Improving the measurement properties of the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R): deriving a valid measurement total for the calculation of change

Background The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score is a widely used measure of functional status in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS), but recent evidence has raised doubts about its validity. The objective was to examine the measurement properties of the ALSFRS-R, aiming to produce valid measurement from all 12 scale items. Method Longitudinal ALSFRS-R data were collected between 2013-2020 from 1120 people with ALS recruited from 35 centers, together with other scales in the Trajectories of Outcomes in Neurological Conditions-ALS (TONiC-ALS) study. The ALSFRS-R was analyzed by confirmatory factor analysis (CFA), Rasch Analysis (RA) and Mokken scaling. Results No definite factor structure of the ALSFRS-R was confirmed by CFA. RA revealed the raw score total to be invalid even at the ordinal level because of multidimensionality; valid interval level subscale measures could be found for the Bulbar, Fine-Motor and Gross-Motor domains but the Respiratory domain was only valid at an ordinal level. All four domains resolved into a single valid, interval level measure by using a bifactor RA. The smallest detectable difference was 10.4% of the range of the interval scale. Conclusion A total ALSFRS-R ordinal raw score can lead to inferential bias in clinical trial results due to its non-linear nature. On the interval level transformation, more than 5 points difference is required before a statistically significant detectable difference can be observed. Transformation to interval level data should be mandatory in clinical trials

Fit for purpose? A cross-sectional study to evaluate the acceptability and usability of HeadUp, a novel neck support collar for neurological neck weakness

The HeadUp collar (previously known as the Sheffield Support Snood) provides support for neck weakness caused by amyotrophic lateral sclerosis (ALS) and has shown to be superior to alternative options in a small cohort of patients from one single center. Here we report the assessment of the HeadUp collar in a larger cohort of patients, exploring the use in other neurological conditions and expanding to other centers across the UK and Ireland. An interventional cross-sectional study design was implemented to investigate the usability and acceptability of the HeadUp collar. A total of 139 patients were recruited for the study, 117 patients had a diagnosis of ALS and 22 patients presented with neck weakness due to other neurological conditions. Participants were assessed at baseline, fitted a HeadUp collar and followed-up one month later. The performance of the HeadUp collar was rated favorably compared to previously worn collars in terms of the ability to eat, drink and swallow. Findings suggest that the collar also permitted a more acceptable range of head movements whilst maintaining a good level of support. We conclude that the HeadUp collar is a suitable option for patients with neck weakness due to ALS and other neurological conditions

Acceptance and commitment therapy for people living with motor neuron disease: an uncontrolled feasibility study

Background Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND. Methods PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months. Results Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status. Conclusions There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway

Immunomodulatory treatment for amyotrophic lateral sclerosis/ motor neuron disease (Protocol)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the efficacy and harms or adverse events of immunomodulatory therapies in people with ALS compared with a placebo, no additional treatment, or a standard-of-care protocol (with or without riluzole, edaravone, or both)

Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates

Objective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12. Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories. Results: In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King’s stage ≥3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated (p < .01). Conclusion: Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care

New vegetation type map of India prepared using satellite remote sensing: comparison with global vegetation maps and utilities

A seamless vegetation type map of India (scale 1: 50,000) prepared using medium-resolution IRS LISS-III images is presented. The map was created using an on-screen visual interpretation technique and has an accuracy of 90%, as assessed using 15,565 ground control points. India has hitherto been using potential vegetation/forest type map prepared by Champion and Seth in 1968. We characterized and mapped further the vegetation type distribution in the country in terms of occurrence and distribution, area occupancy, percentage of protected area (PA) covered by each vegetation type, range of elevation, mean annual temperature and precipitation over the past 100 years. A remote sensing-amenable hierarchical classification scheme that accommodates natural and semi-natural systems was conceptualized, and the natural vegetation was classified into forests, scrub/shrub lands and grasslands on the basis of extent of vegetation cover. We discuss the distribution and potential utility of the vegetation type map in a broad range of ecological, climatic and conservation applications from global, national and local perspectives. Weused 15,565 ground control points to assess the accuracy of products available globally (i.e., GlobCover, Holdridge’s life zone map and potential natural vegetation (PNV) maps). Hence we recommend that the map prepared herein be used widely. This vegetation type map is the most comprehensive one developed for India so far. It was prepared using 23.5m seasonal satellite remote sensing data, field samples and information relating to the biogeography, climate and soil. The digital map is now available through a web portal (http://bis.iirs.gov.in)

A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial

Background Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities. Methods The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. Discussion This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS. Trial registration ClinicalTrials.gov NCT03800524. Registered on January 11, 2019

New vegetation type map of India prepared using satellite remote sensing: Comparison with global vegetation maps and utilities

International audienceA seamless vegetation type map of India (scale 1: 50,000) prepared using medium-resolution IRS LISS-III images is presented. The map was created using an on-screen visual interpretation technique and has an accuracy of 90%, as assessed using 15,565 ground control points. India has hitherto been using potential vegetation/forest type map prepared by Champion and Seth in 1968. We characterized and mapped further the vegetation type distribution in the country in terms of occurrence and distribution, area occupancy, percentage of protected area (PA) covered by each vegetation type, range of elevation, mean annual temperature and precipitation over the past 100 years. A remote sensing-amenable hierarchical classification scheme that accommodates natural and semi-natural systems was conceptualized, and the natural vegetation was classified into forests, scrub/shrub lands and grasslands on the basis of extent of vegetation cover. We discuss the distribution and potential utility of the vegetation type map in a broad range of ecological, climatic and conservation applications from global, national and local perspectives. We used 15,565 ground control points to assess the accuracy of products available globally (i.e., GlobCover, Holdridge’s life zone map and potential natural vegetation (PNV) maps). Hence we recommend that the map prepared herein be used widely. This vegetation type map is the most comprehensive one developed for India so far. It was prepared using 23.5 m seasonal satellite remote sensing data, field samples and information relating to the biogeography, climate and soil. The digital map is now available through a web portal (http://bis.iirs.gov.in)