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• W2975264648 abstract "<ns4:p><ns4:bold>Introduction</ns4:bold>: The <ns4:italic>C9orf72</ns4:italic> hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The <ns4:italic>C9orf72</ns4:italic> repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients.</ns4:p><ns4:p> <ns4:bold>Methods</ns4:bold>: Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and <ns4:italic>C9orf72</ns4:italic> testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by <ns4:italic>C9orf72</ns4:italic> status.</ns4:p><ns4:p> <ns4:bold>Results</ns4:bold>: In total, 630 cases were included, of which 58 (9.2%) carried the <ns4:italic>C9orf72</ns4:italic> repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish <ns4:italic>C9orf72</ns4:italic> normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance.</ns4:p><ns4:p> <ns4:bold>Conclusions</ns4:bold>: Our results confirm findings from Portugal that the <ns4:italic>C9orf72</ns4:italic> repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the <ns4:italic>C9orf72</ns4:italic> expansion.</ns4:p>" @default.
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• W2975264648 date "2019-09-26" @default.
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• W2975264648 title "The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort" @default.
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• W2975264648 doi "https://doi.org/10.12688/hrbopenres.12940.1" @default.
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