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

The role of illness perceptions in adherence to surveillance in patients with familial adenomatous polyposis (FAP)

Objective The aim of the study was to examine patients' beliefs about having familial adenomatous polyposis (FAP), a hereditary colorectal cancer syndrome, and how these beliefs are associated with adherence to endoscopic surveillance. Methods Adult patients diagnosed with FAP on the national Swedish polyposis register who had undergone prophylactic colorectal surgery (n 209, response rate 76%) completed the Illness Perception Questionnaire (IPQ). Logistic regression analysis was used to investigate the relationships between illness perceptions and adherence, when controlling for demographic and clinical factors. Results FAP was less distressing in men and those with fewer symptoms, reporting less serious consequences and more coherent understanding of FAP. Non-adherence (14%) to surveillance was associated with being older, having undergone surgery less recently and no history of malignancy. Patients' beliefs about their FAP were able to explain unique variance in non-adherence, in particular those who believed FAP was less distressing. Conclusions Patients who were non-adherent to endoscopic surveillance had more positive perceptions about their FAP and, in particular, were less emotionally affected compared to those who adhered. As non-adherence implies a greater risk of future malignancies, special efforts are required to effectively prevent cancer in all patients with FAP. Those who have lived with the condition for a long time, and are not troubled by gastrointestinal symptoms or worried about their FAP, may be in need of specific information and support. Further prospective research is required to examine emotional predictors and consequences of non-adherence

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

The fast transient sky with Gaia

The ESA Gaia satellite scans the whole sky with a temporal sampling ranging from seconds and hours to months. Each time a source passes within the Gaia field of view, it moves over 10 CCDs in 45 s and a lightcurve with 4.5 s sampling (the crossing time per CCD) is registered. Given that the 4.5 s sampling represents a virtually unexplored parameter space in optical time domain astronomy, this data set potentially provides a unique opportunity to open up the fast transient sky. We present a method to start mining the wealth of information in the per CCD Gaia data. We perform extensive data filtering to eliminate known on-board and data processing artefacts, and present a statistical method to identify sources that show transient brightness variations on ~2 hours timescales. We illustrate that by using the Gaia photometric CCD measurements, we can detect transient brightness variations down to an amplitude of 0.3 mag on timescales ranging from 15 seconds to several hours. We search an area of ~23.5 square degrees on the sky, and find four strong candidate fast transients. Two candidates are tentatively classified as flares on M-dwarf stars, while one is probably a flare on a giant star and one potentially a flare on a solar type star. These classifications are based on archival data and the timescales involved. We argue that the method presented here can be added to the existing Gaia Science Alerts infrastructure for the near real-time public dissemination of fast transient events.Comment: 10 pages, 5 figures and 5 tables; MNRAS in pres

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

Ab Initio Modeling of the Herpesvirus VP26 Core Domain Assessed by CryoEM Density

Efforts in structural biology have targeted the systematic determination of all protein structures through experimental determination or modeling. In recent years, 3-D electron cryomicroscopy (cryoEM) has assumed an increasingly important role in determining the structures of these large macromolecular assemblies to intermediate resolutions (6–10 Å). While these structures provide a snapshot of the assembly and its components in well-defined functional states, the resolution limits the ability to build accurate structural models. In contrast, sequence-based modeling techniques are capable of producing relatively robust structural models for isolated proteins or domains. In this work, we developed and applied a hybrid modeling approach, utilizing cryoEM density and ab initio modeling to produce a structural model for the core domain of a herpesvirus structural protein, VP26. Specifically, this method, first tested on simulated data, utilizes the cryoEM density map as a geometrical constraint in identifying the most native-like models from a gallery of models generated by ab initio modeling. The resulting model for the core domain of VP26, based on the 8.5-Å resolution herpes simplex virus type 1 (HSV-1) capsid cryoEM structure and mutational data, exhibited a novel fold. Additionally, the core domain of VP26 appeared to have a complementary interface to the known upper-domain structure of VP5, its cognate binding partner. While this new model provides for a better understanding of the assembly and interactions of VP26 in HSV-1, the approach itself may have broader applications in modeling the components of large macromolecular assemblies

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