Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights: This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

The presence and burden of cognitive issues: discordance between the perception of neurologists and people living with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a common symptom of multiple sclerosis (MS) and occurs in more than 40% of people living with MS (plwMS). No real-world study has assessed the perception of neurologists and plwMS on cognitive issues. METHODS: Using data from the 2011-2019 Adelphi MS Disease Specific Programme database, this real-world, retrospective, cross-sectional multi-cohort study included people aged ≥18 years with relapsing-remitting MS and secondary progressive MS from the United States, UK and the EU. Neurologists provided data on the patient record form for plwMS, with the same plwMS invited to voluntarily complete a patient self-completion form: a questionnaire about their experiences with MS. RESULTS: Of 25,374 plwMS, 4817 who provided information on cognitive and mood symptoms were included in the analysis. Of the plwMS, 68% and 59% reported feeling 'mentally fatigued' and having 'difficulty concentrating', respectively. Neurologists reported only 27% of plwMS as having 'difficulty concentrating' and 15% of plwMS as having 'short-/long-term memory problems'. Neurologists reported cognitive or mood symptoms as 'not experienced' by a higher percentage of participants with relapsing-remitting MS than secondary progressive MS. Of the plwMS who experienced 'difficulty concentrating', most had a concomitant feeling of being 'mentally fatigued' (52%), followed by 'feeling anxious or tense' (49%) and 'feeling depressed' (44%). In plwMS, caregivers reported 'difficulty concentrating' (16%) as the most common cognitive issue. CONCLUSION: A clear discordance was observed between neurologists and plwMS regarding the perception of the cognitive and neuropsychiatric issues. These results underline the under-perception of cognitive and emotional affective symptoms in plwMS during neurological consultations.

Does effort increase or decrease reward valuation? Considerations from cognitive dissonance theory.

The present research tested the effect of manipulated perceived control (over obtaining the outcomes) and effort on reward valuation using the event-related potential known as the Reward Positivity (RewP). This test was conducted in an attempt to integrate two research literatures with opposite findings: Effort justification occurs when high effort leads to high reward valuation, whereas effort discounting occurs when high effort leads to low reward valuation. Based on an examination of past methods used in these literatures, we predicted that perceived control and effort would interactively influence RewP. Consistent with the effort justification literature (cognitive dissonance theory), when individuals have high perceived control, high effort should lead to more reward valuation than low effort should. Consistent with the effort discounting literature, when individuals have low perceived control, low effort should lead to more reward valuation than high effort should. Results supported these interactive and integrative predictions.

Shared Decision-Making in the Treatment of Multiple Sclerosis: Results of a Cross-Sectional, Real-World Survey in Europe and the United States.

Introduction: Multiple sclerosis (MS) is a neurodegenerative disease characterized by progressive deterioration of cognitive and physical functioning, reducing activities of daily living and quality of life (QoL). Several treatments are available that modify the course of the disease and reduce the frequency of relapses. Although effective, all treatment options are accompanied by adverse events, and this study aimed to assess the extent to which patients were involved in the choice of treatment. Methods: Data were drawn from the Adelphi Multiple Sclerosis Disease Specific Program (DSP)™, a cross-sectional survey of healthcare practitioners (HCP) and their patients with MS in real-world clinical settings in Europe and the United States (US) between December 2020 and July 2021. HCPs reported patient demographics, clinical characteristics, current and previous treatment, and treatment outcomes. Patients voluntarily completed questionnaires reporting the physical and psychological impact of their MS and its treatment. Regression analysis with inverse probability of treatment weighting was used to compare treatment outcomes in patients actively involved in their current treatment choice with those who were not. Results: Of a total of 692 patients, median age 40 years and 64% female, mostly diagnosed with relapsing-remitting MS, those who were involved in shared decision-making tended to choose oral therapies such as dimethyl fumarate more often than HCPs. MS had greater impact on physical and psychological functioning in patients whose HCP made treatment decisions solely. Patients involved in decision-making reported greater satisfaction with their treatment and a better QoL. Discussion: Because no single optimal therapy exists for patients with MS, treatments should be individualized with consideration of patients' preferences. Our study shows that shared decision-making is under-utilized in the management of MS and supports the benefits of patient involvement. Conclusion: Patients who have an active role in treatment decision-making show improved wellbeing and QoL, and overall treatment satisfaction.

Motivational intensity and valence are married, but they are not the same person: Commentary on Campbell et al. (2021).

Comments on the article by Campbell et al. (see record 2021-21096-001). Campbell et al. (2021) claimed motivational intensity (approach-avoidance) is a redundant construct that is merely another label for valence (positive-negative). They based their conclusion on a high correlation between valence and motivational intensity when participants rated pictures. We present arguments that their conclusion was based on inadequate evidence. First, we explain how high correlation fails to identify meaningful and consistent affective states where motivational intensity is essential. As a counterargument, we present replicated and cumulative empirical evidence of differences between affective states with equal valence and arousal but different motivational intensities such as desire or enthusiasm versus amusement. Second, we emphasize that correlations do not account for relative differences between valence and motivational intensity levels (which we termed undermotivated and overmotivated affect). We illustrate this by presenting how valence and motivational intensity diverge during watching affective video clips. We conclude the opposite of Campbell's team, that is, motivational intensity is a viable concept deserving further attention. However, studying motivational intensity requires specific strategies to dissect what is possible within affect from the most frequent. We formulate several recommendations regarding the choice of stimuli (overrepresentation of specific categories) and measurement (e.g., measuring dimensions of affect along with a broad range of discrete emotions and motivational concepts). This might improve the study in affective science toward stronger differentiation within the core of human affect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.

INTRODUCTION: Much of the current literature on treatment patterns and disability progression in multiple sclerosis (MS) does not distinguish between the relapsing-remitting and progressive subtypes (including primary [PPMS] and secondary progressive MS [SPMS]), or between active/nonactive disease. Current treatment options for progressive MS are limited, with only one approved product for PPMS and none specifically for nonactive SPMS. Here we report treatment patterns, disability progression, and unmet needs among patients with active and nonactive PPMS and SPMS. METHODS: The annual, cross-sectional survey from the Adelphi Disease Specific Program was used to collect physician-reported data on US adult patients with PPMS and SPMS, including active and nonactive disease. Treatment patterns (including the proportion of patients who were untreated with a disease-modifying therapy [DMT]), disability progression, and unmet need are described from 2016 to 2021. RESULTS: Data were collected for 2067 patients with progressive MS (PPMS, 1583; SPMS, 484). A substantial proportion of patients were untreated across all groups, and this was highest for nonactive PPMS (~ 43%). The proportion of untreated patients generally declined over time but remained high in 2018-2021 (~ 10-38%). Among treated patients, the proportion receiving infusions increased over time to ~ 34-46%, largely driven by ocrelizumab use after approval. Disability progression was reported for most patients (> 50%), including many who were receiving a DMT. Across all disease subtypes, when physicians were asked about the greatest unmet need with current DMTs, they most frequently cited effectiveness (~ 63-87%), and specifically slowing disease progression (~ 32-59%). CONCLUSIONS: This analysis of physician-reported data reveals that patients with progressive MS, particularly those with nonactive disease, frequently remain untreated or continue to decline despite treatment with available DMTs. Thus there is an enduring need for safe and effective treatments for this underserved population.

Influence of physicians' risk perception on switching treatments between high- efficacy and non-high-efficacy disease­modifying therapies in multiple sclerosis.

BACKGROUND: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. OBJECTIVE: Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. METHODS: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. RESULTS: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). CONCLUSIONS: Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.

Further examinations of attitudes toward discrete emotions, with a focus on attitudes toward anger.

The present research aimed to better understand individual differences in attitudes towards emotions with a focus on anger. We report findings of four studies conducted with American and Polish individuals. Results showed that individuals who have more positive attitudes toward anger are higher in trait anger (Studies 1-4), are more likely to think about getting revenge (Study 1), and expect that getting revenge will make them feel good (Studies 1-2). In addition, these individuals are lower in agreeableness and lower in the tendency to engage in avoidance when angered (Studies 1-4). They score lower in humility (Studies 3-4), lower in secure romantic attachment but higher in anxious and avoidance attachment (Study 3). Finally, they are more likely to believe a wide range of conspiracies (Studies 2-4). Discussion focuses on the implications of these results.

Individual differences in dissonance arousal/reduction relate to physical exercise: Testing the action-based model.

INTRODUCTION: The present research was designed to test predictions derived from the action-based model of cognitive dissonance theory. These predictions were that dissonance arousal would be negatively related to effective behavior, and that dissonance reduction would be positively related to effective behavior. METHOD: Dissonance arousal and reduction were measured using an individual differences questionnaire. Effective behavior was measured as amount of physical exercise obtained from an exercise app that measures exercise using GPS (cycling kilometers over one year; Study 1) and from self-reports (number of days during the previous week; Study 2-3). RESULTS: Results suggested that individual differences in dissonance arousal relate to less exercise and that individual differences in dissonance reduction relate to more exercise. Statistically controlling for trait approach and avoidance motivation as well as satisfaction with life revealed that dissonance processes predicted exercise behavior over these traits. This pattern of results was generally consistent across the three studies. Moreover, results from Studies 2-3 suggested possible statistical mediators from the exercise commitment literature of the relationship between trait dissonance arousal/reduction and exercise behavior. DISCUSSION AND CONCLUSION: These results highlight the importance of considering dissonance processes as adaptive ones, and they suggest possible ways of increasing exercise behavior.

Protocol for project MIME: Motivation, inflammation, and Mood in Emerging Adults.

Background: Atypical inflammatory biology is gaining evidence as a risk factor for mood psychopathology; however, little work has attempted to integrate inflammation into extant psychosocial frameworks of risk. Recent work using secondary data analysis has investigated the possibility of an immunocognitive model of mood disorders, in which cognitive vulnerabilities (i.e., rumination on positive or negative affect) increase the effect that arousal-related characteristics (e.g., reward sensitivity) have on inflammatory biology in ways that may confer risk for depression and hypo/mania symptoms. Project MIME (Motivation, Inflammation, and Mood in Emerging Adults) was designed to test this model in the context of a novel, reward-salient stressor (the Anger Incentive Delay Task, AIDT). Methods: This NIMH-funded study will result in a dataset of approximately 100 college undergraduates from a large university in Pennsylvania, United States of America. Eligible participants are recruited from an online screener, have to be 18-22 years old, fluent in English, and successfully answer several items designed to test whether participants randomly answer questions on the screener. Eligible participants are invited to an in-person visit in which they completed the AIDT, blood draws pre- and 50 minutes post-AIDT, and self-report questionnaires. Participants also complete a set of online questionnaires two weeks after the in-person visit. Discussion: Consistent with calls from the NIH director, this study seeks to diversify the tools used in stress research by validating a novel reward-salient stressor (in contrast to the field's reliance on social stressors) with respect to affective and immunological stress reactivity. In addition to this methodological goal, Project MIME is the first study specifically designed to test the immunocognitive model of mood psychopathology. Given the integration of several malleable treatment targets (approach behavior, emotion regulation, inflammation) into this model, results from this study could inform comprehensive, flexible intervention strategies for mood disorder prevention and treatment.

The Impact of Agitation in Dementia on Caregivers: A Real-World Survey.

BACKGROUND: Dementia patients frequently depend on caregivers. Agitation is a common behavioral dementia symptom particularly burdensome to patients and caregivers. OBJECTIVE: To assess the association of agitation severity with non-professional caregiver hours, burden, health status, and productivity. Secondarily, to assess the association of agitation severity with these outcomes for patients receiving remote (not living with the patient) and proximate (living with the patient) caregiving. METHODS: A retrospective analysis of physician and non-professional caregiver-reported data from a US point-in-time survey. Patients were aged ≥50 years, with early cognitive impairment or dementia. Regression analyses compared outcomes by agitation severity; covariates included age, sex, and clinical characteristics. RESULTS: Data were included for 1,349 patients (non-agitated n = 656, agitated n = 693; no care n = 305, remote care n = 248, proximate care n = 691; unknown care n = 105). Greater agitation was significantly associated (p < 0.05) in all caregivers with increasing: Zarit Burden Interview (ZBI) Total Caregiver Burden, Personal Strain, Role Strain, and Guilt; Work Productivity and Activity Index (WPAI) presenteeism, overall work impairment, and total activity impairment. Higher ZBI Total Caregiver Burden, Personal Strain, and Role Strain were associated with greater agitation in proximate caregivers and higher ZBI Guilt associated with greater agitation in remote caregivers (p < 0.05). Higher WPAI presenteeism and total activity impairment were associated (p < 0.05) with greater agitation in proximate caregivers. Caregiving hours increased with increasing agitation for proximate caregiving (p = 0.001). CONCLUSION: Greater agitation severity was associated with higher caregiver burden and lower productivity, with higher indirect costs a likely outcome of agitation.

Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications.

INTRODUCTION: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. METHODS: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts' clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). RESULTS: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). CONCLUSIONS: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.

Agitation in Dementia: Real-World Impact and Burden on Patients and the Healthcare System.

BACKGROUND: At least 90%of patients with dementia experience behavioral or neuropsychiatric symptoms including agitation, psychotic symptoms, apathy, depression, and sleep disturbances. Agitation has been reported to be experienced by 60%of patients with mild cognitive impairment and 76%of patients with Alzheimer's disease. OBJECTIVE: We aimed to assess the impact of agitation in patients with dementia on healthcare resource utilization (HCRU) and healthcare costs. METHODS: This was a retrospective analysis of physician-reported patient data from a point-in-time survey. Patients included were aged≥50 years, with early cognitive impairment or dementia. Agitated and non-agitated patients were compared. Regression analyses assessed the relationship of agitation score (calculated from number/severity of agitation symptoms) with outcomes, with covariates including age and Mini-Mental State Examination score. Sensitivity analyses compared patients with 0 and≥2 agitation symptoms following propensity score matching on the base-case covariates. RESULTS: Data were included for 1,349 patients (agitated, n = 693; non-agitated, n = 656). Based on regression analyses, agitation score was correlated with proportion of patients with professional caregivers (p < 0.01), institutionalized (p < 0.01), hospitalized in a psychiatric ward (p < 0.05), and receiving an antipsychotic/antidepressant (both p < 0.001); number of consultations with a healthcare professional (HCP), psychiatrist, or psycho-geriatrician; number and cost of hospitalizations (p < 0.01); cost of HCP consultations (p < 0.001); and total direct healthcare costs (p < 0.001). Sensitivity analyses generally supported the base-case analysis. CONCLUSION: Agitation in dementia is associated with increased HCRU and healthcare costs. Effective therapies are needed to address agitation in dementia, with the potential to alleviate patient impact, HCRU, and healthcare costs.

Impact of Dementia-Related Behavioral Symptoms on Healthcare Resource Use and Caregiver Burden: Real-World Data from Europe and the United States.

BACKGROUND: Dementia is commonly accompanied by neurobehavioral symptoms; however, the relationship between such symptoms and health-related outcomes is unclear. OBJECTIVE: To investigate the impact of specific neurobehavioral symptoms in dementia on healthcare resource use (HCRU), patient quality of life (QoL), and caregiver burden. METHODS: Data were taken from the 2015/16 Adelphi Real World Dementia Disease Specific Programme™, a point-in-time survey of physicians and their consulting dementia patients. Multiple regression analyses were used to examine associations between patient symptom groups and health-related outcomes. RESULTS: Each patient symptom group of interest (patients with agitation/aggression and related symptoms [AARS] with psychosis, patients with AARS without psychosis, and patients with other behavioral symptoms) had a positive association with HCRU variables (i.e., HCRU was greater), a negative association with proxy measures of patient QoL (i.e., QoL was decreased), and a positive association with caregiver burden (i.e., burden was greater) compared with patients with no behavioral symptoms (control group). The magnitude of effect was generally greatest in patients with AARS with psychosis. Regression analysis covariates that were found to be most often significantly related to the outcomes were dementia severity and the patients' living situation (i.e., whether they were in nursing homes or living in the community). CONCLUSION: Combinations of behavioral symptoms, particularly involving AARS plus psychosis, may have a detrimental impact on health-related outcomes such as HCRU, patient QoL, and caregiver burden in dementia. Our results have implications for intervention development in patients who report clusters of symptoms and caregivers, and for identifying at-risk individuals.

Real-world assessment of "OFF" episode-related healthcare resource utilization among patients with Parkinson's disease in the United States.

AIMS: Within 5 years of initiating carbidopa/levodopa, ∼50% of patients with Parkinson's disease (PD) experience "OFF" episodes; little is known about the cost burden. We investigated the association of "OFF" episodes with patient characteristics, healthcare resource utilization (HCRU), and healthcare costs. METHODS: Analyses used neurologist-provided data from the US-specific 2017 and 2019 Adelphi Real World Disease Specific Programme for PD, including duration of "OFF" episodes and HCRU for 10-12 consecutive patients. Patients were grouped by presence/absence of "OFF" episodes and by average hours of daily "OFF" time. Between-group differences were assessed for demographics, personal circumstances, and clinical characteristics. Regression analyses modeled the relationship of "OFF" episodes with HCRU and costs. RESULTS: Of 1,309 patients, 41% experienced "OFF" episodes, 25% of whom were "OFF" ≥4 h/day. Patients having "OFF" episodes had more severe PD, were diagnosed for longer, and were younger than those without "OFF" (p < .0001). "OFF" episodes were associated with a greater number of prescribed PD drugs (p < .0001). Patients without "OFF" episodes were more likely to have full-time employment and less likely to be retired or unemployed because of PD (p < .001). Patients with and without "OFF" episodes had different living situations (p < .001): patients experiencing "OFF" were less likely to live alone and more likely to live in a nursing home and have a professional caregiver (p < .001). In the past 12 months, the number of hospitalizations, intensive care admissions, and emergency room visits; nights hospitalized; costs of consultations and hospitalizations; and total direct costs were all higher for patients experiencing "OFF" episodes (p < .05). CONCLUSION: Patients with PD and "OFF" episodes had higher HCRU and costs than those without "OFF," suggesting that "OFF" episodes contribute to the economic burden of PD. Further research is warranted to examine the extent that current PD treatments and treatment patterns impact HCRU and costs.

Real-world assessment of the impact of "OFF" episodes on health-related quality of life among patients with Parkinson's disease in the United States.

BACKGROUND: Many patients with Parkinson's disease (PD) who receive carbidopa/levodopa experience symptom reemergence or worsening, or "OFF" episodes. This study assessed the association of "OFF" episodes with health-related quality of life (HRQoL). METHODS: US-specific data from the 2017 and 2019 Adelphi Real World Disease Specific Programme for PD, a real-world cross-sectional survey, were used. Neurologists provided data for 10-12 consecutive patients with PD who completed the 39-item Parkinson's Disease Questionnaire (PDQ-39) and the EuroQol 5-Dimension (EQ-5D). Data were grouped by patients who experienced "OFF" episodes versus those who did not and by average hours of daily "OFF" time. Differences between patient groups were assessed for demographics and clinical characteristics; regression analyses were used to model the relationship between HRQoL and "OFF" episodes with age, sex, body mass index, current PD stage on the Hoehn and Yahr scale, and number of concomitant conditions related and unrelated to mobility as covariates. RESULTS: Data from 722 patients were analyzed. Overall, 321 patients (44%) had "OFF" episodes (mean of 2.9 h of daily "OFF" time). Patients who experienced "OFF" episodes were less likely to work full-time and more likely to live with family members other than their spouse/partner or reside in a long-term care facility than those without "OFF" episodes. The presence of "OFF" episodes, regardless of the average hours of daily "OFF" time, was significantly associated with high scores (reflecting poor HRQoL) on most PDQ-39 dimensions and the summary index and low scores (reflecting poor health status) on the EQ-5D health utility index, visual analog scale (VAS), and all dimensions. Furthermore, increased average hours of daily "OFF" time was significantly correlated with higher scores for all PDQ-39 dimensions and the summary index, as well as with the EQ-5D health utility index and VAS scores. Patients with "OFF" episodes experienced reduced HRQoL even after correcting for potentially confounding variables. CONCLUSIONS: This study demonstrated that the occurrence of "OFF" episodes in patients with PD is associated with reduced HRQoL and that the impact on HRQoL increased incrementally with increasing average hours of daily "OFF" time.

Supine body posture reduces cognitive conflict processing: Evidence from N450 Stroop interference.

Previous research has revealed that a supine body posture, as compared to a sitting upright posture, decreases approach motivation and cognitive dissonance reduction. The present research was designed to test whether a supine body posture would decrease cognitive conflict processing, the process that occurs prior to cognitive dissonance reduction. Previous research using the Stroop task has found event-related potentials (N450, error-related negativity [ERN]) that are associated with cognitive conflict processing. In the current experiment, participants (N = 35) completed a color-naming Stroop task while sitting upright or supine (within-subjects, counterbalanced). Results revealed that as compared to the upright posture, the supine posture reduced the N450 Stroop interference effect but not the ERN.

Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis.

OBJECTIVE: This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). METHODS: Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing-remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. RESULTS: This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5-7.7) vs. oral DMT, 5.6 (2.6-12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) - 10.0% (- 6.1 to - 15.0%) vs. oral DMT, - 13.0% (- 8.5 to - 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) - 11% (- 7.1 to - 16.0%) vs. oral DMT, - 9.7% (- 5.0 to - 14.0%) vs. injectable DMT]. CONCLUSION: This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.

Multiple sclerosis (MS) is the most common progressive neurological disease in young adults. It typically starts between the ages of 20 and 40 years­arguably some of the most productive years of an individual's life­and it has a large impact on many aspects of everyday life for the rest of a person's life. The reduction in the ability to do routine activities, including working, results in a large economic burden. Disease-modifying treatments (DMTs) available for MS, particularly high-efficacy DMTs, have been shown to improve work productivity. This study looked at work and activity impairment using the Work Productivity and Activity Impairment Questionnaire in patients with MS who were treated with ocrelizumab (OCR) or other DMTs for ≥ 6 months. A total of 630 patients with relapsing­remitting MS (RRMS) or secondary progressive MS (SPMS) from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis were included in the study, including 90, 316 and 224 patients who completed ≥ 6 months of treatment with OCR, oral or injectable therapy. Compared with patients receiving oral or injectable DMTs, those receiving OCR had higher odds of employment [odds ratio (OR) vs. oral DMT 3.4; OR vs. injectable DMT 5.6], lower overall work productivity impairment (difference vs. oral DMT − 10%; difference vs. injectable DMT − 13%) and lower activity impairment (difference vs. oral DMT − 11%; difference vs. injectable DMT − 9.7%). These findings in patients with RRMS or SPMS being treated in the real world suggest that OCR may reduce the impact of MS disease on work productivity more than other DMTs.

The effort-doors task: Examining the temporal dynamics of effort-based reward processing using ERPs.

Aberrant reward processing is a cardinal feature of various forms of psychopathology. However, recent research indicates that aberrant reward processing may manifest at temporally distinct substages and involve interdependent subcomponents of reward processing. To improve our understanding of both the temporal dynamics and distinct subcomponents of reward processing, we added an effort manipulation to the "doors" reward-task paradigm, to derive behavioral and event-related potential (ERP) measures of effort-based reward processing. Behavioral measures consisting of reaction time, response rate, and response rate change were used to index effort expenditure, and ERP measures were used to index attention allocated toward effort-completion cues, anticipation of reward, valuation of reward, and attention toward monetary feedback. Reduced response rate and slowing of response were evident during the high effort versus the low effort condition. ERP findings indicated increased attention to signals of high- compared to low-effort completion cues-as well as reduced anticipation of rewards, and reduced attention toward feedback information following high effort expenditure. Participants showing the most response-rate slowing evidenced the greatest reward devaluation following high versus low effort. Findings demonstrate that the addition of an effort expenditure manipulation to the doors reward paradigm produced reliable ERP and behavioral measures of effort-based reward processing, providing opportunities for future researchers to utilize the effort-doors task to parse the temporal dynamics of both anticipatory and consummatory reward processing components.

The Effect of Perceived Effort on Reward Valuation: Taking the Reward Positivity (RewP) to Dissonance Theory.

The present research was designed to test whether the subjective experience of more effort related to more reward valuation as measured by a neural response. This prediction was derived from the theory of cognitive dissonance and its effort justification paradigm. Young adult participants (n = 82) engaged in multiple trails of a low or high effort task that resulted in a loss or reward on each trial. Neural responses to the reward (loss) cue were measured using EEG so that the event-related potential known as the Reward Positivity (RewP) could be assessed. Results revealed no significant differences between low and high effort conditions on the RewP. However, within the high effort condition, a more subjective experience of effort was associated with a larger RewP. This research extends past research on the effort justification paradigm of cognitive dissonance theory by suggesting that effort justification is associated with an implicit measure of reward valuation. It, therefore, challenges recent perspectives on dissonance processes that posit that these evaluative changes should only occur on explicit but not implicit measures.