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The European Journal of Health... Nov 2021This systematic review aimed to comprehensively collect and summarise the current body of knowledge regarding the cost-of-illness of amyotrophic lateral sclerosis, to...
OBJECTIVES
This systematic review aimed to comprehensively collect and summarise the current body of knowledge regarding the cost-of-illness of amyotrophic lateral sclerosis, to identify cost-driving factors of the disease and to consider the development of costs over the course of disease. Further, the review sought to assess the methodological quality of the selected studies.
METHODS
A systematic review was performed using the databases MEDLINE, Embase, Cochrane Library and PsycINFO. Studies examining the economic burden of amyotrophic lateral sclerosis on a patient or national level written in English or German published from the year 2001 onwards were included. Additional searches were conducted. Study characteristics and results were extracted and compared.
RESULTS
In summary, 20 studies were included in this review. Most studies investigated costs per patient, amounting to total costs between €9741€ to €114,605. Six studies confirmed a rise in costs with disease progression, peaking close to the death of a patient. National costs for amyotrophic lateral sclerosis varied between €149 million and €1329 million.
CONCLUSION
Most of these studies suggest the economic burden of amyotrophic lateral sclerosis to be considerable. However, further research is needed to establish a cost-effective health policy in consideration of disease severities.
Topics: Amyotrophic Lateral Sclerosis; Cost of Illness; Cost-Benefit Analysis; Disease Progression; Humans
PubMed: 34143346
DOI: 10.1007/s10198-021-01328-7 -
Journal of Pain and Symptom Management Apr 2022Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disease (MND), and sialorrhea is a known symptom in patients with ALS, which may cause a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disease (MND), and sialorrhea is a known symptom in patients with ALS, which may cause a social embarrassment and discomfort. However, people do not pay attention to sialorrhea up to now. This study is aimed at conducting a systematic review and meta-analysis of the pooled prevalence of sialorrhea in ALS patients all around the world and raising awareness of salivation.
METHODS
We searched PubMed and EMBASE databases to obtain the comprehensive literatures which reported the prevalence of sialorrhea. We used AHRQ and NOS to evaluate the literature quality. Subgroup analyses were performed based on screening instruments and severity of sialorrhea. At the meantime, sensitivity analyses was also conducted to identify the source of heterogeneity.
RESULTS
A total of 17 eligible studies which included 21 groups of data reported prevalence of sialorrhea. The pooled prevalence of sialorrhea among ALS patients was 30.8% (95% CI: 20.0%-44.2%). For studies using ALSFRS-R, direct questioning, postal survey, and ALSSoL average and ALSFRS-R, the pooled prevalence of sialorrhea was 22.7%, 25.8%, 29.8% and 52.0% respectively. According to the severity of sialorrhea, the prevalence of mild, moderate, and severe sialorrhea were 25.1%, 11.2%, and 10.5%, respectively. And none of the studies alone had a significant effect on the overall prevalence of sialorrhea after we eliminated each study separately in sensitivity analyses.
CONCLUSIONS
Sialorrhea is a relatively common symptom in ALS patients with a comparatively high prevalence. In our study, we found that the prevalence of sialorrhea in ALS patients is relatively higher than the results based on direct questioning or postal survey. Therefore, we deduced that sialorrhea should be evaluated by more complex professional assessment scales to improve the quality of life and improve early prognosis of disease.
Topics: Amyotrophic Lateral Sclerosis; Humans; Prevalence; Quality of Life; Salivation; Sialorrhea
PubMed: 34920148
DOI: 10.1016/j.jpainsymman.2021.12.005 -
Diagnostic Pathology Mar 2024Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis... (Review)
Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.
METHODS
PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.
RESULTS
A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.
CONCLUSION
Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.
Topics: Humans; Exosomes; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Biomarkers; DNA-Binding Proteins; Disease Progression
PubMed: 38429818
DOI: 10.1186/s13000-024-01473-6 -
Journal of Clinical Neuroscience :... Aug 2021To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS).
METHODS
PubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AA was calculated by AA = APB/ADM and split-hand index (SI) was calculated by SI = (APB × FDI)/ADM. The mean differences (MD) in APB/ADM and SI between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SI.
RESULTS
Pooled results of five studies including 339 patients showed that 50% (95%CI: 35%-65%) of patients with ALS presented split hand. APB/ADM in patients with ALS was significantly lower than healthy population (MD: -0.38, 95%CI: -0.48, -0.28). SI in patients with ALS was significantly lower than healthy controls (MD: -5.87, 95%CI: -6.28, -5.46) and neuromuscular controls (MD: -5.60, 95%CI: -5.78, -5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SI. The sensitivity and specificity for SI were 78% and 81% (cut-off value: 5.2-11.8), respectively.
CONCLUSION
Half of ALS patients might show split hand sign. SI could be a potential biomarker in the diagnosis of ALS.
Topics: Amyotrophic Lateral Sclerosis; Atrophy; Hand; Humans; Muscle Weakness; Muscle, Skeletal; Sensitivity and Specificity
PubMed: 34275566
DOI: 10.1016/j.jocn.2021.06.015 -
Journal of Neurology Oct 2023Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within 3-5 years after the onset of this disease. Nowadays, no drug can effectively slow down the progression of this disease. High-calorie therapy, an emerging complementary alternative treatment, has been reported in studies to prolong the survival time of patients, prevent muscle atrophy and provide a better prognosis. However, no systematic review and meta-analysis were performed to summarize the evidence of this therapy. This meta-analysis comprehensively evaluates the effectiveness and safety of high-calorie therapy for treating ALS.
METHODS
We searched the electronic databases from inception to 1 April 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid/Medline, and ProQuest. Randomized controlled trials (RCTs) that met the inclusion criteria were performed by meta-analysis. All statistical analyses were performed in STATA software.
RESULTS
A total of six eligible RCTs were included in this meta-analysis, involving 370 ALS patients. The meta-analyses showed that high-calorie therapy had superiority in improving body weight (SMD = 1, 95% CI 0.36, 1.65) and BMI (SMD = 0.83, 95% CI 0.02, 1.63). With respect to safety, there was no difference between the high-calorie therapy and the control group regarding the number of adverse events (RR = 3.61, 95% CI 0.08, 162.49). However, ALSFRS-R scores (SMD = 0.34, 95% CI - 0.4, 1.08), survival rate (RR = 1.23, 95% CI 0.98, 1.55), and lipid profile (LDL: SMD = 0.21, 95% CI - 0.33, 0.75; HDL: SMD = 0.17, 95% CI - 0.37, 0.71; TC: SMD = 0.21, 95% CI - 0.33, 0.75), CRP (SMD = 0.85, 95% CI - 1.37, 3.06) showed no significant difference compared to the control groups.
CONCLUSIONS
High-calorie therapy is effective in gaining weight and BMI with few side effects. However, no significant superiority was detected in ALSFRS-R scores, survival time, lipid profile, and CRP indicator. The overall quality of the included studies is high, and the results have some credibility, but future corroboration by high-quality RCTs is also expected.
Topics: Humans; Amyotrophic Lateral Sclerosis; Lipids
PubMed: 37369861
DOI: 10.1007/s00415-023-11838-4 -
Acta Neurologica Belgica Aug 2022Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons.... (Meta-Analysis)
Meta-Analysis
Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons. Several studies about the effects of statins drug on the risk of ALS showed contradictory results and evidence for this is inconclusive. So we aimed to perform a meta-analysis on previous studies to clarify the association between statin use and risk of ALS. The databases including PubMed, Scopus, and Web of science were searched in February 2021 for studies that reported the association between statin use and risk of ALS. The eligible studies had to provide a report on the effect of statin and the incidence of ALS while comparing it to the control group. Articles that had low statin exposure time, the absence of a control group and an unknown number of ALS patients were excluded. The rate ratio and 95% confidence interval (CI) were used for association measures in case-control and cohort studies. After full-text and abstract review, data from 8 studies with a total of 547,622 participants and 13,890 cases of ALS were entered in the present meta-analysis. We combined eight studies using a random-effect model and the RR for statin users among groups was 0.98 (95% CI 0.80-1.20) which indicates no association between statin and incidence of ALS. Also high heterogeneity was detected across the studies (Q value = 26.62, P = .00; I = 72.71%). In our meta-analysis study, we found no association between statin use and an increase in ALS incidence. This result is in line with some previous studies and provides strong evidence that denies the possible association between statin uptake and disease induction.
Topics: Amyotrophic Lateral Sclerosis; Case-Control Studies; Cohort Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence
PubMed: 34322852
DOI: 10.1007/s13760-021-01753-8 -
Brain Communications 2020Various studies have suggested that a neurotoxic cerebrospinal fluid profile could be implicated in amyotrophic lateral sclerosis. Here, we systematically review the... (Review)
Review
Various studies have suggested that a neurotoxic cerebrospinal fluid profile could be implicated in amyotrophic lateral sclerosis. Here, we systematically review the evidence for cerebrospinal fluid cytotoxicity in amyotrophic lateral sclerosis and explore its clinical correlates. We searched the following databases with no restrictions on publication date: PubMed, Embase and Web of Science. All studies that investigated cytotoxicity following exposure to cerebrospinal fluid from amyotrophic lateral sclerosis patients were considered for inclusion. Meta-analysis could not be performed, and findings were instead narratively summarized. Twenty-eight studies were included in our analysis. Both participant characteristics and study conditions including cerebrospinal fluid concentration, exposure time and culture model varied considerably across studies. Of 22 studies assessing cell viability relative to controls, 19 studies reported a significant decrease following exposure to cerebrospinal fluid from patients with amyotrophic lateral sclerosis, while three early studies failed to observe any difference. Seven of eight studies evaluating apoptosis observed significant increases in the levels of apoptotic markers following exposure to cerebrospinal fluid from patients with amyotrophic lateral sclerosis, with the remaining study reporting a qualitative difference. Although five studies investigated the possible relationship between cerebrospinal fluid cytotoxicity and patient characteristics, such as age, gender and disease duration, none demonstrated an association with any of the factors. In conclusion, our analysis suggests that cerebrospinal fluid cytotoxicity is a feature of sporadic and possibly also of familial forms of amyotrophic lateral sclerosis. Further research is, however, required to better characterize its underlying mechanisms and to establish its possible contribution to amyotrophic lateral sclerosis pathophysiology.
PubMed: 33094283
DOI: 10.1093/braincomms/fcaa121 -
PloS One 2016To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS.
OBJECTIVE
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
METHODS
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
RESULTS
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
CONCLUSION
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Neurofilament Proteins
PubMed: 27732645
DOI: 10.1371/journal.pone.0164625 -
Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496 -
Brain and Behavior Mar 2022Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting cortical and spinal motor neurons. There is a lack of optimal biomarkers to... (Review)
Review
INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting cortical and spinal motor neurons. There is a lack of optimal biomarkers to diagnose and prognosticate the ALS patients. C-reactive protein (CRP), an inflammatory marker, has shown promising results in ALS patients.
MATERIALS AND METHODS
PubMed, Embase, and Google Scholar databases were searched from 2000 to June 1, 2021 for suitable studies showing the relationship between CRP and ALS. The concentration of CRP levels was assessed between ALS patients and controls. Further, end outcomes like ALS functional rating scale (ALSFRS-R), survival status, and mortality risks were assessed in relation to CRP levels.
RESULTS
Eleven studies including five case-control, five cohorts, and one randomized control study were assessed. There were 2785 ALS patients and 3446 healthy controls. A significant increment in CRP levels among ALS patients in comparison with healthy controls were seen in most of the studies. ALSFRS-R and disease progression were found to be significantly correlated with CRP levels. Overall accuracy of CRP in CSF was 62% described in a single study.
CONCLUSION
Although CRP has shown promise as a prognostic biomarker, extensive cohort studies are required to assess its prognostic value and accuracy in diagnosing ALS taking into account the confounding factors.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; C-Reactive Protein; Disease Progression; Humans; Neurodegenerative Diseases
PubMed: 35201675
DOI: 10.1002/brb3.2532