Prioritising target non-pharmacological interventions for research in Parkinson’s Disease: Achieving consensus from key stakeholders

Background: In 2014 Parkinson’s UK conducted a research prioritisation exercise with stakeholders highlighting important clinical research questions. The exercise highlighted the need for effective interventions to be developed and tested to tackle a range of non-motor symptoms including: sleep quality, stress and anxiety, mild cognitive impairment, dementia and urinary problems. The present work set out to build on this exercise by prioritising types of non-pharmacological interventions to be tested to treat the identified non-motor symptoms. Methods: A Patient and Public Involvement Exercise was used to reach consensus on intervention priorities for the treatment on non-motor symptoms. Some Delphi techniques were also used to support the feedback collected. A first-round prioritisation survey was conducted followed by a panel discussion. Nineteen panellists completed the first-round survey (9 people with Parkinson’s and 10 professionals working in Parkinson’s) and 16 participated in the panel discussion (8 people with Parkinson’s and 8 professionals working in Parkinson’s). A second-round prioritization survey was conducted after the panel discussion with 13 people with Parkinson’s. Results: Physical activity, third wave cognitive therapies and cognitive training were rated as priority interventions for the treatment of a range of non-motor symptoms. There was broad agreement on intervention priorities between health care professionals and people with Parkinson’s. A consensus was reached that research should focus on therapies which could be used to treat several different non-motor symptoms. In the context of increasing digitisation, the need for human interaction as an intervention component was highlighted.3 Conclusion: Bringing together Parkinson’s professionals and people with Parkinson’sresulted in a final treatment priority list which should be both feasible to carry out in routine clinical practice and acceptable to both professionals and people with Parkinson’s. The workshop further specified research priorities in Parkinson’s disease based on the current evidence base, stakeholder preferences, and feasibility. Research should focus on developing and testing non-pharmacological treatments which could be effective across a range of symptoms but specifically focusing on tailored physical activity interventions, cognitive therapies and cognitive training

Barriers to reporting non-motor symptoms to health-care providers in people with Parkinson's

Background: Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. Methods: 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. Results: A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). Conclusion: A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being

Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, α-crystallin

AbstractNon-enzymic glycosylation (glycation) of structural proteins has been widely studied as a possible mechanism in the long-term complications of diabetes. Here we show that glycation inactivates malate dehydrogenase. Aspirin affords some protection against the glycation, but α-crystallin, a lens protein which appears to act as a molecular chaperone in other systems, is much more effective. For example, 5 mM glucose completely inactivates malate dehydrogenase in four days, and 5 μg α-crystallin/ml provides complete protection against this inactivation. Fructose, a superior glycating agent, inactivates the enzyme in 24 hours but even so the same low concentration of α-crystallin is able to protect 80% of the activity. Other proteins provide no protection at the same concentration. The inactivation of malate dehydrogenase and other enzymes by glycation could play a role in diabetic complications, and molecular chaperones like α-crystallin could serve to protect them

Guided Poster Tour

Objective 1) To identify patient barriers to help-seeking for non-motor symptoms (NMS) from their Parkinson’s healthcare provider, 2) To determine whether barriers are symptom specific (e.g. embarrassment disclosing sexual problems) or patient specific (e.g. misattribution of a range of NMS to old age). Background NMS are common in Parkinson’s disease (PD) and cause significant distress and decreased quality of life. A high rate of non-declaration of NMS by patients to healthcare providers means that many NMS remain unrecognized and untreated, even in specialist clinical services. Current understanding of the factors preventing disclosure of NMS to healthcare professions is limited. Method 358 PD patients completed the Non-motor Symptom Questionnaire and a barriers to help-seeking for NMS questionnaire developed from previous qualitative work. A Generalised Estimating Equation was used to determine whether barriers were symptom or individual specific. Results The sample had a mean age of 66.3 years, mean disease duration of 5.9 years and were 52.5% male. Urinary urgency was the most common NMS (65%) and sexual dysfunction was the symptom most frequently not disclosed (52%). Barriers to symptom disclosure varied dependent on symptom type. Pain and sleep problems were commonly not thought to be symptoms of PD. Bowel and bladder symptoms were often simply accepted as part of daily life and participants were unsure about the availability of effective treatments. Patients experienced embarrassment discussing sexual dysfunction. Conclusion Our results highlight the barriers which prevent PD patients reporting NMS to their Parkinson’s clinical team and the diversity of these barriers between different NMS. Strategies to improve rates of reporting must target individual NMS. For example, effective interventions might provide information regarding treatment efficacy for bowel and bladder symptoms or develop communication skills and normalising information for sexual dysfunction. The study provides the information needed to develop such individualised interventions. Increasing rates of disclosure of NMS by patients to their Parkinson’s healthcare providers will ensure patients receive appropriate clinical care which may increase quality of life and well-being

Examining Chemotherapy-Related Cognitive Changes in Colorectal Cancer Patients: A Feasibility Trial

Introduction: Research suggests that chemotherapy may be related to decline in patients’ cognitive functions. Objectives: To assess the feasibility and acceptability of a multi-site study designed to examine the nature and extent of chemotherapy-related cognitive changes in colorectal cancer patients. Method: Data was collected over 8 months using objective and self-reported measures of cognitive functioning and self-reported quality of life, fatigue and mood questionnaires. The assessment battery was administered pre- and mid-chemotherapy treatment to a consecutive sample of colorectal cancer patients across three Londonbased NHS Trusts. Participants included patients who had undergone colorectal surgery and were scheduled to have adjuvant chemotherapy treatment, or no further cancer treatment. Main outcome measures: Recruitment procedures, rate of recruitment, suitability of exclusion/inclusion criteria, acceptability of data collection procedures and the battery, and attrition rates. Results: From 1 April 2014 to 1 December 2014, 42 eligible participants were invited to take part in the trial. Of the 17 that completed pre-chemotherapy assessments, only 1 withdrew at follow-up due to reasons of ill health from disease recurrence. All participants completed the entire battery and indicated that they found the trial acceptable. Conclusions: What went wrong: Strained researcher resources; loss of eligible participants to competing studies, restrictive upper age limit. Possible solutions: Removal of upper age limit, an increased dedicated research team to increase rate of recruitment. The large multi-site study is feasible with suggested amendments and is acceptable to patients and medical teams. Acceptability of trial to medical teams is further evidenced by requests of collaboration from two additional London based NHS Trusts. Lessons learned: This feasibility trial provides evidence to other researchers designing similar studies in this area of an acceptable design and the need for appropriate funding for resources to recruit large enough consecutive samples of patients with solid tumour cancers

What influences withdrawal because of rejection of telehealth - the whole systems demonstrator evaluation

Purpose: The widespread deployment of telehealth (TH) has been conducted in the absence of any clear understanding of how acceptable these devices are to patients. One potential limitation of the widespread deployment of TH is that patients may refuse. Moreover an understanding of the reasons for refusing to use TH devices will provide an understanding of the barriers. Design/methodology/approach: This investigation from the Whole Systems Demonstrator (WSD) programme, a pragmatic cluster randomised controlled trial into the effectiveness of TH, examined reasons for patients in the intervention cohort of the trial refusing TH, and the potential barriers to its deployment. Findings: Active rejection of the TH intervention was the most frequent reason for withdrawal. After examination of trial-related, health, socio-demographic, cognitive, emotional and behavioural factors, patients diagnosed with diabetes, as opposed to heart failure or chronic obstructive pulmonary disease, and patients' beliefs about the acceptability of the intervention predicted whether or not they withdrew from the trial because of the intervention. Originality/value: Beliefs that the TH intervention resulted in increased accessibility to care, satisfaction with equipment and fewer concerns about the privacy, safety and discomfort associated with using TH equipment predicted continued participation in the WSD trial. Findings suggest that potentially modifiable beliefs about TH predict those more likely to reject the intervention. These findings have important implications for understanding individual differences in the acceptance of TH and subsequent success in mainstreaming TH in healthcare services. © Emerald Group Publishing Limited

Cost-effectiveness of telehealth in people with social care needs: the Whole Systems Demonstrator cluster randomised trial

Introduction: The Whole Systems Demonstrator pilots introduced telehealth and telecare into three local authority areas using an integrated approach to deliver health and social care to those with high care needs and long-term conditions. Proponents of these technologies have given cost savings as one rationale for advocating their introduction and widespread implementation; proponents have also advocated their potential to improve the quality of life for their users. Until recently, evaluations of telehealth and telecare in high-income countries have been based on relatively small-scale pilots; few such evaluations have been designed as randomised controlled trials. The WSD study was a pragmatic cluster-randomised control trial, representing the largest-scale trial of telehealth and telecare to be carried out in the UK. This presentation focuses on the results of the WSD telecare questionnaire study. Objectives: To examine the costs and cost-effectiveness of telecare compared to standard support and treatment. Methods: Economic evaluation conducted in parallel with a pragmatic cluster-randomised controlled trial of Telecare. 2600 people with social care needs participated in a trial of a community-based telecare intervention in three English local authority areas. Approximately half of the participants in the telecare trial also consented to participate in the WSD telecare questionnaire study, which collected information on a number of patient-reported outcome measures and also on the self-reported use of a range of health and social services. Health and social costs were calculated by attaching nationally applicable unit costs to self-reported service use data. The unit costs of telecare support and treatment provided were calculated drawing on administrative and financial data sources and interviews with key informants. The primary outcome for the cost-effectiveness analysis was the quality-adjusted life year (QALY). Secondary outcomes included measures of health-related quality of life and well-being. We employed multivariate analyses to explore the cost-effectiveness of the intervention Results: The presentation will describe the results of the economic evaluation of telecare, addressing the cost of care and treatment packages used by those participating in the telecare questionnaire study and the results of the cost-effectiveness analysis. These results will be available by the time of the presentation. Conclusions: These will be available by the time of the presentation

RVS Spectra of Gaia Photometric Science Alerts

Gaia Photometric Science Alerts (GPSA) publishes Gaia G magnitudes and Blue Photometer (BP) and Red Photometer (RP) low-resolution epoch spectra of transient events. 27 high-resolution spectra from Gaia's Radial Velocity Spectrometer (RVS) of 12 GPSAs have also been published. These 27 RVS epoch spectra are presented next to their corresponding BP and RP epoch spectra in a single place for the first time. We also present one new RVS spectrum of a 13th GPSA that could not be published by the GPSA system. Of the 13 GPSA with RVS spectra, five are photometrically classified as unknown, five as supernovae (three as SN Ia, one as SN II, one as SN IIP), one as a cataclysmic variable, one as a binary microlensing event and one as a young stellar object. The five GPSAs classified as unknown are potential scientific opportunities, while all of them are a preview of the epoch RVS spectra that will be published in Gaia's fourth data release

Coproducing Knowledge of the Implementation of Complex Digital Health Interventions for Adults with Acquired Brain Injury and their Communication Partners: Protocol for a Mixed Methods Study.

BACKGROUND: The Social Brain Toolkit, conceived and developed in partnership with stakeholders, is a novel suite of web-based communication interventions for people with brain injury and their communication partners. To support effective implementation, the developers of the Social Brain Toolkit have collaborated with people with brain injury, communication partners, clinicians, and individuals with digital health implementation experience to coproduce new implementation knowledge. In recognition of the equal value of experiential and academic knowledge, both types of knowledge are included in this study protocol, with input from stakeholder coauthors. OBJECTIVE: This study aims to collaborate with stakeholders to prioritize theoretically based implementation targets for the Social Brain Toolkit, understand the nature of these priorities, and develop targeted implementation strategies to address these priorities, in order to support the Social Brain Toolkit's implementation. METHODS: Theoretically underpinned by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework of digital health implementation, a maximum variation sample (N=35) of stakeholders coproduced knowledge of the implementation of the Social Brain Toolkit. People with brain injury (n=10), communication partners (n=11), and clinicians (n=5) participated in an initial web-based prioritization survey based on the NASSS framework. Survey completion was facilitated by plain English explanations and accessible captioned videos developed through 3 rounds of piloting. A speech-language pathologist also assisted stakeholders with brain injury to participate in the survey via video teleconference. Participants subsequently elaborated on their identified priorities via 7 web-based focus groups, in which researchers and stakeholders exchanged stakeholder perspectives and research evidence from a concurrent systematic review. Stakeholders were supported to engage in focus groups through the use of visual supports and plain English explanations. Additionally, individuals with experience in digital health implementation (n=9) responded to the prioritization survey questions via individual interview. The results will be deductively analyzed in relation to the NASSS framework in a coauthorship process with people with brain injury, communication partners, and clinicians. RESULTS: Ethical approval was received from the University of Technology Sydney Health and Medical Research Ethics Committee (ETH20-5466) on December 15, 2020. Data were collected from April 13 to November 18, 2021. Data analysis is currently underway, with results expected for publication in mid-2022. CONCLUSIONS: In this study, researchers supported individuals with living experience of acquired brain injury, of communicating with or clinically supporting someone post injury, and of digital health implementation, to directly access and leverage the latest implementation research evidence and theory. With this support, stakeholders were able to prioritize implementation research targets, develop targeted implementation solutions, and coauthor and publish new implementation findings. The results will be used to optimize the implementation of 3 real-world, evidence-based interventions and thus improve the outcomes of people with brain injury and their communication partners. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35080

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process