change from baseline in best corrected visual acuity in treated and control eyes at 24 months post treatment) was not statistically different between treated eyes (−2.63 letters, standard error of the mean 2.76) and control eyes (+2.67 letters, standard error of the mean 0.768) in all 30 participants (p = 0.08). Greater loss of visual fields, possibly surgery-induced, was observed in treated eyes. Six serious adverse events were reported in the treated eyes of four participants: one surgery-related and two inflammation-related serious adverse events involving clinically significant decreases in best corrected visual acuity, and three serious adverse events in one participant involving reduction in central retinal sensitivity, but with best corrected visual acuity remaining stable. Limitations No evidence of possible efficacy of the intervention was observed, as a meaningful difference in comparative change from baseline in best corrected visual acuity in treated and control eyes was not discernible at 24 months post treatment. As choroideremia is a very slow degeneration, best corrected visual acuity in control eyes did not decline significantly during the assessment period. Conclusion Although this study has not presented evidence that reduction in visual fields caused by the intervention would be justified by the possible rescue of best corrected visual acuity, a more definitive assessment may be provided by long-term monitoring of trial participants in an observational study (NCT03584165). Trial registration This study is registered as ISRCTN15602229 (www.isrctn.com/) and NCT02407678 (https://clinicaltrials.gov/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/66/35) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information. Plain language summary Choroideremia is a rare eye disease caused by a defective gene that prevents the cells in the retina, the light-sensitive layer at the back of the eye, from functioning normally. The disease usually affects males, although females can also develop the disease. In childhood, choroideremia patients initially experience ‘night blindness’, or difficulty in seeing in low light. As the disease progresses, there is a gradual loss in the peripheral vision, eventually resulting in ‘tunnel vision’ and finally in complete blindness by late adulthood. The aim of this study was to investigate if gene therapy was able to prevent further vision loss in patients suffering from choroideremia. The gene therapy for choroideremia uses a modified non-pathogenic virus, called a viral vector, to carry healthy copies of the affected gene into the retinal cells and thereby help the cells to function normally. Thirty male participants from two NHS eye hospitals took part in the study. Each participant received gene therapy in one eye, with the other eye left untreated for purposes of comparison. The condition and function of the treated and untreated (control) eyes were then monitored at regular time points over a 24-month period. A meaningful difference in the comparative rate of vision loss in the treated and control eyes was not observed during the 24-month assessment period of this study. However, it should be noted that choroideremia is a very slow degeneration and vision loss in the control eyes did not decline significantly during this period. Three participants experienced worse vision in their treated eyes, including one case of sight loss caused by severe inflammation that did not respond to medication. Additional data are being collected in a follow-on observational study to track the long-term progress of retinal degeneration in the treated eyes and control eyes of the participants. Scientific summary Background Choroideremia is an X-linked inherited retinal degeneration, affecting approximately 1 in 50,000 people, that begins in childhood with nyctalopia and loss of peripheral vision and gradually progresses to blindness in adulthood. Null mutations in the CHM gene cause a deficiency of Rab escort protein 1 (REP1), leading to degeneration of the retinal pigment epithelium (RPE), followed by secondary degeneration of photoreceptors and the choroid. As the central cone photoreceptors are generally preserved until the late stages of choroideremia, due to the centripetal nature of the degeneration, patients usually retain good visual acuity until degeneration encroaches on the fovea. Gene therapy, a procedure whereby a disease is treated at the genetic level by intracellular delivery of a therapeutic transgene, is an appealing strategy for treating choroideremia. Furthermore, the eye is an attractive site for gene therapy for several reasons. Surgical access is relatively straightforward and gene therapy products can be administered directly to cells in the outer retina (photoreceptors and RPE) by subretinal injection. Potential adverse events can be detected and monitored directly via ocular examination. Therapeutic outcomes can be measured directly using non-invasive assessments of visual function and retinal anatomy, with an untreated contralateral eye available as a control. The risk of systemic immune reactions is reduced by the anatomical compartmentalisation of the eye and the immunological privilege provided by the blood–retina barrier. Moreover, the small tissue volume of the subretinal space means that the therapeutic dose required to treat the retina is several thousand times lower in comparison with doses required for treatment of other organs, further reducing the risk of systemic adverse reactions. Most gene therapies developed thus far as potential treatments for inherited retinal diseases have utilised recombinant adeno-associated virus (AAV) particles as vectors to deliver therapeutic transgenes to target cells in the retina. This gene therapy for choroideremia uses an AAV serotype 2 (AAV2) vector encoding human REP1 protein (AAV2-REP1) that was first tested in human subjects in a phase I/II safety and dose escalation study (NCT01461213) at Oxford (UK). A cohort of six participants was initially treated with a dose of up to 1 × 1010 vector particles administered subretinally in one eye, followed by a cohort of eight participants treated with a higher dose of up to 1 × 1011 vector particles. Two serious adverse events (SAEs) occurred during the clinical trial, comprising a case of retinal thinning due to surgical complications and a case of postoperative inflammation, but otherwise the study data confirmed the safety and possible efficacy of the AAV2-REP1 vector for treatment for choroideremia (Xue K, Jolly JK, Barnard AR, Rudenko A, Salvetti AP, Patrício MI, et al. Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia. Nat Med 2018;24:1507–12). An additional 18 choroideremia patients were subsequently treated with a dose of up to 1 × 1011 particles of the same AAV2-REP1 vector administered subretinally in one eye – 6 participants in a phase I/II study (NCT02077361) at Edmonton (Canada), 6 participants in a phase II study (NCT02553135) at Miami (USA) and 6 participants in a phase II study (NCT02671539) at Tübingen (Germany). These studies showed that the AAV2-REP1 vector was generally well tolerated, with a subset of participants achieving clinically significant improvements in best corrected visual acuity (BCVA). One SAE involving a case of postoperative inflammation was reported in the Edmonton study (Dimopoulos IS, Hoang SC, Radziwon A, Binczyk NM, Seabra MC, MacLaren RE, et al. Two-year results after AAV2-mediated gene therapy for choroideremia: the Alberta experience. Am J Ophthalmol 2018;193:130–42). There were no cases of postoperative inflammation reported in the 12 choroideremia patients treated in Tübingen and Miami. In the Tübingen study, a pre-existing degenerative macular hole opened up in one of the participants during surgery but subsequently closed spontaneously (Fischer MD, Ochakovski GA, Beier B, Seitz IP, Vaheb Y, Kortuem C, et al. Efficacy and safety of retinal gene therapy using adeno-associated virus vector for patients with choroideremia: a randomized clinical trial. JAMA Ophthalmol 2019;137:1247–54). In the Miami study, two participants developed an atrophic retinal hole in a non-functioning macular area (Lam BL, Davis JL, Gregori NZ, MacLaren RE, Girach A, Verriotto JD, et al. Choroideremia gene therapy phase 2 clinical trial: 24-month results. Am J Ophthalmol 2019;197:65–73). In view of these satisfactory clinical outcomes, which indicated that gene therapy for choroideremia using the AAV2-REP1 vector demonstrated a good safety profile and sustained gains in BCVA in a proportion of trial participants, the REGENERATE (REP1 gene replacement therapy) phase II study (NCT02407678) was initiated to assess the efficacy of gene therapy (dose of up to 1 × 1011 particles of the AAV2-REP1 vector administered subretinally in one eye) in 30 choroideremia patients at an earlier stage of the disease and therefore still possessing substantial areas of surviving retinal tissue, thereby facilitating the measurement of area changes in order to assess the effect of gene therapy on retinal deterioration. Objectives The aim of the REGENERATE study was to investigate the efficacy and safety of a single subretinal injection of AAV2-REP1 in participants with a confirmed diagnosis of choroideremia over an assessment period of 24 months post treatment. The primary safety-related outcome was change from baseline in BCVA in treated eyes at 24 months post treatment, with prospective efficacy evaluated by comparative change from baseline in BCVA in treated and untreated contralateral (control) eyes. Secondary outcomes included comparative change from baseline in mean retinal sensitivity (microperimetry) and retinal anatomy (area of autofluorescence) in treated and control eyes at 24 months post treatment, as well as change from baseline in safety-related immunological and physiological indicators. Methods Study design The REGENERATE study is an open-label Phase II clinical trial investigating the efficacy and safety of AAV2-REP1 vector-mediated gene therapy for treatment of choroideremia. In contrast to other interventional studies, the REGENERATE study recruited choroideremia patients at an earlier stage of the disease and therefore still possessing substantial areas of surviving retinal tissue. The intention behind this study design was to facilitate the measurement of changes in the area of surviving RPE (determined by fundus autofluorescence) in order to assess the effect of gene therapy on retinal deterioration. Whereas in changes in BCVA and other measures of visual function in the treated eye could be compared against baseline values, assessment of the anatomical rate of degeneration ideally required the untreated contralateral eye to be used as an internal control. This condition required, in turn, the inclusion of participants having a fairly symmetrical disease. In consequence, randomisation of treatment of one eye or the other was also required to avoid selection bias. Sample size As this was an exploratory study to assess a new end point (comparative change from baseline in the area of surviving RPE in the treated and control eyes, determined by fundus autofluorescence), there was no predetermined power calculation to determine the number of trial participants. Instead, data from this trial will be used for future power calculations. A sample size of 30 participants in the REGENERATE study was deemed sufficiently statistically powered to show a signal in the primary end point of efficacy (comparative change from baseline in BCVA in the treated and control eyes) based on power calculations from the original phase I/II study (NCT01461213). Study setting The REGENERATE study was conducted at two NHS eye hospitals, namely, the Oxford Eye Hospital and Moorfields Eye Hospital. These sites were selected based on their expertise and prior experience in conducting clinical trials of retinal gene therapies and their access to specialist clinics for patients with inherited retinal diseases. Participants Participants were males aged 18 years or above, with a clinical phenotype of choroideremia, confirmed genetic or molecular diagnosis and having BCVA better than or equal to 6/60 (20/200; LogMAR 1.0). Candidates were excluded if they had an additional cause for sight loss (e.g. amblyopia) or any other significant ocular and non-ocular disease or disorder which, in the opinion of the investigator, might put them at risk through participation in the study. Allocation for treatment Participants in the REGENERATE study were assigned to one or both of the following cohorts: Cohort 1 included all participants and compared changes in BCVA and other measures of visual function in the treated eye against baseline values. Cohort 2 included the subset of participants with symmetrical disease for whom selection of the treated eye was randomised and compared the rate of anatomical degeneration in the treated eye and the untreated contralateral (control) eye. In the participants with asymmetrical disease (and therefore not included in Cohort 2), the decision about which eye to treat was made on clinical grounds and the worse-affected eye was chosen. Note that randomisation was not used for assigning treatment (vs. placebo/standard care as in randomised controlled trials) to participants included in Cohort 2, but solely for selection of the eye to be treated in these participants for whom the progress of retinal degeneration was relatively symmetrical between the two eyes, defined as a difference in BCVA of no more than one line of letters, as measured on an Early Treatment Diabetic Retinopathy Study chart; and no more than 25% difference in the area of surviving RPE, as measured by fundus autofluorescence. Intervention Adeno-associated virus serotype 2 vector encoding Rab escort protein 1 vector suspension (1 × 1012 vector particles per ml) was supplied by Nightstar Therapeutics (London, UK), now part of Biogen Inc. (Cambridge, MA, USA). Up to 0.1 ml of AAV2-REP1 vector suspension, corresponding to a dose of up to 1 × 1011 vector particles, was administered to the treated eye by subretinal injection. The dose varied slightly dependent on the amount of residual retina. Hence, in more advanced patients, 0.03–0.05 ml might have been sufficient to detach the target area of retina completely. The concentration of vector remained the same. The surgical technique for subretinal administration of the AAV2-REP1 vector suspension has been described previously (MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet 2014;383:1129–37). All surgeries took place at the participating hospital sites using the standard BIOM® (binocular indirect ophthalmic microscope) operating system (OCULUS Optikgeräte GmbH, Wetzlar, Germany). The retina was detached with 0.1–0.5 ml of balanced salt solution injected through a subretinal cannula connected to a vitreous injection set. A dose of up to 1 × 1011 vector particles was then injected into the subretinal fluid through the same entry site. Control eyes received no intervention. Assessments Functional assessments included BCVA, contrast sensitivity, dark adaptometry and central visual field mapping (using microperimetry), while anatomical assessments included imaging techniques such as optical coherence tomography and fundus autofluorescence. Safety tests included assessments of ocular and general physical condition, as well as standard blood tests of common physiological markers. Biological samples were also analysed to monitor vector shedding and immunogenicity. Cohort 1 comprised the 30 participants who enrolled in this study, of whom 28 participants had symmetrical disease and were therefore also assigned to Cohort 2. The statistical analyses were therefore performed on the total cohort comparing visual function and anatomical degeneration in treated versus control eyes. Summary statistics of each assessed variable was performed for treated eyes versus control eyes. Data involving a comparison of an assessed variable between the treated and untreated eyes (of each participant) were estimated as the difference between the eyes (with a 95% confidence interval) and simple analysis of change from baseline (paired t-test) was performed at 24 months post treatment. As most participants (93%) had symmetric disease, analysis of covariance was deemed unnecessary. Results Clinical outcomes Overall, BCVA remained relatively stable in treated and control eyes over the 24-month assessment period. A statistically significant deterioration in visual fields was observed in treated eyes compared with control eyes, possibly caused by surgery-induced damage in some treated eyes as manifested by increased loss of autofluorescence and retinal sensitivity at the edges of surviving islands of retinal tissue. The treated eyes underwent retinal detachment prior to injection of the vector suspension into the subretinal space, and this procedure itself can lead to some degree of reduction in central retinal sensitivity and autofluorescence. However, the statistical significance of the comparative reduction in visual fields in treated and control eyes was lost when central retinal sensitivity and area of autofluorescence were analysed in uncomplicated cases. In eyes with no complications, retinal degeneration continued centripetally in both treated and control eyes. Safety Most adverse events were treatable, controlled and resolved without sequelae. Six SAEs were reported in the treated eyes of four participants: one surgery-related and two inflammation-related SAEs involving clinically significant decreases in BCVA and three SAEs in one participant involving reduction in central retinal sensitivity but with BCVA remaining stable. Discussion Main findings of the study There has been no signal of possible efficacy of the intervention (in terms of comparative change from baseline in BCVA between treated and control eyes) over the 24-month assessment period. Overall, BCVA remained relatively stable in treated eyes over the 24-month assessment period. Therefore, in terms of the primary safety-related end point (change from baseline in BCVA in treated eyes at 24 months post treatment), the safety profile of the REGENERATE trial was comparable to other choroideremia gene therapy studies that evaluated the same AAV2-REP1 vector. Limitations of the study No evidence of possible efficacy of the intervention was observed, as a meaningful difference in comparative change from baseline in BCVA in treated and control eyes was not discernible over the 24-month assessment period. As choroideremia is a very slow degeneration, BCVA in control eyes did not decline significantly during the assessment period. Future investigations Future investigations will include a long-term assessment of BCVA, central retinal sensitivity and area of autofluorescence in REGENERATE trial participants in an observational study (SOLSTICE: NCT03584165). Possible approaches to further the investigation of gene therapy for choroideremia include the optimisation of inclusion criteria for subjects still retaining a healthy central retina, which may be more amenable to rescue by gene therapy. Conclusion Although this study has not presented evidence that reduction in visual fields caused by the intervention would be justified by the possible rescue of BCVA, a more definitive assessment may be provided by long-term monitoring of trial participants in an observational study (NCT03584165). Trial registration This study is registered as ISRCTN15602229 (www.isrctn.com/) and NCT02407678 (https://clinicaltrials.gov/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/66/35) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information.

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD.

The topic of attentional focus (focus of attention, FOA) in musical learning and performance has recently received increasing interest, as the growing number of empirical studies inspired by the established FOA paradigm in sports by Wulf and colleagues in 1998. The current systematical review aims at collecting, abstracting, and categorizing relevant data to show which kinds of FOA instructions were applied in experimental designs and what kinds of dependent variables were used to measure the effects of FOA instruction on musical performance. The three main inclusion criteria in the selection process were experimental design, detailed descriptions of FOA instructions, and outcome measures (OMs). A systematic search was conducted with a complex search term in four scientific databases in March 2023. For presenting and synthesizing results, we used data collection and an inductive-deductive data categorization. Fifteen studies with a total sample size of 401 participants were included out of 387 records initially identified. We collected 53 different FOA instruction citations from the 15 studies and classified them into 9 FOA subcategories, of which the most applied were bodily focus (21%), sound focus (15%), and visual focus (14%). Selected studies used 63 OMs that were abstracted to 10 different OM categories with expert ratings (27%) and acoustical analysis (22%) as the most applied dependent variables. Data categorization and abstraction of additional study information show multiple combinations of FOA instructions, OMs, participants’ instruments and expertise, and musical tasks. Finally, studies show no consistent results of superiority of either external or internal or otherwise different FOA considering positive effects on musical performance. Limitations of the review lie in the small study sample, possible criticism of applied eligibility criteria, and subjectivity of data categorization. We propose a research agenda with a more exploratory approach that comprehensively and qualitatively examines the dimensions of musical goals to create a database that could provide a foundation for developing a music-specific FOA model.

Background Ultrasound therapy is one of the preferred conservative treatments for patients with plantar fasciitis. This study aims to evaluate the effectiveness of therapeutic ultrasound in decreasing pain intensity and improving functional disability in patients with plantar fasciitis. Methods Five randomised control trials (RCT) were selected based on an electronic search in PubMed, Trip Database and PEDro. To be included in the systematic review, the study should be an RCT which investigated the effectiveness of therapeutic ultrasound conducted in patients with plantar fasciitis with pain intensity and functional disability as outcome measures. Only studies published in peer-reviewed journals written in the English language were included. The quality of the selected studies was measured by the PEDro scale. Results All the included studies showed that ultrasound therapy is beneficial in reducing pain score and improving functional disability, except one study did not recommend using ultrasound therapy for plantar fasciitis. Moreover, regarding another outcome measure, two studies found that ultrasound therapy reduces thickness and tenderness in plantar fasciitis and improves static and dynamic balance. Conclusion After reviewing the five studies, this systematic review support using ultrasound therapy to decrease pain and improve functional disability in patients with plantar fasciitis. Study Registration https://osf.io/xftzy/.

Quantitative measurement of physical activity may complement neurological evaluation and provide valuable information on patients’ daily life. We evaluated longitudinal changes of physical activity in patients with Friedreich ataxia (FRDA) using remote monitoring with wearable sensors. We performed an observational study in 26 adult patients with FRDA and 13 age-sex matched healthy controls (CTR). Participants were asked to wear two wearable sensors, at non-dominant wrist and at waist, for 7 days during waking hours. Evaluations were performed at baseline and at 1-year follow-up. We analysed the percentage of time spent in sedentary or physical activities, the Vector Magnitude on the 3 axes (VM3), and average number of steps/min. Study participants were also evaluated with ataxia clinical scales and functional tests for upper limbs dexterity and walking capability. Baseline data showed that patients had an overall reduced level of physical activity as compared to CTR. Accelerometer-based measures were highly correlated with clinical scales and disease duration in FRDA. Significantly changes from baseline to l-year follow-up were observed in patients for the following measures: (i) VM3; (ii) percentage of sedentary and light activity, and (iii) percentage of Moderate-Vigorous Physical Activity (MVPA). Reduction in physical activity corresponded to worsening in gait score of the Scale for Assessment and Rating of Ataxia. Real-life activity monitoring is feasible and well tolerated by patients. Accelerometer-based measures can quantify disease progression in FRDA over 1 year, providing objective information about patient’s motor activities and supporting the usefulness of these data as complementary outcome measure in interventional trials.

IntroductionMyoelectric pattern recognition systems have shown promising control of upper limb powered prostheses and are now commercially available. These pattern recognition systems typically record from up to 8 muscle sites, whereas other control systems use two-site control. While previous offline studies have shown 8 or fewer sites to be optimal, real-time control was not evaluated.MethodsSix individuals with no limb absence and four individuals with a transradial amputation controlled a virtual upper limb prosthesis using pattern recognition control with 8 and 16 channels of EMG. Additionally, two of the individuals with a transradial amputation performed the Assessment for Capacity of Myoelectric Control (ACMC) with a multi-articulating hand and wrist prosthesis with the same channel count conditions.ResultsUsers had significant improvements in control when using 16 compared to 8 EMG channels including decreased classification error (p = 0.006), decreased completion time (p = 0.019), and increased path efficiency (p = 0.013) when controlling a virtual prosthesis. ACMC scores increased by more than three times the minimal detectable change from the 8 to the 16-channel condition.DiscussionThe results of this study indicate that increasing EMG channel count beyond the clinical standard of 8 channels can benefit myoelectric pattern recognition users.

Abstract Aims Standard outcome sets enable the value-based evaluation of health care delivery. Whereas the attainment of expert opinion has been structured using methods such as the modified-Delphi process, standardized guidelines for extraction of candidate outcomes from literature are lacking. As such, we aimed to describe an approach to obtain a comprehensive list of candidate outcomes for potential inclusion in standard outcome sets. Methods This study describes an iterative saturation approach, using randomly selected batches from a systematic literature search to develop a long list of candidate outcomes to evaluate healthcare. This approach can be preceded with an optional benchmark review of relevant registries and Clinical Practice Guidelines and data visualization techniques (e.g. as a WordCloud) to potentially decrease the number of iterations. The development of the International Consortium of Health Outcome Measures Heart valve disease set is used to illustrate the approach. Batch cutoff choices of the iterative saturation approach were validated using data of 1000 simulated cases. Results Simulation showed that on average 98% (range 92–100%) saturation is reached using a 100-article batch initially, with 25 articles in the subsequent batches. On average 4.7 repeating rounds (range 1–9) of 25 new articles were necessary to achieve saturation if no outcomes are first identified from a benchmark review or a data visualization. Conclusion In this paper a standardized approach is proposed to identify relevant candidate outcomes for a standard outcome set. This approach creates a balance between comprehensiveness and feasibility in conducting literature reviews for the identification of candidate outcomes.