scholarly journals Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study

2019 ◽  
Vol 90 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Ryuji Kaji ◽  
Takashi Imai ◽  
Yasuo Iwasaki ◽  
Koichi Okamoto ◽  
Masanori Nakagawa ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rating Scale ◽  
Controlled Study ◽  
P Value ◽  
High Dose ◽  
Time Interval ◽  
Registration Number ◽  
Randomised Controlled ◽  
Post Hoc ◽  
Lateral Sclerosis

ObjectiveTo evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS).Methods373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset).ResultsNo significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months’ duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups.ConclusionAlthough ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early.Trial registration numberNCT00444613.

scholarly journals Plasma exchange with albumin replacement and disease progression in amyotrophic lateral sclerosis: a pilot study

2021 ◽  
Author(s):  
Mónica Povedano ◽  
Andrés Paipa ◽  
Miquel Barceló ◽  
Michael K. Woodward ◽  
Sandra Ortega ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Pilot Study ◽  
Disease Progression ◽  
Plasma Exchange ◽  
Rating Scale ◽  
Open Label ◽  
Primary Endpoints ◽  
Rate Of Decline ◽  
Post Hoc ◽  
Lateral Sclerosis

Abstract Background Plasma exchange (PE) is used to treat a range of neurological disorders. Based on results demonstrated in Alzheimer’s disease, we theorized that PE with albumin replacement (PE-A) might alter the metabolic profile of plasma and cerebrospinal fluid in patients with amyotrophic lateral sclerosis (ALS) by removing disease-inducing molecules. The aim of this study was to evaluate the effect of PE-A on disease progression in ALS. Methods In this open-label, non-controlled, single-arm, prospective pilot study, 13 adults with ALS had 6 months’ treatment with PE-A 5% and 6 months’ follow-up. Primary endpoints were changes from baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC) through 48 weeks. A post hoc analysis compared individual patient data with the expected ALSFRS-R progression slope. Results The median ALSFRS-R score declined throughout the study, although the rate of decline was slower than expected in seven patients at treatment end and in five patients at study end. Six patients remained in the same baseline slope progression category, and four patients improved their slope category at treatment end. Median FVC decreased significantly during the study. Treatment was well tolerated. Of 330 PE-A procedures, 0.9% were associated with potentially related adverse events. Conclusion Although functional impairment progressed, about two-thirds of patients showed a slower than expected rate of decline at treatment end. Most patients had unaltered (54.5%) or reduced (36.4%) ALSFRS-R slope progression at treatment end. Further evaluation of PE-A in controlled studies involving more patients is warranted. EudraCT number 2013-004842-40. Trial registration ClinicalTrials.gov identifier: NCT02479802.

scholarly journals Changes in Retinal OCT and Their Correlations with Neurological Disability in Early ALS Patients, a Follow-Up Study

2019 ◽  
Vol 9 (12) ◽  
pp. 337 ◽  
Author(s):  
Pilar Rojas ◽  
Rosa de Hoz ◽  
Ana I. Ramírez ◽  
Antonio Ferreras ◽  
Elena Salobrar-Garcia ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rating Scale ◽  
P Value ◽  
Ophthalmological Examination ◽  
Fiber Layer ◽  
Neurological Disability ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Visual Changes

Background: To compare early visual changes in amyotrophic lateral sclerosis (ALS) patients with healthy controls in a baseline exploration, to follow-up the patients after 6 months, and to correlate these visual changes with neurological disability. Methods: All patients underwent a comprehensive neurological and ophthalmological examination. A linear mixed analysis and Bonferroni p-value correction were performed, testing four comparisons as follows: Control baseline vs. control follow-up, control baseline vs. ALS baseline, control follow-up vs. ALS follow-up, and ALS baseline vs. ALS follow-up. Results: The mean time from the diagnosis was 10.80 ± 5.5 months. The analysis of the optical coherence tomography (OCT) showed: (1) In ALS baseline vs. control baseline, a macular significantly increased thickness of the inner macular ring temporal and inferior areas; (2) in ALS follow-up vs. ALS baseline, a significant macular thinning in the inner and outer macular ring inferior areas; (3) in ALS follow-up vs. ALS baseline, a significant peripapillary retinal nerve fiber layer (pRNFL) thinning in the superior and inferior quadrants; and (4) ALS patients showed a moderate correlation between some OCT pRNFL parameters and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Conclusion: The OCT showed retinal changes in patients with motoneuron disease and could serve as a complementary tool for studying ALS.

Fat-rich versus carbohydrate-rich nutrition in ALS: a randomised controlled study

2022 ◽  
pp. jnnp-2021-328331
Author(s):  
Johannes Dorst ◽  
Judith Doenz ◽  
Katharina Kandler ◽  
Jens Dreyhaupt ◽  
Hayrettin Tumani ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Body Weight ◽  
Weight Gain ◽  
Gastrointestinal Symptoms ◽  
Food Supplements ◽  
Controlled Study ◽  
Randomised Controlled Study ◽  
Loss Of Appetite ◽  
Randomised Controlled ◽  
Lateral Sclerosis

ObjectiveThere is growing evidence that the course of amyotrophic lateral sclerosis (ALS) may be influenced beneficially by applying high-caloric food supplements (HCSs). However, it is unknown which composition of nutrients offers optimal tolerability and weight gain.MethodsWe conducted a randomised controlled study (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS); TOLCAL-ALS study) in 64 patients with possible, probable or definite ALS according to El Escorial criteria. Patients were randomised into four groups: a high-caloric fatty supplement (HCFS; 405 kcal/day, 100% fat), an ultra-high-caloric fatty supplement (UHCFS; 810 kcal/day, 100% fat), an ultra-high-caloric, carbohydrate-rich supplement (UHCCS; 900 kcal/day, 49% carbohydrates) and an open control (OC) group without any supplement. The primary endpoint was tolerability. Patients were followed up over 4 weeks.ResultsGastrointestinal side effects were most frequent in the UHCFS group (75.0%), while loss of appetite was most frequent in the UHCCS group (35.3%). During intervention, patients gained +0.9 kg/month of body weight (IQR −0.9 to 1.5; p=0.03) in the HCFS group and +0.9 kg/month (IQR −0.8 to 2.0; p=0.05) in the UHCFS group. A non-significant trend for weight gain (+0.6 kg/month (IQR −0.3 to 1.9; p=0.08)) was observed in the UHCCS group. Patients in OC group continued to lose body weight (−0.5 kg/month, IQR −1.4 to 1.3; p=0.42).InterpretationThe findings suggest that HCSs frequently cause mild to moderate tolerability issues in patients with ALS, most notably gastrointestinal symptoms in high-fat supplements, and loss of appetite in high-carbohydrate supplements. All three HCSs tested are suited to increase body weight.

scholarly journals Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis—A Retrospective Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1623
Author(s):  
Maria Viktoria Requardt ◽  
Dennis Görlich ◽  
Torsten Grehl ◽  
Matthias Boentert
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Disease Progression ◽  
Rating Scale ◽  
Rapid Decline ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Hazard Ratios ◽  
Sum Score ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS. Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Patients were stratified according to five distinct clinical phenotypes: classical ALS; bulbar ALS; ALS with frontotemporal dementia (ALS-FTD); upper motor neuron predominant (UMNP); and lower motor neuron predominant (LMNP). Results: This study confirmed higher age at symptom onset, shorter latency to diagnosis and more rapid decline in the revised ALS Functional Rating Scale sum score as predictors of poor prognosis. Hazard ratios for shorter survival were higher in patients with ALS-FTD versus classical ALS, and in patients with versus without chronic obstructive pulmonary disease (COPD). Mean survival was longest in the UMNP phenotype group. Conclusions: This study confirmed established predictors of shorter survival in ALS and showed that concomitant COPD in particular relates to poor outcome.

scholarly journals Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregivers’ Lives

2021 ◽  
Vol 11 (6) ◽  
pp. 748
Author(s):  
Pavel Schischlevskij ◽  
Isabell Cordts ◽  
René Günther ◽  
Benjamin Stolte ◽  
Daniel Zeller ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Functional Status ◽  
Disease Severity ◽  
Caregiver Burden ◽  
Rating Scale ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Daily Routine ◽  
Work Lives ◽  
Lateral Sclerosis

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 patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ 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. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ 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 caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, 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 CGs’ 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 CGs’ 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.

scholarly journals Effects of Ketamine Gargle for Post-operative Sore Throat, Hoarseness of Voice and Cough Under General Anaesthesia- A Randomised Control Study

2021 ◽  
Author(s):  
Dinesh Chauhan ◽  
Ankit Mankad ◽  
Jigisha Mehta ◽  
Tejash H Sharma
Keyword(s):  
General Anaesthesia ◽  
Endotracheal Intubation ◽  
Normal Saline ◽  
Healing Process ◽  
Voice Quality ◽  
Controlled Study ◽  
P Value ◽  
Time Duration ◽  
C 30 ◽  
Randomised Controlled

Introduction: Majority of the patient undergo endotracheal intubation for various time duration, when given general anaesthesia. Injury in airway mucosa or vocal cords due to endotracheal intubation can be a contributing factor. Ketamine without affecting local healing process has an anti-proinflammatory effect as it limits exacerbation of systemic inflammation. Aim: To study the role of ketamine gargles as a pharmacological measure in order to attenuate POST, HOV and cough followed by endotracheal intubation during surgeries under general anaesthesia. Materials and Methods: A randomised controlled study was carried out for a duration of 22 months from the institutional ethical committee (Study Approval No. SVIEC/ON/MEDI/BNPG18/D19046), on 50 patients of American Society of Anaesthesiologists (ASA) grade I and II. They were allocated into two groups of 25 patients. Group (K): ketamine 50 mg in 29 mL 0.9% normal saline and Group (C): 30 mL 0.9% normal saline. Patients were advised to gargle for 30 seconds just 5 minutes prior to induction of anaesthesia. Patients were intubated with appropriate size of the endotracheal tube and were extubated when fully awake and conscious. Pateints were shifted to postoperative ward and were kept in propped up position with oxygen. Pateints were assessed at 1,2,4,24 hours for incidence of POST, HOV and cough. Assessment was made as per the 4 point scale grading system. The statistical analysis was performed using unpaired t-test, p<0.05 considered statistically significant. Results: In terms of POST grading in both K and C groups p-value was statistically significant (p<0.05) at 1 and at 2 hours postoperatively. In terms of HOV, in group K voice quality issues were reduced till 24 hours, (p<0.05). In terms of cough, in group K there was a significant reduction in complaints of cough till 4 hours postoperatively, (p<0.05). Conclusion: Ketamine gargles is effective in attenuating POST and cough till 2 hours and HOV till 4 hours postoperatively in patients following endotracheal intubation.

scholarly journals A double-blind randomized placebo-controlled study of low dose mirtazapine once daily in patients of major depressive disorders on escitalopram

2019 ◽  
Vol 8 (5) ◽  
pp. 1067
Author(s):  
Mallikarjuna Rao I. ◽  
Usha Kiran Prayaga ◽  
Dharma Rao Uppada ◽  
Ramachandra Rao E. ◽  
B. L. Kudagi
Keyword(s):  
Depressive Disorders ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Study ◽  
P Value ◽  
Chi Square ◽  
Double Blind ◽  
Increased Risk ◽  
Significant Difference ◽  
Chi Square Test

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.

scholarly journals LAPAROSCOPIC CHOLECYSTECTOMY;

2013 ◽  
Vol 20 (05) ◽  
pp. 699-706
Author(s):  
HEMMATPOOR BEHZAD ◽  
MAHVAR TAYEBEH ◽  
MAKHSOSI BEHNAM REZA ◽  
Saeb Morteza
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Shoulder Pain ◽  
Rating Scale ◽  
Controlled Study ◽  
P Value ◽  
Medical Sciences ◽  
Preoperative Administration ◽  
Elective Laparoscopic Cholecystectomy ◽  
Double Blinded ◽  
To Receive

Background: shoulder pain after laparoscopic procedure is a frequent complication encountered in surgery ward. Severaltreatments have been proposed to reduce it. This study aimed to evaluate the efficacy of preoperative administration of gabapentin inpreventing and attenuating Post Laparoscpoic Shoulder Pain (PLSP) after laparoscopic cholecystectomy. Design: In a randomised,double blinded placebo controlled study. Setting: Woman's Hospital, Kermanshah University of Medical Sciences. Period: April 2011 toMarch 2012. Material and methods: 90 patients of ASA physical status I-II undergoing elective laparoscopic cholecystectomy wererandomly allocated to receive gabapentin 600 mg or placebo ,half an hour before surgery. The presence analgesia and side effects wererecorded for 12h postoperatively in same times. Results: Incidence Verbal Rating Scale (VRS) ≥ 4 at different times after arrival to PACUwere significantly lower in gabapentin group in arrival (P Value= 0.003) and then after 30 miniute (P Value= 0.02) and 2 (P Value=0.003), 4 (P Value= 0.03) and 6 (P Value= 0.04) hours after arrival to Post Anesthesia Care Unit (PACU). But this sigificancy lost at 12hours (P Value= 0.07) after arrival to PACU. Also there was a reduction in amounts of postoperative in ward analgesic consumption. Sideeffects were not different between two groups. Conclusions: 600 mg gabapentin as premedication is effective and safe for reducing postlaparoscopicshoulder pain intensity after general laparoscopy compared with placebo.

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