A Survey of People With Parkinson's and Their Carers: The Management of Pain in Parkinson's.

BACKGROUND: Pain in Parkinson's is problematic but under treated in clinical practice. Healthcare professionals must understand the impact of pain in Parkinson's and patient preferences for management. OBJECTIVE: To understand the impact of pain in Parkinson's and to understand current management and preferences for pain management. METHODS: We conducted a national survey with 115 people with Parkinson's (PwP) and 10 carers. Both closed and open questions were used. The questions focused on how pain affected the individual, healthcare professional involvement in supporting pain management, current pain management strategies and views on future pain management interventions. We used descriptive statistics to summarize closed responses and thematic analysis to summarize open question responses. RESULTS: 70% of participants reported pain impacted their daily life. Pain had a multifactorial impact on participants, affecting movement, mood and quality of life. Improved pain management was viewed to have the potential to address each of these challenges. Pain affected a number of different sites, with low back pain and multiple sites being most frequently reported. Exercise was the most frequently noted strategy (38%) recommended by healthcare professionals for pain management. PwP would value involvement from healthcare professionals for future pain management, but also would like to self-manage the condition. Medication was not suggested as a first line strategy. CONCLUSIONS: Despite reporting engagement in some strategies to manage pain, pain still has a wide-ranging impact on the daily life of PwP. Results from this survey highlight the need to better support PwP to manage the impact of pain.

The effect of visually manipulating back size and morphology on back perception, body ownership, and attitudes towards self-capacity during a lifting task.

Body re-sizing illusions can profoundly alter perception of our own body. We investigated whether creating the illusion of a muscled and fit-looking back (Strong) influenced perceived back size, body ownership, and attitudes towards self-capacity during a lifting task. Twenty-four healthy male volunteers performed a standardised lifting task while viewing real-time (delay < 20 ms) video of their own back through a head-mounted display under four different conditions (Normal size, Strong, Reshaped, Large; order randomised). The MIRAGE-mediated reality system was used to modify the shape, size, and morphology of the back. Participants were poor at recognizing the correct appearance of their back, for both implicit (perceived width of shoulders and hips) and explicit (questionnaire) measures of back size. Visual distortions of body shape (Reshaped condition) altered implicit back size measures. However, viewing a muscled back (Strong condition) did not result in a sense of agency or ownership and did not update implicit perception of the back. No conditions improved perceptions/attitudes of self-capacity (perceived back strength, perceived lifting confidence, and perceived back fitness). The results lend support for the importance of the embodiment of bodily changes to induce changes in perception. Further work is warranted to determine whether increased exposure to illusory changes would alter perceptions and attitudes towards self-capacity or whether different mechanisms are involved.

Evidence that subclinical somatoform dissociation is not characterised by heightened awareness of proprioceptive signals.

INTRODUCTION: It has been suggested that abnormal perceptual processing and somatosensory amplification may be contributory factors to somatoform symptom reporting. A key source of somatosensory information is proprioception, yet the perception and integration of this sense has not been sufficiently investigated in those prone to somatoform disorders. METHODS: Subclinical groups of high- and low-scorers on the Somatoform Dissociation Questionnaire made judgements about the location of their unseen hand following congruent or incongruent visuo-proprioceptive feedback, which was manipulated using a MIRAGE-mediated reality system. RESULTS: No differences were found between groups, with both groups displaying normal proprioceptive accuracy under congruent conditions and equivalent visuo-proprioceptive integration under incongruent conditions. CONCLUSIONS: The results suggest that amplification of, or abnormal weighting for, proprioceptive signals is not a contributing factor to somatoform symptom reporting.

Coproduction and Usability of a Smartphone App for Falls Reporting in Parkinson Disease.

OBJECTIVE: The purpose of this study was to coproduce a smart-phone application for digital falls reporting in people with Parkinson disease (PD) and to determine usability using an explanatory mixed-methods approach. METHODS: This study was undertaken in 3 phases. Phase 1 was the development phase, in which people with PD were recruited as co-researchers to the project. The researchers, alongside a project advisory group, coproduced the app over 6 months. Phase 2 was the implementation phase, in which 15 people with PD were invited to test the usability of the app. Phase 3 was the evaluation phase, in which usability was assessed using the systems usability scale by 2 focus groups with 10 people with PD from phase 2. RESULTS: A prototype was successfully developed by researchers and the project advisory group. The usability of the app was determined as good (75.8%) by people with PD when rating using the systems usability scale. Two focus groups (n = 5 per group) identified themes of 1) usability, 2) enhancing and understanding management of falls, and 3) recommendations and future developments. CONCLUSIONS: A successful prototype of the iFall app was developed and deemed easy to use by people with PD. The iFall app has potential use as a self-management tool for people with PD alongside integration into clinical care and research studies. IMPACT: This is the first digital outcome tool to offer reporting of falls and near-miss fall events. The app may benefit people with PD by supporting self-management, aiding clinical decisions in practice, and providing an accurate and reliable outcome measure for future research. LAY SUMMARY: A smartphone application designed in collaboration with people who have PD to record their falls was acceptable and easy to use by people with PD.

Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.

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.

Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

The value of co-creating a clinical outcome assessment strategy for clinical trial research: process and lessons learnt.

BACKGROUND: In support of UCB pharmaceutical research programs, the aim of this research was to implement a novel process for patient involvement in a multidisciplinary research group to co-create a clinical outcome assessment strategy to accurately reflect the experience of people living with early-stage Parkinson's. Patient experts were an integral part of the decision-making process for patient-reported outcome (PRO) research and instrument development. METHODS: In partnership with two patient organizations (Parkinson's UK and the Parkinson's Foundation), 6 patient experts were recruited into a multidisciplinary research group alongside clinical, patient engagement and involvement, regulatory science, and outcome measurement experts. The group was involved across two phases of research; the first phase identified what symptoms are cardinal to the experience of living with early-stage Parkinson's and the second phase involved the development of PRO instruments to better assess the symptoms that are important to people living with early-stage Parkinson's. Patient experts were important in performing a variety of roles, in particular, qualitative study protocol design, conceptual model development, and subsequent co-creation of two PRO instruments. RESULTS: Involving people with Parkinson's in PRO research ensured that the expertise of these representatives from the Parkinson's community shaped and drove the research; as such, PRO instruments were being developed with the patient at the forefront. Working with patient experts required considerable resource and time allocation for planning, communication, document development, and organizing meetings; however, their input enriched the development of PRO instruments and was vital in developing PRO instruments that are more meaningful for people with Parkinson's and clinicians. CONCLUSIONS: Conducting PRO research, in the context of clinical development involving pharmaceutical companies, requires balancing regulatory and scientific rigor with tight time constraints. Incorporating a multi-stakeholder perspective, which included patient experts as joint investigators, had a strong positive impact on our research, despite the logistical complexities of their involvement. Due to the input of patient experts, the innovative clinical outcome assessment strategy and the co-created novel PRO instruments were more relevant and holistic to the patient experience of early-stage Parkinson's.

Patient-reported outcome (PRO) instruments allow people living with a disease and participating in a clinical study to describe the symptoms and experiences that they consider meaningful. PRO instruments use tools such as questionnaires and scales to capture patient perspectives on a treatment that might not be captured by a clinical measurement. It is recommended that the patient community and patient experts are included in the development of PRO instruments to accurately capture information that is important to them. Building on the experience of a recent PRO research project in support of UCB pharmaceutical programs, this article provides recommendations on how pharmaceutical companies can partner with patient organizations and involve patient experts as joint investigators in the co creation of PRO instruments. Despite the additional resource and time required, involving patient experts and patient organizations into the research collaboration had a strong positive impact and ensured that the PROs were meaningful to patients (in this instance, people living with early-stage Parkinson's). Patient organizations facilitated patient engagement and recruitment in research activities, maintained communication with the pharmaceutical company's research team, and built trust between collaborators by implementing patient engagement tools and best practices. Patient experts contributed to several parts of the PRO instrument development process: study design, identifying key symptoms and experiences, and developing individual PRO questions. Co-creation between the pharmaceutical company, patient experts, and patient organizations resulted in considerable improvements to typical PRO instrument development for use in clinical trials and is thus recommended.

Development and early qualitative evidence of two novel patient-reported outcome instruments to assess daily functioning in people with early-stage Parkinson's.

BACKGROUND: Previous research on concepts that are important to people living with early-stage Parkinson's indicated that 'functional' slowness, fine motor skills, and subtle gait abnormalities are cardinal concepts that are not comprehensively captured by existing patient-reported outcome (PRO) instruments that are used in clinical practice and research to assess symptoms and daily functioning within this patient population. We sought to develop novel PRO instruments to address this unmet need. METHODS: PRO instrument development was led by a multidisciplinary research group, including people living with Parkinson's (termed 'patient experts'), as well as patient engagement and involvement, regulatory science, clinical, and outcome measurement experts. A first set of PRO instruments, termed Early Parkinson's Function Slowness (42 items) and Early Parkinson's Mobility (26 items), were drafted to capture 'functional' slowness, fine motor skills, and subtle gait abnormalities. These PRO instruments were used in cognitive debriefing interviews with people living with early-stage Parkinson's (who were not involved with the multidisciplinary research group) to identify issues with relevance, clarity, ease of completion, conceptual overlap, or missing concepts. RESULTS: Sixty people living with early-stage Parkinson's were interviewed, which led to refining the items to 45 for the Early Parkinson's Functional Slowness and 23 for the Early Parkinson's Mobility PRO instruments. Refinement included rewording items to address clarity issues, merging or splitting items to address overlap issues, and adding new items to address missing concepts. The Early Parkinson's Function Slowness PRO instrument resulted in a multidimensional instrument covering upper limb, complex/whole body, general activity, and cognitive functional slowness. The Early Parkinson's Mobility PRO instrument resulted in comprehensive coverage of everyday mobility tasks, with a focus on gait concepts, plus complex/whole body, balance, and lower limb mobility. CONCLUSIONS: The Early Parkinson's Function Slowness and Early Parkinson's Mobility PRO instruments aim to address gaps in existing PRO instruments to measure meaningful symptoms and daily functioning in people living with early-stage Parkinson's. Utilizing a meticulous study design led by a multidisciplinary research group that included patient experts helped to ensure that the PRO instruments were patient-centric, content valid, and meaningful from a clinical and measurement perspective.

Patient Experience in Early-Stage Parkinson's Disease: Using a Mixed Methods Analysis to Identify Which Concepts Are Cardinal for Clinical Trial Outcome Assessment.

INTRODUCTION: Qualitative research on patient experiences in early-stage Parkinson's disease (PD) is limited. It is increasingly acknowledged that clinical outcome assessments used in trials do not fully capture the range of symptoms/impacts that are meaningful to people with early-stage PD. We aimed to conceptualize the patient experience in early-stage PD and identify, from the patient perspective, those cardinal symptoms/impacts which might be more useful to measure in clinical trials. METHODS: In a mixed-methods analysis, 50 people with early-stage PD and nine relatives were interviewed. Study design and results interpretation were led by a multidisciplinary group of patient, clinical, regulatory, and outcome measurements experts, and patient organization representatives. Identification of the cardinal concepts was informed by the relative frequency of reported concepts combined with insights from patient experts and movement disorder specialists. RESULTS: A conceptual model of the patient experience of early-stage PD was developed. Concept elicitation generated 145 unique concepts mapped across motor and non-motor symptoms, function, and impacts. Bradykinesia/slowness (notably in the form of "functional slowness"), tremor, rigidity/stiffness, mobility (particularly fine motor dexterity and subtle gait abnormalities), fatigue, depression, sleep/dreams, and pain were identified as cardinal in early-stage PD. "Functional slowness" (related to discrete tasks involving the upper limbs, complex mobility tasks, and general activities) was deemed to be more relevant than "difficulty" to patients with early-stage PD, who report being slower at completing tasks rather than encountering significant impairment with task completion. CONCLUSION: Patient experiences in early-stage PD are complex and wide-ranging, and the currently available patient-reported outcome (PRO) instruments do not evaluate many early-stage PD concepts such as functional slowness, fine motor skills, and subtle gait abnormalities. The development of a new PRO instrument, created in conjunction with people with PD, that fully assesses symptoms and the experience of living with early-stage PD, is required.

We conducted research to find out about the experiences and symptoms that have the greatest impact on everyday living for people with early-stage Parkinson's disease. This research also looked at which symptoms patients think are important to be tracked in clinical trials. The research team running this study included people living with Parkinson's disease (called "patient experts"). The team also included technical experts and representatives of patient organizations. To begin with, people living with early-stage Parkinson's disease and relatives were interviewed. The interviews collected their thoughts on the impact of early-stage Parkinson's disease on their daily lives. These insights revealed which experiences and symptoms were most important. The research team analyzed ideas and quotes from the interviews to create a picture of early-stage Parkinson's disease. The symptoms that mattered the most to people living with early-stage Parkinson's disease were tremor, rigidity/stiffness, fatigue, depression, sleep/dreams, and pain. Another important symptom was slowness of movement (which is called "bradykinesia/slowness"), and in particular "functional slowness," which included tasks involving the upper limbs, complicated movement tasks, and general activities. Effects on mobility were also important, particularly fine motor skills and subtle walking abnormalities. This research shows the wide-ranging effects that early-stage Parkinson's disease has on patients from their perspective. It also shows which effects are important to capture in trials of therapies aimed at this patient group.

The Relative Contributions of Visual and Proprioceptive Inputs on Hand Localization in Early Childhood.

Forming an accurate representation of the body relies on the integration of information from multiple sensory inputs. Both vision and proprioception are important for body localization. Whilst adults have been shown to integrate these sources in an optimal fashion, few studies have investigated how children integrate visual and proprioceptive information when localizing the body. The current study used a mediated reality device called MIRAGE to explore how the brain weighs visual and proprioceptive information in a hand localization task across early childhood. Sixty-four children aged 4-11 years estimated the position of their index finger after viewing congruent or incongruent visuo-proprioceptive information regarding hand position. A developmental trajectory analysis was carried out to explore the effect of age on condition. An age effect was only found in the incongruent condition which resulted in greater mislocalization of the hand toward the visual representation as age increased. Estimates by younger children were closer to the true location of the hand compared to those by older children indicating less weighting of visual information. Regression analyses showed localizations errors in the incongruent seen condition could not be explained by proprioceptive accuracy or by general attention or social differences. This suggests that the way in which visual and proprioceptive information are integrated optimizes throughout development, with the bias toward visual information increasing with age.

A Preliminary Investigation of the Views of People With Parkinson's (With and Without Psychosis) and Caregivers on Participating in Clinical Trials During the Covid-19 Pandemic: An Online Survey.

Background: The coronavirus pandemic is having a profound impact on non-COVID-19 related research, including the delivery of clinical trials for patients with Parkinson's disease. Objectives: A preliminary investigation to explore the views of Parkinson's disease (PD) patients, with and without experience of psychosis symptoms, and carers on the resumption of clinical research and adaptations to trials in light of COVID-19. Methods: An anonymous self-administered online survey was completed by 30 PD patients and six family members/carers via the Parkinson's UK Research Support Network to explore current perceptions on taking part in PD research and how a planned clinical trial for psychosis in PD may be adapted so participants feel safe. Results: Ninety-one percent of respondents were enthusiastic about the continuation of non-COVID-19 related research as long as certain safety measures were in place. Ninety-four percent stated that they would be happy to complete assessments virtually. However, they noted that care should be taken to ensure that this does not exclude participants, particularly those with more advanced PD who may require assistance using portable electronic devices. Regular and supportive communication from the research team was also seen as important for maintaining the psychological well-being of participants while taking part in the trial. Conclusions: In the era of COVID-19 pandemic, standard approaches will have to be modified and rapid adoption of virtual assessments will be critical for the continuation of clinical research. It is important that alongside the traditional methods, new tools are developed, and older ones validated for virtual assessments, to allow safe and comprehensive assessments vital for ongoing research in people with Parkinson's.

Embodying the illusion of a strong, fit back in people with chronic low back pain. A pilot proof-of-concept study.

OBJECTIVE: This proof-of-concept pilot study aimed to investigate if a visual illusion that altered the size and muscularity of the back could be embodied and alter perception of the back. METHODS: The back visual illusions were created using the MIRAGE multisensory illusion system. Participants watched real-time footage of a modified version of their own back from behind. Participants undertook one experimental condition, in which the image portrayed a muscled, fit-looking back (Strong), and two control conditions (Reshaped and Normal) during a lifting task. Embodiment, back perception as well as pain intensity and beliefs about the back during lifting were assessed. RESULTS: Two participants with low back pain were recruited for this study: one with altered body perception and negative back beliefs (Participant A) and one with normal perception and beliefs (Participant B). Participant A embodied the Strong condition and pain and fear were less and both perceived strength and confidence were more than for the Normal or the Reshaped condition. Participant B did not embody the Strong condition and reported similar levels of pain, fear strength and confidence across all three conditions. DISCUSSION: An illusion that makes the back look strong successfully induced embodiment of a visually modified back during a lifting task in a low back pain patient with altered body perception. Both participants tolerated the illusion, there were no adverse effects, and we gained preliminary evidence that the approach may have therapeutic potential.

The Effect of Visual, Spatial and Temporal Manipulations on Embodiment and Action.

The feeling of owning and controlling the body relies on the integration and interpretation of sensory input from multiple sources with respect to existing representations of the bodily self. Illusion paradigms involving multisensory manipulations have demonstrated that while the senses of ownership and agency are strongly related, these two components of bodily experience may be dissociable and differentially affected by alterations to sensory input. Importantly, however, much of the current literature has focused on the application of sensory manipulations to external objects or virtual representations of the self that are visually incongruent with the viewer's own body and which are not part of the existing body representation. The current experiment used MIRAGE-mediated reality to investigate how manipulating the visual, spatial and temporal properties of the participant's own hand (as opposed to a fake/virtual limb) affected embodiment and action. Participants viewed two representations of their right hand inside a MIRAGE multisensory illusions box with opposing visual (normal or grossly distorted), temporal (synchronous or asynchronous) and spatial (precise real location or false location) manipulations applied to each hand. Subjective experiences of ownership and agency towards each hand were measured alongside an objective measure of perceived hand location using a pointing task. The subjective sense of agency was always anchored to the synchronous hand, regardless of physical appearance and location. Subjective ownership also moved with the synchronous hand, except when both the location and appearance of the synchronous limb were incongruent with that of the real limb. Objective pointing measures displayed a similar pattern, however movement synchrony was not sufficient to drive a complete shift in perceived hand location, indicating a greater reliance on the spatial location of the real hand. The results suggest that while the congruence of self-generated movement is a sufficient driver for the sense of agency, the sense of ownership is additionally sensitive to cues about the visual appearance and spatial location of one's own body.

Developmental Changes in Sensitivity to Spatial and Temporal Properties of Sensory Integration Underlying Body Representation.

The closer in time and space that two or more stimuli are presented, the more likely it is that they will be integrated together. A recent study by Hillock-Dunn and Wallace (2012) reported that the size of the visuo-auditory temporal binding window - the interval within which visual and auditory inputs are highly likely to be integrated - narrows over childhood. However, few studies have investigated how sensitivity to temporal and spatial properties of multisensory integration underlying body representation develops in children. This is not only important for sensory processes but has also been argued to underpin social processes such as empathy and imitation (Schütz-Bosbach et al., 2006). We tested 4 to 11 year-olds' ability to detect a spatial discrepancy between visual and proprioceptive inputs (Experiment One) and a temporal discrepancy between visual and tactile inputs (Experiment Two) for hand representation. The likelihood that children integrated spatially separated visuo-proprioceptive information, and temporally asynchronous visuo-tactile information, decreased significantly with age. This suggests that spatial and temporal rules governing the occurrence of multisensory integration underlying body representation are refined with age in typical development.

Give It a Tug and Feel It Grow: Extending Body Perception Through the Universal Nature of Illusory Finger Stretching.

If British teenage boy asks you to pull his finger, it is usually an indication that he simultaneously wishes to break wind. If you were to tell him that you could pull his finger and stretch it to twice its length, you might expect a similarly irreverent response yet when we pulled the fingers of nearly 600 children and adolescents, 93% reported the illusion of stretching. Grossly distorted body representations need not be the preserve of clinical disorders and can reliably be induced in healthy participants across all ages.