38 research outputs found
Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen
Background and purpose: This was an investigation of treatment expectations and of the perception of therapy in adult patients with 5q-associated spinal muscular atrophy (5q-SMA) receiving nusinersen.
Methods: A prospective, non-interventional observational study of nusinersen treatment in adult 5q-SMA patients was conducted at nine SMA centers in Germany. The functional status, treatment expectations and perceived outcomes were assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-extended (ALS-FRS-ex), the Measure Yourself Medical Outcome Profile (MYMOP2), the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and the Net Promoter Score (NPS).
Results: In all, 151 patients were included with a median age of 36 years (15-69 years). SMA type 3 (n = 90, 59.6%) prevailed, followed by type 2 (33.8%) and type 1 (6.6%). In SMA types 1-3, median ALS-FRS-ex scores were 25, 33 and 46 (of 60 scale points), respectively. MYMOP2 identified distinct treatment expectations: head verticalization (n = 13), bulbar function (n = 16), arm function (n = 65), respiration (n = 15), trunk function (n = 34), leg function (n = 76) and generalized symptoms (n = 77). Median symptom severity decreased during nusinersen treatment (median observational period 6.1 months, 0.5-16 months) from 3.7 to 3.3 MYMOP2 score points (p < 0.001). The convenience of drug administration was critical (49.7 of 100 TSQM-9 points, SD 22); however, the overall treatment satisfaction was high (74.3, SD 18) and the recommendation rating very positive (NPS +66).
Conclusions: Nusinersen was administered across a broad range of ages, disease durations and motor function deficits. Treatment expectations were highly differentiated and related to SMA type and functional status. Patient-reported outcomes demonstrated a positive perception of nusinersen therapy in adult patients with 5q-SMA
Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregiversâ Lives
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patientsâ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregiversâ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patientsâ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patientsâ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the Kingâs Stages for ALS. The caregiversâ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregiversâ burden was high (mean ZBI = 26/88, 0 = no burden, â„24 = highly burdened) and correlated with patientsâ functional status (rp = â0.555, p < 0.001, n = 242). It was influenced by the CGsâ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patientsâ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGsâ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = â0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patientsâ impairment in daily routine (rs = â0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGsâ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGsâ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.peer-reviewe
mCommerce- utveckling av mobila tjÀnster
TvÄ tydliga förÀndringar som prÀglar dagens samhÀlle Àr: ökad mobilitet och behov av
tjÀnster. Dessa gav grunden för utveckling och expansion av den elektroniska
marknadsplatsen med mobiliteten i fokus. Denna marknadsplats refereras till som
mCommerce och prÀglas av utbudet av mobila tjÀnster. Tidigare erfarenheter frÄn
eCommerce visade att en ny marknad borde undersökas innan den expanderar för att
undvika misslyckande. Denna rapport undersökte hur mCommerce marknaden, med
mobiltelefoni som en teknologi, ser ut idag samt hur företag som erbjuder mobila tjÀnster och
potentiella anvÀndare ser pÄ möjligheter som marknaden erbjuder. PÄ grund av att
mCommerce Àmne Àr ganska nytt och outforskat, anvÀndes de befintliga teorierna inom
eCommerce samt empiriska undersökningar av bÄde kvalitativa och kvantitativa typen.
Syftet var att tillÀmpa nÄgra utvalda teorier pÄ hur mobila tjÀnster kan utvecklas för att bli
attraktiva ur anvÀndarens synpunkt. Detta resulterade i nÄgra viktiga faktorer som borde tas
hÀnsyn till vid utveckling av mobila tjÀnster. Dessa faktorer Àr: vikten av kundkÀnnedom,
kostnad, informationspresentation d.v.s. design samt val av teknologi. För att fÄ en överblick
över vilka tjÀnster som finns pÄ denna marknad, har tjÀnsterna klassificerats enligt följande:
tidsviktiga-personliga, tidsviktiga-mindre personliga, mindre tidsviktiga-personliga, mindre
tidsviktiga-mindre personliga. Rapporten visade att mCommerce har en potential för en ljus
framtid
Nusinersen Wearing-Off in Adult 5q-Spinal Muscular Atrophy Patients
The antisense oligonucleotide nusinersen was the first drug treatment available for all types of 5q-spinal muscular atrophy (SMA). The dosing regime has been derived from pivotal clinical trials in infants and children. The efficacy of nusinersen in severely affected adult SMA patients is still questionable, as no placebo-controlled trials have been conducted. In the present study, we systematically examined wearing-off phenomena during nusinersen maintenance dosing using a patient-centered approach. We found that adult SMA patients perceived wearing-off after nearly half of 51 investigated nusinersen administrations, primarily within the last month prior to the next administration. Symptoms and functions affected were mainly general strength and arm and leg muscle function next to endurance and independence in daily routine. Lack of walking ability and higher body mass index were characteristic phenotypic features in patients with consistent wearing-off effects. We assume that specific SMA phenotypes might benefit from higher dosing, shorter treatment intervals, change of treatment administration or a combination of all. Efforts towards treatment optimization may result in higher efficacy in distinct phenotypes
An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment
Background!#!Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA.!##!Objective!#!To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO).!##!Methods!#!We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated.!##!Results!#!75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants withââ„â4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14Â months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue.!##!Conclusion!#!Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period