The article The immediate impact of the COVID‑19 pandemic on motor neuron disease services and mortality in Scotland, written by Stella A. Glasmacher, Juan Larraz, Arpan R. Mehta, Patrick K. A. ...Kearns, Michael Wong, Judith Newton, Richard Davenport, George Gorrie, Ian Morrison, Javier Carod Artal, Siddharthan Chandran, Suvankar Pal and CARE-MND Consortium, was originally published online on 5 September 2020 with Open Access under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
Objectives
Scotland benefits from an integrated national healthcare team for motor neurone disease (MND) and a tradition of rich clinical data capture using the Scottish MND Register (launched in ...1989; one of the first national registers). The Scottish register was re-launched in 2015 as
C
linical
A
udit
R
esearch and
E
valuation of MND (CARE-MND), an electronic platform for prospective, population-based research. We aimed to determine if incidence of MND is changing over time.
Methods
Capture–recapture methods determined the incidence of MND in 2015–2016. Incidence rates for 2015–2016 and 1989–1998 were direct age and sex standardised to allow time-period comparison. Phenotypic characteristics and socioeconomic status of the cohort are described.
Results
Coverage of the CARE-MND platform was 99%. Crude incidence in the 2015–2017 period was 3.83/100,000 person-years (95% CI 3.53–4.14). Direct age-standardised incidence in 2015 was 3.42/100,000 (95% CI 2.99–3.91); in 2016, it was 2.89/100,000 (95% CI 2.50–3.34). The 1989–1998 direct standardised annual incidence estimate was 2.32/100,000 (95% CI 2.26–2.37). 2015–2016 standardised incidence was 66.9% higher than Northern European estimates. Socioeconomic status was not associated with MND.
Conclusions
Our data show a changing landscape of MND in Scotland, with a rise in incidence by 36.0% over a 25-year period. This is likely attributable to ascertainment in the context of improved neurological services in Scotland. Our data suggest that CARE-MND is a reliable national resource and findings can be extrapolated to the other Northern European populations.
Abstract Background Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic ...epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype–phenotype associations. Methods Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology. Results 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score ( p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1 . One individual carried both a C9orf72 expansion and SOD1 variant. Conclusions Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.
Background
We investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication.
Methods
Patients ...were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for
C9orf72
repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls.
Results
58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known
SOD1
p.(Ile114Thr) variant. Significant variants in
FIG4
, hnRNPA2B1, SETX, SQSTM1, TAF15,
and
VAPB
were detected. 2 individuals had a variant in the
SPAST
gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic
C9orf72
repeat expansions.
Conclusions
Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the
SOD1
variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of
C9orf72
is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication.
Background and purpose
This study was undertaken to determine the prevalence of multimorbidity in people with motor neuron disease (MND) and to identify whether specific patterns of multimorbidity ...impact survival beyond age alone.
Methods
We performed a retrospective analysis of the Scottish national MND register from 1 January 2015 to 29 October 2019. People with amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy were included. We fitted latent class regression models incorporating comorbidities (class indicators), age, sex, and bulbar onset (covariates), and survival (distal outcome) with multimorbidity as a hypothesised latent variable. We also investigated the association between the Charlson Comorbidity Index and survival in Cox regression and compared its discrimination and calibration to age alone.
Results
A total of 937 people with MND were identified (median age = 67 years, 60.2% male); 64.8% (n = 515) had two or more comorbidities. We identified a subpopulation with high prevalence of cardiovascular disease, but when accounting for the relationship between age and individual comorbidities, there was no difference in survival. Both Charlson Comorbidity Index (hazard ratio HR per unit increase = 1.11, 95% confidence interval CI = 1.07–1.15, p < 0.0001) and age (HR per year increase = 1.04, 95% CI = 1.03–1.05, p < 0.0001) were significantly associated with survival, but discrimination was higher for age compared to Charlson Comorbidity Index (C‐index = 0.63 vs. 0.59).
Conclusions
Multimorbidity is common in MND, necessitating holistic interdisciplinary management, but age is the dominant predictor of prognosis in people with MND. Excluding people with MND and multimorbidity from trial participation may do little to homogenise the cohort in terms of survival potential and could harm generalisability.
In this population‐based study (n=937), 64% of people with motor neuron disease had at two or more comorbidities. Age rather than multimorbidity was the dominant predictor of prognosis in people with MND.
Objectives: Launched in 1989, the Scottish Motor Neuron Disease Register (SMNDR) has provided a resource for prospective clinical data collection. However, in 2015 we aimed to evolve a system to ...allow: i) A patient-centered approach to care based on recognized standards, ii) Harmonized data sharing between Scottish health professionals in "real-time", iii) Regular audit of care to facilitate timely improvements in service delivery, and iv) Patient participation in a diverse range of observational and interventional research studies including clinical trials. Methods: We developed a standardized national electronic data platform-Clinical Audit Research and Evaluation of MND (CARE-MND) which integrates clinical audit and research data fields. Data completion pre- and post-CARE-MND were compared, guided by recently published National Institute for Clinical Excellence (NICE) recommendations. Statistical difference in data capture between time periods was assessed using Z-test of proportions. Results: Data field completion for the historical 2011-2014 period ranged from 4 to 95%; median 50%. CARE-MND capture ranged from 32 to 98%; median 87%. 15/17 fields were significantly more complete post-CARE-MND (p < 0.001). All MND nurse/allied health specialists in Scotland use the CARE-MND platform. Management of MND in Scotland is now coordinated through a standardized template. Conclusions: Through CARE-MND, national audits of MND care and interventions have been possible, leading to protocols for harmonized service provision. Stratification of the MND population is facilitating participation in observational and interventional studies. CARE-MND can act as a template for other neurological disorders.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
