Search

Background & Aims To investigate the safety and adverse event profile of sorafenib plus radioembolization (Y90) compared to Y90 alone in patients awaiting liver transplantation. Methods 20 patients with HCC were randomized to Y90 alone (Group A) or Y90+sorafenib (Group B). Adverse events, dose reductions, and peri-transplant complications were assessed. Results All patients in the sorafenib group necessitated dose reductions. Seventeen of 20 patients underwent liver transplantation; median time-to-transplant was 7.8months (range: 4.2-20.3) and similar between groups (p=0.35). In the sorafenib group, there were 4/8 peri-transplant (<30days) biliary complications (p=0.029) and 3/8 acute rejections (p=0.082); there were none in the Y90-only group. Survival rates were 70% (Group A) and 72% (Group B) at 3years (p=0.57). Conclusions The addition of sorafenib to Y90 necessitated dose reductions in all patients awaiting transplantation. Preliminary data suggest that the combination was associated with more peri-transplant biliary complications and potentially trended towards more acute rejections. Caution should be exercised when considering sorafenib in the transplant setting. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

The present report reveals the findings of surveys conducted jointly by Sindh Wildlife Department (SWD), Government of Sindh and WWF Pakistan, Islamabad (WWF-P) during November-December, 2008 and February 2009 with the objectives to confirm the existence of Smooth coated otter (Lutrogale perspicillita sindica) in different areas in Sindh and to identify various threats to otter population. An area of about 5,000 km was traversed covering 36 different sites in 12 districts of Sindh province where there were reports of otter existence. The existence of otter was confirmed at 25 sites in 11 districts. Evidence like recent otter tracks, remains of fish eaten by otter, otter spraints, and holts was gathered and local residents and fishermen were interviewed to verify the existence of otter at every site. Five sites located in four different districts were identified where an otter population exists throughout the year, whereas otters visited all the other sites occasionally over different seasons, in search of food. Various threats to the species identified during the surveys included hunting for fur, habitat degradation, water pollution, weak enforcement of wildlife laws, increasing tourism and competition and conflicts between otters and fishermen. The total population of Smooth coated otter was also estimated over the 25 sites as 178. [ABSTRACT FROM AUTHOR]

Problem: There exists a strong impetus to improve the ergonomic properties of dental instruments and devices, which can be associated with repetitive stress injuries and musculoskeletal disorders that are common in dental professionals. However, no comprehensive methods exist for quantifying non-invasively, in vivo and in real time the ergonomics and efficacy of clinical dental instruments. Purpose: The purpose of this study was to compare ergonomic and coronal polishing performance of 4 prophylaxis handpieces using novel surface Electromyography (sEMG) and image analysis techniques. Methods: Wireless EMG electrodes (Freeemg™, BTS Engineering) recorded activity in 4 hand and arm muscles during standardized baseline activity and coronal polishing in 10 volunteer dental hygienists. Using typodont models sprayed with artificial biofilm and attached to a dental chair, Subjects polished each quadrant for 15s. Participants were filmed, and photographs documented biofilm removal. Next, additional time needed to complete polishing the entire typodont was recorded. Visual analog scale (VAS) measures of comfort and fatigue in hand, wrist, finger, palm and arm were noted. Participants rested 20 minutes between the 4 study arms, each of which tested a different, masked handpiece: (1) Premier Dental AeroPro™, (2) Dentsply Sirona Nupro Freedom™ cordless without foot pedal, (3) Dentsply Sirona Nupro Freedom™ with foot pedal, (4) Ultradent™ corded. Testing sequence was randomized. VAS evaluations of comfort and fatigue (scale 0-10); polishing efficacy (surface area; ImageJ software) and speed; muscle work (EMGanalyzer software™); and postural quantification (scale 0-1; ImageMeasurement software™) measures were compared for each handpiece. Statistical analysis was performed using analysis of variance with repeated measures. Significant findings were followed up with pairwise comparisons using the Tukey method to adjust for multiple comparisons. Results: AeroPro™ cleaned significantly more surfaces in 60s than Nupro™ without foot control and Ultradent™ (p<0.05), and it cleaned the entire typodont significantly faster than the other handpieces (p<0.05). Participants reported significantly less fatigue and better comfort after using AeroPro™ than all other handpieces (p<0.05). During the first 60s of polishing, Ultradent™ used significantly less work than the other handpieces for the dorsal interosseous muscle, Nupro™ with foot control used significantly less work for the flexor pollicis longus, and AeroPro™ used less muscle work in the abductor pollicis brevis and extensor digitorum communis (significant for abductor pollicis brevis p<0.05). AeroPro™ used significantly less total muscle work over the entire polishing period (p<0.05). All handpieces performed equally for ergonomic forearm position, but AeroPro™ performed significantly better for back, neck and torso posture (p<0.05). Conclusions: Using novel sEMG and image analysis techniques in a simulated clinical environment, it was determined that coronal polishing with AeroPro™ was accomplished faster with less operator fatigue, muscle work, and postural discomfort. Study funding source: LAMMP NIH/NIBIB P41EB05890; the Arnold and Mabel Beckman Foundation; Premier Dental. [ABSTRACT FROM AUTHOR]

Background: Despite the proliferation of digital interventions such as Electronic Immunization Registries (EIR), currently, there is little evidence regarding the use of EIR data to improve immunization outcomes in resource-constrained settings. To achieve the Sustainable Development Goal (SDG) of ensuring healthy lives and well-being for all ages, particularly for newborns and children under the age of 5 (goal 3b), it is essential to generate and use quality data for evidence-based decision making to overcome barriers inherent in immunization systems. In Pakistan, only 66 % of children receive all basic vaccinations, and in Sindh province, the number is even lower at 49 %. In 2012, IRD developed and piloted Zindagi Mehfooz (Safe Life; ZM) ElR, an Android-based platform that records and analyses individual-level child data in real-time. In 2017 in collaboration with Expanded Programme for Immunization (EPI) Sindh, ZM was scaled-up across the entire Sindh province and is currently being used by 2521 government vaccinators in 1539 basic health facilities, serving >48 million population.Objective: The study aims to demonstrate how big immunization data from the ZM-EIR is being leveraged in Sindh, Pakistan for actionable decision making via three use cases (a) improving performance management of vaccinators to increase geographical coverage, (b) quantifying the impact of provincial accelerated outreach activities, and (c) examining the impact of the COVID-19 pandemic on routine immunization coverage to help devise a tailored approach for future efforts.Methods: From October 2017 to April 2020, more than 2.9 million children and 0.9 million women have been enrolled, and more than 22 million immunization events have been recorded in the ZM-EIR. We extracted de-identified data from ZM-EIR for January 1, 2019 - April 20, 2020, period. Given the needs of each use case, monthly and daily indicators on vaccinator performance (attendance and compliance), daily immunization visits, and the number of antigens administered were calculated. Geo-coordinate data of antigen administration was extracted and displayed on geographic maps using QGIS. All generated reports were shared at fixed frequency with various stakeholders, such as partners at EPI-Sindh, for utilization in decision making and informing policy.Result: Our use-cases demonstrate the use of EIR data for data-driven decision making. From January - December 2019, the monthly monitoring of program indicators helped increase the vaccinator attendance from 44% to 88%, while an 85 % increase in geographical coverage was observed in a polio-endemic super high-risk union council (SHRUC) in Karachi. The analysis of daily average antigens administered during accelerated outreach efforts (AOE) as compared to routine activities showed an increase in average daily Pentavalent-3, Measles-1, and Measles-2 vaccines administered by 103%, 154%, and 180% respectively. These findings helped decide to continue the accelerated effort in high-risk areas (compared to the entire province) rather than discontinuing the activity due to high costs. During COVID-19 lockdown, the daily average number of child immunizations reduced from 16,649 to 4335 per day, a decline of 74% compared to 6 months preceding COVID-19 lockdown. ZM-EIR data is currently helping to shape the planning and implementation of critical strategies to mitigate the impact of the COVID-19 pandemic.Conclusion: The big data for vaccines generated through EIRs is a powerful tool to monitor immunization work-force and ensure chronically missed communities are identified and covered through targeted strategies. Geospatial data availability and analysis is changing the way EPI review meetings occur with stakeholders, taking data-driven decisions for better planning and resource allocation. In the fight against COVID-19 pandemic, as governments gradually begin to shift from containing the outbreak to strategizing a plan for sustaining the essential health services, the countries that will emerge most successful are likely the ones who can best use technology and real-time data for targeted efforts. [ABSTRACT FROM AUTHOR]

Background and Objective: The terminal complement inhibitor eculizumab is approved in the USA for the treatment of patients with acetylcholine receptor antibody-positive generalized myasthenia gravis (MG). The ELEVATE study aimed to examine clinical-practice outcome data on eculizumab effectiveness in US adults with MG (generalized or ocular). This paper reports the findings on MG exacerbations and crises and associated healthcare resource utilization, and the use of rescue therapy., Methods: A retrospective chart review was conducted of US adults with MG who initiated eculizumab. Outcomes assessed for up to 2 years before and after eculizumab initiation included percentages and rates per patient per year (PPPY) of exacerbations and crises (the latter defined as intubation/impending intubation), healthcare resource utilization, and rescue therapy administration., Results: A total of 119 patients diagnosed with MG were enrolled in the study; 92 patients had ≥ 3 months of data both before and during eculizumab therapy and were included in the analyses. The mean rate of MG exacerbations decreased from 0.385 PPPY before eculizumab initiation to 0.152 PPPY during eculizumab treatment (p = 0.0034); the mean rate of MG crises decreased from 0.411 to 0.056 PPPY (p = 0.0018). Rates of healthcare resource utilization and rescue therapy use also decreased significantly during eculizumab treatment., Conclusions: This retrospective chart review analysis provides evidence for a beneficial impact of eculizumab treatment on the incidence of MG exacerbations and crises and associated healthcare resource utilization in clinical practice, and on rescue therapy use. These data further support the therapeutic benefits of eculizumab in patients with MG., (© 2024. The Author(s).)

Background: Dental instrumentation with hand-held devices is associated with discomfort, fatigue and musculoskeletal diseases or repetitive stress injuries. The goal of this in vivo study was to determine the effect of an ergonomic handle sheath on muscle work, comfort and fatigue associated with (a) piezoelectric scaling by hygienists with and without musculoskeletal disorders (MSDs), and (b) dental cavity preparation by healthy dentists using a dental micromotor. Materials and Methods: Two groups of ten hygienists each tested the piezoelectric scaler. Hygienists in Group 1 had no MSDs, while those in Group 2 had been diagnosed with MSDs. Additionally, ten dentists with no MSDs used a dental micromotor to prepare four standardized cavities. Time-based work in four muscles, comfort and fatigue were recorded in the presence and absence of an add-on soft, insulating handle sheath. Data were analyzed using a repeated measures analysis of variance model with Tukey's post-hoc test. Results: Comfort, fatigue and muscle work were significantly better for both devices when the sheath was used. While hygienists with MSDs used more muscle work to complete the set scaling task, and the sheath-related reduction in work was somewhat greater, these MSD-related differences did not quite reach significance. Conclusions: The results of this pilot study show that the ergonomic performance of an ultrasonic scaler and a dental micromotor may be improved by the use of an ergonomic handle sheath.

Background: Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG., Objectives: To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study., Design: A randomised, double-blind, placebo-controlled phase III study., Methods: Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-‍ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed., Results: Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg ( n  = 5), 10 mg/kg ( n  = 8) or placebo ( n  = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred., Conclusion: This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies., Trial Registration: ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials‌register.eu/ctr-search/trial/2019-000968-18/GB)., (© The Author(s), 2024.)

Background/objectives: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States., Methods: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use., Results: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy., Discussion: Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab., (© 2024. The Author(s).)

Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG)., Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA., Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors., Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG., (© 2024. The Author(s).)

Background and Purpose: The efficacy and safety of ravulizumab, a terminal complement C5 inhibitor, in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) were demonstrated in the CHAMPION MG study (NCT03920293). This analysis aimed to characterize the latency to onset of a clinically meaningful therapeutic effect for ravulizumab., Methods: Post hoc analysis of data collected for up to 60 weeks from CHAMPION MG was performed to assess the timing of response to ravulizumab. Response was analyzed based on reductions of ≥2 and ≥3 points (minimal clinically important differences [MCIDs]) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, respectively, and on more rigorous reductions of ≥3 and ≥5 points, respectively. Time to first response was assessed using the Kaplan-Meier product-limit method., Results: The median (95% confidence interval) time to first response was 2.1 (2.1-2.6) and 4.1 (2.3-10.0) weeks for reductions of ≥2 and ≥3 points in MG-ADL total score, respectively (n = 139), and 4.1 (2.1-10.0) and 18.3 (11.0-33.4) weeks for reductions of ≥3 and ≥5 points in QMG total score, respectively (n = 134). Cumulative response rates at Week 60 (data cut-off) were 88% and 82% for ≥2- and ≥3-point MG-ADL score reductions, respectively, and 86% and 59% for ≥3- and ≥5-point QMG score reductions, respectively., Conclusions: The median times to MCID with ravulizumab treatment in patients with AChR Ab+ gMG were ~2 weeks and ~4 weeks based on MCID MG-ADL and QMG total score reductions, respectively., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

(1) Background: Musculoskeletal disorders (MSDs), discomfort, fatigue, pain, and other acute and chronic work-related injuries are common among dental clinicians. Hand instruments constitute a primary risk factor for these conditions. The overall goal of this study was to compare in dental hygienists with healthy hands, and in those with MSDs, the effect of three different handle designs on instrumentation-related muscle work, comfort, fatigue, and quality of tactile feedback. (2) Methods: Clinicians tested three periodontal curettes: one with a novel adaptive silicone handle, another with a rigid resin handle, and the third with a rigid silicone handle. Ten hygienists-five with MSDs and five without-each scaled three typodonts using the three different curettes. Statistical analysis was performed using a General Linear Model (GLIM) and Tukey's post hoc test, and a significance level of p < 0.05 was implemented. (3) Results: On average, mean comfort and fatigue across all instruments were significantly worse in testers with MSDs, who also expended significantly more work to complete the same task. In all testers, a novel adaptive handle design was associated with significantly reduced total muscle work and post-instrumentation fatigue, as well as better comfort than conventional rigid handle designs. (4) Conclusions: An adaptive curette handle design demonstrated significantly better ergonomic outcomes than conventional rigid curette handle designs. Hygienists with MSDs expend significantly more muscle work during dental instrumentation.

Objectives: The objective of this research was to generate psychometric evidence supporting the myasthenia gravis (MG) symptoms patient-reported outcome (PRO) scales as a fit-for-purpose measure of severity of core symptoms of MG and provide information allowing their meaningful interpretation using data from a phase 3 study in MG., Methods: Data from the MycarinG study, a phase 3 study of rozanolixizumab in patients with generalized MG who experience moderate to severe symptoms (ClinicalTrials.gov Identifier: NCT03971422) were analyzed with both classical test theory (CTT) and Rasch measurement theory (RMT). Meaningful within-individual change and group-level meaningful change were estimated for three MG Symptoms PRO scales using anchor- and distribution-based methods. Anchor-based methods used patient global impression of severity (PGIS) and change (PGIC) in MG symptoms as anchors., Results: Good measurement properties of the MG Symptoms PRO scales were shown in the sample of 200 participants: good to excellent reliability (test-retest and internal consistency reliability) and validity (associations between items and scores within the MG Symptoms PRO scales and between the MG Symptoms PRO scores and other clinical outcomes-MG ADL, QMG score, MGC score, and MGFA classes-were as expected); and the items showed good coverage of the continuum and fit to the Rasch model. Triangulation of the anchor- and distribution-based method results led to the definition of clinically meaningful within-patient improvement in scores for Muscle Weakness Fatigability (-16.67), Physical Fatigue (-20.00), and Bulbar Muscle Weakness (-20.00), with associated ranges. Benchmarks are also proposed for the interpretation of group-level results., Conclusion: The strong psychometric performance of the MG Symptoms PRO scales and the information generated to guide its interpretation supports its use in clinical trials for demonstrating the clinical benefits of new treatments targeting core symptoms of MG (muscle weakness fatigability, physical fatigue, bulbar muscle weakness, respiratory muscle weakness, and ocular muscle weakness)., Competing Interests: AR and KC were employees of Modus Outcomes, a patient-centered outcome research consultancy that received payment from UCB to conduct this research. TM was an employee and a shareholder of UCB Pharma. The authors declare that this research and the MycarinG clinical study mentioned herein were funded by UCB Pharma. The funder was involved in the study design, data collection and analysis, decision to publish and preparation of the manuscript., (Copyright © 2024 Regnault, Habib, Creel, Kaminski and Morel.)

Background: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients., Objective: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis., Methods: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing)., Results: ChatGPT-4 (n=98) provided 93 (95%) responses with accurate information, and 82 (84%) were comprehensive. ChatGPT-3.5 (n=83) provided 74 (89%) responses with accurate information, and 66 (79%) were comprehensive. When examined by question category, ChatGTP-4 and ChatGPT-3.5 provided 53 (95%) and 48 (86%) comprehensive responses, respectively, to "general questions" (n=56). When examined by subject, ChatGPT-4 and ChatGPT-3.5 performed best in response to cardiology questions (n=12) with both models producing 10 (83%) comprehensive responses. For gastroenterology (n=15), ChatGPT-4 received comprehensive grades for 9 (60%) responses, and ChatGPT-3.5 provided 8 (53%) responses. Overall, 96 of 98 (98%) responses for ChatGPT-4 and 73 of 83 (88%) for ChatGPT-3.5 were reproducible. The readability of ChatGPT-4's responses ranged from 10th to beyond graduate US grade levels with an average of 15.5 (SD 1.9)., Conclusions: Large language models are a promising tool for accurate and reliable health information for patients living with amyloidosis. However, ChatGPT's responses exceeded the American Medical Association's recommended fifth- to sixth-grade reading level. Future studies focusing on improving response accuracy and readability are warranted. Prior to widespread implementation, the technology's limitations and ethical implications must be further explored to ensure patient safety and equitable implementation., (©Ryan C King, Jamil S Samaan, Yee Hui Yeo, Yuxin Peng, David C Kunkel, Ali A Habib, Roxana Ghashghaei. Originally published in JMIR Cardio (https://cardio.jmir.org), 19.04.2024.)

Background and Objectives: Myasthenia gravis (MG) is a rare neuromuscular disorder where IgG antibodies damage the communication between nerves and muscles, leading to muscle weakness that can be severe and have a significant impact on patients' lives. MG exacerbations include myasthenic crisis with respiratory failure, the most serious manifestation of MG. Recent studies have found MG prevalence increasing, especially in older patients. This study examined trends in hospital admissions and in-hospital mortality for adult patients with MG and readmissions and postdischarge mortality in older (65 years or older) adults with MG., Methods: Data from the Nationwide Inpatient Sample (NIS), an all-payer national database of hospital discharges, were used to characterize trends in hospitalizations and in-hospital mortality related to MG exacerbations and MG crisis among adult patients aged 18 years or older. The Medicare Limited Data Set, a deidentified, longitudinal research database with demographic, enrollment, and claims data was used to assess hospitalizations, length of stay (LOS), readmissions, and 30-day postdischarge mortality among fee-for-service Medicare beneficiaries aged 65 years or older. The study period was 2010-2019. Multinomial logit models and Poisson regression were used to test for significance of trends., Results: Hospitalization rates for 19,715 unique adult patients and 56,822 admissions increased from 2010 to 2019 at an average annualized rate of 4.9% (MG noncrisis: 4.4%; MG crisis: 6.8%; all p < 0.001). Readmission rates were approximately 20% in each study year for both crisis and noncrisis hospitalizations; the in-hospital mortality rate averaged 1.8%. Among patients aged 65 years or older, annualized increases in hospitalizations were estimated at 5.2%, 4.2%, and 7.7% for all, noncrisis, and crisis hospitalizations, respectively (all p < 0.001). The average LOS was stable over the study period, ranging from 11.3 to 13.1 days, but was consistently longer for MG crisis admissions. Mortality among patients aged 65 years or older was higher compared with that in all patients, averaging 5.0% across each of the study years., Discussion: Increasing hospitalization rates suggest a growing burden associated with MG, especially among older adults. While readmission and mortality rates have remained stable, the increasing hospitalization rates indicate that the raw numbers of readmissions-and deaths-are also increasing. Mortality rates are considerably higher in older patients hospitalized with MG.

Background: To compare fatigue, comfort, and muscle work associated with the use of two periodontal curettes during scaling: one with a novel adaptive design, the other with a conventional non-adaptive design., Methods: Twelve hygienists scaled a typodont using two Universal Barnhart 5/6 curettes: (1) a prototype featuring an adaptive silicone-covered handle (Curette A), and (2) a stainless-steel curette (Curette B). Surface Electromyography (sEMG) traced muscle work. Hand positions, fatigue, comfort, pinch, and grasp strength were recorded. Paired t-tests and a repeated measures ANOVA with covariates were tested for differences. The significance level was set at p < 0.05., Results: Curette A performed significantly better in all categories. Pinch and grasp strength and fatigue were significantly reduced post-instrumentation for Curette B. Curette A required significantly less (i) total muscle work and (ii) work in individual muscles. Comfort, correct grasp, and blade adaptation were significantly better using Curette A., Conclusions: A curette featuring a novel adaptive handle design demonstrated significantly improved ergonomic performance. Additional clinical studies are needed to solidify our understanding of the potential short- and long-term benefits of the novel curette handle design., Practical Implications: A novel adaptive curette handle design that enables the clinician to adapt the instrument across the index finger may reduce musculoskeletal burden and fatigue, as well as improve comfort during periodontal instrumentation., Competing Interests: The authors declare no conflict of interest.

Objective: This article summarizes the clinical features, diagnostic criteria, differential diagnosis, pathogenesis, and prognosis of Guillain-Barré syndrome (GBS), with insights into the current and future diagnostic and therapeutic interventions for this neuromuscular syndrome., Latest Developments: GBS is an acute, inflammatory, immune-mediated polyradiculoneuropathy that encompasses many clinical variants and divergent pathogenic mechanisms that lead to axonal, demyelinating, or mixed findings on electrodiagnostic studies. The type of antecedent infection, the development of pathogenic cross-reactive antibodies via molecular mimicry, and the location of the target gangliosides affect the subtype and severity of the illness. The data from the International GBS Outcome Study have highlighted regional variances, provided new and internationally validated prognosis tools that are beneficial for counseling, and introduced a platform for discussion of GBS-related open questions. New research has been undertaken, including research on novel diagnostic and therapeutic biomarkers, which may lead to new therapies., Essential Points: GBS is among the most frequent life-threatening neuromuscular emergencies in the world. At least 20% of patients with GBS have a poor prognosis and significant residual deficits despite receiving available treatments. Research is ongoing to further understand the pathogenesis of the disorder, find new biomarkers, and develop more effective and specific treatments., (Copyright © 2023 American Academy of Neurology.)

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access., Methods: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers. The survey was completed by 38 individuals living with gMG, of which the majority were non-White/Caucasian, unemployed, low income, and enrolled in public insurance. Common SDOH challenges, awareness/utilization of available PSPs, and unmet needs were identified., Results: Financial and mental health concerns were the most common among individuals living with gMG and experiencing SDOH barriers throughout diagnosis, accessing treatment, initiating treatment, and continuing treatment. Awareness and utilization of existing support services were low, especially when accessing treatment. Educational, financial, and personalized support with high "human touch" were commonly perceived as the most valuable resources., Implications: To better serve the needs of individuals with gMG experiencing SDOH barriers, PSPs should use a targeted approach to offer services tailored to harder-to-reach populations. Further, providers, advocacy groups, manufacturers, and public organizations in the gMG ecosystem should strengthen collaborations with PSPs to enable individuals living with gMG to access the services they need to improve their health outcomes., Competing Interests: TH, KP, CB, and GP are employed by argenx (Boston, MA, United States). AA is a Patient Education Speaker for argenx. AH receives research support from Alexion/AstraZeneca, argenx, UCB, Immunovant, Regeneron, Cabaletta Bio, Viela Bio/Horizon, and Genentech, and has received honoraria from UCB, argenx, Alexion, Immunovant, Regeneron, and Genentech/Roche. SS, CZ, DM, MS, and AW are employed by ZS Associates (Evanston, IL, United States) and serve as paid consultants for argenx., (Copyright © 2023 Hughes, Anderson, Habib, Perez, Bergin, Suchotliff, Zvosec, McDaniel, Sato, Whangbo and Phillips.)

Background and Objectives: The goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1., Methods: This phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests., Results: In part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs., Discussion: Despite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo., Trial Registration Information: Clinical Trials Registration: NCT03124459., Classification of Evidence: This study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX., (© 2022 American Academy of Neurology.)

DMD pathogenic variants for Duchenne and Becker muscular dystrophy are detectable with high sensitivity by standard clinical exome analyses of genomic DNA. However, up to 7% of DMD mutations are deep intronic and analysis of muscle-derived RNA is an important diagnostic step for patients who have negative genomic testing but abnormal dystrophin expression in muscle. In this study, muscle biopsies were evaluated from 19 patients with clinical features of a dystrophinopathy, but negative clinical DMD mutation analysis. Reverse transcription-polymerase chain reaction or high-throughput RNA sequencing methods identified 19 mutations with one of three pathogenic pseudoexon types: deep intronic point mutations, deletions or insertions, and translocations. In association with point mutations creating intronic splice acceptor sites, we observed the first examples of DMD pseudo 3'-terminal exon mutations causing high efficiency transcription termination within introns. This connection between splicing and premature transcription termination is reminiscent of U1 snRNP-mediating telescripting in sustaining RNA polymerase II elongation across large genes, such as DMD. We propose a novel classification of three distinct types of mutations identifiable by muscle RNA analysis, each of which differ in potential treatment approaches. Recognition and appropriate characterization may lead to therapies directed toward full-length dystrophin expression for some patients., (© 2022 Wiley Periodicals LLC.)