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

Nuclear Bar Catalyzed Star Formation: 13^CO, C18^O and Molecular Gas Properties in the Nucleus of Maffei 2

(Abridged) We present resolution maps of CO, its isotopologues, and HCN from in the center of Maffei 2. The J=1-0 rotational lines of 12^CO, 13^CO, C18^O and HCN, and the J=2-1 lines of 13^CO and C18^O were observed with the OVRO and BIMA arrays. The 2-1/1-0 line ratios of the isotopologues constrain the bulk of the molecular gas to originate in low excitation, subthermal gas. From LVG modeling, we infer that the central GMCs have n(H_2) ~10^2.75 cm^-3 and T_k ~ 30 K. Continuum emission at 3.4 mm, 2.7 mm and 1.4 mm was mapped to determine the distribution and amount of HII regions and dust. Column densities derived from C18^O and 1.4 mm dust continuum fluxes indicate the CO conversion factor in the center of Maffei 2 is lower than Galactic by factors of ~2-4. Gas morphology and the clear ``parallelogram'' in the Position-Velocity diagram shows that molecular gas orbits within the potential of a nuclear (~220 pc) bar. The nuclear bar is distinct from the bar that governs the large scale morphology of Maffei 2. Giant molecular clouds in the nucleus are nonspherical and have large linewidths. Dense gas and star formation are concentrated at the sites of the x_1-x_2 orbit intersections of the nuclear bar, suggesting that the starburst is dynamically triggered.Comment: 50 pages, 14 figures, accepted for publication in Ap

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

Vaccination timing of low-birth-weight infants in rural Ghana: a population-based, prospective cohort study

Objective: To investigate delays in first and third dose diphtheria–tetanus–pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. Methods: We used data from a large, population-based vitamin A trial in 2010–2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0–2.4 kg; 1.5–1.9 kg; and <1.5 kg) with infants weighing ≥2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). Findings: Compared with non-low-birth-weight infants (n=18 979), those with low birth weight (n=3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43–0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50–0.80). Infants weighing 1.5–1.9 kg (n=386) had vaccination rates approximately 25% lower than infants weighing ≥2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. Conclusion: Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays

Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings

BACKGROUND: Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes. MAIN BODY: Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time. CONCLUSION: High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies

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

Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome

Removal of internal transcribed spacer 2 (ITS2) from pre-ribosomal RNA is essential to make functional ribosomes. This complicated processing reaction begins with a single endonucleolytic cleavage followed by exonucleolytic trimming at both new cleavage sites to generate mature 5.8S and 25S rRNA. We reconstituted the 7S -> 5.8S processing branch within ITS2 using purified exosome and its nuclear cofactors. We find that both Rrp44's ribonuclease activities are required for initial RNA shortening followed by hand over to the exonuclease Rrp6. During the in vitro reaction, ITS2-associated factors dissociate and the underlying 'foot' structure of the pre-60S particle is dismantled. 7S pre-rRNA processing is independent of 5S RNP rotation, but 26S -> 25S trimming is a precondition for subsequent 7S -> 5.8S processing. To complete the in vitro assay, we reconstituted the entire cycle of ITS2 removal with a total of 18 purified factors, catalysed by the integrated activities of the two participating RNA-processing machines, the Las1 complex and nuclear exosome

Insight, cognition and quality of life in Alzheimer's disease

Background: The detrimental impact of dementia upon patient health-related quality of life (HRQL) is well established, as is the importance of improving HRQL. However, relatively little is known about the natural history of HRQL in dementia and those factors influencing it. This limited knowledge potentially restricts the evaluation of the efficacy of interventions designed to improve HRQL. One such area concerns the relationship between HRQL and patient insight. It remains unclear what impact, if any, impaired insight has upon a patient's HRQL. The present study aimed to investigate the relationship between insight and HRQL in a sample of patients with Alzheimer's disease (AD) and their carers. Methods: 256 patients with AD were recruited as part of AddNeuroMed, a multicentre European AD biomarkers study. Of these, 174 completed a quality-of-life measure in addition to a comprehensive battery of clinical and neuropsychological assessments. Results: Insight was found to be differentially related to patient perceptions of HRQL in mild and moderate dementia. Within moderate dementia, impaired insight was associated with better perceived HRQL. Conversely, cognition, but not insight, was associated with impaired HRQL in mild dementia. Insight was not found to be associated with carer perceptions of patient HRQL. Conclusion: Impairment of insight is associated with better HRQL in moderate dementia. This finding has implications for interventions which focus on increasing patient awareness and orientation, as impairment of insight appears to have a positive impact upon HRQL