People living with ALS (plwALS) experience motor control loss, speech/swallowing difficulties, respiratory insufficiency, and early death. Advancing disease stage is typically associated with a greater burden on the health care system, and delays in diagnosis can result in substantial health care resource utilization (HCRU).
Abstract Background Amyotrophic lateral sclerosis (ALS) is characterized by a rapid disease course, with disease severity being associated with declining health-related quality of life (HRQoL) in persons living with ALS (pALS). The main objective of this study was to assess the impact of disease progression on HRQoL across King’s, Milano-Torino Staging (MiToS), and physician-judgement clinical staging. Additionally, we evaluated the impact of the disease on the HRQoL of care partners (cALS). Methods Data were sourced from the Adelphi ALS Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists, pALS and cALS presenting in a real-world clinical setting between July 2020 and March 2021 in Europe and the United States. Results Neurologists ( n = 142) provided data for 880 pALS. There were significant negative correlations between all three clinical staging systems and EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) utility scores and visual analogue scale (VAS) ratings. Although not all differences were significant, 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) scores showed a stepwise increase in HRQoL impairment at each stage of the disease regardless of the staging system. At later stages, high levels of fatigue and substantial activity impairment were reported. As pALS disease states progressed, cALS also experienced a decline in HRQoL and increased burden. Conclusions Across outcomes, pALS and cALS generally reported worse outcomes at later stages of the disease, highlighting an unmet need in this population for strategies to maximise QoL despite disease progression. Recognition and treatment of symptoms such as pain and fatigue may lead to improved outcomes for pALS and cALS.
Zuranolone (SAGE-217) is a novel, investigational positive allosteric modulator of GABAA receptors being investigated in major depressive disorder (MDD). This analysis of phase 2 data quantified the benefit and risk of zuranolone (30mg) versus placebo and antidepressants in terms of number needed to treat (NNT) and number needed to harm (NNH).Rates of response, remission, and all-cause discontinuation for zuranolone and 11 antidepressant comparators were obtained from the zuranolone phase 2 clinical study (N=89) and a published network meta-analysis, respectively. An indirect treatment comparison was conducted using the Bucher method to compare zuranolone to standard-of-care.Zuranolone demonstrated greater benefit compared to placebo on Day 3 (NNT range for response=4-5, NNT for remission=10) and at Day 15 (NNT=3 for response and remission). Compared to SSRIs and SNRIs, zuranolone at Day 15 showed improved treatment response (NNT=4 [95% CI = 3; 16] and 5 [95% CI = 3; 25], respectively) and remission (NNT=4 [95% CI = 2; 13] and 4 [95% CI = 2; 18], respectively). This was accompanied by a reduction in all-cause discontinuation, with negative NNH values (-57 and -28), respectively.Variations in study design across the included trials may limit the generalizability of results.With a small positive NNT as early as Day 3 indicating robust benefit and a negative NNH indicating reduced harm, this analysis based on a phase 2 study suggests that patients with MDD may benefit from the benefit-to-risk profile of zuranolone.
OBJECTIVE:
To evaluate the feasibility and utility of a shoe-worn inertial sensor to measure gait abnormalities in Huntington disease (HD) in the home setting.
BACKGROUND:
Clinical rating scales provide only point assessments of disease-related impairments in HD, lack sensitivity, and require that a clinician experienced in the scale’s use evaluate the patient. A tool that would allow longitudinal, objective, quantitative measurement of impairments may offer advantages over standard clinical rating scales.
DESIGN/METHODS:
This was a pilot, single-blind, controlled observational study. Five ambulatory HD subjects and 5 age/gender-matched healthy controls wore inertial sensors manufactured by APDM, Inc. attached to each shoe during waking hours for 7 days. Gait parameters calculated from the sensors included stride length([percnt]height); stride velocity([percnt]height/sec); step duration(sec); double support time([percnt]); pitch at toe off (degrees) and heel strike (degrees); cadence(steps/min); and variability in each of these measures. Following blinded descriptive data analysis by APDM, independent samples t-tests were used to compare means for selected gait metrics between HD and control subjects, and Pearson correlation coefficients were used to interrogate the relationships between gait metrics, chorea score, and Total Functional Capacity (TFC, a measure of disease severity).
RESULTS:
Subjects were able to successfully apply, wear and charge the sensors. Blinded gait analysis correctly identified the HD and control subjects for 4/5 pairs. Significant differences were found between HD/control groups in mean(SD) stride length [53.96(9.25), 67.68(7.25), p=0.03]; mean(SD) variability per week (as measured by coefficient of variation) in stride length [28.57(5.54), 20.27(3.78), p=0.02] and pitch at toe off [25.57(4.00), 17.56(4.07), p=0.01]. Lower TFC scores correlated with greater variability in stride length[R=-0.82]; pitch at toe off[R=-0.80]; and increased double support time[R=-0.75]. Higher chorea scores correlated with shorter stride length[R=-0.76].
CONCLUSIONS:
Inertial sensors may offer a feasible mechanism to objectively measure clinically-relevant gait abnormalities in HD.
Study Supported by:
Vertex Pharmaceuticals, Inc Disclosure: Dr. Hogarth has received research support from Vertex Pharmaceuticals. Dr. Lenahan has nothing to disclose. Dr. Portillo has nothing to disclose. Dr. Ramachandran has received personal compensation from Vertex Pharmaceuticals as an employee, Dr. Stenson has received personal compensation for activities with Vertex Pharmaceuticals as an employee. Dr. Legedza has received personal compensation for activities with Vertex Pharmaceuticals, Inc. as an employee. Dr. Botfield has received personal compensation for activities with Vertex Pharmaceuticals as an employee. Dr. Horak has received personal compensation for activities with Consensus Medical, North American Education, and APDM. Dr. McNames has received personal compensation for activities with APDM, Inc,. as an employee. Dr. El-Gohary has received personal compensation for activities with APDM, Inc. as an employee.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)