scholarly journals The MITOS system predicts long-term survival in amyotrophic lateral sclerosis

2015 ◽  
Vol 86 (11) ◽  
pp. 1180-1185 ◽  
Author(s):  
Irene Tramacere ◽  
Eleonora Dalla Bella ◽  
Adriano Chiò ◽  
Gabriele Mora ◽  
Graziella Filippini ◽  
...  

ObjectiveThe choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.MethodsAnalyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or >23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models.ResultsDisease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or >23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37/45) and 63% specificity (95% CI 55% to 71%, n=92/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50/70) and 68% specificity (95% CI 60% to 77%, n=76/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to predict survival at 12 and 18 months was 1 for the ALS-MITOS (ie, loss of at least one function) and a decline ranging from 6 to 9 points for the ALSFRS-R.ConclusionsThe ALS-MITOS system can reliably predict the course of ALS up to 18 months and can be considered a novel and valid outcome measure in RCTs.

Author(s):  
Philip J. Choi ◽  
Michael Murn ◽  
Roberta Turner ◽  
Richard Bedlack

Background: Amyotrophic Lateral Sclerosis (ALS) is a terminal neuromuscular disease with patients dying within 3-5 years of diagnosis. Most patients choose to forego invasive life sustaining measures. Timing of hospice referral can be challenging given the advancement of non-invasive ventilation (NIV) technology. Objective: To describe the characteristics of patients enrolled in hospice from an ALS clinic at 1 academic medical center and to perform a cost analysis for patients who remained on ventilator support. Methods: Retrospective cross-sectional study of patients enrolled in hospice over a 2-year period. Clinical characteristics included ALS Functional Rating Scale Revised (ALSFRS-R) score, Forced Vital Capacity (FVC), use of NIV and mechanical insufflation-exsufflation (MIE), riluzole use, and length of stay in hospice. A cost analysis was performed for patients enrolled in Duke Home Care and Hospice. Results: 85 of 104 patients who died were enrolled in hospice. Median days enrolled in hospice was 84. Patients who continued on NIV had similar hospice length of stay as those on no respiratory support (88 versus 80 days, p = 0.83). Bulbar patients had a trend toward shorter length of stay in hospice than limb onset patients (71 versus 101 days, p = 0.49). Cost analysis showed that hospice maintained a mean net operating revenue of $3234.50 per patient who continued on NIV. Conclusions: Hospice referrals for ALS patients on NIV can be challenging. This study shows that even with continued NIV use, most ALS patients die within the expected 6 months on home hospice, and care remains cost effective for hospice agencies.


Thorax ◽  
2001 ◽  
Vol 56 (9) ◽  
pp. 708-712
Author(s):  
P K Plant ◽  
J L Owen ◽  
M W Elliott

BACKGROUNDNon-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation. The second aim was to determine the long term survival of patients treated with and without NIV.METHODSIn this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998. Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic factors were identified using logistic regression analysis. All patients were followed until death or 1 January 1999.RESULTSAt enrolment the H+ concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and Paco2 (OR 1.14 per kPa, 95% CI 1.14 to 1.81, p<0.01) were associated with treatment failure. Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80). After 4 hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to 0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84 to 0.99, p=0.04) were associated with success. Median length of survival was 16.8 months in those treated with NIV and 13.4 months in those receiving standard treatment (p=0.12). The trend in improved survival was attributable to prevention of death during the index admission.CONCLUSIONInitial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation. NIV reduces this risk and progress should be monitored using change in respiratory rate and pH. The long term survival after NIV is sufficiently good to render treatment appropriate.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1220
Author(s):  
Ruojie He ◽  
Minying Zheng ◽  
Ling Lian ◽  
Xiaoli Yao

(1) Background: The aim of this longitudinal study was to evaluate the association between disease progression according to the Milano–Torino staging (MITOS) system and long-term survival in Chinese patients with amyotrophic lateral sclerosis (ALS). We also examined factors affecting MITOS progression. (2) Methods: Patients were enrolled and underwent follow-up at 6, 12, 18, and 24 months, and their demographic and clinical data, including the Milano–Torino stage, Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS-R) score and neuropsychiatric data, were evaluated. The sensitivity and specificity of predicting survival outcomes based on MITOS progression and ALSFRS-R score decline from baseline to 6 months were compared. The associations between MITOS progression from baseline to 6 months and survival outcome at 12, 18 and 24 months were examined, and factors associated with disease progression were evaluated with subgroup analyses. (3) Results: Among the 100 patients included, 74% were in stage 0 at baseline, and approximately 95% progressed to a higher stage of the MITOS system at 24 months. MITOS progression from baseline to 6 months and ALSFRS-R decline showed comparable value for predicting survival at 12, 18, and 24 months. MITOS progression from baseline to 6 months is strongly associated with death outcomes. Older age at onset and increased depression and anxiety scores may be related to disease progression. (4) Conclusions: MITOS progression during the early disease course could serve as a prognostic marker of long-term survival and may have utility in clinical trials. Age at onset and diagnosis and neuropsychiatric factors might be associated with disease progression.


2021 ◽  
Vol 14 (8) ◽  
pp. 705
Author(s):  
Hideki Houzen ◽  
Takahiro Kano ◽  
Kazuhiro Horiuchi ◽  
Masahiro Wakita ◽  
Azusa Nagai ◽  
...  

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.


Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. 806-808 ◽  
Author(s):  
Héctor R. Martínez ◽  
María Teresa González-Garza ◽  
Jorge Moreno-Cuevas ◽  
César E. Escamilla-Ocañas ◽  
Juan Miguel Tenorio-Pedraza ◽  
...  

Respirology ◽  
2017 ◽  
Vol 22 (6) ◽  
pp. 1212-1218 ◽  
Author(s):  
Bart Vrijsen ◽  
Bertien Buyse ◽  
Catharina Belge ◽  
Goele Vanpee ◽  
Philip Van Damme ◽  
...  

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