Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

How, when, and why is social class linked to mental health and wellbeing? A systematic meta-review.

RATIONALE: Meta-reviews synthesising research on social class and mental health and wellbeing are currently limited and focused on specific facets of social class (e.g., social capital) or mental health and wellbeing (e.g., mental health disorders), and none sought to identify mechanisms in this relationship. OBJECTIVES: The present meta-review sought to (1) assess the overall relationship between social class and mental health and wellbeing, (2) determine the mechanisms that act in this relationship, and (3) evaluate the strength of evidence available. METHODS: The protocol was prospectively registered on PROSPERO (CRD42021214731). We systematically searched twelve databases in September 2022 and identified 149 eligible reviews from 38,257 records screened. Quality of evidence was assessed with the JBI levels of evidence and risk of bias with the ROBIS tool. RESULTS: A large but low-quality evidence base points to class-based inequalities in mental health and wellbeing, with the strongest available evidence linking lower social positions to an increased risk of depression. In terms of different facets of stratification, the best available evidence suggests that deprivation (e.g., poverty), socioeconomic status, income, and subjective social status are consequential for individuals' mental health and wellbeing. However, high-quality evidence for the roles of education, occupation, other economic resources (e.g., wealth), and social capital is currently limited. Most reviews employed individual-level measures (e.g., income), as opposed to interpersonal- (e.g., social capital) or community-level (e.g., neighbourhood deprivation) measures. Considering mechanisms, we found some evidence for mediation via subjective social status, sense of control, and experiences of stress and trauma. There was also some evidence that higher socioeconomic status can provide a buffer for neighbourhood deprivation, lower social capital, and lower subjective social status. CONCLUSIONS: Future research employing experimental or quasi-experimental methods, and systematic reviews with a low risk of bias, are necessary to advance this area of research.

Misdiagnosis of amyotrophic lateral sclerosis in clinical practice in Europe and the USA: a patient chart review and physician survey.

OBJECTIVE: Delays in amyotrophic lateral sclerosis (ALS) diagnosis can result in compromised disease management and unnecessary costs. We examined the extent of ALS misdiagnosis in the US and Europe. METHODS: Data were collected via the Adelphi ALS Disease Specific Programme™, a cross-sectional survey of physicians and a medical chart review of their consulting patients with ALS in France, Germany, Italy, Spain, the UK (EU5), and the US. Between July 2020 and March 2021, eligible physicians (primary speciality neurology, active involvement in managing patients with ALS) abstracted data from patients (≥18 years old) with confirmed ALS. RESULTS: Overall, 138 physicians completed the survey (EU5 107, US 31), with data reviewed from 795 patient medical charts (EU5 568, US 227); 278 (35.0%) patients (EU5 183 [32.2%], US 95 [41.9%]) had received ≥1 initial misdiagnosis based on symptoms later attributed to ALS. Mean (SD) time from symptom onset to first healthcare professional consultation was 3.8 (5.2) months (EU5 4.3 [4.8] months, US 2.6 [5.8] months). Mean (SD) time from symptom onset to ALS diagnosis was 8.2 (12.5) months (EU5 9.6 [14.0] months, US 5.0 [6.8] months) and increased to 10.4 (17.9) for patients with a misdiagnosis (compared with 6.9 [7.2] for patients with no misdiagnosis). Physician-identified barriers to timely ALS diagnosis included the similarity of symptoms to other conditions and delayed referral to neurologists. CONCLUSIONS: Misdiagnosis of ALS is frequent, with a protracted diagnostic pathway. Targeted education of patients and physicians about signs and symptoms and benefits of prompt referral to multidisciplinary care are needed.

Time from amyotrophic lateral sclerosis symptom onset to key disease milestones: analysis of data from a multinational cross-sectional survey.

OBJECTIVE: To determine the average time from Amyotrophic Lateral Sclerosis (ALS) symptom onset to 11 pre-defined milestones, overall and according to ALS progression rate and geographic location. METHODS: Data were drawn from the Adelphi Real World ALS Disease-Specific ProgrammeTM, a point-in-time survey of neurologists caring for people living with ALS (pALS) conducted in France, Germany, Italy, Spain, the United Kingdom and the United States from 2020-2021. ALS progression rate was calculated using time since symptom onset and ALS Functional Rating Scale Revised score. RESULTS: Survey results were available for N = 1003 pALS (progression rate for N = 867). Mean time from symptom onset was 3.8 months to first consultation, 8.0 months to diagnosis, 16.2 months to employment change (part-time/sick leave/retirement/unemployment), 17.5 months to use of a walking aid, 18.5 months to first occurrence of caregiver support, 22.8 months to use of a wheelchair, 24.6 months to use of a communication aid, 27.3 months to use of a respiratory aid, 28.6 months to use of gastrostomy feeding, 29.7 months to use of eye gaze technology and 30.3 months to entering a care facility. Multivariate analysis indicated significant effects of fast (versus slow) progression rate on time to reach all 11 milestones, as well as US (versus European) location, age, body mass index and bulbar onset (versus other) on time to reach milestones. CONCLUSIONS: pALS rapidly reached clinical and disease-related milestones within 30 months from symptom onset. Milestones were reached significantly faster by pALS with fast versus slow progression. Geographic differences were observed.

Healthcare resource utilization at different stages of amyotrophic lateral sclerosis: Results from a real-world survey.

People with amyotrophic lateral sclerosis (pALS) require complex, multi-disciplinary care, resulting in extensive healthcare resource utilization (HCRU). To investigate the relationship between HCRU and ALS progression, the study objectives were (i) to characterize HCRU in pALS and (ii) to establish whether this varied according to disease stage, as defined using three different methodologies: neurologist-defined early/mid/late stage, the King's clinical staging system for ALS, and the Milan Torino Staging system for ALS (MiToS). Real-world data were drawn from the Adelphi ALS Disease-Specific Programme™, a point-in-time survey of neurologists in France, Germany, Italy, Spain, the UK, and the USA conducted July 2020-March 2021. The analysis included survey responses from 142 physicians with respect to 880 pALS. With advancing ALS stage, significant differences were observed in the number of healthcare professional consultations and X-rays per person (both p < 0.05 for all staging systems), and the proportion of pALS with emergency room admissions, intensive care unit admissions, and assisted ventilation (all p < 0.05 for all staging systems). Across stages, >55% of pALS received care from a general neurologist and a general/primary care practitioner. With increasing stage, there was a significant difference in the proportion receiving care from a physical therapist, pulmonologist/respiratory care practitioner, respiratory therapist, speech/language therapist, and palliative care team, and in the proportion receiving care only from professional caregivers (all p < 0.05 for all staging systems). This study confirmed the substantial HCRU required to support pALS through all stages of ALS and highlighted an increasing need for healthcare resources as the disease progresses.

Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum: Revelations from the MANAGE-PD validation cohort.

INTRODUCTION: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories. METHODS: Device-aided therapy-naïve patients receiving oral treatments were identified from the Adelphi Parkinson's Disease Programme. Patients were categorized (category 1 to 3) using MANAGE-PD. PD-specific QoL (PDQ-39), care partner burden (ZBI), satisfaction with current treatment, healthcare resource utilization, associated healthcare costs, and future treatment discussion with providers were measured. Categories were compared using ANOVA, t-test, chi square and adjusted regression analyses. RESULTS: Of the analytical sample (n = 2709), 18.9% were inadequately controlled on current therapy and potentially eligible for device-aided therapies (category 3). As expected, they had worse patient/caregiver reported outcomes versus patients in categories 1 or 2. However, the degree of difference in healthcare resource utilization, including: greater number of hospitalizations, emergency room (ER) visits and consultations, higher likelihood of being recipients of respite care, and greater PD treatment burden, was unexpected. Importantly, of patients in category 3 and their care partners, >40% did not report discussions with providers about device-aided therapies. CONCLUSION: MANAGE-PD category 3 patients had significantly higher burden on healthcare resources versus patients well-controlled with oral treatment or requiring only oral medication adjustments; yet almost half had no discussion on device-aided therapies with providers. Device-aided therapies may be considered in these patients.

Promoting Publications Through Plastic Surgery Journal Instagram Accounts: Is It Worth It?

PURPOSE: Journals are increasingly using social media to increase article engagement. We aim to determine the impact of Instagram promotion on, and identify social media tools that effectively enhance, plastic surgery article engagement and impact. METHODS: Instagram accounts for Plastic and Reconstructive Surgery , Annals of Plastic Surgery , Aesthetic Surgery Journal , and Aesthetic Plastic Surgery were reviewed for posts published by February 8, 2022. Open access journal articles were excluded. Post caption word count and number of likes, tagged accounts, and hashtags were recorded. Inclusion of videos, article links, or author introductions was noted. All articles from journal issues published between the dates of the first and last posts promoting articles were reviewed. Altmetric data approximated article engagement. Citation numbers from the National Institutes of Health iCite tool approximated impact. Differences in engagement and impact of articles with and without Instagram promotion were compared by Mann-Whitney U tests. Univariate and multivariable regressions identified factors predictive of more engagement (Altmetric Attention Score, ≥5) and citations (≥7). RESULTS: A total of 5037 articles were included, with 675 (13.4%) promoted on Instagram. Of posts featuring articles, 274 (40.6%) included videos, 469 (69.5%) included article links, and 123 included (18.2%) author introductions. Promoted articles had higher median Altmetric Attention Scores and citations ( P < 0.001). On multivariable analysis, using more hashtags predicted higher article Altmetric Attention Scores (odds ratio [OR], 1.85; P = 0.002) and more citations (OR, 1.90; P < 0.001). Including article links (OR, 3.52; P < 0.001) and tagging more accounts (OR, 1.64; P = 0.022) predicted higher Altmetric Attention Scores. Including author introductions negatively predicted Altmetric Attention Scores (OR, 0.46; P < 0.001) and citations (OR, 0.65; P = 0.047). Caption word count had no significant impact on article engagement or impact. CONCLUSIONS: Instagram promotion increases plastic surgery article engagement and impact. Journals should use more hashtags, tag more accounts, and include manuscript links to increase article metrics. We recommend that authors promote on journal social media to maximize article reach, engagement, and citations, which positively impacts research productivity with minimal additional effort in designing Instagram content.

Rapid Assessment of Membrane Protein Quality by Fluorescent Size Exclusion Chromatography.

During membrane protein structural elucidation and biophysical characterization, it is common to trial numerous protein constructs containing different tags, truncations, deletions, fusion partner insertions, and stabilizing mutations to find one that is not aggregated after extraction from the membrane. Furthermore, buffer screening to determine the detergent, additive, ligand, or polymer that provides the most stabilizing condition for the membrane protein is an important practice. The early characterization of membrane protein quality by fluorescent size exclusion chromatography provides a powerful tool to assess and rank different constructs or conditions without the requirement for protein purification, and this tool also minimizes the sample requirement. The membrane proteins must be fluorescently tagged, commonly by expressing them with a GFP tag or similar. The protein can be solubilized directly from whole cells and then crudely clarified by centrifugation; subsequently, the protein is passed down a size exclusion column, and a fluorescent trace is collected. Here, a method for running FSEC and representative FSEC data on the GPCR targets sphingosine-1-phosphate receptor (S1PR1) and serotonin receptor (5HT2AR) are presented.

The Burden of Progressive Supranuclear Palsy on Patients, Caregivers, and Healthcare Systems by PSP Phenotype: A Cross-Sectional Study.

Progressive supranuclear palsy (PSP) is a rare, relentlessly progressive, ultimately fatal neurodegenerative brain disease. The objective of this study was to assess the burden of PSP on patients, caregivers, and healthcare systems by PSP phenotype. Data were drawn from the Adelphi PSP Disease Specific Programme™, a cross-sectional study of neurologists and people living with PSP in the United States of America, France, Germany, Italy, Spain, and the United Kingdom. All people living with PSP with a reported phenotype were included. PSP phenotype was reported for 242 patients (mean age: 70.2 years, 58% male): PSP-Richardson's syndrome, n = 96; PSP-predominant Parkinsonism, n = 88; PSP-predominant corticobasal syndrome, n = 28; PSP-predominant speech/language disorder, n = 12; PSP-progressive gait freezing, n = 9; PSP-predominant frontal presentation, n = 9. Most patients reported impaired cognitive, motor, behavioral and ocular functionality; 67-100% of patients (across phenotypes) had moderate-to-severe disease at the time of data collection. Post-diagnosis, the majority were provided with a visual and/or mobility aid (55-100%, across phenotypes), and/or required home modification to facilitate their needs (55-78%, across phenotypes). Patients required multiple types of healthcare professionals for disease management (mean 3.6-4.4, across phenotypes), and the majority reported receiving care from at least one caregiver (mean 1.3-1.8, across phenotypes). There is a high burden on patients, caregivers, and healthcare systems across all PSP phenotypes. Although phenotypes manifest different symptoms and are associated with different diagnostic pathways, once diagnosed with PSP, patients typically receive similar care.

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study.

The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs). Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05). Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.

Atypical Treatment Switches in Schizophrenia Patients: Drivers and Associated Outcomes.

Objective: To describe and compare demographics and outcomes among patients with schizophrenia who have switched atypical treatments versus non-switchers. Methods: Data were extracted from the Adelphi Schizophrenia Disease Specific Programme™ conducted from January to May 2014 in the United States. Participating physicians provided information on their next 10 consulting schizophrenia patients aged ≥ 18 years; the same patients were invited to voluntarily complete a patient self-completion form (PSC). Patients were considered switchers (S) or non-switchers (NS) based on their physician-provided treatment history. S were patients who had switched, stopped or added an atypical treatment within the last 2 years. NS had no treatment changes within the last 2 years or were receiving their first-line treatment (for ≥ 3 months). Demographics, clinical characteristics and outcomes among S and NS were compared using both descriptive and multivariate statistics. Results: One-hundred fifty physicians provided data on 1003 patients with schizophrenia (395 S, 608 NS); 500 patients completed a PSC (170 S, 330 NS). When compared with NS, S were more likely to be unemployed (p=0.0060), have a caregiver (p<0.0001), have greater activity impairment as assessed by Work and Productivity Activity Impairment (p=0.0031), be hospitalized for schizophrenia (p<0.0001) and have had a greater mean number of hospitalizations in the last 12 months (p=0.0012). NS vs S were more likely to have much or very much improved illness (p<0.0001) and less severe disease (p<0.0001) as assessed by Clinical Global Impression. Conclusion: Despite switching drugs, some schizophrenia patients continue to have high levels of disease burden, suggesting that currently available therapies are insufficiently effective in these patients.

Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries.

BACKGROUND: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria. METHODS: Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. RESULTS: From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden. CONCLUSIONS: 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.

Surface-tethered planar membranes containing the ß-barrel assembly machinery: a platform for investigating bacterial outer membrane protein folding.

The outer membrane of Gram-negative bacteria presents a robust physicochemical barrier protecting the cell from both the natural environment and acting as the first line of defense against antimicrobial materials. The proteins situated within the outer membrane are responsible for a range of biological functions including controlling influx and efflux. These outer membrane proteins (OMPs) are ultimately inserted and folded within the membrane by the ß-barrel assembly machine (Bam) complex. The precise mechanism by which the Bam complex folds and inserts OMPs remains unclear. Here, we have developed a platform for investigating Bam-mediated OMP insertion. By derivatizing a gold surface with a copper-chelating self-assembled monolayer, we were able to assemble a planar system containing the complete Bam complex reconstituted within a phospholipid bilayer. Structural characterization of this interfacial protein-tethered bilayer by polarized neutron reflectometry revealed distinct regions consistent with known high-resolution models of the Bam complex. Additionally, by monitoring changes of mass associated with OMP insertion by quartz crystal microbalance with dissipation monitoring, we were able to demonstrate the functionality of this system by inserting two diverse OMPs within the membrane, pertactin, and OmpT. This platform has promising application in investigating the mechanism of Bam-mediated OMP insertion, in addition to OMP function and activity within a phospholipid bilayer environment.

Associations Between Relapses and Psychosocial Outcomes in Patients With Schizophrenia in Real-World Settings in the United States.

Aim: To assess associations between relapses and psychosocial outcomes in adult patients with schizophrenia treated in United States (US) healthcare settings. Methods: Data were derived from a point-in-time survey of psychiatrists and their patients with schizophrenia conducted across the US, France, Spain, China, and Japan between July and October 2019. For the purposes of this analysis, only data from US practitioners and patients were included. Disease-specific programmes (DSPs) are large surveys with a validated methodology conducted in clinical practise; they describe current disease management, disease burden, and associated treatment effects (clinical and physician-perceived). Participating psychiatrists completed patient record forms for their next 10 consecutive adult consulting patients with schizophrenia, with the same patients invited to voluntarily complete a patient self-completion (PSC) questionnaire. Surveys contained questions on the patients' disease background, treatment history, prior hospitalisation due to schizophrenia relapse and a series of psychosocial outcomes. Associations between relapses in the last 12 months and psychosocial outcomes were examined using multiple regression. Results: A total of 124 psychiatrists provided data on 1,204 patients. Of these, 469 patients (mean age, 39.6 years; 56.5% male) had known hospitalisation history for the last 12 months and completed a PSC; 116 (24.7%) patients had ≥1 relapse. Compared to patients without relapses, patients who relapsed were more likely to be homeless, unemployed, previously incarcerated, and currently have difficulties living independently (all p < 0.05). Patients who experience a relapse also had greater working impairment and poorer quality of life compared with those who did not relapse. In general, psychosocial outcomes became poorer with an increasing number of relapses. Conclusions: In this population of patients with schizophrenia from the US, relapse was significantly associated with poor psychosocial outcomes, with a greater number of relapses predicting worse outcomes. Early intervention to reduce the risk of relapse may improve psychosocial outcomes in patients with schizophrenia.

Treatment Goals in Schizophrenia: A Real-World Survey of Patients, Psychiatrists, and Caregivers in the United States, with an Analysis of Current Treatment (Long-Acting Injectable vs Oral Antipsychotics) and Goal Selection.

PURPOSE: To understand similarities and differences in patient treatment goals as selected by US psychiatrists, adult patients with schizophrenia, and their caregivers in a real-world setting in the United States, including stratification by current medication and age. PATIENTS AND METHODS: Data were drawn from the Adelphi Schizophrenia Disease Specific Programme™, a point-in-time survey of psychiatrists and their consulting adult patients with schizophrenia, conducted from June to October 2019. Psychiatrists completed record forms for their next 8 consecutive outpatients and (where possible) 2 inpatients matching inclusion criteria. Participating psychiatrists, patients, and caregivers completed treatment goal questionnaires as part of the survey. RESULTS: Psychiatrists (n = 124) provided data on 1204 patients with schizophrenia, including 1135 on drug treatment (207 inpatients [18%] and 928 outpatients [82%]); questionnaires were completed by 555 patients and 135 caregivers. Decrease in disease symptoms was identified as the most important patient treatment goal by patients (64%), psychiatrists (selecting for 63% of patients), and caregivers (selecting for 68% of patients). Patients, psychiatrists, and caregivers similarly rated the least important goals (less sexual problems and less weight gain). Patients indicated their current medication helped to reach their most important goals: decrease in disease symptoms (68%) and thinking more clearly (39%). Findings based on analysis of treatment goals by treatment and age were similar to overall trends. CONCLUSION: These findings, including identification of a primary consensus goal of decrease in disease symptoms, may help with discussions between patients with schizophrenia, psychiatrists, and caregivers to inform effective management strategies and encourage shared decision-making.

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.

Epistemic Consultants and the Regulation of Policy Knowledge in the Obama Administration.

The agencies of the government of the United States of America, such as the Food and Drug Administration or the Environmental Protection Agency, intervene in American society through the collection, processing, and diffusion of information. The Presidency of Barack Obama was notable for updating and redesigning the US government's information infrastructure. The White House enhanced mass consultation through open government and big data initiatives to evaluate policy effectiveness, and it launched new ways of communicating with the citizenry. In this essay we argue that these programs spelled out an emergent epistemology based on two assumptions: dispersed knowledge and a critique of judgment. These programs have redefined the evidence required to justify and design regulatory policy and conferred authority to a new kind of expert, which we call epistemic consultants.

Assessing patient preferences for switching from warfarin to direct oral anticoagulants.

Warfarin remains the most commonly prescribed oral anticoagulant in the United States, but it has disadvantages such as dietary interactions and frequent laboratory monitoring. Direct oral anticoagulants (DOACs) have been introduced as safer and equally effective alternatives to warfarin. This study assessed patient preference for warfarin or DOAC based on a willingness to pay more for potential DOAC benefits. Current warfarin patients with atrial fibrillation or venous thromboembolism enrolled in the University of Utah Health Thrombosis Service were given a one-time electronic survey that assessed preferences between warfarin and DOACs using scenarios comparing effectiveness, safety, and convenience. When DOACs were preferred, patients were asked how much more they would be willing to pay monthly for the perceived advantages associated with DOACs. With 123 completed surveys, 68% of patients preferred to stay on warfarin. No particular factor influenced patient preference (lack of routine laboratory monitoring, lower risks of major bleeding, and fewer dietary interactions). Reduced stroke risk was associated with the highest value (willing to pay an additional $21). Considering all factors, patients preferring DOACs would pay a median $18 extra per month for the additional benefits. Prior exposure to DOACs was associated with preference for DOACs. Many patients currently taking warfarin preferred to stay on warfarin when given the choice, despite DOAC benefits. Willingness to pay extra for DOAC advantages did not exceed $20 in the majority of survey respondents. Previous DOAC exposure influences patient preference and perceived value for DOACs.

Substrate polyspecificity and conformational relevance in ABC transporters: new insights from structural studies.

Transport of molecules and ions across biological membranes is an essential process in all organisms. It is carried out by a range of evolutionarily conserved primary and secondary transporters. A significant portion of the primary transporters belong to the ATP-binding cassette (ABC) superfamily, which utilise the free-energy from ATP hydrolysis to shuttle many different substrates across various biological membranes, and consequently, are involved in both normal and abnormal physiology. In humans, ABC transporter-associated pathologies are perhaps best exemplified by multidrug-resistance transporters that efflux many xenobiotic compounds due to their remarkable substrate polyspecificity. Accordingly, understanding the transport mechanism(s) is of great significance, and indeed, much progress has been made in recent years, particularly from structural studies on ABC exporters. Consequently, the general mechanism of 'alternate access' has been modified to describe individual transporter nuances, though some aspects of the transport process remain unclear. Moreover, as new information has emerged, the physiological relevance of the 'open-apo' conformation of MsbA (a bacterial exporter) has been questioned and, by extension, its contribution to mechanistic models. We present here a comprehensive overview of the most recently solved structures of ABC exporters, focusing on new insights regarding the nature of substrate polyspecificity and the physiological relevance of the 'open-apo' conformation. This review evaluates the claim that the latter may be an artefact of detergent solubilisation, and we hypothesise that the biophysical properties of the membrane play a key role in the function of ABC exporters allowing them to behave like a 'spring-hinge' during their transport cycle.