Sensitivity and specificity of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to detect dysarthria in individuals with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Given the widespread use of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure disease progression in ALS and recent reports demonstrating its poor sensitivity, we aimed to determine the sensitivity and specificity of the ALSFRS-R bulbar subscale and speech item to detect validated clinical ratings of dysarthria in individuals with ALS. METHODS: Paired ALSFRS-R and validated Speech Intelligibility Test (SIT) data from individuals with ALS were analyzed. Trained raters completed duplicate, independent, and blinded ratings of audio recordings to obtain speech intelligibility (%) and speaking rate (words per minute, WPM). Binary dysarthria profiles were derived (dysarthria ≤96% intelligible and/or <150 WPM). Data were obtained using the Kruskal-Wallis test, receiver-operating characteristic (ROC) curve, area under the curve (AUC), sensitivity and specificity percentages, and positive/negative predictive values (PPV/NPV). RESULTS: A total of 250 paired SIT and ALSFRS-R data points were analyzed. Dysarthria was confirmed in 72.4% (n = 181). Dysarthric speakers demonstrated lower ALSFRS-R bulbar subscale (8.9 vs. 11.2) and speech item (2.7 vs. 3.7) scores (P < .0001). The ALSFRS-R bulbar subscale score had an AUC of 0.81 (95% confidence interval [CI] 0.75 to 0.86). A subscale score of ≤11 yielded a sensitivity of 86%, specificity of 57%, PPV of 84%, and NPV of 60% to correctly identify dysarthria status. The ALSFRS-R speech item score demonstrated an AUC of 0.81 to detect dysarthria (95% CI 0.76 to 0.85), with sensitivity of 79%, specificity of 75%, PPV of 89%, and NPV of 58% for a speech item cutpoint of ≤3. DISCUSSION: The ALSFRS-R bulbar and speech item subscale scores may be useful, inexpensive, and quick tools for monitoring dysarthria status in ALS.

Respiratory Strength Training in Amyotrophic Lateral Sclerosis: A Double-Blind, Randomized, Multicenter, Sham-Controlled Trial.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the short-term physiologic effect and one-year functional effect of a 12-week inspiratory and expiratory respiratory strength training (RST) program in individuals with amyotrophic lateral sclerosis (ALS). METHODS: A double-blinded, randomized, sham-controlled trial was conducted in 45 individuals with early-stage ALS. Participants were randomized into 12 weeks of active RST (30% load, n = 23) or sham RST (0% load, n = 22). An intent-to-treat analysis was conducted. Linear regression of pre-post change with group status and pretest scores as predictors was conducted. Primary outcomes included maximum expiratory and inspiratory pressure (MEP, MIP), and secondary outcomes were cough spirometry and forced vital capacity. Exploratory follow-up outcomes included one-year global and bulbar decline (ALS Functional Rating Scale-Revised [ALSFRS-R] total and bulbar subscale slope), oral intake status, and time to noninvasive ventilation (NIV). RESULTS: TheRST completion rate was 91% with no RST-related adverse events. A 12-week RST program led to increases in MEP (p = 0.004), but not MIP (p = 0.33). On average, MEP increased by 20.8 cm H2O after active RST (95% CI +7.6 to +33.9) and decreased by 1.0 cm H2O (95% CI -9.1 to +7.2) after sham RST. Mean MIP increased by 8.9 cm H2O (95% CI +1.5 to +16.3) and 4.8 cm H2O (95% CI -0.6 to +10.2) for the active and sham groups, respectively. Regarding secondary outcomes, RST led to significant increases in cough peak inspiratory flow (p = 0.02); however, it did not affect cough expiratory flow (p = 0.06) or FVC (p = 0.60). Regarding 12-month outcomes, a significant difference in the ALSFRS-R bulbar subscale slope was observed across treatment groups, with a more than two-fold faster rate of bulbar decline in the sham vs active RST groups observed (-0.29 vs -0.12 points/month, p = 0.02). Total ALSFRS-R slope, feeding status, and time to NIV did not differ across treatment groups (p > 0.05). DISCUSSION: RST was well tolerated and led to improvements in some, but not all, short and long-term outcomes. RST represents a proactive rehabilitative intervention that could increase physiologic capacity of specific breathing and airway clearance functions during the early stages of ALS. Further work is needed to determine optimal training intensity, resistance load specifications, and potential long-term functional outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that a mild-intensity respiratory strength training program improves maximum expiratory pressure, but not maximum inspiratory pressure, in patients with early-stage ALS.

Discriminant Ability of the Eating Assessment Tool-10 to Detect Swallowing Safety and Efficiency Impairments.

OBJECTIVES/HYPOTHESIS: Quick, sensitive dysphagia screening tools are necessary to identify high-risk patients for further evaluation in busy multidisciplinary amyotrophic lateral sclerosis (ALS) clinics. We examined the relationship between self-perceived dysphagia using the validated Eating Assessment Tool-10 (EAT-10) and videofluoroscopic analysis of swallowing safety and efficiency. STUDY DESIGN: Prospective, observational, longitudinal study. METHODS: Individuals with ALS completed the EAT-10 and a videofluoroscopic swallowing study. Duplicate, independent, blinded analyses of the validated Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale were performed to index swallowing safety and efficiency (mild dysphagia: DIGEST ≥ 1, moderate dysphagia: DIGEST ≥ 2). A between-groups analysis of variance with Games-Howell test for post-hoc pairwise comparisons was performed to examine EAT-10 scores across dysphagia severity levels. Receiver operator characteristic curve analysis, area under the curve (AUC), sensitivity, specificity, positive-negative predictive values (PPV, NPV), and odds ratios (OR) were derived. RESULTS: Four hundred and thirty five paired EAT-10 and DIGEST scores were analyzed. Mean EAT-10 score was 8.48 (95% confidence interval [CI]: 7.63-9.33). Individuals with dysphagia demonstrated higher EAT-10 scores (mild: 4.1 vs. 11.3, moderate: 6.0 vs. 17.5, P < .001). Mean EAT-10 scores increased across DIGEST levels (D0: 4.1, D1: 7.9, D2: 15.1, D3: 20.4, D4: 39.0). For mild dysphagia, an EAT-10 cut score of 3 was optimal: AUC 0.74 (95% CI: 0.69-0.78; sensitivity: 77%; specificity: 53%; PPV: 71%; NPV: 60%; OR: 3.5). An EAT-10 cut score of 7 optimized detection of moderate dysphagia: AUC 0.83 (95% CI: 0.78-0.87; sensitivity: 81%; specificity: 66%; PPV: 39%; NPV: 93%; OR: 8.1). CONCLUSION: The EAT-10 is an easy-to-administer dysphagia screening tool with good discriminant ability for use in ALS clinics. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2319-2326, 2022.

Discriminant ability of the 3-ounce water swallow test to detect aspiration in amyotrophic lateral sclerosis.

BACKGROUND: Given the need for quick and accurate dysphagia screening tools to optimize referral workflows and resource utilization in fast-paced multidisciplinary amyotrophic lateral sclerosis (ALS) clinics, we evaluated the discriminant ability of the 3 oz. water swallow test (WST) to detect aspiration in individuals with ALS. METHODS: A total of 212 paired 3 oz. WST (index test) and standardized videofluoroscopic swallow studies (reference test) were completed in individuals with a confirmed diagnosis of ALS. Blinded raters analyzed swallowing safety using the validated penetration-aspiration scale (PAS; non-aspirator: PAS < 6; aspirator: PAS ≥ 6). Receiver operating characteristic curve analysis, area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated. KEY RESULTS: Index test: 78 (36.8%) WSTs were scored as a fail and 134 (63.2%) as a pass. REFERENCE TEST: Aspiration was confirmed in 67 (31.6%) reference tests with 145 (68.4%) reference tests verified as having no aspiration. Sensitivity and specificity of the 3 oz. WST to detect radiographically confirmed aspiration was 55.2% and 71.7%, respectively (AUC: 0.635, PPV: 47.4%, NPV: 77.6%). CONCLUSIONS & INFERENCES: In this dataset, the 3 oz. WST did not demonstrate adequate sensitivity or specificity to detect aspiration in people with ALS as a stand-alone dysphagia screening tool.

An Initiative to Improve 30-Day Readmission Rates Using a Transitions-of-Care Clinic Among a Mixed Urban and Rural Veteran Population.

BACKGROUND/OBJECTIVE: Hospital readmissions in the United States, especially in patients at high-risk, cost more than $17 billion annually. Although care transitions is an important area of research, data are limited regarding its efficacy, especially among rural patients. In this study, we describe a novel transitions-of-care clinic (TOCC) to reduce 30-day readmissions in a Veterans Health Administration setting that serves a high proportion of rural veterans. METHODS: In this quality improvement initiative we conducted a pre-post study evaluating clinical outcomes in adult patients at high risk for 30-day readmission (Care Assessment Needs score > 85) discharged from the Iowa City Veterans Affairs (ICVA) Health Care System from 2017 to 2020. The ICVA serves 184,000 veterans across 50 counties in eastern Iowa, western Illinois, and northern Missouri, with more than 60% of these patients residing in rural areas. We implemented a multidisciplinary TOCC to provide in-person or virtual follow-up to high-risk veterans after hospital discharge. The main purpose of this study was to assess how TOCC follow-up impacted the monthly 30-day patient readmission rate. RESULTS: The TOCC resulted in a 19.2% relative reduction in 30-day readmission rates in the 12-month postimplementation period compared to the preimplementation period (9.2% vs 11.4%, P = .04). Virtual visits were more popular than in-person visits among both urban and rural veterans. There was no difference in outcomes between these two follow-up options, and both groups had reduced readmission rates compared to non-TOCC follow-up. CONCLUSIONS: A multidisciplinary TOCC within the ICVA featuring both virtual and in-person visits reduced the 30-day readmission rate. This reduction was particularly notable among patients with congestive heart failure.

Swallowing screening practice patterns for nurses in the cardiac surgery intensive care unit.

AIMS AND OBJECTIVES: The current study surveyed nurse practice patterns for performing swallowing screens in an academic cardiac intensive care unit (ICU). It aimed to index: training and levels of confidence in conducting dysphagia screens; screening methods employed; timing and frequency of implement; and subsequent plan of care in identified high-risk patients. BACKGROUND: Swallowing impairment (dysphagia) is common following cardiac surgery and associated with significant morbidity and mortality. Early and accurate detection of dysphagia is therefore critical to afford implementation of interventions to optimise patient care. Currently, no validated instruments or guidelines exist for nursing screening of dysphagia in this setting. METHODS: An anonymous and voluntary 10-item mixed-methods online survey was conducted using Qualtrics software. Nonprobability purposive sampling was utilised to recruit nurses working in an academic 24-bed cardiac ICU. Thematic analysis using operationally defined coding, SRQR checklist and descriptive statistics were employed. RESULTS: Sixty-nine nurses completed the survey during a 1-month period, representing an 84% response rate. Formal training in performing swallowing screens was reported in 18.6% of nurses. In rank order, reported level of confidence was the following: "moderately" (49%); "somewhat" (35%); "not" (13%); and "very" (3%). The majority of nurses performed screens within 1 hr (40.6%) or between 1-4 hr (43.8%) of extubation. Fifteen different methods were utilised to screen swallowing function by nurses who reported a total of 31 different clinical signs indicative of dysphagia. CONCLUSIONS: Survey data of practicing nurses in an academic cardiac ICU revealed limited formal training in swallowing screening methodology, a high degree of variability in screening methods employed and low levels of agreement for dysphagia signs. RELEVANCE TO CLINICAL PRACTICE: Data highlight a knowledge gap and need for the development of formal education and validated rapid nursing dysphagia screening tools for standardised implementation in the cardiac surgery ICU setting.

Diagnostic utility of the amyotrophic lateral sclerosis Functional Rating Scale-Revised to detect pharyngeal dysphagia in individuals with amyotrophic lateral sclerosis.

OBJECTIVE: The ALS Functional Rating Scale-Revised (ALSFRS-R) is the most commonly utilized instrument to index bulbar function in both clinical and research settings. We therefore aimed to evaluate the diagnostic utility of the ALSFRS-R bulbar subscale and swallowing item to detect radiographically confirmed impairments in swallowing safety (penetration or aspiration) and global pharyngeal swallowing function in individuals with ALS. METHODS: Two-hundred and one individuals with ALS completed the ALSFRS-R and the gold standard videofluoroscopic swallowing exam (VFSE). Validated outcomes including the Penetration-Aspiration Scale (PAS) and Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) were assessed in duplicate by independent and blinded raters. Receiver operator characteristic curve analyses were performed to assess accuracy of the ALSFRS-R bulbar subscale and swallowing item to detect radiographically confirmed unsafe swallowing (PAS > 3) and global pharyngeal dysphagia (DIGEST >1). RESULTS: Although below acceptable screening tool criterion, a score of ≤ 3 on the ALSFRS-R swallowing item optimized classification accuracy to detect global pharyngeal dysphagia (sensitivity: 68%, specificity: 64%, AUC: 0.68) and penetration/aspiration (sensitivity: 79%, specificity: 60%, AUC: 0.72). Depending on score selection, sensitivity and specificity of the ALSFRS-R bulbar subscale ranged between 34-94%. A score of < 9 optimized classification accuracy to detect global pharyngeal dysphagia (sensitivity: 68%, specificity: 68%, AUC: 0.76) and unsafe swallowing (sensitivity:78%, specificity:62%, AUC: 0.73). CONCLUSIONS: The ALSFRS-R bulbar subscale or swallowing item did not demonstrate adequate diagnostic accuracy to detect radiographically confirmed swallowing impairment. These results suggest the need for alternate screens for dysphagia in ALS.

Provisional best practices guidelines for the evaluation of bulbar dysfunction in amyotrophic lateral sclerosis.

INTRODUCTION: Universally established comprehensive clinical bulbar scales objectively assessing disease progression in amyotrophic lateral sclerosis (ALS) are currently lacking. The goal of this working group project is to design a best practice set of provisional bulbar ALS guidelines, available for immediate implementation within all ALS clinics. METHODS: ALS specialists across multiple related disciplines participated in a series of clinical bulbar symposia, intending to identify and summarize the currently accepted best practices for the assessment and management of bulbar dysfunction in ALS Results: Summary group recommendations for individual speech, Augmentative and Alternative Communication (AAC), and swallowing sections were achieved, focusing on the optimal proposed level of care within each domain. DISCUSSION: We have identified specific clinical recommendations for each of the 3 domains of bulbar functioning, available for incorporation within all ALS clinics. Future directions will be to establish a formal set of bulbar guidelines through a methodological and evidence-based approach. Muscle Nerve 59:531-531, 2019.

Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial.

INTRODUCTION: The purpose of this study was to determine the impact of an in-home expiratory muscle strength training (EMST) program on pulmonary, swallow, and cough function in individuals with amyotrophic lateral sclerosis (ALS). METHODS: EMST was tested in a prospective, single-center, double-blind, randomized, controlled trial of 48 ALS individuals who completed 8 weeks of either active EMST (n = 24) or sham EMST (n = 24). The primary outcome to assess treatment efficacy was change in maximum expiratory pressure (MEP). Secondary outcomes included: cough spirometry; swallowing; forced vital capacity; and scoring on the ALS Functional Rating Scale-Revised. RESULTS: Treatment was well tolerated with 96% of patients completing the protocol. Significant differences in group change scores were noted for MEP and Dynamic Imaging Grade of Swallowing Toxicity scores (P < 0.02). No differences were noted for other secondary measures. DISCUSSION: This respiratory training program was well-tolerated and led to improvements in respiratory and bulbar function in ALS. Muscle Nerve 59:40-46, 2019.

Best practices protocol for the evaluation of bulbar dysfunction: summary recommendations from the NEALS bulbar subcommittee symposium.

OBJECTIVE: The aim of this Symposium was to develop a consensus based, bulbar assessment protocol for implementation within NEALS clinics. METHODS: A one-day symposium, held in April 2017, was organized into Speech and Swallowing sections to establish summary recommendations for the assessment of bulbar dysfunction within each group. RESULTS: Summary recommendations included speech referrals and AAC evaluations at initial visit, CNS-BFS, maximum sustained phonation, and speaking rate. Dysarthria evaluation included the speech subsystem involvement of respiration, phonation, resonance, and articulation. Specific recommendations for swallowing were established for each of the following domains: dietary/oral intake, airway defense physiologic capacity, swallow safety screen, patient-reported swallow-related outcomes, oral sensorimotor exam, and pulmonary function. Practice parameters focused upon patient education and unresolved questions included the use of videofluoscopy, monitoring diet progression, and swallow safety screening. CONCLUSIONS: The working goal is to establish a clinical bulbar protocol, designed to be incorporated within ALS clinics and ultimately to formulate a best practice set of bulbar ALS guidelines, available for implementation throughout the international ALS community.

Molecular encapsulation in pyrogallolarene hexamers under nonequilibrium conditions.

Pyrogallol[4]arene is a macrocycle with a concave surface and 12 peripheral hydroxyl groups that mediate its self-assembly to form hexamers of octahedral symmetry in the solid state, in solution, and in the gas phase. These hexamers enclose approximately 1300 Å(3) of space, which is filled with small molecules. In this study, we show that solvent-free conditions for guest entrapment in these hexamers, using molten guest molecules as solvent and allowing the capsules to assemble during cooling, results in exceptionally kinetically stable encapsulation complexes that are not formed in the presence of solvent and are not thermodynamically stable. The capsules' kinetic stabilities are strongly dependent on the size and shape of both guest and solvent molecules, with larger or nonplanar molecules with rigid geometries providing enhanced stability. The greatest observed barrier to guest exchange, ΔG(‡) = 32 ± 0.7 kcal mol(-1) for encapsulated CCl(4) → encapsulated pyrene, is, to the best of our knowledge, indicative of the most powerful kinetic trap ever observed for a synthetic, hydrogen-bonded encapsulation complex. Detailed NMR studies of the structures of the assemblies and the kinetics and mechanisms for guest exchange reveal that subtle differences in guest and solvent structure can impart profound effects on the behavior of the systems. Kinetic and thermodynamic stability, capsule symmetry and structure, guest tumbling rates, susceptibility to disruption by polar solvents, and even the mechanism for equilibration-the presence or absence of supramolecular intermediates-are all greatly influenced. The strongest observed kinetic traps provide encapsulation complexes that are not at equilibrium but are nonetheless indefinitely persistent at ambient temperatures, a property that invites future applications of supramolecular chemistry in open systems where equilibrium is not possible.