Stigma and health outcomes in multiple sclerosis: a systematic review.

BACKGROUND: Stigma is increasingly recognised as contributing to disability in MS. This systematic review aimed to answer the following question: To what extent is stigma associated with psychological and physical health outcomes in MS? METHODS: The inclusion criteria were: scientific publication of original quantitative research in adults with MS and/or Clinically Isolated Syndrome; outcome measures including a measurement of stigma and psychological and/or physical health; peer reviewed articles in the English language. Pubmed, PsycINFO and Science Direct were searched in November 2023. The Joanna Briggs Institute Critical Appraisal Tool was used to assess the methodological quality and risk of bias in all of the identified studies. The following data was extracted: (1) author and publication year, (2) country, (3) design, (4) sample size and demographics, (5) stigma measure, (6) psychological and/or physical health outcomes, 8) key findings. RESULTS: 18 Studies were identified, reporting in total 22,021 adult participants with multiple sclerosis, with individual sample sizes ranging from 33 to 6,670. The review consistently identified stigma to be significantly associated with adverse psychological and physical health outcomes in all 18 identified studies. Over half of all identified studies investigated depression and stigma and over half investigated quality of life and stigma, and a significant association was demonstrated for both of these variables with stigma in all of these studies. DISCUSSION: Limitations are that most studies were Western with primarily white participants. Only variables studied could be reported and therefore only a selective perspective of stigma in MS could be explored. A meta-analysis was not feasible, due to the variety of stigma definitions and measures employed. A model of stigma in MS is presented and possible interventions to manage stigma in MS are discussed. A need for international action to develop a consensus measure of MS stigma and determine the trajectory and causal dynamics of MS stigma is highlighted.

Active Visual Art Therapy and Health Outcomes: A Systematic Review and Meta-Analysis.

Importance: Art therapy has a long-standing tradition in patient treatment. As scientific interest in its use has recently grown, a comprehensive assessment of active visual art therapy is crucial to understanding its potential benefits. Objective: To assess the association of active visual art therapy with health outcomes across patient groups and comparators. Data Sources: The systematic literature search included the Cochrane Library, Embase, MEDLINE, CINAHL, ERIC, American Psychological Association PsycArticles, American Psychological Association PsycInfo, PSYNDEX, the German Clinical Trials Register, and ClinicalTrials.gov. No filters regarding language were applied. The search covered all dates before March 2021. Data analysis was conducted from April 24 to September 8, 2023. Study Selection: Randomized clinical trials with any type of patient population comparing the intervention with any control not using active visual art therapy were included. Two researchers independently screened the abstracts and full texts. Data Extraction and Synthesis: Data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and study quality was evaluated using the Cochrane Risk of Bias tool. Data were synthesized using narrative summaries, forest plots, and random effects meta-analyses. Main Outcome and Measures: In line with the protocol, all outcome measures of the included studies were extracted. Results: The search identified 3104 records, of which 356 outcomes of 69 studies were included, with a total of approximately 4200 participants, aged 4 to 96 years, in the review. The meta-analyses included 50 studies and 217 outcomes of 2766 participants. Treatment indications included mental, neurological, and other somatic disorders, and prevention. Most outcome measures focused on depression, anxiety, self-esteem, social adjustment, and quality of life. Art therapy was associated with an improvement in 18% of the 217 outcomes compared with the controls (1%), while 81% showed no improvement. The standardized mean difference in the change from baseline of the meta-analyses of 0.38 (95% CI, 0.26-0.51) and posttest analysis of 0.19 (95% CI, 0.12-0.26) also indicated an improvement of outcomes associated with art therapy. Overall study quality was low. Conclusions and Relevance: In this systematic review and meta-analysis of randomized clinical trials, visual art therapy was associated with therapeutic benefits for some outcomes, although most studies were of low quality. Further good-quality studies are needed to provide additional insights for its best possible integration into routine care.

Development of a core outcome set of clinical research on the integration of traditional Chinese and Western medicine for spinal metastases: a study protocol.

BACKGROUND: In recent years, the incidence of spinal metastasis (SM) has been increasing steadily. In response to this serious public health problem, researchers have made progress by using the integration of traditional Chinese and Western medicine. However, considerable heterogeneity in the definition and measurement of outcomes across clinical research studies, along with the lack of uniform measurement standards for study data, makes it difficult for researchers to compare different treatments. Therefore, it is crucial to accurately evaluate clinical research on the integration of traditional Chinese and Western medicine for SM. METHODS: This study protocol outlines a comprehensive research programme based on the Core Outcome Set Standards Protocol Items. The study consists of four phases: a literature review, semistructured interviews, a two-round modified Delphi survey, a consensus meeting. Phase 1 involves a comprehensive literature review to extract outcomes used in current clinical studies of integrated traditional Chinese and Western medicine or Western medicine for the treatment of SM. A semistructured interview format will be used to survey patients and caregivers in phase 2 to collect suggestions from the patient perspective. Phase 3 involves a two-round modified Delphi survey to complete a prioritisation evaluation of outcomes to generate a candidate list for core outcome set (COS). Finally, phase 4 involves a face-to-face consensus meeting to review and establish the COS. ETHICS AND DISSEMINATION: Conducted in response to the current dilemma of SM, the study was endorsed by the Spine Oncology Group of the Orthopaedic Surgeons Branch of the Chinese Physicians' Association. It will be developed and reported through a rigorous process, with the results of the study to be published in a peer-reviewed journal.Registration: COMET Registry: COMET 2938; https://www.comet-initiative.org/Studies/Details/2938.

Outcome measures used in adolescent sport-related concussion research: a scoping review.

OBJECTIVES: To provide an overview of the outcome measures currently used after sports-related concussion (SRC) in adolescents, categorising by the constructs they assess, follow-up duration and their feasibility of use. DESIGN: Scoping review. DATA SOURCES: We searched three electronic databases (MEDLINE, EMBASE and CINAHL). We also undertook citation tracking of the included articles and searched for ongoing or unpublished trials using ClinicalTrials.gov and Theses Global. ELIGIBILITY CRITERIA: Studies tracking concussion recovery in adolescent athletes. RESULTS: 15 782 records were identified. After initial title and abstract screening, we retrieved 87 studies for full-text screening, with 75 studies fulfilling the eligibility criteria and included in the review, comprising 13 107 participants (9480 male, 3615 female and 12 unreported), ranging in age from 5 to 19 years. 46 different outcome measures were used, with Post-Concussion Symptom Scale (n=42) and Immediate Post-Concussion Assessment and Cognitive Testing (n=21) the most common. Most outcome measures quantified aspects of sensorimotor function including balance, oculomotor function and cognition. Follow-up duration ranged from 7 days to 1 year. 60% of studies ceased follow-up assessments within 6 weeks post-SRC. CONCLUSIONS: Adolescent SRC literature uses a wide range of outcome measures. Most research quantifies cognitive/fatigue domains in the acute/subacute stages post-SRC, using male participants. Other key domains such as anxiety/mood, migraine and key modifiers (cervical and sleep disturbance) are less well represented in the literature. Many of the outcome measures used in current research are associated with high cost and require highly qualified examiners, creating barriers to their implementation in some adolescent sporting environments. STUDY REGISTRATION: https://doi.org/10.17605/OSF.IO/N937E.

rTMS for Poststroke Pusher Syndrome: A Randomized, Patient-Blinded Controlled Clinical Trial.

BACKGROUND: Patients with poststroke pusher syndrome (PS) require longer duration of rehabilitation and more supplemental care after discharge. Effective treatment of PS remains a challenge. The role of repetitive transcranial magnetic stimulation (rTMS) for PS has not been examined. OBJECTIVE: Assess the efficacy of rTMS for patients with poststroke PS in reducing pushing behavior, enhancing motor recovery and improving mobility. METHODS: A randomized, patient- and assessor-blinded sham-controlled trial with intention-to-treat analysis was conducted. Thirty-four eligible patients with poststroke PS were randomly allocated to receive either rTMS or sham rTMS for 2 weeks. Pushing behavior on the Burke lateropulsion scale and scale for contraversive pushing, motor function on Fugl-Meyer assessment scale-motor domain (FMA-m) and mobility on modified Rivermead mobility index were measured at baseline, 1 and 2 weeks after intervention. Repeated-measures analysis of covariance was used for data analysis. RESULTS: There was no significant interaction between intervention and time on Burke lateropulsion scale (F = 2.747, P = .076), scale for contraversive pushing (F = 1.583, P = .214), or change of modified Rivermead mobility index (F = 1.183, P = .297). However, a significant interaction between intervention and time was observed for FMA-m (F = 5.464, P = .019). Post hoc comparisons of FMA-m show better improvement in rTMS group with mean differences of 12.7 (95% CI -7.3 to 32.7) and 15.7 (95% CI -4.6 to 36.0) at post-treatment week 1 and week 2 respectively. CONCLUSIONS: rTMS did not demonstrate significant efficacy in improving pushing behavior and mobility in patients with PS. However, rTMS might have potential effect in enhancing motor function for patients with PS. REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200058015 at http://www.chictr.org.cn/searchprojen.aspx) on March 26, 2022.

Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Gait disturbances are exacerbated in people with Parkinson's disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. OBJECTIVE: To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. METHODS: Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. RESULTS: The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. CONCLUSION: Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12622000101785.

Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data.

BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.

Evaluating cognitive assessment tools for patients with major depressive disorder receiving electroconvulsive therapy: A systematic review and meta-analysis.

BACKGROUND: Major Depressive Disorder (MDD) affects 350 million people worldwide. Electroconvulsive therapy (ECT) is effective, yet research on cognitive assessments post-treatment is lacking. This study systematically reviews and meta-analyzes the effectiveness of cognitive assessment tools post-ECT to optimize MDD treatment. METHODS: Following PRISMA guidelines, this review was pre-registered on PROSPERO (CRD42023470318). Searches were conducted across nine databases up to November 12, 2023. Quality assessment for Randomized Controlled Trials (RCTs) and quasi-experimental studies was performed using the Cochrane risk of bias tool, JBI critical appraisal tools, and the Jadad scale. Meta-analyses for short-term and long-term cognitive function involved 24 and 18 tools, respectively. FINDINGS: Thirty studies (20 RCTs and 10 quasi-experimental) involving 2462 MDD patients were evaluated. Results indicated no significant differences in overall short-term and long-term cognitive functions post-ECT. Short-term analysis showed impairments in memory, learning, and verbal abilities but improvements in attention and processing speed. Long-term analysis revealed enhancements in memory, learning, verbal, and visuospatial abilities compared to baseline. Based on GRADE classification, we recommend 11 tools for assessing acute cognitive function and 10 tools for chronic cognitive impairment. These tools demonstrated high reliability and validity, supporting their clinical use. INTERPRETATION: These findings provide critical evidence for future ECT clinical guidelines in managing MDD. The recommended tools can aid clinicians in adjusting ECT regimens, identifying early cognitive changes, and improving therapeutic outcomes in MDD treatment.

Self-compassion-based online group psychotherapy for bereavement-related grief: The COMPACT feasibility trial.

OBJECTIVE: This study aimed to examine the feasibility and effectiveness of online group psychotherapy focused on self-compassion for individuals experiencing bereavement-related grief. METHOD: This single-arm feasibility trial involved participants aged 18 years or older who had experienced bereavement at least 6 months prior the five-week intervention. Outcomes were measured at baseline, immediately post-intervention, and 4 and 12 weeks later. The primary endpoint was the percentage of participants who completed four out of five sessions; the pre-defined feasibility criterion was 70%. Secondary endpoints included measures of grief, depression, anxiety, self-compassion, and resilience. RESULTS: The program was conducted in three courses with 18, 26, and 16 participants, respectively. The primary endpoint was met for 83.1% of participants (54/65). Cohen's d effect sizes ([95% CI] 12 weeks vs. baseline) for grief, depression, anxiety, self-compassion, and resilience were - 0.25 [-0.52, 0.03], -0.64 [-0.94, -0.34], -0.48 [-0.77, -0.19], 0.50 [0.21, 0.79], and - 0.07 [-0.34, 0.21], respectively. CONCLUSIONS: Online group psychotherapy focused on self-compassion for individuals with bereavement-related grief is feasible and effective for addressing grief and psychological distress. Randomized controlled trials are warranted to confirm the intervention's efficacy. TRIAL REGISTRATION NUMBER: UMIN000048554, registered 2 August 2022.

Association between psychosocial factors and left ventricular assist device implant outcomes: A systematic review.

BACKGROUND: Psychosocial assessment is a core component of the multidisciplinary evaluation for left ventricular assist device (LVAD) implantation. The degree to which psychosocial conditions are considered a contraindication to LVAD implantation continues to be debated. This systematic review examines modifiable psychosocial factors as predictors of outcomes in patients undergoing LVAD implantation. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search resulted in 2509 articles. After deduplication, abstract and full-text review, 20 relevant articles were identified. RESULTS: Included studies evaluated socioeconomic status (n = 6), caregiver characteristics (n = 6), non-adherence (n = 6), substance use (n = 13), and psychiatric disorder (n = 8). The most commonly measured outcomes were all-cause death, readmission rate, and adverse events. Studies varied widely in definition of each psychosocial factor and selected outcomes. No psychosocial factor was consistently associated with a specific outcome in all studies. Socioeconomic status was generally not associated with outcomes. Non-adherence, psychiatric disorder, and substance use were associated with higher risks of mortality, adverse events, and/or readmission. Findings on caregiver characteristics were mixed. CONCLUSION: Of the psychosocial factors studied, non-adherence, psychiatric disorder, and substance use were the most consistently associated with an increased risk of mortality, readmission, and/or adverse events. Heterogeneity in research methodology and study quality across studies precludes firm conclusions regarding the impact of psychosocial factors on long-term patient outcomes. The results of this review reveal a need for adequately powered studies that use uniform definitions of psychosocial factors to clarify relationships between these factors and outcomes after LVAD implantation.

Predictors of six-month change in health-related quality of life in people with multiple sclerosis: A secondary data analysis of a randomized controlled trial.

BACKGROUND: Symptomatic treatment in people with multiple sclerosis (pwMS) requires multidisciplinary rehabilitation to alleviate disease progression and increasing health-related quality of life (HRQoL). However, the participant- and disease-specific factors that predict sustained improvement in HRQoL in pwMS undergoing inpatient rehabilitation remain unclear. Identifying these factors can help individually tailor inpatient rehabilitation programmes. Therefore, the aim of this study was to identify factors of pwMS at clinic entry for a three-week multidisciplinary inpatient rehabilitation that predict the change in physical and mental HRQoL over six months. METHODS: This is a secondary data analysis of a randomized controlled trial (NCT04356248) conducted at the Valens Rehabilitation Centre, Switzerland. HRQoL was assessed with the Medical Outcome Study 36-item Short Form Health Survey (SF-36) at clinic entry (T0; baseline) and six months after (T3; six-month follow-up). Data for 99 pwMS (mean age in years: 49.60 ± 10.17 SD, mean Expanded Disability Status Scale (EDSS) score: 4.62 ± 1.33 SD, 68.7 % female) were analysed using multiple linear regression. Outcome variables were six-month change in SF-36 Physical (ΔPCS) and Mental Component Scale (ΔMCS) scores. Predictor variables included baseline scores of PCS or MCS, fatigue, anxiety, depressive mood, cardiorespiratory fitness (V̇O2peak/kg), self-efficacy, smoking status, education level, age, EDSS, sex, time since diagnosis and MS phenotype. RESULTS: The regression model with ΔPCS as outcome variable explained 18.6 % of the variance of the ΔPCS score (p = .003). Lower PCS score (p < .001) and lower depressive mood (p = .032) at baseline predicted higher ΔPCS score. The regression model with ΔMCS as outcome variable explained 26.8 % of the variance of the ΔMCS score (p < .001). Lower MCS score (p < .001) and longer time since diagnosis (p = .048) at baseline predicted higher ΔMCS score. CONCLUSION: PwMS with lower physical HRQoL and better mood at clinic entry improved most in physical HRQoL over six months. PwMS with lower mental HRQoL and longer time since diagnosis at clinic entry improved most in mental HRQoL over six months. The results of this study contribute to the development of individualized rehabilitation programmes with the aim of maintaining and/or improving HRQoL of pwMS beyond the inpatient rehabilitation stay.

A systematic review and meta-analysis of the effectiveness of interventions targeting the parent-child relationship in families of children with an intellectual disability.

BACKGROUND: The review aimed to investigate the effectiveness of parent-child relationship interventions for families of children with intellectual disability up to 12 years old. METHODS: Quasi-experimental or randomised controlled trials (RCTs) of interventions targeting the parent-child relationship where ≥50% of children had an intellectual disability were included. Meta-analyses of parent-child relationship outcomes and child outcomes used standardised mean difference as the effect size. RESULTS: Twenty-seven papers were included (N = 1325). Parent-child relationship outcomes improved significantly (n = 1325; g = 1.08, 95% CI: 0.64, 1.52) with a large effect size that was robust to sensitivity analyses. Child developmental outcomes improved significantly (n = 1082; g = 0.65, 95% CI: 0.23, 1.07), and indicated a large effect size for child socialisation and communication. CONCLUSIONS: Findings suggest that interventions targeting parent-child relationship quality are associated with substantial improvements in parent-child relationship and may improve child outcomes related to socialisation and communication.

'A Meaningful Difference, but Not Ultimately the Difference I Would Want': A Mixed-Methods Approach to Explore and Benchmark Clinically Meaningful Changes in Aphasia Recovery.

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, < 65 years; n = 3, males) and eight speech pathologists (n = 4, hospital setting; n = 4, community setting) participated in one of four focus groups (duration: 92-112 min). Four themes were identified describing meaningful change as follows: (1) different for every single person; (2) small continuous improvements; (3) measured by progress towards personally relevant goals; and (4) influenced by personal factors. 'Slightly improved' was agreed as the threshold of MIC on the anchor-rating scale (75%-92%) within 6 months of stroke, whereas after 6 months there was a trend towards supporting 'much improved' (36%-66%). CONCLUSION: Our mixed-methods research with people with aphasia and speech pathologists provides novel evidence to inform the definition of MIC in aphasia rehabilitation. Future research will aim to establish MIC values for core OMIs. PATIENT OR PUBLIC CONTRIBUTION: This work is the result of engagement between people with lived experience of post-stroke aphasia, including people with aphasia, family members, clinicians and researchers. Engagement across the research cycle was sought to ensure that the research tasks were acceptable and easily understood by participants and that the outcomes of the study were relevant to the aphasia community. This engagement included the co-development of a plain English summary of the results. Advisors were remunerated in accordance with Health Consumers Queensland guidelines. Interview guides for clinicians were piloted by speech pathologists working in aphasia rehabilitation.

Pozelimab for CHAPLE disease: results from in-trial interviews and clinical outcome assessments.

BACKGROUND: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634). METHODS: Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change. RESULTS: Ten patients (aged 3-19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from "mild" to "very severe" at baseline to "no signs or symptoms" at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores. CONCLUSIONS: Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04209634 .

Heterogeneous Outcome Selection and Incomplete Prespecification of Outcomes in Systematic Reviews: A Case Study on Pressure Injury.

OBJECTIVE: To understand how reviewers select and prespecify outcomes for systematic reviews (SRs), the authors report on the outcomes used in SRs of pressure injury (PI) intervention and treatment and evaluate their completeness of prespecification. DATA SOURCES: The authors searched four electronic databases for SRs involving PI prevention and/or treatments. STUDY SELECTION: Inclusion criteria were SRs and meta-analyses evaluating interventions for preventing or treating PI. Studies without systematic search or risk-of-bias assessment, conference proceedings, and articles not in Chinese or English were excluded. DATA EXTRACTION: Two reviewers extracted and categorized the outcomes in domains, assessing outcome prespecification using a five-element framework. Data items included study characteristics, target population, type of interventions, and outcome variables. DATA SYNTHESIS: This review included 95 SRs that reported a total of 432 instances of 24 different outcome domains. An average of four outcome domains were reported per SR. The most frequently reported domains were PI healing, PI occurrence, and PI status. Of the 62 SRs that prespecified primary outcomes, 40 (64.52%) reported more than one primary outcome. Only 24 of the 432 instances (5.56%) were completely specified. Among the 24 outcome domains, 12 (50.00%) were listed as primary outcomes at least once. Primary outcomes were more completely specified than nonprimary outcomes. CONCLUSIONS: Systematic reviews of PI prevention and/or treatment report diverse, incompletely prespecified outcomes, highlighting the need for a core outcome set to standardize key clinical outcomes.

Process indicators outshine outcome measures: assessing hospital quality of care in breast cancer treatment in China.

Reporting the results of quality indicators can narrow the gap in the quality of care between hospitals. While most studies rely on outcome indicators, they may not accurately measure the quality of care. Process indicators are not only strongly associated with treatment outcomes, but are also more sensitive to whether patients are treated accurately, enabling timely intervention. Our study aims to investigate whether process indicators provide a more reasonable assessment of hospital quality of care compared to outcome indicators. Data were sourced from the Specific Disease Medical Service Quality Management and Control System in China. A total of 113,942 patients with breast cancer treated in 298 hospitals between January 2019 and April 2023 were included in this retrospective study. The rankability of 11 process indicators was calculated and used as a weight to create a new composite indicator. The composite indicators and outcome measures were compared using the O/E ratio categories. Finally, in order to determine the impact of different years on the results, a sensitivity analysis was conducted using bootstrap sampling. The rankability ( ρ ) values of the eleven process indicators showed significant differences, with the highest ρ value for preoperative cytological or histological examination before surgery (0.919). The ρ value for the outcome indicator was 0.011. The rankability-weighting method yielded a comprehensive score ( ρ  = 0.883). The comparison with categorical results of the outcome indicator has different performance classifications for 113 hospitals (37.92%) for composite scores and 140 (46.98%) for preoperative cytological or histological examinationbefore surgery. Process indicators are more suitable than outcome indicators for assessing the quality of breast cancer care in hospitals. Healthcare providers can use process indicators to identify specific areas for improvement, thereby driving continuous quality improvement efforts.

A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis.

BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.

Utilisation of standardised outcomes measures by clinical Physiotherapists working in Namibia: a nationwide cross-sectional study.

Introduction: The utilisation of standardised outcome measures (SOMs) is crucial for evaluating patients' health status. Physiotherapists are highly recommended to use SOMs routinely. Despite the well-documented benefits of using SOMs, the utilisation of SOMs in clinical practice is still problematic particularly in Africa. In Namibia, there is dearth of information about SOMs utilisation by physiotherapists and the associated factors. This study was aimed at determining the extent of routine utilisation of SOMs and the associated demographic and work-related factors among physiotherapists. Methods: A cross-sectional, nationwide, online survey was conducted and all registered qualified physiotherapists and intern physiotherapists working in public or private hospitals/clinics were invited to participate. Data was analysed using Statistical Package for the Social Sciences (SPSS) version 29.0. The Chi-square (χ2) and Fishers exact test investigated the relationship between the associated factors and routine SOMs utilisation. The alpha level was set at 0.05. Results: Of 230 participants who received the invitational link, 99 (43.0%) responded timeously to the call to participate. Although 97.9% (n=94) of the participants indicated having used at least one type of SOMs in the last six months, the frequency of utilisation varied. Routine utilisation, defined as 70%-100% of the time, was reported in only 49.0% of the participants. The Chi-square test only showed significant findings for gender (p=0.01) and clinical specialty (p=0.004). The odds of utilising SOMs were 4.13 greater among physiotherapists with a clinical specialty and 3.88 times greater for females than males. Conclusion: The rates for routine utilisation of SOMs by Namibian physiotherapists are unfavourable. Female gender and clinical specialty influenced the utilisation of SOMs in daily clinical practice. Cognisant of the study limitations, these results call for the need to improve the routine utilisation of the SOMs in Namibia.

Report From the Second Global Scientific Conference on Clinical Trial Design and Outcome Measures for RDH12-Associated Inherited Retinal Degeneration.

Translational Relevance: A multi-stakeholder, patient centric approach will be critical to the design of future successful clinical trials with outcome measures relevant to the RDH12-IRD population.