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1.
Addict Behav ; 157: 108101, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38986353

RESUMO

INTRODUCTION: Little is known about the prevalence and predictors of adolescents' intention to quit or reduce use of e-cigarettes and/or cannabis. METHODS: Frequencies of intention to change (quit, reduce) e-cigarettes and/or cannabis use were examined among 23,915 surveyed middle and high school students with sole and co-use. Predictors of intention to change were identified via LASSO/multilevel logistic regression. RESULTS: Among those with sole e-cigarette use (n = 543), 40.9 % intended to quit and 24.1 % intended to reduce; non-daily e-cigarette use predicted intention to quit and reduce e-cigarettes (p's < 0.03). Among those with sole cannabis use (n = 546), 10.6 % intended to quit and 25.1 % intended to reduce; absence of cannabis cravings predicted intention to reduce cannabis use (p < 0.01). Among those with co-use (n = 816), 26.2 % intended to either quit or reduce (quit/reduce) both substances, 27.5 % intended to quit/reduce e-cigarettes only, and 6.9 % intended to quit/reduce cannabis only. No predictors emerged for intention to change e-cigarette use among those with co-use (p's > 0.09), but younger age, lack of poly-tobacco use, and lack of cannabis craving predicted intention to quit/reduce cannabis use (p's < 0.04). CONCLUSIONS: More than half of adolescents with past-month e-cigarette use, regardless of concurrent cannabis use, expressed interest in changing their use. However, only heaviness of e-cigarette use emerged as a predictor of intention to change suggesting. While fewer students expressed interest in changing their cannabis use, cannabis cravings and poly-tobacco use predicted intent to change. Overall, findings emphasize the need to tailor interventions towards adolescents engaging in more problematic substance use patterns.

2.
ACS Appl Mater Interfaces ; 16(28): 37255-37264, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38979642

RESUMO

Preventing nonspecific binding is essential for sensitive surface-based quantitative single-molecule microscopy. Here we report a much-simplified RainX-F127 (RF-127) surface with improved passivation. This surface achieves up to 100-fold less nonspecific binding from protein aggregates compared to commonly used polyethylene glycol (PEG) surfaces. The method is compatible with common single-molecule techniques including single-molecule pull-down (SiMPull), super-resolution imaging, antibody-binding screening and single exosome visualization. This method is also able to specifically detect alpha-synuclein (α-syn) and tau aggregates from a wide range of biofluids including human serum, brain extracts, cerebrospinal fluid (CSF) and saliva. The simplicity of this method further allows the functionalization of microplates for robot-assisted high-throughput single-molecule experiments. Overall, this simple but improved surface offers a versatile platform for quantitative single-molecule microscopy without the need for specialized equipment or personnel.


Assuntos
Imagem Individual de Molécula , alfa-Sinucleína , Proteínas tau , Humanos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/química , Proteínas tau/metabolismo , Proteínas tau/química , Imagem Individual de Molécula/métodos , Propriedades de Superfície , Polietilenoglicóis/química , Agregados Proteicos
3.
Brain Commun ; 6(3): fcae178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863577

RESUMO

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-ß peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-ß aggregate ratio is increased almost 2-fold in patients with Parkinson's disease (n = 20) compared with controls (n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-ß aggregates than control saliva (P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease (n = 17) and controls (n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods.

4.
NPJ Parkinsons Dis ; 10(1): 113, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849413

RESUMO

There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.

5.
Brain ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833182

RESUMO

Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons, and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Besides the prominent immune alterations seen in the central nervous system (CNS), including the infiltration of T-cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T-cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of PD, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of PD. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in PD and the implications of this for better understanding the overall pathogenesis of this disease.

6.
Mov Disord Clin Pract ; 11(7): 814-824, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38696333

RESUMO

BACKGROUND: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. OBJECTIVES: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia. METHODS: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. RESULTS: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co-develop two open-access resources: one for people with PD and their families, and one for healthcare professionals. CONCLUSION: Using artistic and creative workshops, co-learning and striving for diverse voices, we co-produced relevant resources for a wider audience to improve conversations about PD dementia.


Assuntos
Cuidadores , Demência , Doença de Parkinson , Humanos , Doença de Parkinson/psicologia , Demência/psicologia , Feminino , Cuidadores/psicologia , Masculino , Idoso , Pessoa de Meia-Idade , Comunicação , Idoso de 80 Anos ou mais
7.
J Healthc Manag ; 69(3): 205-218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728546

RESUMO

GOAL: Growing numbers of hospitals and payers are using call centers to answer patients' clinical and administrative questions, schedule appointments, address billing issues, and offer supplementary care during public health emergencies and national disasters. In 2020, the Veterans Health Administration (VA) implemented VA Health Connect, an enterprise-wide initiative to modernize call centers. VA Health Connect is designed to improve the care experience with the convenience, flexibility, and simplicity of a single toll-free number connected to a range of 24/7 virtual services. The services are organized into four areas: administrative guidance for scheduling and general inquiries; pharmacy support for medication matters; clinical triage for evaluation of symptoms and recommended care; and virtual visits with providers for urgent and episodic care. Through a qualitative evaluation of VA Health Connect, we sought to identify the factors that affected the development of this program and to compile considerations to support the implementation of other enterprise-wide initiatives. METHODS: The evaluation team interviewed 29 clinical and administrative leads from across the VA. These leads were responsible for the modernization of their local service networks. PhD-level qualitative methodologists conducted the interviews, asking participants to reflect on barriers and facilitators to modernization and implementation. The team employed a rapid qualitative analytic approach commonly used in healthcare research to distill robust results. PRINCIPAL FINDINGS: A review of the early implementation of VA Health Connect found: (1) deadlines proved challenging but provided momentum for the initiative; (2) a balance between standardized processes and local adaptations facilitated implementation; (3) attention to staffing, hiring, and training of call center staff before implementation expedited workflows; (4) establishing national and local leadership commitment to the innovation from the onset increased team cohesion and efficacy; and (5) anticipating information technology infrastructure needs prevented delays to modernization and implementation. PRACTICAL APPLICATIONS: Our findings suggest that healthcare systems would benefit from anticipating likely obstacles (e.g., delays in software implementations and negotiations with unions), thus providing ample time to secure leadership buy-in and identify local champions, communicating early and often, and supporting flexible implementation to meet local needs. VA leadership can use this evaluation to refine implementation, and it could also have important implications for regulators, federal health exchanges, insurers, and other healthcare systems when determining resource levels for call centers.


Assuntos
United States Department of Veterans Affairs , Estados Unidos , United States Department of Veterans Affairs/organização & administração , Humanos , Atenção à Saúde/organização & administração , Pesquisa Qualitativa
8.
JAMA Surg ; 159(4): 438-444, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38381415

RESUMO

Importance: Care transition models are structured approaches used to ensure the smooth transfer of patients between health care settings or levels of care, but none currently are tailored to the surgical patient. Tailoring care transition models to the unique needs of surgical patients may lead to significant improvements in surgical outcomes and reduced care fragmentation. The first step to developing surgical care transition models is to understand the surgical discharge process. Objective: To map the surgical discharge process in a sample of US hospitals and identify key components and potential challenges specific to a patient's discharge after surgery. Design, Setting, and Participants: This qualitative study followed a cognitive task analysis framework conducted between January 1, 2022, and April 1, 2023, in Veterans Health Administration (VHA) hospitals. Observations (n = 16) of discharge from inpatient care after a surgical procedure were conducted in 2 separate VHA surgical units. Interviews (n = 13) were conducted among VHA health care professionals nationwide. Exposure: Postoperative hospital discharge. Main Outcomes and Measures: Data were coded according to the principles of thematic analysis, and a swim lane process map was developed to represent the study findings. Results: At the hospitals in this study, the discharge process observed for a surgical patient involved multidisciplinary coordination across the surgery team, nursing team, case managers, dieticians, social services, occupational and physical therapy, and pharmacy. Important components for a surgical discharge that were not incorporated in the current care transition models included wound care education and supplies; pain control; approvals for nonhome postdischarge locations; and follow-up plans for wounds, ostomies, tubes, and drains at discharge. Potential challenges to the surgical discharge process included social situations (eg, home environment and caregiver availability), team communication issues, and postdischarge care coordination. Conclusions and Relevance: These findings suggest that current and ongoing studies of discharge care transitions for a patient after surgery should consider pain control; wounds, ostomies, tubes, and drains; and the impact of challenging social situations and interdisciplinary team coordination on discharge success.


Assuntos
Assistência ao Convalescente , Alta do Paciente , Humanos , Hospitalização , Transferência de Pacientes , Dor
9.
Lancet ; 403(10423): 293-304, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245249

RESUMO

Parkinson's disease is a progressive neurodegenerative condition associated with the deposition of aggregated α-synuclein. Insights into the pathogenesis of Parkinson's disease have been derived from genetics and molecular pathology. Biochemical studies, investigation of transplanted neurons in patients with Parkinson's disease, and cell and animal model studies suggest that abnormal aggregation of α-synuclein and spreading of pathology between the gut, brainstem, and higher brain regions probably underlie the development and progression of Parkinson's disease. At a cellular level, abnormal mitochondrial, lysosomal, and endosomal function can be identified in both monogenic and sporadic Parkinson's disease, suggesting multiple potential treatment approaches. Recent work has also highlighted maladaptive immune and inflammatory responses, possibly triggered in the gut, that accelerate the pathogenesis of Parkinson's disease. Although there are currently no disease-modifying treatments for Parkinson's disease, we now have a solid basis for the development of rational neuroprotective therapies that we hope will halt the progression of this disabling neurological condition.


Assuntos
Doença de Parkinson , Animais , Humanos , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , alfa-Sinucleína/metabolismo , Encéfalo/patologia , Modelos Animais , Neurônios
10.
Disabil Health J ; 17(1): 101515, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37620242

RESUMO

BACKGROUND: Persons with disabilities experience significant physical, attitudinal, and communication-based barriers to accessing care. These challenges are exacerbated for rural-dwelling persons with disabilities. Although US Veterans experience disabilities at a higher rate than non-Veterans and are also more likely to dwell in rural locations, research examining the accessibility of VA care for rural Veterans with disabilities is limited. OBJECTIVES: With a focus on access and accessibility, we sought to explore the experiences of rural Veterans with disabilities who receive care at VA. METHODS: We conducted 30 qualitative interviews with rural-dwelling Veterans who experience at least one of three types of disabilities: hearing loss, vision loss, and mobility loss. Using a descriptive qualitative approach, we focused on creating a taxonomy of potential access barriers experienced among this population. RESULTS: Participants reported experiencing access barriers in five main areas, including policies and operational processes at VA clinics; navigating VA campuses and clinics; limited transportation and parking options; communicating with healthcare personnel and occasional negative interactions; and challenges due to pandemic-related changes in policies and procedures. CONCLUSION: These findings suggest that Veterans with disabilities may experience a host of challenges and access barriers while navigating the VA Healthcare system. While these challenges have been reported among individuals with disabilities receiving care in other healthcare settings, they have not been assessed in VA specifically. Given its focus on caring for Veterans with service-aggravated conditions and its commitment to equity and inclusion, addressing access barriers among Veterans with disabilities should be a high priority for VA.


Assuntos
Pessoas com Deficiência , Veteranos , Humanos , Estados Unidos , Acessibilidade aos Serviços de Saúde , População Rural , Pesquisa Qualitativa , United States Department of Veterans Affairs
11.
Brain ; 147(3): 923-935, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-37757857

RESUMO

The development of dementia is a devastating aspect of Parkinson's disease (PD), affecting nearly half of patients within 10 years post-diagnosis. For effective therapies to prevent and slow progression to PD dementia (PDD), the key mechanisms that determine why some people with PD develop early dementia, while others remain cognitively unaffected, need to be understood. Neuroinflammation and tau protein accumulation have been demonstrated in post-mortem PD brains, and in many other neurodegenerative disorders leading to dementia. However, whether these processes mediate dementia risk early on in the PD disease course is not established. To this end, we used PET neuroimaging with 11C-PK11195 to index neuroinflammation and 18F-AV-1451 for misfolded tau in early PD patients, stratified according to dementia risk in our 'Neuroinflammation and Tau Accumulation in Parkinson's Disease Dementia' (NET-PDD) study. The NET-PDD study longitudinally assesses newly-diagnosed PD patients in two subgroups at low and high dementia risk (stratified based on pentagon copying, semantic fluency, MAPT genotype), with comparison to age- and sex-matched controls. Non-displaceable binding potential (BPND) in 43 brain regions (Hammers' parcellation) was compared between groups (pairwise t-tests), and associations between BPND of the tracers tested (linear-mixed-effect models). We hypothesized that people with higher dementia risk have greater inflammation and/or tau accumulation in advance of significant cognitive decline. We found significantly elevated neuroinflammation (11C-PK11195 BPND) in multiple subcortical and restricted cortical regions in the high dementia risk group compared with controls, while in the low-risk group this was limited to two cortical areas. The high dementia risk group also showed significantly greater neuroinflammation than the low-risk group concentrated on subcortical and basal ganglia regions. Neuroinflammation in most of these regions was associated with worse cognitive performance (Addenbrooke's Cognitive Examination-III score). Overall neuroinflammation burden also correlated with serum levels of pro-inflammatory cytokines. In contrast, increases in 18F-AV-1451 (tau) BPND in PD versus controls were restricted to subcortical regions where off-target binding is typically seen, with no relationship to cognition found. Whole-brain 18F-AV-1451 burden correlated with serum phosphorylated tau181 levels. Although there was minimal regional tau accumulation in PD, regional neuroinflammation and tau burden correlated in PD participants, with the strongest association in the high dementia risk group, suggesting possible co-localization of these pathologies. In conclusion, our findings suggest that significant regional neuroinflammation in early PD might underpin higher risk for PDD development, indicating neuroinflammation as a putative early modifiable aetiopathological disease factor to prevent or slow dementia development using immunomodulatory strategies.


Assuntos
Demência , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doenças Neuroinflamatórias , Demência/diagnóstico por imagem , Gânglios da Base , Inflamação/complicações , Progressão da Doença
12.
Mov Disord ; 39(2): 433-438, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38140767

RESUMO

BACKGROUND: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. OBJECTIVES: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. METHODS: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. RESULTS: Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. CONCLUSIONS: The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/diagnóstico , Índice de Gravidade de Doença , Testes de Estado Mental e Demência , Sociedades Médicas
14.
Anal Chem ; 95(41): 15254-15263, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37782556

RESUMO

The formation of soluble α-synuclein (α-syn) and amyloid-ß (Aß) aggregates is associated with the development of Parkinson's disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aß aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aß)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aß aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Agregados Proteicos , alfa-Sinucleína/metabolismo , Peptídeos beta-Amiloides/metabolismo
15.
J Neurosci ; 43(42): 7028-7040, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37669861

RESUMO

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetization-transfer-weighted imaging of the LC. Parameters of "race models" of go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer nondecision times, and more lapses of attention. The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioral modeling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioral changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimization of noradrenergic treatment is likely to benefit from stratification according to LC integrity.SIGNIFICANCE STATEMENT Response inhibition deficits contribute to clinical symptoms and poor outcomes in people with Parkinson's disease and progressive supranuclear palsy. We used cognitive modeling of performance of a response inhibition task to identify disease-specific mechanisms of abnormal inhibitory control. Response inhibition in both patient groups was associated with the integrity of the noradrenergic locus coeruleus, which we measured in vivo using ultra-high field MRI. We propose that the imaging biomarker of locus coeruleus integrity provides a trans-diagnostic tool to explain individual differences in response inhibition ability beyond the classic nosological borders and diagnostic criteria. Our data suggest a potential new stratified treatment approach for Parkinson's disease and progressive supranuclear palsy.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Humanos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/psicologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Locus Cerúleo , Teorema de Bayes
16.
Front Public Health ; 11: 1203558, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37670822

RESUMO

Background: Adolescents who use alcohol and other drugs on school campuses are at heightened risk for adverse consequences to their health and wellbeing. Schools have historically turned to punitive approaches as a first-line response to substance use. However, punishment is an ineffective deterrent for substance use and may cause harm and increase inequities. iDECIDE (Drug Education Curriculum: Intervention, Diversion, and Empowerment) was developed as a scalable and youth-centered drug education and diversion program that can be used as a skills-based alternative to punishment. We aim to evaluate the effectiveness of the iDECIDE curriculum as an alternative to punishment (ATP) for school-based substance use infractions in the context of a large pragmatic clinical effectiveness study. Methods: We will conduct a Type 1, hybrid effectiveness-implementation trial. Using a stepped wedge design with approximately 90 middle and high schools in Massachusetts, we will randomly allocate the timing of implementation of the iDECIDE curriculum compared to standard disciplinary response over approximately 36 months. We will test the overarching hypothesis that student-level outcomes (knowledge of drug effects and attitudes about substance use; frequency of substance use; school connectedness) improve over time as schools transition from a standard disciplinary response to having access to iDECIDE. The secondary aims of this trial are to (1) explore whether change in student-level outcomes vary according to baseline substance use, number of peers who use alcohol or other drugs, age, gender, and school urbanicity, and (2) determine the acceptability and feasibility of the iDECIDE curriculum through qualitative stakeholder interviews. Discussion: Substance use continues to be a major and rapidly evolving problem in schools. The importance of moving away from punishment to more restorative approaches is widely accepted; however, scalable alternatives have not yet been identified. This will be the first study to our knowledge to systematically evaluate an ATP for students who violate the school substance use policy and is well poised to have important implications for policy making.


Assuntos
Punição , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Humanos , Currículo , Instituições Acadêmicas , Etanol , Trifosfato de Adenosina
17.
J Parkinsons Dis ; 13(6): 1011-1033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37545260

RESUMO

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.


Assuntos
Doença de Parkinson , Humanos , Consenso , Progressão da Doença , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Qualidade de Vida
18.
Geriatrics (Basel) ; 8(4)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37489322

RESUMO

BACKGROUND: Patient priorities care (PPC) is an effective age-friendly health systems (AFHS) approach to aligning care with goals derived from 'what matters'. The purpose of this quality improvement program was to evaluate the fidelity and feasibility of the health priorities identification (HPI) process in VA Community Living Centers (CLC). METHODS: PPC experts worked with local CLC staff to guide the integration of HPI into the CLC and utilized a Plan-Do-Study-Act (PDSA) model for this quality improvement project. PPC experts reviewed health priorities identification (HPI) encounters and interdisciplinary team (IDT) meetings for fidelity to the HPI process of PPC. Qualitative interviews with local CLC staff determined the appropriateness of the health priorities identification process in the CLC. RESULTS: Over 8 months, nine facilitators completed twenty HPI encounters. Development of a Patient Health Priorities note template, staff education and PPC facilitator training improved fidelity and documentation of HPI encounters in the electronic health record. Facilitator interviews suggested that PPC is appropriate in this setting, not burdensome to staff and fostered a person-centered approach to AFHS. CONCLUSIONS: The HPI process is an acceptable and feasible approach to ask the 'what matters' component of AFHS in a CLC setting.

19.
Mov Disord Clin Pract ; 10(6): 980-986, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37332651

RESUMO

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (-1.8 [95% CI -2.3, -1.3] vs. -1.9 [95% CI -2.6, -1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

20.
J Adolesc Health ; 73(3): 428-436, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37318411

RESUMO

PURPOSE: There has been growing interest in reserving punishment as a last resort to address substance use in schools. However, there is significant variability in adoption of alternative approaches. This study reported school personnel's perceptions of diversion programs, identified characteristics of schools/districts that currently have diversion programs, and defined barriers of implementation of diversion programs. METHODS: One hundred fifty six school stakeholders from Massachusetts' K-12 schools, including district administrators, principals and vice principals, school resource officers, guidance counselors, and nurses, completed a web-based survey in May-June 2020. Participants were recruited through e-mail distributed via professional listservs, direct school outreach, and community coalitions. The web survey queried beliefs, attitudes, and actions that schools take regarding substance use infractions as well as perceived barriers to implementing diversion programs. RESULTS: Participants endorsed strong beliefs that punishment was an appropriate school response for student substance use, particularly for nontobacco-related infractions. Despite these personal beliefs, diversion programs were rated as more effective but less commonly used than punitive approaches (37% of respondents reported having diversion programs in their schools/districts vs. 85% used punitive approaches) (p < .03). Punishment was more likely to be used to respond to cannabis, alcohol, and other substances compared to tobacco (p < .02). Primary barriers of implementing diversion programs included funding, staff training, and parental support. DISCUSSION: Based on school personnel perceptions, these findings lend further support for a transition away from punishment and toward more restorative alternatives. However, barriers to sustainability and equity were identified that warrant consideration when implementing diversion programs.


Assuntos
Instituições Acadêmicas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Inquéritos e Questionários , Atitude , Massachusetts
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