Patient engagement in research: lessons learned from CAPTURE ALS, a longitudinal observational ALS study.

Objective: There are compelling ethical and practical reasons for patient engagement in research (PEIR), however, evidence for best practices remains limited. We investigated PEIR as implemented in CAPTURE ALS, a longitudinal observational study, from study inception through the first 2.5 years of operations. Methods: Data were drawn from three engagement initiatives: a community-led letter-writing campaign; consultation with patient and caregiver focus groups; and a study-embedded 'participant partner advisory council' (PPAC). Data were derived retrospectively from study documentation. We used the International Association of Public Participation (IAP2) participation spectrum as a framework for investigation. Results: 2401 letters from community members to the Canadian government affirmed study objectives and advocated for funding. Feedback from focus group consultation influenced study design and supported the study's data-sharing plan. PPAC collaboration shaped all aspects of the study. Contributions included: co-creation of governance documents, input on study protocols and public-facing communication, and development of engagement webinars for study participants and feedback surveys. Effective communication practices fostered collaboration and helped avoid tokenistic engagement. CAPTURE ALS encompassed all IAP2 participation levels. Conclusions: CAPTURE ALS was shaped by meaningful engagement initiatives over the course of the study. Lessons learned included: begin early and embed PEIR within research; build relationships and foster mutual learning; be flexible, open to adaptation, and seek diversity. Primary challenges included funding for early implementation, time needed to maintain relationships, and attrition due to disease progression. All IAP2 participation levels contributed to meaningful PEIR. 'Empowerment' was demonstrated through advocacy.

Asynchronous online focus groups for research with people living with amyotrophic lateral sclerosis and family caregivers: usefulness, acceptability and lessons learned.

BACKGROUND: People with amyotrophic lateral sclerosis (ALS) face disability- and travel-related barriers to research participation. We investigate the usefulness and acceptability of asynchronous, online focus groups (AOFGs) for research involving people affected by ALS (patients and family caregivers) and outline lessons learned. METHODS: The ALS Talk Project, consisting of seven AOFGs and 100 participants affected by ALS, provided context for this investigation. Hosted on the secure itracks Board™ platform, participants interacted in a threaded web forum structure. Moderators posted weekly discussion questions and facilitated discussion. Data pertaining to methodology, participant interaction and experience, and moderator technique were analyzed using itracks and NVivo 12 analytics (quantitative) and conventional content analysis and the constant-comparative approach (qualitative). RESULTS: There was active engagement within groups, with post lengths averaging 111.48 words and a complex network of branching interactions between participants. One third of participant responses included individual reflections without further interaction. Participants affirmed their co-group members, offered practical advice, and discussed shared and differing perspectives. Moderators responded to all posts, indicating presence and probing answers. AOFGs facilitated qualitative and quantitative data-gathering and flexible response to unanticipated events. Although total participation fell below 50% after 10-12 weeks, participants valued interacting with peers in an inclusive, confidential forum. Participants used a variety of personal devices, browsers, and operating systems when interacting on the online platform. CONCLUSIONS: This methodological examination of AOFGs for patient-centred investigations involving people affected by ALS demonstrates their usefulness and acceptability, and advances knowledge of online research methodologies. Lessons learned include: early identification of research goals and participant needs is critical to selecting an AOFG platform; although duration longer than 10-12 weeks may be burdensome in this population, participants were positive about AOFGs; AOFGs offer real world flexibility enabling response to research challenges and opportunities; and, AOGFs can effectively foster safe spaces for sharing personal perspectives and discussing sensitive topics. With moderators playing an important role in fostering engagement, AOFGs facilitated rich data gathering and promoted reciprocity by fostering the exchange of ideas and interaction between peers. Findings may have implications for research involving other neurologically impaired and/or medically vulnerable populations.

What do people affected by amyotrophic lateral sclerosis want from health communications? Evidence from the ALS Talk Project.

INTRODUCTION/AIMS: Health communication is central to effective, supportive amyotrophic lateral sclerosis (ALS) clinical care. Guidance for ALS communication is limited, focuses on diagnosis disclosure, and frequently relies on expert consensus and/or reviews. Patient-based evidence is needed to guide ALS health communication. We investigated how the experiences of ALS patients and family caregivers can inform effective communication practices from diagnosis to end-of-life. METHODS: Data were drawn from the ALS Talk Project, an asynchronous, online focus group study. Seven focus groups and five interviews (105 participants) were conducted. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: We found four primary themes: communication content, communication circumstances, information sufficiency, and communication manner. Data indicate participants relied on clinicians for medical information but also wanted practical information; health communication should attend to the circumstances within which conversations occur; information must be sufficient for individual needs, without overwhelming; and an empathetic, direct, and honest manner facilitated trust. Participants identified communication challenges and strategies to improve communication across major themes, including stepwise approaches and conversations tailored to individuals and their heterogeneous disease experiences. DISCUSSION: Healthcare professionals should discuss patient/caregiver communication preferences early in the therapeutic relationship, co-develop a communication agreement, and update the agreement in response to changing needs and disease progression. This will foster regular discussion of information needs and promote timely discussions of challenging topics, including advance care, while giving patients and families a sense of control. Findings may have implications for other neuromuscular disease and/or seriously ill populations.

Primary lateral sclerosis natural history study - planning, designing, and early enrollment.

Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.

Amyotrophic lateral sclerosis (ALS) health charities are central to ALS care: perspectives of Canadians affected by ALS.

OBJECTIVE: Expert consensus guidelines recommend referral of people with amyotrophic lateral sclerosis (ALS) to ALS health charities for support. Limited research indicates that patients and families value interaction with these volunteer sector organizations. We investigated how patient support from Canadian ALS health charities (ALS Societies) is experienced by those affected by ALS, and whether patient-centered outcomes validate recommendations for referral. METHODS: Data were drawn from the ALS Talk Project, an asynchronous online focus group study. Patients and family caregivers were recruited from regions across Canada. Seven groups met online for 14 weeks between January and July 2020. Seventy-eight participants made statements about ALS Societies. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: Participants viewed ALS Societies as integral to the healthcare system. The Societies acted as patient navigators and filled perceived care gaps, including psychological support. They provided critical practical assistance, particularly equipment loans and peer support groups; comprehensive disease-related and real-life information; and personal connections. They facilitated knowledge of research, emerging therapies, and research opportunities. Delayed referral to ALS Society supports and information resources was a concern for some participants. CONCLUSIONS: ALS Societies provide patients with critical practical, informational, and emotional support and play an overarching role as patient/research navigators. Patient-centred outcomes support patient referral to ALS Societies. Communication about the services provided should be a standard component of clinical care, with choice of access left to individuals. Clinical conversations should be supplemented with information resources developed by these voluntary sector organizations.

Covid-19 threat and coping: application of protection motivation theory to the pandemic experiences of people affected by amyotrophic lateral sclerosis.

BACKGROUND: People with amyotrophic lateral sclerosis (ALS) are at high risk for severe outcomes from Covid-19 infection. Researchers exploring ALS and Covid-19 have focused primarily on system response and adaptation. Using Protection Motivation Theory, we investigated how people with ALS and family caregivers appraised and responded to Covid-19 threat, the 'costs' associated with pandemic response, and how health professionals and systems can better support people affected by ALS who are facing public health emergencies. METHODS: Data were drawn from the 'ALS Talk Project,' an asynchronous, moderated focus group study. Participants were recruited from regions across Canada. Seven groups met online over 14 weeks between January and July 2020. Fifty-three participants contributed to Covid-19 discussions. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: Participants learned about the Covid-19 pandemic from the media. They rapidly assessed their vulnerability and responded to Covid-19 threat by following recommendations from health authorities, information monitoring, and preparing for worst-case scenarios. Adopting protective behaviors had substantial response costs, including adaptations for medical care and home support workers, threatened access to advance care, and increased caregiver burden. Participants expressed need for ALS-specific, pandemic information from trusted health professionals and/or ALS health charities. Telemedicine introduced both conveniences and costs. Prior experience with ALS provided tools for coping with Covid-19. Threat and coping appraisal was a dynamic process involving ongoing vigilance and adaptation. Findings draw attention to the lack of emergency preparedness among participants and within health systems. CONCLUSIONS: Clinicians should engage ALS patients and families in ongoing discussions about pandemic coping, strategies to mitigate response costs, care pathways in the event of Covid-19 infection, and changing information about Covid-19 variants and vaccines. Healthcare systems should incorporate flexible approaches for medical care, leveraging the benefits of telemedicine and facilitating in-person interaction as needed and where possible. Research is needed to identify strategies to mitigate response costs and to further explore the interaction between prior experience and coping. Further study is also needed to determine how communication about emergency preparedness might be effectively incorporated into clinical care for those with ALS and other medically vulnerable populations.

Lung volume recruitment improves volitional airway clearance in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: In this study we evaluated the effects of lung volume recruitment treatment (LVR), a low-tech, low-cost, manual "breath-stacking" technique used to help people cough with enough force to clear their airways, thereby reducing the risk of aspiration and choking, on five volitional airway clearance and protection behaviors used by people living with amyotrophic lateral sclerosis (PwALS). METHODS: Using a repeated-measures cross-over design, 29 PwALS performed five volitional airway clearance and protection behaviors in LVR treatment and in no-treatment, control conditions. Peak cough flow (PCF) was used to measure maximum expiratory rate during forced expiration, throat clearing, hawking, post-swallow coughing, and the supraglottic swallowing maneuver. Comparisons were made as a function of condition (treatment or control) and three time-points (pretreatment, and 15 and 30 minutes posttreatment). RESULTS: LVR treatment had a significant positive effect on maximum expiratory rates during all tested airway clearance and protection behaviors. Increased PCF values lasted for up to 30 minutes post-LVR for all tested behaviors in the treatment condition. DISCUSSION: We found that LVR treatment could increase control over airway clearance in PwALS, as well as provide improved airway protection for up to 30 minutes, the duration of a typical meal. This study has implications for patient care. These include offering patients control over some of the most feared symptoms of ALS, particularly choking during activities of daily living, and enhanced ALS respiratory care in low-resource settings. Findings may have implications for other neurodegenerative disorders in which dysphagia occurs with retained sensory function.

Communication About End of Life for Patients Living With Amyotrophic Lateral Sclerosis: A Scoping Review of the Empirical Evidence.

Background: Communication about end of life, including advance care planning, life-sustaining therapies, palliative care, and end-of-life options, is critical for the clinical management of amyotrophic lateral sclerosis patients. The empirical evidence base for this communication has not been systematically examined. Objective: To support evidence-based communication guidance by (1) analyzing the scope and nature of research on health communication about end of life for amyotrophic lateral sclerosis; and (2) summarizing resultant recommendations. Methods: A scoping review of empirical literature was conducted following recommended practices. Fifteen health-related and three legal databases were searched; 296 articles were screened for inclusion/exclusion criteria; and quantitative data extraction and analysis was conducted on 211 articles with qualitative analysis on a subset of 110 articles that focused primarily on health communication. Analyses summarized article characteristics, themes, and recommendations. Results: Analysis indicated a multidisciplinary but limited evidence base. Most reviewed articles addressed end-of-life communication as a peripheral focus of investigation. Generic communication skills are important; however, substantive and sufficient disease-related information, including symptom management and assistive devices, is critical to discussions about end of life. Few articles discussed communication about specific end-of-life options. Communication recommendations in analyzed articles draw attention to communication processes, style and content but lack the systematized guidance needed for clinical practice. Conclusions: This review of primary research articles highlights the limited evidence-base and consequent need for systematic, empirical investigation to inform effective communication about end of life for those with amyotrophic lateral sclerosis. This will provide a foundation for actionable, evidence-based communication guidelines about end of life. Implications for research, policy, and practice are discussed.

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.

Transitions in Amyotrophic Lateral Sclerosis: Patient and Caregiver Experiences.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) presents many transitions for persons/people with ALS (PwALS) and their caregivers. Transitions are passages from one life phase, condition, or status to another. We used qualitative methods to understand how PwALS and caregivers experience transitions throughout their ALS journey. METHODS: PwALS and their caregivers were recruited from a multidisciplinary ALS clinic in Edmonton, Canada. We recruited patients at the stage of ALS that home mechanical ventilation, a feeding tube, and/or assistive communication technology had been offered. Semi-structured interviews were audio-recorded, transcribed, and analyzed using qualitative thematic analysis. RESULTS: We interviewed 14 PwALS and 15 caregivers and identified 5 recurring themes. The importance of community was identified by many PwALS and caregivers who expressed feelings of loneliness and isolation. Most caregivers were spouses and couples navigated a change in their relationship roles as one spouse transitioned to becoming a caregiver while the other transitioned to dependency. The caregiver spouses reported a sense of "total responsibility" that encompassed continual vigilance for the PwALS's well-being, managing their household and finances. PwALS and caregivers reported transitioning to reliance on life-sustaining medical devices; early adoption and information on these devices increased their quality of life. Participants also wanted more and earlier information on advanced care planning. PwALS and caregivers identified adapting to new forms of communication as a necessity. CONCLUSION: ALS presents many transitions for PwALS and caregivers. Understanding these transitions is important for ALS healthcare professionals who seek to implement best care practices.

Provincial Differences in the Diagnosis and Care of Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. METHODS: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. RESULTS: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. CONCLUSIONS: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.

Rituximab in refractory myasthenia gravis: a prospective, open-label study with long-term follow-up.

We examined the clinical effectiveness of rituximab in fourteen patients with refractory myasthenia gravis (MG). Manual muscle testing (MMT) score was recorded at baseline and followed during the course of the study. Steroid dose, frequency of intravenous immunoglobulin (IVIG) infusions, and plasma exchange (PLEX) were also monitored throughout the duration of the study. All patients responded dramatically to rituximab, as measured by a change in MMT score, prednisone dose, or the frequency of IVIG infusions or PLEX. Rituximab appears safe and effective for the treatment of refractory MG. It should be considered as a therapeutic option in refractory patients.

Attitudes Regarding Palliative Sedation and Death Hastening Among Swiss Physicians: A Contextually Sensitive Approach.

In Switzerland, where assisted suicide but not euthanasia is permitted, the authors sought to understand how physicians integrate palliative sedation in their practice and how they reflect on existential suffering and death hastening. They interviewed 31 physicians from different care settings. Five major attitudes emerged. Among specialized palliative care physicians, convinced, cautious and doubtful attitudes were evident. Within unspecialized settings, palliative sedation was more likely to be considered as death hastening: clinicians either avoid it with an inexperienced attitude or practice it with an ambiguous attitude, raising the issue of unskilled and abusive uses of sedatives at the end of life.

Breaking bad news in amyotrophic lateral sclerosis: the need for medical education.

The manner in which physicians deliver difficult diagnoses is an area of discontent for patients with amyotrophic lateral sclerosis (ALS). The American Academy of Neurology's Practice Parameter for care of the ALS Patient recommended teaching and evaluating strategies for disclosing the diagnosis (10). Our objective was to examine residents' ability in and perceptions of communicating the diagnosis of ALS. Twenty-two resident physicians were videotaped and rated by two ALS neurologists as they delivered an ALS diagnosis to a standardized patient (SP) during an objective structured clinical examination (OSCE). Residents self-rated immediately after the OSCE, again after viewing their videotape, and completed a survey regarding the OSCE and delivering difficult diagnoses. OSCE performance was suboptimal, particularly for communication skills and empathy. The two examiners' scores correlated except for the empathy subscore. Residents' self-assessments did not align with the examiners' scores either before or after watching their videotape. The survey uncovered residents' apprehension and dissatisfaction with their training in diagnosis delivery. The results highlight a need for resident education in delivering an ALS diagnosis. The lack of correlation between residents' and examiners' scoring requires further study. Evaluation of empathy is particularly challenging. Residents agreed that OSCE participation was worthwhile.

Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy.

BACKGROUND: Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy control subjects were studied. RESULTS: In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.