Assessing the Measurement Properties of the Self-Administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): A Rasch Analysis.

OBJECTIVE: The self-administered version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is used to monitor function and disease progression in individuals with amyotrophic lateral sclerosis (ALS). However, the performance of the self-administered ALSFRS-R has not been assessed using Rasch Measurement Theory. Therefore, the purpose of this study was to examine the psychometric properties of the self-administered ALSFRS-R using Rasch analysis. METHODS: Rasch analysis was performed on self-administered ALSFRS-R data from individuals with ALS across Canada. The following 6 aspects of Rasch analysis were examined using RUMM2030: fit via residuals and chi-square statistics, targeting via person-item threshold maps, dependency via item residual correlations, unidimensionality through principal components analysis of residuals, reliability via person separation index, and stability through differential item functioning analyses for sex, age, and language. RESULTS: Analysis was performed on 122 participants (mean age: 52.9 years; 62.8% men). The overall scale demonstrated good fit, reliability, and stability; however, multidimensionality was found. To address this issue, items were divided into 3 subscales (bulbar, motor, and respiratory function), and Rasch analysis was performed for each subscale. The subscales demonstrated good fit, reliability, stability, and unidimensionality. However, there were still issues with item dependency for all subscale and targeting for bulbar and respiratory subscales. CONCLUSIONS: The self-administered ALSFRS-R is reliable, internally valid, and stable across sex, age, and language subgroups; however, it is recommended that the ALSFRS-R be scored by subscale. Future studies can look at revising and/or adding items to tackle misfit, redundancy, and ceiling effects. IMPACT: Self-administered measures are simple to administer and inexpensive. The self-administered ALSFRS-R was found to be psychometrically sound and can be used as a tool to monitor disease progression and function in ALS.

The effect of rurality and distance from care on health outcomes, environmental barriers, and healthcare utilization patterns in persons with traumatic spinal cord injury.

STUDY DESIGN: Cohort study. OBJECTIVES: To evaluate the association between residential living location and health outcomes, environmental barriers, quality of life, and healthcare utilization patterns after traumatic spinal cord injury (tSCI). SETTING: Community setting, Atlantic Canada. METHODS: An ambispective study of data collected on a subset of individuals enrolled in the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2012 to 2018. Outcomes were analyzed using two measures of rurality: postal codes at community follow-up (rural versus urban) and residential travel distance to the nearest RHSCIR facility (>100 km versus ≤100 km). Outcomes studied included the Craig Hospital Inventory of Environmental Factors-Short Form (CHIEF-SF), Short Form-36 Version 2 (SF36v2), Life Satisfaction Questionnaire (LISAT-11), Spinal Cord Independence Measure (SCIM), secondary health complications and healthcare utilization patterns. Outcomes were assessed 9 to 24 months post-discharge from initial hospitalization. RESULTS: 104 participants were studied, 21 rural and 83 urban based on postal codes at community follow-up. 59 participants lived more than 100 km away from the nearest RHSCIR facility, while 45 participants lived within 100 km. Individuals from urban area codes reported a greater magnitude of perceived barriers on the policies and work/school subscales of the CHIEF-SF. No differences in function, quality of life, and healthcare utilization patterns according to the measures of rurality were observed. Individuals living >100 km from the nearest RHSCIR facility reported greater rates of sexual dysfunction. CONCLUSIONS: Despite differences in environmental barriers, individuals from urban and rural locations in Eastern Canada reported similar health outcomes and quality of life after tSCI.

Application of annotation-agnostic RNA sequencing data analysis tools for biomarker discovery in liquid biopsy.

RNA sequencing analysis is an important field in the study of extracellular vesicles (EVs), as these particles contain a variety of RNA species that may have diagnostic, prognostic and predictive value. Many of the bioinformatics tools currently used to analyze EV cargo rely on third-party annotations. Recently, analysis of unannotated expressed RNAs has become of interest, since these may provide complementary information to traditional annotated biomarkers or may help refine biological signatures used in machine learning by including unknown regions. Here we perform a comparative analysis of annotation-free and classical read-summarization tools for the analysis of RNA sequencing data generated for EVs isolated from persons with amyotrophic lateral sclerosis (ALS) and healthy donors. Differential expression analysis and digital-droplet PCR validation of unannotated RNAs also confirmed their existence and demonstrates the usefulness of including such potential biomarkers in transcriptome analysis. We show that find-then-annotate methods perform similarly to standard tools for the analysis of known features, and can also identify unannotated expressed RNAs, two of which were validated as overexpressed in ALS samples. We demonstrate that these tools can therefore be used for a stand-alone analysis or easily integrated into current workflows and may be useful for re-analysis as annotations can be integrated post hoc.

Urbanization, air pollution, and water pollution: Identification of potential environmental risk factors associated with amyotrophic lateral sclerosis using systematic reviews.

Introduction: Despite decades of research, causes of ALS remain unclear. To evaluate recent hypotheses of plausible environmental factors, the aim of this study was to synthesize and appraise literature on the potential associations between the surrounding environment, including urbanization, air pollution and water pollution, and ALS. Methods: We conducted a series (n = 3) of systematic reviews in PubMed and Scopus to identify epidemiological studies assessing relationships between urbanization, air pollution and water pollution with the development of ALS. Results: The combined search strategy led to the inclusion of 44 articles pertaining to at least one exposure of interest. Of the 25 included urbanization studies, four of nine studies on living in rural areas and three of seven studies on living in more highly urbanized/dense areas found positive associations to ALS. There were also three of five studies for exposure to electromagnetic fields and/or proximity to powerlines that found positive associations to ALS. Three case-control studies for each of diesel exhaust and nitrogen dioxide found positive associations with the development of ALS, with the latter showing a dose-response in one study. Three studies for each of high selenium content in drinking water and proximity to lakes prone to cyanobacterial blooms also found positive associations to ALS. Conclusion: Whereas markers of air and water pollution appear as potential risk factors for ALS, results are mixed for the role of urbanization.

Patient Reported Outcome Measures in Adult Spinal Muscular Atrophy: A Scoping Review and Graphical Visualization of the Evidence.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a hereditary neuromuscular disease with an estimated prevalence of 1/10 000 births. SMA is increasingly recognized as a multi-system disease with a need to study additional under-recognized health domains such as quality of life, fatigue, bulbar function, respiratory function, and independence. OBJECTIVE: Identify and assess reported evidence from the literature investigating Patient Reported Outcome Measures (PROMs) in adults with SMA. Develop a novel method drawing from network theory to graphically depict the literature, PROMs, and supporting psychometric evidence. METHODS: A scoping review was completed following PRISM-ScR, COSMIN and JBI scoping review guidelines. Literature investigating PROMs in adult SMA or neuromuscular disease was identified from peer-reviewed and grey databases. A network graph was derived from extracted data. RESULTS: 5292 articles were retrieved, 81 articles met inclusion criteria; corresponding to 31 unique PROMs. Only two PROMs were developed specifically for SMA. Few PROMs covered multiple domains of health. Most PROMs were incompletely validated, focusing on concurrent validity, and few assessed responsiveness or internal consistency. CONCLUSIONS: PROMs are emerging tools for monitoring and assessing adults with SMA. Despite their potential benefits, additional validation studies should be completed prior to their use for clinical decision-making. Network graphics may represent a technique to aid in the visualization of evidence supporting a scoping review.

Spasticity Management Teams, Evaluations, and Tools: A Canadian Cross-Sectional Survey.

OBJECTIVE: The objective of this study is to determine the physical evaluations and assessment tools used by a group of Canadian healthcare professionals treating adults with spasticity. METHODS: A cross-sectional web-based 19-question survey was developed to determine the types of physical evaluations, tone-related impairment measurements, and assessment tools used in the management of adults with spasticity. The survey was distributed to healthcare professionals from the Canadian Advances in Neuro-Orthopedics for Spasticity Congress database. RESULTS: Eighty study participants (61 physiatrists and 19 other healthcare professionals) completed the survey and were included. Nearly half (46.3%, 37/80) of the participants reported having an inter- or trans-disciplinary team managing individuals with spasticity. Visual observation of movement, available range of motion determination, tone during velocity-dependent passive range of motion looking for a spastic catch, spasticity, and clonus, and evaluation of gait were the most frequently used physical evaluations. The most frequently used spasticity tools were the Modified Ashworth Scale, goniometer, and Goal Attainment Scale. Results were similar in brain- and spinal cord-predominant etiologies. To evaluate goals, qualitative description was used most (37.5%). CONCLUSION: Our findings provide a better understanding of the spasticity management landscape in Canada with respect to staffing, physical evaluations, and outcome measurements used in clinical practice. For all etiologies of spasticity, visual observation of patient movement, Modified Ashworth Scale, and qualitative goal outcomes descriptions were most commonly used to guide treatment and optimize outcomes. Understanding the current practice of spasticity assessment will help provide guidance for clinical evaluation and management of spasticity.

An international survey of the structure and process of care for traumatic spinal cord injury in acute and rehabilitation facilities: lessons learned from a pilot study.

BACKGROUND: To describe the key findings and lessons learned from an international pilot study that surveyed spinal cord injury programs in acute and rehabilitation facilities to understand the status of spinal cord injury care. METHODS: An online survey with two questionnaires, a 74-item for acute care and a 51-item for rehabilitation, was used. A subset of survey items relevant to the themes of specialized care, timeliness, patient-centeredness, and evidence-based care were operationalized as structure or process indicators. Percentages of facilities reporting the structure or process to be present, and percentages of indicators met by each facility were calculated and reported separately for facilities from high-income countries (HIC) and from low and middle-income countries (LMIC) to identify "hard to meet" indicators defined as those met by less than two-thirds of facilities and to describe performance level. RESULTS: A total of 26 acute and 26 rehabilitation facilities from 25 countries participated in the study. The comparison of the facilities based on the country income level revealed three general observations: 1) some indicators were met equally well by both HIC and LMIC, such as 24-hour access to CT scanners in acute care and out-patient services at rehabilitation facilities; 2) some indicators were hard to meet for LMIC but not for HIC, such as having a multidisciplinary team for both acute and rehabilitation settings; and 3) some indicators were hard to meet by both HIC and LMIC, including having peer counselling programs. Variability was also observed for the same indicator between acute and rehabilitation facilities, and a wide range in the total number of indicators met among HIC facilities (acute 59-100%; rehabilitation 36-100%) and among LMIC facilities (acute: 41-82%; rehabilitation: 36-93%) was reported. CONCLUSIONS: Results from this international pilot study found that the participating acute and rehabilitation facilities on average adhered to 74% of the selected indicators, suggesting that the structure and processes to provide ideal traumatic spinal cord injury care were broadly available. Recruiting a representative sample of SCI facilities and incorporating regional attributes in future surveys will be helpful to examine factors affecting adherence to indicators.

Canadian Stroke Best Practice Recommendations: Virtual Stroke Rehabilitation Interim Consensus Statement 2022.

ABSTRACT: The seventh edition of the Canadian Stroke Best Practice Recommendations for Rehabilitation and Recovery following Stroke includes a new section devoted to the provision of virtual stroke rehabilitation. This consensus statement uses Grading of Recommendations, Assessment, Development and Evaluations methodology and Appraisal of Guidelines for Research & Evaluation II principles. A literature search was conducted using PubMed, Embase, and Cochrane databases. An expert writing group reviewed all evidence and developed recommendations, as well as consensus-based clinical considerations where evidence was insufficient for a recommendation. All recommendations underwent internal and external review. These recommendations apply to hospital, ambulatory care, and community-based settings where virtual stroke rehabilitation is provided. This guidance is relevant to health professionals, people living with stroke, healthcare administrators, and funders. Recommendations address issues of access, eligibility, consent and privacy, technology and planning, training and competency (for healthcare providers, patients and their families), assessment, service delivery, and evaluation. Virtual stroke rehabilitation has been shown to safely and effectively increase access to rehabilitation therapies and care providers, and uptake of these recommendations should be a priority in rehabilitation settings. They are key drivers of access to high-quality evidence-based stroke care regardless of geographical location and personal circumstances in Canada.

Association of Peripheral Serum MicroRNAs With Persistent Phantom Limb Pain in Individuals With Amputation.

OBJECTIVE: Individuals with major limb amputation(s) frequently experience phantom limb sensations, which are described as vivid impressions of either parts or entire missing limb(s). Despite the high incidence and prevalence of phantom limb pain, the underlying pathophysiology of phantom limb pain remains poorly understood. The objective of this study was to evaluate a possible role of microRNAs in the pathophysiology of phantom limb pain. DESIGN: Adults with acquired limb amputation and varying degrees of phantom limb pain consented to provide clinical data and blood samples. One hundred forty participants with single or multiple limb amputation(s) were enrolled. The Visual analog scale and neuropathic pain symptom inventory were administered to evaluate the pain. Serum samples were analyzed for microRNA expression and bioinformatic analysis was performed. RESULTS: Sixty-seven participants did not experience phantom limb pain, whereas 73 participants experienced varying severities of phantom limb pain measured on a pain scale. Linear regression analysis suggested that the time since amputation is inversely related to severity of the pain. A significantly increased expression of 16 microRNAs was observed in participants experiencing phantom limb pain. Bioinformatic analysis shows a possible role of these microRNAs in regulating genes expressed in peripheral neuropathy. CONCLUSIONS: This study provides the first evidence of association of microRNA in phantom limb pain.

Management of sleep-disordered breathing in three spinal cord injury rehabilitation centres around the world: a mixed-methods study.

STUDY DESIGN: Mixed-methods observational study. OBJECTIVE: To describe the sleep-disordered breathing (SDB) management models of three spinal cord injury (SCI) rehabilitation centres that are screening, diagnosing and treating uncomplicated SDB, and to determine their common elements. SETTING: Three specialist SCI rehabilitation centres. METHODS: Data collection at each site included direct observations and interviews with lead clinical staff and an audit of SDB-related clinical practice in 2019. Detailed descriptions of the models of care, including process maps, were developed. A theory-based analysis of the common elements of the three care models was undertaken. RESULTS: At each centre a multidisciplinary team, consisting of medical, allied health and/or nursing staff, provided a comprehensive SDB management service that included screening, diagnosis and treatment. Inpatients with SCI were assessed for SDB with overnight oximetry and/or polygraphy. Further assessment of patient symptoms, respiratory function, and hypercapnia supported the diagnostic process. Treatment with positive airway pressure was initiated on the ward. Having a collaborative, skilled team with strong leadership and adequate resources were the key, common enablers to providing the service. CONCLUSION: It is feasible for multi-disciplinary SCI rehabilitation teams to independently diagnose and treat uncomplicated SDB without referral to specialist sleep services provided they are adequately resourced with equipment and skilled staff. Similar models of care could substantially improve access to SDB treatment for people with SCI. Further research is required to determine the non-inferiority of these alternatives to specialist care.

Refining items for a preference-based, amyotrophic lateral sclerosis specific, health-related quality of life scale.

Objective: The aim of this study was to refine the items of a preference-based amyotrophic lateral sclerosis health-related quality of life scale (PB-ALS HRQL scale) based on domains generated in a previous study. Methods: Survey methodology was used to assess item importance rating (IR) and independence. Median importance was calculated for each item and a rating of "very important" was required for the item to remain. Correlations were used to examine item independence. Highly correlated items (rs > 0.7) were considered for removal. Cognitive debriefing (CD) interviews, conducted by Zoom, telephone, or email based on participant preference and communication needs, were used to identify potential issues. Participants provided feedback about wording, clarity, response options, and recall period on randomly selected items. Items were considered finalized when three sequential CD participants approved the item with no revisions. Results: Thirty-four people with ALS (PALS, n = 16 females; age range 44-78 years; ALS Functional Rating Scale-Revised [ALSFRS-R] range 0-48) in Canada completed the survey; a subset of 18 PALS completed CD interviews (n = 8 female; age range 44-71 years; ALSFRS-R range 0-48). Four items were highly correlated with one or more items, were not rated as very important, or were not approved via CD and were removed. Conclusions: The final four-response option PB-ALS Scale includes eight items: recreation and leisure, mobility, interpersonal interactions and relationships, eating and swallowing, handling objects, communicating, routine activities, and mood. The next step is to translate the PB-ALS Scale into French and develop a scoring algorithm based on PALS' preferences.

The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to update the 2016 version of the Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient, outpatient and community SCI rehabilitation settings in Canada. METHODS: The guidelines were updated in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The working group identified and reviewed 46 additional relevant articles published since the last version of the guidelines. The panel agreed on 3 new screening and diagnosis recommendations and 8 new treatment recommendations. Two key changes to these treatment recommendations included the introduction of general treatment principles and a new treatment recommendation classification system. No new recommendations to model of care were made. CONCLUSIONS: The CanPainSCI recommendations for the management of neuropathic pain after SCI should be used to inform practice.

Genetic testing for amyotrophic lateral sclerosis in Canada - an assessment of current practices.

Objective: To understand current genetic testing practices at Canadian ALS clinics. Methods: An online survey and phone interviews, with clinicians practicing in 27 ALS clinics in Canada, were employed to collect data. Quantitative and qualitative analyses were conducted. Results: Ninety-three percent (25/27) of ALS clinics in Canada are routinely ordering genetic testing for familial ALS, while 33% (9/27) of clinics are routinely ordering genetic testing for sporadic ALS. Barriers to genetic testing include a perceived lack of an impact on treatment plan, difficulty in obtaining approvals, primarily from provincial Ministries of Health, and limited access to genetic counseling. Predictive testing practices were found to be the most variable across the country. The average wait time for a symptomatic patient living with ALS to see a genetic counselor in Canada is 10 months (range 0-36 months). Conclusions: Access to genetic testing, and testing practices, vary greatly across Canadian ALS clinics. There may be patients with a monogenetic etiology to their ALS who are not being identified given that genetic testing for patients diagnosed with ALS is not routinely performed at all clinics. This study highlights potential inequities for patients with ALS that can arise from variability in health care delivery across jurisdictions, in a federally-funded, but provincially-regulated, health care system. Clinical trials for both symptomatic ALS patients and pre-symptomatic ALS gene carriers are ongoing, and ALS clinicians in Canada are motivated to improve access to genetic testing for ALS.

Characteristics of phantom limb pain in U.S. civilians and service members.

OBJECTIVES: The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes). This study aimed to identify the key characteristics of phantom limb sensation (PLS) and pain (PLP) in a current sample of Americans with limb loss. METHODS: This cross-sectional study is the first large-scale (n=649) study on PLP in the current population of Americans with limb loss. A convenience sample of military and civilian persons missing one or more major limbs was surveyed regarding their health history and experience with phantom limb phenomena. RESULTS: Of the participants surveyed, 87% experienced PLS and 82% experienced PLP. PLS and PLP typically first occurred immediately after amputation (47% of cases), but for a small percentage (3-4%) onset did not occur until over a year after amputation. Recent PLP severity decreased over time (ß=0.028, 95% CI: -0.05-0.11), but most participants reported PLP even 10 years after amputation. Higher levels of recent PLP were associated with telescoping (ß=0.123, 95% CI: 0.04-0.21) and higher levels of pre-amputation pain (ß=0.104, 95% CI: 0.03-0.18). Those with congenitally missing limbs experienced lower levels of recent PLP (t (37.93)=3.93, p<0.01) but there were no consistent differences in PLP between other amputation etiologies. CONCLUSIONS: Phantom limb phenomena are common and enduring. Telescoping and pre-amputation pain are associated with higher PLP. Persons with congenitally missing limbs experience lower levels of PLP than those with amputation(s), yet PLP is common even in this subpopulation.

Do Generic Preference-Based Measures Accurately Capture Areas of Health-Related Quality of Life Important to Individuals with Amyotrophic Lateral Sclerosis: A Content Validation Study.

OBJECTIVE: The objectives of this study were to 1) assess the content validity of generic preference-based measures (GPBMs), and (2) examine the convergent validity of the EuroQol 5 Dimension 5 Level (EQ-5D-5L), against the Patient Generated Index (PGI) in Amyotrophic Lateral Sclerosis (ALS). METHODS: Participants were recruited from 3 clinical sites across Canada. The PGI, EQ-5D-5L and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) were administered through an online or hardcopy survey and scores compared for convergent validation. Domains nominated by participants as important to their health-related quality of life were generated using the PGI, classified using the International Classification of Functioning, Disability and Health (ICF) and mapped onto GPBMs to determine content coverage. RESULTS: Fifty-two participants (N=28 female; 61.3 ± 11.6 mean age ± standard deviation (SD); 3.5 ± 2.9 mean ± SD years since diagnosis) completed this study. The top three ICF domains identified by participants were recreation and leisure, lower limb mobility, and interpersonal relationships. The Quality of Well-Being Self-Administered (QWB-SA) scale had the highest content coverage (87%) and the Health Utilities Index 3 (HUI3) had the lowest (33%). Two domains were covered by all GPBMs and no GPBM included all domains identified as important by participants. A moderate correlation coefficient of 0.52 between the PGI and EQ-5D-5L was found. CONCLUSION: The majority of GPBMs covered only approximately half of the domains important to individuals with ALS suggesting the need for an ALS specific preference-based measure to better reflect the health-related quality of life of this population.

Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process.

BACKGROUND: Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed. METHODS: Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain. RESULTS: There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5-5 mg of each cannabinoid once or twice daily and titrates by 2.5-5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day. CONCLUSIONS: In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.

A Canadian Adult Spinal Muscular Atrophy Outcome Measures Toolkit: Results of a National Consensus using a Modified Delphi Method.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. OBJECTIVE: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. METHODS: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. RESULTS: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. CONCLUSIONS: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

Circulating cell-free DNA as potential diagnostic tools for amyotrophic lateral sclerosis.

DNA methylation has garnered much attention in recent years for its diagnostic potential in multiple conditions including cancer and neurodegenerative diseases. Conversely, advances regarding the potential diagnostic relevance of DNA methylation status have been sparse in the field of amyotrophic lateral sclerosis (ALS) even though patients diagnosed with this condition would significantly benefit from improved molecular assays aimed at furthering the current diagnostic and therapeutic options available. This review will provide an overview of the current diagnostic approaches available for ALS diagnosis and discuss the potential clinical usefulness of DNA methylation. We will also present examples of DNA methylation as a diagnostic tool in various types of cancer and neurodegenerative conditions and expand on how circulating cfDNA methylation may be leveraged for the early detection of ALS. In general, this article will reinforce the importance of cfDNA methylation as diagnostic tools and will further highlight its clinical relevance for persons diagnosed with ALS.

COVID-19 and spinal cord injury and disease: results of an international survey as the pandemic progresses.

STUDY DESIGN: An online survey. OBJECTIVES: To follow-up with and re-query the international spinal cord community's response to the Coronavirus Disease 2019 (COVID-19) pandemic by revisiting questions posed in a previous survey and investigating new lines of inquiry. SETTING: An international collaboration of authors and participants. METHODS: Two identical surveys (one in English and one in Spanish) were distributed via the internet. Responses from both surveys were pooled and analyzed for demographic and response data. RESULTS: Three hundred and sixty-six respondents were gathered from multiple continents and regions. The majority (63.1%) were rehabilitation physicians and only 12.1% had patients with spinal cord injury/disease (SCI/D) that they knew had COVID-19. Participants reported that the COVID-19 pandemic had caused limited access to clinician and support services and worsening medical complications. Nearly 40% of inpatient clinicians reported that "some or all" of their facilities' beds were being used by medical and surgical patients, rather than by individuals requiring inpatient rehabilitation. Respondents reported a 25.1% increase in use of telemedicine during the pandemic (35% used it before; 60.1% during), though over 60% felt the technology incompletely met their patients' needs. CONCLUSION: The COVID-19 pandemic has negatively impacted the ability of individuals with SCI/D to obtain their "usual level of care." Moving forward into a potential "second wave" of COVID-19, patient advocacy and efforts to secure access to thorough and accessible care are essential.