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Traditional drug development in Parkinson's disease (PD) faces significant challenges because of its protracted timeline and high costs. In response, innovative master protocols are emerging and designed to address multiple research questions within a single overarching protocol. These trials may offer advantages such as increased efficiency, agility in adding new treatment arms, and potential cost savings. However, they also present organizational, methodological, funding, regulatory, and sponsorship challenges. We review the potential of master protocols, focusing on platform trials, for disease modifying therapies in PD. These trials share a common control group and allow for the termination or addition of treatment arms during a trial with non-predetermined end. Specific issues exist for a platform trial in the PD field considering the heterogeneity of patients in terms of phenotype, genotype and staging, the confounding effects of symptomatic treatments, and the choice of outcome measures with no consensus on a non-clinical biomarker to serve as a surrogate and the slowness of PD progression. We illustrate these aspects using the examples of the main PD platform trials currently in development with each one targeting distinct goals, populations, and outcomes. Overall, platform trials hold promise in expediting the evaluation of potential therapies for PD. However, it remains to be proven whether these theoretical benefits will translate into increased production of high-quality trial data. Success also depends on the willingness of pharmaceutical companies to engage in such trials and whether this approach will ultimately hasten the identification and licensing of effective disease-modifying drugs. © 2024 International Parkinson and Movement Disorder Society.
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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.
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Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/diagnóstico , Índice de Gravidade de Doença , Testes de Estado Mental e Demência , Sociedades MédicasRESUMO
An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson's disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson's disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson's disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson's disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson's disease.
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COVID-19 , Doença de Parkinson , HumanosRESUMO
OBJECTIVE: A diagnosis of Parkinson's often leads to uncertainty about the future and loss of perceived control. Peer support may offer a means to address these concerns and promote self-management. DESIGN: A programme evaluation of the feasibility and potential effects of 'First Steps', utilising a pragmatic step wedge approach. Comparing First Steps (intervention) to (control) conditions.Setting: In the community at four sites in southern England.Participants: Newly diagnosed (≤ 12months) people with Parkinson's.Intervention: First Steps was a 2-day peer-conceived, developed and led intervention to support self-management.Main measures: At 0, 12 and 24 weeks anxiety and depression (Hospital, Anxiety and Depression Scale, HADS), daily functioning (World Health Organisation Disability Assessment Schedule, WHODAS), physical activity, quality of life (EQ5D), carer strain and service utilisation were assessed. RESULTS: Between February 2018 and July 2019, 36 participants were enrolled into intervention and 21 to control conditions, all were included in statistical analysis. Lost to follow up was n = 1 (intervention) and n = 1 adverse event was reported (control, unrelated). Of the 36 allocated to the intervention n = 22 participants completed both days of First Steps during the study period. Completion of outcome measures was >95% at 24 weeks. Small effects favouring the intervention were found for HADS (odds ratio (OR) = 2.06, 95% confidence interval (CI) 0.24:17.84), Carer Strain Index (OR = 2.22, 95% CI 0.5:9.76) and vigorous (d = 0.42, 95% CI -0.12:0.97) and total physical activity (d = 0.41, 95% CI -0.13:0.95). EQ5D, WHOSDAS and service utilisation, was similar between groups. CONCLUSIONS: First Steps was feasible and safe and we found potential to benefit physical activity, mental health and carer strain. Further research with longer-term follow up is warranted.
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Doença de Parkinson , Autogestão , Humanos , Qualidade de Vida , Avaliação de Programas e Projetos de Saúde , Doença de Parkinson/diagnóstico , Modalidades de FisioterapiaRESUMO
BACKGROUND: Parkinson disease can impose substantial distress and costs on patients, their families and caregivers, and health care systems. To address these burdens for families and health care systems, there is a need to better support patient self-management. To achieve this, an overview of the current state of the literature on self-management is needed to identify what is being done, how well it is working, and what might be missing. OBJECTIVE: The aim of this scoping review was to provide an overview of the current body of research on self-management interventions for people with Parkinson disease and identify any knowledge gaps. METHODS: The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) and Population, Intervention, Comparator, Outcome, and Study type frameworks were used to structure the methodology of the review. Due to time and resource constraints, 1 reviewer systematically searched 4 databases (PubMed, Ovid, Scopus, and Web of Science) for the evaluations of self-management interventions for Parkinson disease published in English. The references were screened using the EndNote X9 citation management software, titles and abstracts were manually reviewed, and studies were selected for inclusion based on the eligibility criteria. Data were extracted into a pre-established form and synthesized in a descriptive analysis. RESULTS: There was variation among the studies on study design, sample size, intervention type, and outcomes measured. The randomized controlled trials had the strongest evidence of effectiveness: 5 out of 8 randomized controlled trials found a significant difference between groups favoring the intervention on their primary outcome, and the remaining 3 had significant effects on at least some of the secondary outcomes. The 2 interventions included in the review that targeted mental health outcomes both found significant changes over time, and the 3 algorithms evaluated performed well. The remaining studies examined patient perceptions, acceptability, and cost-effectiveness and found generally positive results. CONCLUSIONS: This scoping review identified a wide variety of interventions designed to support various aspects of self-management for people with Parkinson disease. The studies all generally reported positive results, and although the strength of the evidence varied, it suggests that self-management interventions are promising for improving the care and outcomes of people with Parkinson disease. However, the research tended to focus on the motor aspects of Parkinson disease, with few nonmotor or holistic interventions, and there was a lack of evaluation of cost-effectiveness. This research will be important to providing self-management interventions that meet the varied and diverse needs of people with Parkinson disease and determining which interventions are worth promoting for widespread adoption.
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Doença de Parkinson , Autogestão , Análise Custo-Benefício , Humanos , Doença de Parkinson/terapiaRESUMO
Older people are disproportionately affected by the COVID-19 pandemic, which has had a profound impact on research as well as clinical service delivery. This commentary identifies key challenges and opportunities in continuing to conduct research with and for older people, both during and after the current pandemic. It shares opinions from responders to an international survey, a range of academic authors and opinions from specialist societies. Priorities in COVID-19 research include its specific presentation in older people, consequences for physical, cognitive and psychological health, treatments and vaccines, rehabilitation, supporting care homes more effectively, the impact of social distancing, lockdown policies and system reconfiguration to provide best health and social care for older people. COVID-19 research needs to be inclusive, particularly involving older people living with frailty, cognitive impairment or multimorbidity, and those living in care homes. Non-COVID-19 related research for older people remains of critical importance and must not be neglected in the rush to study the pandemic. Profound changes are required in the way that we design and deliver research for older people in a world where movement and face-to-face contact are restricted, but we also highlight new opportunities such as the ability to collaborate more widely and to design and deliver research efficiently at scale and speed.
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Betacoronavirus , Pesquisa Biomédica/métodos , Infecções por Coronavirus/epidemiologia , Atenção à Saúde/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Idoso , COVID-19 , Humanos , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Exercise is key to a healthy and productive life. For people with Parkinson's, exercise has reported benefits for controlling motor and non-motor symptoms alongside the use of pharmacological intervention. For example, exercise prolongs independent mobility and improves sleep, mood, memory and quality of life, all further enhanced through socialisation and multidisciplinary team support. Recent research suggests that optimally prescribed exercise programmes following diagnosis may alter neurophysiological processes, possibly slowing symptom progression.Given its benefits, professionals should encourage and motivate people with Parkinson's to exercise regularly from the time of diagnosis and provide guidance on what exercise to do. We provide examples of how the growing body of evidence on exercise for people with Parkinson's is revolutionising the services they are provided. We also highlight new resources available to help the wider support network (people such as volunteers, partners and friends of people with Parkinson's) with an interest in exercise promote a consistent message on the benefits of exercise.
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Terapia por Exercício/métodos , Exercício Físico/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/reabilitação , Terapia por Exercício/normas , HumanosRESUMO
Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.
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Doenças Assintomáticas , Mucosa Intestinal/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Humanos , Intestinos/inervação , Intestinos/patologia , Pessoa de Meia-Idade , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Doença de Parkinson/patologia , Sensibilidade e EspecificidadeAssuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismoRESUMO
In the UK, guidance exists to aid clinicians and patients deciding when treatment for Parkinson's disease (PD) should be initiated and which therapies to consider. National Institute for Health and Care Excellence (NICE) guidance recommends that before starting PD treatment clinicians should discuss the following: the patient's individual clinical circumstances; lifestyle; preferences; needs and goals; as well as the potential benefits and harms of the different drug classes. Individualization of medicines and management in PD significantly improves patients' outcomes and quality of life. This article aims to provide simple and practical guidance to help clinicians address common, but often overlooked, co-morbidities. A multi-disciplinary group of PD experts discussed areas where clinical care can be improved by addressing commonly found co-morbidities in people with Parkinson's (PwP) based on clinical experience and existing literature, in a roundtable meeting organized and funded by Bial Pharma UK Ltd. The experts identified four core areas (bone health, cardiovascular risk, anticholinergic burden, and sleep quality) that, if further standardized may improve treatment outcomes for PwP patients. Focusing on anticholinergic burden, cardiac risk, sleep, and bone health could offer a significant contribution to personalizing regimes for PwP and improving overall patient outcomes. Within this opinion-based paper, the experts offer a list of guiding factors to help practitioners in the management of PwP.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Qualidade de Vida , Estilo de Vida , Antagonistas Colinérgicos/uso terapêutico , SonoRESUMO
BACKGROUND: There is significant unmet need for effective and efficiently delivered care for people with Parkinson's disease (PwP). We undertook a service improvement initiative to co-develop and implement a new care pathway, Home Based Care (HBC), based on supported self-management, remote monitoring and the ability to trigger a healthcare contact when needed. OBJECTIVE: To evaluate feasibility, acceptability and safety of Home Based Care. METHODS: We evaluated data from the first 100 patients on HBC for 6 months. Patient monitoring, performed at baseline and 6-monthly, comprised motor (MDS-UPDRS II and accelerometer), non-motor (NMSQ, PDSS-2, HADS) and quality of life (PDQ) measures. Care quality was audited against Parkinson's UK national audit standards. Process measures captured feasibility. Acceptability was assessed using a mixed-methods approach comprising questionnaires and semi-structured interviews. RESULTS: Between October 2019 and January 2021, 108 PwP were enrolled onto HBC, with data from 100 being available at 6 months. Over 90% of all questionnaires were returned, 97% were complete or had <â3 missing items. Reporting and communications occurred within agreed timeframes. Compared with baseline, after 6m on HBC, PD symptoms were stable; more PwP felt listened to (90% vs. 79%) and able to seek help (79% vs. 68%). HBC met 93% of national audit criteria. Key themes from the interviews included autonomy and empowerment. CONCLUSIONS: We have demonstrated acceptability, feasibility and safety of our novel remotely delivered Parkinson's care pathway. Ensuring scalability will widen its reach and realize its benefits for underserved communities, enabling formal comparisons with standard care and cost-effectiveness evaluation.
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Doença de Parkinson , Autogestão , Humanos , Doença de Parkinson/terapia , Procedimentos Clínicos , Qualidade de Vida , Estudos de Viabilidade , Atenção à SaúdeRESUMO
In 2011, the UK medical research charity Cure Parkinson's set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson's disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.
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Ensaios Clínicos como Assunto , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêuticoRESUMO
Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.
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Ensaios Clínicos como Assunto , Doença de Parkinson , Participação do Paciente , Humanos , Doença de Parkinson/terapia , Ensaios Clínicos como Assunto/normas , Projetos de Pesquisa , Participação da Comunidade , Reino Unido , Técnica DelphiRESUMO
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.
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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 maisRESUMO
INTRODUCTION: Parkinson's disease (PD) is the second most common neurological disease globally, for which currently no one definitive cause or cure exists. Estimates suggest that 145 000 people with Parkinson's (PwP) live in the UK. PD presents with motor and non-motor symptoms fluctuating significantly in and between individuals continually throughout the day. PD adversely affects activities of daily living, quality of life and well-being. Self-efficacy is an important belief to improve for PwP as it enables the individual to develop confidence in their ability to exert control over their own motivation, behaviour and social environment. This scoping review aims to identify digital technologies which have been shown to positively impact on promoting self-efficacy in PwP. METHODS AND ANALYSES: Six bibliographic databases MEDLINE, PsycINFO, Web of Science, CINAHL, EMBASE and IEEE Xplore will be searched from the date of their inception to the May 2023. The primary outcome will be to identify interventions which are associated with a change in self-efficacy in PwP to enable positive and negative outcomes, as well as safety to be evaluated. The secondary outcomes of this review will focus on the intervention's proposed mechanisms for success, particularly looking at the impact they had on positive behaviour change(s) or modification(s) on study participants. ETHICS AND DISSEMINATION: This scoping review will not require ethical approval as it will use data collected from previously published primary studies. The findings of this review will be published in peer-reviewed journals and widely disseminated.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Autoeficácia , Atividades Cotidianas , Qualidade de Vida , Tecnologia Digital , Literatura de Revisão como AssuntoRESUMO
BACKGROUND: Parkinson disease (PD) is the second most prevalent neurodegenerative disease, with around 10 million people with PD worldwide. Current assessments of PD symptoms are conducted by questionnaires and clinician assessments and have many limitations, including unreliable reporting of symptoms, little autonomy for patients over their disease management, and standard clinical review intervals regardless of disease status or clinical need. To address these limitations, digital technologies including wearable sensors, smartphone apps, and artificial intelligence (AI) methods have been implemented for this population. Many reviews have explored the use of AI in the diagnosis of PD and management of specific symptoms; however, there is limited research on the application of AI to the monitoring and management of the range of PD symptoms. A comprehensive review of the application of AI methods is necessary to address the gap of high-quality reviews and highlight the developments of the use of AI within PD care. OBJECTIVE: The purpose of this protocol is to guide a systematic review to identify and summarize the current applications of AI applied to the assessment, monitoring, and management of PD symptoms. METHODS: This review protocol was structured using the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) and the Population, Intervention, Comparator, Outcome, and Study (PICOS) frameworks. The following 5 databases will be systematically searched: PubMed, IEEE Xplore, Institute for Scientific Information's Web of Science, Scopus, and the Cochrane Library. Title and abstract screening, full-text review, and data extraction will be conducted by 2 independent reviewers. Data will be extracted into a predetermined form, and any disagreements in screening or extraction will be discussed. Risk of bias will be assessed using the Cochrane Collaboration Risk of Bias 2 tool for randomized trials and the Mixed Methods Appraisal Tool for nonrandomized trials. RESULTS: As of April 2023, this systematic review has not yet been started. It is expected to begin in May 2023, with the aim to complete by September 2023. CONCLUSIONS: The systematic review subsequently conducted as a product of this protocol will provide an overview of the AI methods being used for the assessment, monitoring, and management of PD symptoms. This will identify areas for further research in which AI methods can be applied to the assessment or management of PD symptoms and could support the future implementation of AI-based tools for the effective management of PD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46581.
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As the population ages, neurodegenerative diseases are becoming more prevalent, making it crucial to comprehend the underlying disease mechanisms and identify biomarkers to allow for early diagnosis and effective screening for clinical trials. Thanks to advancements in gene expression profiling, it is now possible to search for disease biomarkers on an unprecedented scale.Here we applied a selection of five machine learning (ML) approaches to identify blood-based biomarkers for Alzheimer's (AD) and Parkinson's disease (PD) with the application of multiple feature selection methods. Based on ROC AUC performance, one optimal random forest (RF) model was discovered for AD with 159 gene markers (ROC-AUC = 0.886), while one optimal RF model was discovered for PD (ROC-AUC = 0.743). Additionally, in comparison to traditional ML approaches, deep learning approaches were applied to evaluate their potential applications in future works. We demonstrated that convolutional neural networks perform consistently well across both the Alzheimer's (ROC AUC = 0.810) and Parkinson's (ROC AUC = 0.715) datasets, suggesting its potential in gene expression biomarker detection with increased tuning of their architecture.
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Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/diagnóstico , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Aprendizado de Máquina , Biomarcadores , Redes Neurais de Computação , Doença de Parkinson/diagnóstico , Doença de Parkinson/genéticaRESUMO
People living with mobility-limiting conditions such as Parkinson's disease can struggle to physically complete intended tasks. Intent-sensing technology can measure and even predict these intended tasks, such that assistive technology could help a user to safely complete them. In prior research, algorithmic systems have been proposed, developed and tested for measuring user intent through a Probabilistic Sensor Network, allowing multiple sensors to be dynamically combined in a modular fashion. A time-segmented deep-learning system has also been presented to predict intent continuously. This study combines these principles, and so proposes, develops and tests a novel algorithm for multi-modal intent sensing, combining measurements from IMU sensors with those from a microphone and interpreting the outputs using time-segmented deep learning. It is tested on a new data set consisting of a mix of non-disabled control volunteers and participants with Parkinson's disease, and used to classify three activities of daily living as quickly and accurately as possible. Results showed intent could be determined with an accuracy of 97.4% within 0.5 s of inception of the idea to act, which subsequently improved monotonically to a maximum of 99.9918% over the course of the activity. This evidence supports the conclusion that intent sensing is viable as a potential input for assistive medical devices.
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BACKGROUND: Design of disease modification (DM) trials for Parkinson's disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities. OBJECTIVE: To seek stakeholder consensus on phase 3 trials' overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ. METHODS: An international expert panel comprising people with Parkinson's (PwP), care partners (CP), clinical scientists, representatives from industry, funders and regulators participated in a survey-based Delphi study. Survey items were informed by a scoping review of DM trials and PwP input. Respondents scored item agreement over 3 rounds. Scores and reasoning were summarized by participant group each round until consensus, defined as≥70% of at least 3 participant groups falling within the same 3-point region of a 9-point Likert scale. RESULTS: 92/121 individuals from 13 countries (46/69 PwP, 13/18 CP, 20/20 clinical scientists, representatives from 8/8 companies, 4/5 funders, and 1/1 regulator) completed the study. Consensus was reached on 14/31 survey items: 5/8 overall goals and structure, 1/8 Eligibility criteria, 7/13 outcome measures, and 1/2 trial delivery items. Extent of stakeholder endorsement for 428 reasons for scores was collated across items. CONCLUSIONS: This is the first systematic multi-stakeholder consultation generating a unique repository of perspectives on pivotal aspects of DM trial design including those of PwP and CP. The panel endorsed outcomes that holistically measure PD and the importance of inclusive trials with hybrid delivery models. Areas of disagreement will inform mitigating strategies of researchers to ensure successful delivery of future trials.