Background:Essential tremor (ET) is one of the most common movement disorders. Previous estimates of ET prevalence vary due to multiple factors. This study estimated the prevalence of diagnosed ET. Methods:The prevalence of diagnosed ET was estimated among adults with continuous enrollment in 2022 and ≥1 additional year of prior baseline enrollment in the Merative™ MarketScan® Research Databases, a US administrative claims database. ET was defined as ≥2 ET claims within 12 months of one another during the 2016-2022 study period. The proportion of patients receiving treatment was defined as having a claim for possible medication for ET in 2022 among those with diagnosed ET who had an additional 6 months of follow-up following the first ET diagnosis claim. Age-standardized estimates of the number of US adults with diagnosed ET were calculated using 2024 US population census projections. Results:The prevalence of diagnosed ET was 0.28% before age standardization, ranging from 0.06% (18-40 years) to 1.61% (≥75 years); 74% of patients overall received possible treatment. After standardization, prevalence was 0.42%; in 2024, 1.1 million US adults were estimated to have diagnosed ET. Estimates of the prevalence of diagnosed ET in the US were susceptible to the choice of case definition, nearly doubling (ie, 2.1 million US adults) with a more sensitive definition. Discussion:ET affects a substantial proportion of the US adult population. Selecting appropriate case definitions and using methods such as standardization are critical for estimating valid and generalizable chronic condition prevalences with real-world data. Highlights:This study found that 1.1 million US adults were estimated to have been diagnosed with essential tremor, with the sensitivity analyses yielding additional estimates. Estimating reliable and generalizable prevalences of diagnosed chronic conditions requires selection of appropriate case definitions and standardization to the general population.

Objective: To estimate the prevalence of diagnosed and drug-treated pediatric essential tremor (ET) using two US healthcare claims databases. Background: Pediatric ET diagnosis may represent early-onset familial ET and is predominantly diagnosed through tertiary centers. The prevalence of pediatric ET is not well-understood. Design/Methods: A retrospective cohort study used the Merative™ MarketScan® Research Databases (MarketScan®) and Symphony Integrated Dataverse (IDV®) (01/01/2016–12/31/2019) to estimate the number of US children (age <18 years) with ET. ET diagnosis was defined as ≥2 medical claims containing ICD-10-CM code G25.0 ≥1 and ≤365 days apart. Patients with drug-treated ET were defined as those with ≥180 days of observability following ET diagnosis who subsequently received any ET medication in 2019. Age-adjusted prevalence was used to estimate the number of US children with diagnosed and drug-treated ET. Results: Estimated age-adjusted numbers (95% CIs) of US children diagnosed with ET were 8362 (7626–9230) and 6281 (5923–6629) using MarketScan and IDV, respectively. Less than half of those diagnosed with ET received pharmacological treatment for ET. Specifically, the estimated proportions (95% CIs) of pediatric patients with drug-treated ET were 33.7% (28.7%–38.7%) and 38.1% (34.8%–41.3%), respectively. Estimated age-adjusted numbers (95% CIs) of pediatric patients with drug-treated ET were 2749 (2299–3238) and 2409 (2186–2655), respectively. Beta-blockers (57% and 55%, respectively) and anticonvulsants (36% and 44%, respectively) were the most common drug classes prescribed among treated patients. The most frequently prescribed beta-blocker and anticonvulsant were propranolol (55% and 52%, respectively) and topiramate (15% and 17%, respectively). Conclusions: To our knowledge, this is the first study to estimate the US prevalence of pediatric ET using large claims databases. Pediatric ET appears rare and, concordant with the literature, less common in children than in adults. Observed low drug-treatment rates are consistent with the slow, progressive nature of ET. Disclosure: Mr. Saad has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Mr. Saad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evidinno Outcomes Research Inc.. Mr. Saad has received stock or an ownership interest from Jazz Pharmaceuticals. Dr. Markowitz has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Markowitz has stock in Jazz Pharmaceuticals, UCB Pharmaceuticals, J&J. Ms. Gibbs has received personal compensation for serving as an employee of Aetion, Inc. Mr. Fuller has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Mr. Fuller has received stock or an ownership interest from D F. Dr. Ni has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Ni has stock in Jazz Pharmaceuticals. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cala Health. Dr. Pahwa has received personal compensation in the range of $0-$499 for serving as a Consultant for Global Kinetics. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allevion. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Photopharmics. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wren. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Biohaven. The institution of Dr. Pahwa has received research support from Boston Scientific. The institution of Dr. Pahwa has received research support from EIP. The institution of Dr. Pahwa has received research support from Global Kinetics. The institution of Dr. Pahwa has received research support from Amneal. The institution of Dr. Pahwa has received research support from Neuraly. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Pharma 2B. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theranexus. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Voyager. The institution of Dr. Pahwa has received research support from Neuroderm. Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda. Dr. Lyons has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Lyons has a non-compensated relationship as a President with International Essential Tremor Foundation that is relevant to AAN interests or activities. Dr. Baladi has stock in Jazz Pharmaceuticals . Ms. Lin has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Ms. Lin has stock in Jazz Pharmaceuticals. Ms. Lin has received publishing royalties from a publication relating to health care.

Background: Feedback from wearable biosensors may help assess motor function in Parkinson's disease (PD) patients and titrate medication. Kinesia 360 continuously monitors motor symptoms via wrist and ankle sensors. Methods: PD0049 was a 12-week pilot study to investigate whether using Kinesia 360 at home could improve motor symptom management in PD patients starting transdermal dopamine agonist rotigotine. Adults with PD and insufficiently controlled motor symptoms (prescribed rotigotine) were randomized 1:1 to Control Group (CG) or Experimental Group (EG) before starting rotigotine. Motor symptoms were assessed in all patients at baseline and Week 12 (W12) using Unified PD Rating Scale (UPDRS) III and Kinesia ONE, which measures standardized motor tasks via a sensor on the index finger. Between baseline and W12, EG used Kinesia 360 at home; clinicians used the data to supplement standard care in adjusting rotigotine dosage. Results: At W12, least squares mean improvements in UPDRS II (-2.1 vs 0.5, p = 0.004) and UPDRS III (-5.3 vs -1.0, p = 0.134) were clinically meaningfully greater, and mean rotigotine dosage higher (4.8 vs 3.9 mg/24 h) in EG (n = 19) vs CG (n = 20). Mean rotigotine dosage increase ( +2.8 vs + 1.9 mg/24 h) and mean number of dosage changes (2.8 vs 1.8) during the study were higher in EG vs CG. Tolerability and retention rates were similar. Conclusion: Continuous, objective, motor symptom monitoring using a wearable biosensor as an adjunct to standard care may enhance clinical decision-making, and may improve outcomes in PD patients starting rotigotine.

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

Introduction: Clinical assessment of motor symptoms in Parkinson's disease (PD) is subjective and may not reflect patient real-world experience. This two-part pilot study evaluated the accuracy of the NIMBLE wearable biosensor patch (containing an accelerometer and electromyography sensor) to record body movements in clinic and home environments versus clinical measurement of motor symptoms. Methods: Patients (Hoehn & Yahr 2-3) had motor symptom fluctuations and were on a stable levodopa dose. Part 1 investigated different sensor body locations (six patients). In Part 2, 21 patients wore four sensors (chest, and most affected side of shin, forearm and back-of-hand) during a 2-day clinic- and 1-day home-based evaluation. Patients underwent Unified Parkinson's Disease Rating Scale assessments on days 1-2, and performed pre-defined motor activities at home on day 3. An algorithm estimated motor-symptom severity (predicted scores) using patch data (in-clinic); this was compared with in-clinic motor symptom assessments (observed scores). Results: The overall correlation coefficient between in-clinic observed and sensor algorithm-predicted scores was 0.471 (p = 0.031). Predicted and observed scores were identical 45% of the time, with a predicted score within a +/- 1 range 91% of the time. Exact accuracy for each activity varied, ranging from 32% (pronation/supination) to 67% (rest-tremor-amplitude). Patients rated the patch easy-to-use and as providing valuable data for managing PD symptoms. Overall patch-adhesion success was 97.2%. The patch was safe and generally well tolerated. Conclusions: This study showed a correlation between sensor algorithm-predicted and clinician-observed motor symptom scores. Algorithm refinement using patient populations with greater symptom-severity range may potentially improve the correlation.

The purpose of this study was to conduct a post-hoc benefit–risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit–Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression–Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom–related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high–density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression–Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit–risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment.

Objective: The objective of this study was to quantify patients' preferences related to benefits and risks of antipsychotic treatments for schizophrenia and to assess the relative importance of treatment attributes and adherence.Methods: Treatment-related preferences among U.S. residents with a self-reported physician diagnosis of schizophrenia were assessed via a discrete-choice experiment. Patients chose between competing hypothetical scenarios characterized by improvements in positive symptoms, negative symptoms, and social functioning; incidence of weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia; and medication formulation. Preferences were estimated by using a random-parameters logit model, and the impact of adherence was estimated with conditional logit models.Results: The final sample consisted of 271 patients. Complete improvement in positive symptoms was the most preferred outcome (relative importance score of 10.0), followed by elimination of hyperglycemia (3.6, 95% confidence interval [CI] = 2.6-4.6), improvement in negative symptoms (3.0, CI = 1.6-4.3), reduced weight gain (2.6, CI = 1.2-4.0), avoidance of hyperprolactinemia (1.7, CI = .9-2.6), improved social functioning (1.5, CI = .4-2.5), and avoidance of EPS (1.0, CI = .3-1.8). Patients judged a daily pill superior to monthly injections (p < .01) and monthly injections superior to injections every three months (p < .01) for adherent patients and monthly injections superior to a daily pill for nonadherent patients (p = .01).Conclusions: Persons who self-identified as having schizophrenia judged improvement in positive symptoms as the most important treatment benefit. Hyperglycemia was identified as the most important adverse event. Patients judged oral formulations to be better than monthly injections for adherent patients and monthly injections to be a better choice for nonadherent patients.

Hospital-discharged patients with schizoaffective disorder have a high risk of re-hospitalization. However, limited data exist evaluating critical post-discharge periods during which the risk of re-hospitalization is significant.

Patients suffering from schizophrenia tend to have high rates of medical comorbidities and mortality.This study evaluated the healthcare costs of patients with schizophrenia and specific comorbidities relative to patients without schizophrenia with the same comorbidities, using Medicaid insurance claims databases from five states (from 2001-2010). The most common comorbidities were hypertension (48.8%), substance abuse (39.1%) and diabetes (28.4%). Patients with schizophrenia incurred greater all-cause monthly healthcare costs (cost difference [95% CI]: US$978 [933; 1024]) and comorbidity-related costs (cost difference [95% CI]: US$288 [269; 307]). Schizophrenia was also associated with significantly higher comorbidity-related costs in each comorbidity subgroup (among the three most common comorbidities: 99% higher in hypertension, 293% in substance abuse, and 105% in diabetes). The results suggest that patients with schizophrenia and comorbidities common in patients with schizophrenia had higher all-cause and comorbidity-related healthcare costs compared with patients without schizophrenia with the same comorbidities.

OBJECTIVE The objectives were to quantify psychiatrists' judgments of the benefits and risks of antipsychotic treatments of patients with schizophrenia and to evaluate how patient adherence history affects these judgments. METHODS Weights assigned by respondents to risks, benefits, and alternative drug formulations in the treatment of schizophrenia were assessed via a Web-based survey by using a discrete-choice experiment. Respondents in the United States and the United Kingdom chose among alternative scenarios characterized by various levels of improvement in positive symptoms, negative symptoms, social functioning, weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia and by formulation. The effect of patient adherence history on respondents' judgments was also assessed. Random-parameters logit and bivariate probit models were estimated. RESULTS The sample included 394 psychiatrists. Improvement in positive symptoms from "no improvement" to "very much improved" was the most preferred outcome over the range of improvements included and was assigned a relative importance score of 10. Other outcomes, in decreasing order of importance, were improvement in negative symptoms from "no improvement" to "very much improved" (5.2; 95% confidence interval [CI]=4.2-6.2), social functioning from "severe problems" to "mild problems" (4.6, CI=3.8-5.4), no hyperglycemia (1.9, CI=1.5-2.4), <15% weight gain (1.5, CI=.9-2.0), no hyperprolactinemia (1.3, CI=.8-1.6), and no EPS (1.1, CI=.7-1.5). As adherence decreased, formulation became more important than modest efficacy changes and injections were preferred to daily pills (p<.05). CONCLUSIONS Psychiatrists favored treatments that primarily improve positive symptoms. Choice of formulation became more important as likely adherence declined.

Glutamate-gated ion channels embedded within the neuronal membrane are the primary mediators of fast excitatory synaptic transmission in the CNS. The ion channel of these glutamate receptors contains a pore-lining transmembrane M3 helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype, opening of the ion channel pore, mediated by displacement of the M3 helices away from the central pore axis, occurs in a highly concerted fashion, but the associated temporal movements of the peripheral helices are unknown. To address the gating dynamics of the peripheral helices, we constrained the relative movements of the linkers that connect these helices to the ligand-binding domain using engineered cross-links, either within (intra-GluN1 or GluN2A) or between subunits. Constraining the peripheral linkers in any manner dramatically curtailed channel opening, highlighting the requirement for rearrangements of these peripheral structural elements for efficient gating to occur. However, the magnitude of this gating effect depended on the specific subunit being constrained, with the most dramatic effects occurring when the constraint was between subunits. Based on kinetic and thermodynamic analysis, our results suggest an asynchrony in the displacement of the peripheral linkers during the conformational and energetic changes leading to pore opening. Initially there are large-scale rearrangements occurring between the four subunits. Subsequently, rearrangements occur within individual subunits, mainly GluN2A, leading up to or in concert with pore opening. Thus, the conformational changes induced by agonist binding in NMDA receptors converge asynchronously to permit pore opening.

This study aimed to assess antipsychotic adherence patterns and all-cause and schizophrenia-related health care utilization and costs sequentially during critical clinical periods (i.e., before and after schizophrenia-related hospitalization) among Medicaid-enrolled patients experiencing a schizophrenia-related hospitalization.

Background: Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available.Methods: This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of covariance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity.Results: Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [ paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p < 0.001]. Similarly, risk of relapse after withdrawal of paliperidone ER treatment (placebo group of the paliperidone ER study) was higher than after withdrawal of PP (paliperidone ER placebo/PP placebo HR, 2.25; 95% CI, 1.59-3.18; p < 0.001). Stabilised schizophrenic subjects treated with PP maintained functioning demonstrated by the same proportions of subjects with mild to no difficulties in functioning at DB baseline and end point [Personal and Social Performance (PSP) scale total score > 70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar.Conclusions: This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.