The effects of a home-based arm ergometry exercise programme on physical fitness, fatigue and activity in polio survivors: protocol for a randomised controlled trial.

ABSTRACT: BACKGROUND: Many Polio survivors have reduced mobility, pain and fatigue, which make access to conventional forms of aerobic exercise difficult. Inactivity leads to increased risk of health problems, many of which are prevalent among Polio survivors. Aerobic exercise programmes in Polio survivors should utilise stable muscle groups and should be designed to minimise exacerbation of pain and fatigue. A home-based arm ergometry aerobic exercise programme may represent an affordable and accessible exercise modality, incorporating exercise prescription principles in this group.Methods/design: This is a prospective, single blinded, randomised controlled trial. There are two arms; exercise intervention using arm ergometers and control. Polio survivors meeting eligibility criteria will be recruited and randomly allocated to intervention or control groups. Participants allocated to the intervention group will receive a small arm ergometer and a polar heart rate monitor. They will carry out a home-based moderate intensity (50-70% HRMax) aerobic exercise programme for eight weeks, following instruction by the treating physiotherapist. Assessments will occur at baseline and after eight weeks and will include tests of physical fitness, activity, energy cost of walking, fatigue and quality of life. Clinically feasible assessment tools including the Six Minute Arm Test, the Physical Activity Scale for People with Physical Disabilities questionnaire, the Physiological Cost Index, Fatigue Severity Scale and the SF-36v2 will be utilised. DISCUSSION: The efficacy of a home-based arm ergometry programme in Polio survivors will be examined. No previous trial has examined such a programme using a wide range of outcome measures pertinent to Polio survivors. This study will provide new information on the impact of arm ergometry on physical fitness, activity, body composition, fatigue, pain, muscle strength, and health related quality of life. Also, the study will provide information, which at present is lacking, on safety of aerobic exercise in Polio, as potential negative outcomes of activity including loss of muscle strength, increased pain and fatigue will be closely monitored.Trial registration: Clinicaltrials.gov identifier: NCT01271530

Implementing social health insurance in Ireland: Report of a meeting and workshop held in Dublin, on December 6th 2010

We considered two basic questions, 'Is it possible to implement Social Health Insurance in Ireland?', and 'How can this be done?'. Can Social Health Insurance be implemented in Ireland? Our answer is a very definite yes. Furthermore, there would be many opportunities, while working towards this end, to improve the performance of our health care system. How can it be implemented? This process will need to be actively managed. There are many difficulties in the Irish health services, but also many opportunities. The greatest strengths are the talented, well-trained and very committed staff. Getting and keeping the support of these staff, for the necessary changes in service delivery, will be critical. Ireland has the capacity to make these changes, but without high quality management, a detailed focussed plan for change, and political support, little will happen. Each step in the change needs to be planned to maintain services, improve service delivery, improve service accountability, and improve service governance. Each sector of the service will need someone to lead the change, and mind that service during the change. Primary care remains under-developed. The HSE plan to develop primary care teams (PCT) has not succeeded. There are several established PCTs which work well. In other areas there are informal arrangements for collaboration, which work well. Overall, there are many useful lessons to learn from the experience so far. Future developments will need to place general practice at the centre of primary care. The mechanisms for doing this will vary from place to place, but need to be developed urgently. Acute hospitals face a crisis of governance. Maurice Hayes' (1) recent report on Tallaght hospital gives an idea of the scale of the changes needed. Tallaght is, we believe, not atypical, and is reputed to be by no means the worst governed hospital in the system. This, alone, should provide a pressing motive for change. Redesigning Irish hospitals to a new mission of supporting primary care, of supporting care in the community where possible can, and must, be done. Long-term care for older people is also a challenge. We advise moving to an integrated needs based system with smooth transitions between different degrees of support at home, and different degrees of support in specialized housing facilities including nursing homes. A similar model should apply to other forms of long-term care, for example for people with a substantial disability. Information systems and management processes both need a major overhaul. The health service remains strikingly under-managed, and fixing this will need a substantial culture change within the services. Wide use of standardized formal project management processes will be vital. There is a separate plan being developed to improve health service IT systems, and implementing this needs to be a high priority. We have not considered other key sectors, for example mental health, disability services, and social services. This does not mean that these are unimportant, merely that we had limited time, and a great deal to cover

Development of an Explainable Clinical Decision Support System for the Prediction of Patient Quality of Life in Amyotrophic Lateral Sclerosis

The 36th ACM/SIGAPP Symposium on Applied Computing (SAC 2021), Virtual Event, 22-26 March 2021Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative and currently incurable disease. It causes a rapid decline in motor functions and has a fatal trajectory. The aim of the treatment is mostly to alleviate symptoms and improve the patient’s quality of life (QoL). The goal of this study is to develop a Clinical Decision Support System (CDSS) in order to alert clinicians when a patient is at risk of experiencing a low QoL, so that they are better supported. The source of the data was the Irish ALS Registry and interviews with the 90 patients and their primary informal caregiver at three time-points. In this dataset, there were two different scores to measure a person’s overall QoL, based on the McGill QoL (MQoL) Questionnaire and we worked towards the prediction of both. The method we used for the development of the predictive models was Extreme Gradient Boosting (XGBoost), which was compared to a logistic regression baseline model. We used the SHAP (SHapley Additive exPlanations) values as a technique to provide local and global explanations to the outputs as well as to select the most important features. The total calculated MQoL score was predicted accurately by three features, with a F1-score on the test set equal to 0.81, a recall score of 0.78, and a precision score of 0.84, while, the addition of two features produced similar outcomes (0.79, 0.70 and 0.90 respectively). The three most important features were the age at disease onset, ALSFRS score for orthopnoea and the caregiver’s status pre-caregiving.European Commission - European Regional Development FundScience Foundation IrelandHealth Research BoardAmerican ALS Associatio

Pathological Crying and Laughing in Motor Neuron Disease: Pathobiology, Screening, Intervention

Pathological crying and laughing (PCL) has significant quality-of-life implications in amyotrophic lateral sclerosis (ALS); it can provoke restrictive life-style modifications and lead to social isolation. Despite its high prevalence and quality of life implications, it remains surprisingly understudied. Divergent pathophysiological models have been proposed, centered on corticobulbar tract degeneration, prefrontal cortex pathology, sensory deafferentation, and impaired cerebellar gate-control mechanisms. Quantitative MRI techniques and symptom-specific clinical instruments offer unprecedented opportunities to elucidate the anatomical underpinnings of PCL pathogenesis. Emerging neuroimaging studies of ALS support the role of cortico–pontine–cerebellar network dysfunction in context-inappropriate emotional responses. The characterization of PCL-associated pathophysiological processes is indispensable for the development of effective pharmacological therapies

Tracking a Fast-Moving Disease: Longitudinal Markers, Monitoring, and Clinical Trial Endpoints in ALS

Amyotrophic lateral sclerosis (ALS) encompasses a heterogeneous group of phenotypes with different progression rates, varying degree of extra-motor involvement and divergent progression patterns. The natural history of ALS is increasingly evaluated by large, multi-time point longitudinal studies, many of which now incorporate presymptomatic and post-mortem assessments. These studies not only have the potential to characterize patterns of anatomical propagation, molecular mechanisms of disease spread, but also to identify pragmatic monitoring markers. Sensitive markers of progressive neurodegenerative change are indispensable for clinical trials and individualized patient care. Biofluid markers, neuroimaging indices, electrophysiological markers, rating scales, questionnaires, and other disease-specific instruments have divergent sensitivity profiles. The discussion of candidate monitoring markers in ALS has a dual academic and clinical relevance, and is particularly timely given the increasing number of pharmacological trials. The objective of this paper is to provide a comprehensive and critical review of longitudinal studies in ALS, focusing on the sensitivity profile of established and emerging monitoring markers

Oral Levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

Objective To evaluate the efficacy and safety of oral levosimendan in amyotrophic lateral sclerosis (ALS) patients. This phase 2, randomised, double-blind, placebo-controlled, crossover, 3-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60-90% of predicted from 11 sites in four countries. Methods Patients received levosimendan 1 mg daily, 1 mg bd or placebo during three 14-day crossover periods, and levosimendan 1-2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale (ALSFRS-R), tolerability and safety. Results Of 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being -3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg bd (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg bd (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events. Conclusions Levosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase 3 study to evaluate the longer-term effects of oral levosimendan in ALS is ongoing

Genetic screening in sporadic ALS and FTD.

The increasing complexity of the genetic landscape in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) presents a significant resource and physician training challenge. At least 10% of those diagnosed with ALS or FTD are known to carry an autosomal dominant genetic mutation. There is no consensus on what constitutes a positive family history, and ascertainment is unreliable for many reasons. However, symptomatic individuals often wish to understand as much as possible about the cause of their disease, and to share this knowledge with their family. While the right of an individual not to know is a key aspect of patient autonomy, and despite the absence of definitive therapy, many newly diagnosed individuals are likely to elect for genetic testing if offered. It is incumbent on the practitioner to ensure that they are adequately informed, counselled and supported in this decision

ECAS A-B-C:alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen

BACKGROUND: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a short assessment by which neuropsychological symptoms can be detected and quantified in people with ALS. To avoid potential practice effects with repeated administration, here we present alternative versions of the ECAS suitable for measuring change over time.  OBJECTIVE: To develop two alternate versions of the ECAS: ECAS-B and ECAS-C.  METHOD: One hundred and forty-nine healthy adult participants were recruited. Thirty participants completed a pilot study in developing the alternate versions. Two groups of 40 participants were administered the ECAS-B or ECAS-C and compared to published data of the original ECAS (ECAS-A) to determine equivalence. An additional 39 participants were administered the ECAS consecutively, either repeating the original version (ECAS-A-A-A) serially or the different versions (ECAS-A-B-C) to determine potential practice effects. Recordings of assessments were scored by a second researcher to determine inter-rater reliability.  RESULTS: No significant differences were found between versions (A, B, C) of the composite performance measures of ALS Specific, ALS Non-Specific, and ECAS Total scores. Repeated serial administration of ECAS-A (A-A-A) produced some practice effects for composite scores, whereas no such effects were found when alternate versions were administered serially (A-B-C). Exceptionally high intra-class correlations were found for all three versions of the ECAS suggesting a high degree of rater agreement.  CONCLUSION: The newly developed alternate forms of the ECAS are both highly equitable to the original ECAS-A and enable avoidance of practice effects, thus supporting their use in measuring cognition and behaviour over time

<i>C9orf72 </i>Repeat Expansion Discordance in 6 Multigenerational Kindreds

Background and Objectives:A hexanucleotide repeat expansion in the noncoding region of the C9orf72 gene is the most common genetically identifiable cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in populations of European ancestry. Pedigrees associated with this expansion exhibit phenotypic heterogeneity and incomplete disease penetrance, the basis of which is poorly understood. Relatives of those carrying the C9orf72 repeat expansion exhibit a characteristic cognitive endophenotype independent of carrier status. To examine whether additional shared genetic or environmental risks within kindreds could compel this observation, we have conducted a detailed cross-sectional study of the inheritance within multigenerational Irish kindreds carrying the C9orf72 repeat expansion.Methods:One hundred thirty-one familial ALS pedigrees, 59 of which carried the C9orf72 repeat expansion (45.0% [95% CI 36.7–53.5]), were identified through the Irish population-based ALS register. C9orf72 genotyping was performed using repeat-primed PCR with amplicon fragment length analysis. Pedigrees were further investigated using SNP, targeted sequencing data, whole-exome sequencing, and whole-genome sequencing.Results:We identified 21 kindreds where at least 1 family member with ALS carried the C9orf72 repeat expansion and from whom DNA was available from multiple affected family members. Of these, 6 kindreds (28.6% [95% CI 11.8–48.3]) exhibited discordant segregation. The C9orf72 haplotype was studied in 2 families and was found to segregate with the C9orf72-positive affected relative but not the C9orf72-negative affected relative. No other ALS pathogenic variants were identified within these discordant kindreds.Discussion:Family members of kindreds associated with the C9orf72 repeat expansion may carry an increased risk of developing ALS independent of their observed carrier status. This has implications for assessment and counseling of asymptomatic individuals regarding their genetic risk