Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients

Burkhardt, Christian; Neuwirth, Christoph; Sommacal, Andreas; Andersen, Peter M.; Weber, Markus

doi:10.1371/journal.pone.0177555

Cited by 96 publications

(103 citation statements)

References 34 publications

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“…While no relationship was found with mood, there was a very strong association with PEG nutritional supplements and increased survival duration in the Chi-square test and the conditional random forests (Figure 4) conducted in the present study. The significance of PEG usage in associatively increasing survival is corroborated by recent work [20,53].…”

Section: Palliative Als Interventions Associated With Improved Mood Amentioning

confidence: 61%

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration

Bond

Bowen

Mertens

et al. 2020

Behavioral Sciences

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Associations of modulators of quality of life (QoL) and survival duration are assessed in the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. Major categories include clinical impression of mood (CIM); physical health; patient social support; and usage of interventions, pharmaceuticals, and supplements. Associations were assessed at p < 0.05 and p < 0.001 significance thresholds using applicable methods (Chi-square, t-test, ANOVA, logistical regression, random forests, Fisher’s exact test) within a retrospective cohort of 1585 patients. Factors significantly correlated with positive (happy or normal) mood included family support and usage of bi-level positive airway pressure (Bi-PAP) and/or cough assist. Decline in physical factors like presence of dysphagia, drooling, general pain, and decrease in ALSFRS-R total score or forced vital capacity (FVC) significantly correlated with negative (depressed or anxious) mood (p < 0.05). Use of antidepressants or pain medications had no association with ALS patient mood (p > 0.05), but were significantly associated with increased survival (p < 0.05). Positive patient mood, Bi-PAP, cough assist, percutaneous endoscopic gastrostomy (PEG), and accompaniment to clinic visits associated with increased survival duration (p < 0.001). Of the 47 most prevalent pharmaceutical and supplement categories, 17 associated with significant survival duration increases ranging +4.5 to +16.5 months. Tricyclic antidepressants, non-opioids, muscle relaxants, and vitamin E had the highest associative increases in survival duration (p < 0.05). Random forests, which examined complex interactions, identified the following pharmaceuticals and supplements as most predictive to survival duration: Vitamin A, multivitamin, PEG supplements, alternative herbs, antihistamines, muscle relaxants, stimulant laxatives, and antispastics. Statins, metformin, and thiazide diuretics had insignificant associations with decreased survival.

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Section: Palliative Als Interventions Associated With Improved Mood Amentioning

confidence: 61%

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration

Bond

Bowen

Mertens

et al. 2020

Behavioral Sciences

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“…Our previous study using a Kaplan-Meier analysis did not find NIPPV to affect survival time, albeit an adjusted Cox proportional hazard model showed NIPPV to have a positive effect on the survival rate ( 35 ). Similarly, another study identified NIPPV as a significant survival-promoting factor with Cox proportional hazard regression after adjusting for various cofactors ( 36 ). A study in Taiwan using multivariate logistic regression also identified NIPPV as a predictor of long-term survival ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…Second, other factors may also be involved in disease progression, such as cognitive status, neuropsychological features, and pulmonary function, none of which was investigated at the time of this study. Third, even though an association between genetic variants and different clinical ALS profiles has been identified in several studies ( 1 , 36 ), we did not explore the influence of genetic variants on the staging system.…”

Section: Discussionmentioning

confidence: 99%

Clinical Staging of Amyotrophic Lateral Sclerosis in Chinese Patients

et al. 2018

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Objective: It is important to explore the utility of clinical staging systems in the management of amyotrophic lateral sclerosis (ALS). Our aim was to assess the validity of King's College in a Chinese ALS cohort, by evaluating the duration and informativeness of each stage and examining the association between stage and prognosis.Methods: From May 2008 to December 2016, patients with a likely diagnosis of ALS were registered. We prospectively assessed the progression of the patients through the stages and calculated the duration of each stage.Results: The median duration in Stage 1 was 12.00 months, Stage 2 7.50 months, Stage 3 6.50 months, and Stage 4 4.10 months. Subset analysis revealed that the spinal-onset and early-onset patients had a longer median time in Stage 1 compared to bulbar-onset and late-onset patients, respectively. Riluzole treatment extended the durations of Stages 1 and 2, and the effect was maintained in patients with long-term use of riluzole (>6 months). Patients who initiated long-term riluzole therapy early, in Stage 1 or 2, had a longer Stage 2. Patients who received percutaneous gastrostomy endoscopy (PEG) or non-invasive positive-pressure ventilation (NIPPV) showed longer durations of Stage 4. The differences in survival time measured from each stage to death or censor date were significant.Conclusions: We validated the King's College staging system in a Chinese population, and showed this system to be useful in clinical practice. Patients with bulbar-onset or an age of onset>45 years tended to have rapidly progressing ALS. Riluzole may be more effective when initiated in an early disease stage and continued long-term. PEG and NIPPV treatments can extend disease duration of Stage 4.

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“…PEG has been associated with increased survival in people with ALS. 33,34 It is also associated with improved quality of life in~85% of patients who receive it, with no patients reporting worsened quality of life. 9 Clinical guidelines recommend early tube placement so that patients can benefit from nutritional support before malnutrition, weight loss, and dehydration have further progressed, and before patients are no longer candidates for the surgery to implant a PEG tube.…”

Section: Discussionmentioning

confidence: 99%

Riluzole Oral Suspension: Bioavailability Following Percutaneous Gastrostomy Tube-modeled Administration Versus Direct Oral Administration

Brooks

Bettica

Cazzaniga

2019

Clinical Therapeutics

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Purpose: During amyotrophic lateral sclerosis progression, up to 85% of patients develop dysphagia. Riluzole oral suspension 50 mg/10 mL is bioequivalent to riluzole 50-mg film-coated tablets administered orally under fasting conditions. Here, we compare the bioavailability of a single 50-mg dose of riluzole oral suspension via intragastric tube, a proxy for percutaneous endoscopic gastrostomy administration, with that of oral administration in healthy volunteers under fasting conditions. Secondary objectives included the plasma pharmacokinetic and safety profiles of each administration route. Methods: This was a single-center, single-dose, open-label, randomized, 2-period, 2-sequence, crossover bioequivalence/bioavailability study. Healthy volunteers were randomized to riluzole oral suspension 50 mg/10 mL either via nasogastric tube or orally, with a 5-day washout before crossover. Findings: A total of 32 subjects were randomized (safety population); 30 were eligible for pharmacokinetic analysis. The ratios (nasogastric tube/oral) of the geometric least squares means and the geometric 90% CIs of AUC 0et , AUC 0einf , and C max were calculated to be 90.60% (85.66%e 95.82%), 90.43% (85.47%e95.67%), and 96.99% (89.40%e105.23%), respectively, indicating bioequivalence. No significant differences in C max , T max , K el , and t 1/2el between treatments were found. Overall, riluzole oral suspension was well tolerated. No deaths or other serious adverse events were reported. Implications: In this study, riluzole oral suspension was bioequivalent when administered intragastrically and orally in healthy subjects under fasting conditions. Both administration methods were well tolerated. These results show that intragastric administration of riluzole oral suspension may provide an important formulation option in people with amyotrophic lateral sclerosis who have a percutaneous endoscopic gastrostomy tube.

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Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients

Cited by 96 publications

References 34 publications

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration

Clinical Staging of Amyotrophic Lateral Sclerosis in Chinese Patients

Riluzole Oral Suspension: Bioavailability Following Percutaneous Gastrostomy Tube-modeled Administration Versus Direct Oral Administration

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