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.

Experimental studies of fear conditioning have identified the effectiveness of safety signals in inhibiting fear and maintaining fear-motivated behaviors. In fear conditioning procedures, the presence of safety signals means that the otherwise expected feared outcome will not now occur. Differences in the inhibitory learning processes needed to learn safety are being identified in various psychological and psychiatric conditions. However, despite early theoretical interest, the role of conditioned inhibitors as safety signals in anxiety has been under-investigated to date, in part because of the stringent test procedures required to confirm the demonstration of conditioned inhibition as such. Nonetheless, the theoretical implications of an inhibitory learning perspective continue to influence clinical practice. Moreover, our understanding of safety signals is of additional importance in the context of the increased health anxiety and safety behaviors generated by the COVID-19 pandemic.

Background: Multiple sclerosis (MS) is associated with lower quality of life, reduced social participation, and decreased self-efficacy. The COVID-19 pandemic has had documented effects on the health and wellbeing of people with and without MS. Previous research has demonstrated the positive impact pets can have for people living with long-term conditions. Objectives: To explore the rates of pet ownership and pet attachment in people living with MS and pet ownership associations with quality of life, satisfaction with social roles, and self-efficacy scores; and to explore the effects of the COVID-19 outbreak on people's perceived relationships with their pets. Materials and Methods: A postal questionnaire was distributed to members of a local MS Register and a control group of people without MS. The questionnaire assessed quality of life, satisfaction with social roles, self-efficacy, the perceived roles of pets, and pet-related concerns experienced during the COVID-19 pandemic. Results: No apparent difference in attachment to pets was found between the patient and control groups. Pet ownership and level of attachment were not associated with differences in quality of life or self-efficacy scores in people living with MS. Using multiple regression analysis, pet ownership was associated with a decrease in satisfaction with participation in social roles, but with the estimated effect being small compared to having a diagnosis of MS or being unemployed. Most participants reported that pets had positive roles during the pandemic, and the most reported pet-related concern was access to veterinary treatment. Conclusion: Pet owners both with and without MS reported subjective benefits to their wellbeing from pet ownership during COVID-19, although analysis suggested that pet ownership was associated with a reduction in satisfaction with social roles. The study had several limitations and suggestions are made for future work.

Objective: High-intensity interval training (HIIT) has been shown to be more effective than moderate continuous aerobic exercise for improving cardiorespiratory fitness (CRF) in a limited time frame. However, the length of time required for HIIT to elicit clinically significant improvements in the CRF of older adults is currently unknown. The aim of this study was to compare changes in the CRF of older adults completing identical HIIT protocols of varying durations. Methods: Forty healthy, community-dwelling older adults completed a cardiopulmonary exercise test (CPET) before and after 2, 4, or 6 weeks of fully supervised HIIT on a cycle ergometer, or a no-intervention control period. Results: Anaerobic threshold (AT) was increased only after 4 (+1.9 [SD 1.1] mL/kg/min) and 6 weeks (+1.9 [SD 1.8] mL/kg/min) of HIIT (both P < 0.001), with 6-week HIIT required to elicit improvements in VO2 peak (+3.0 [SD 6] mL/kg/min; P = 0.04). Exercise tolerance increased after 2 (+15 [SD 15] W), 4 (+17 [SD 11] W), and 6 weeks (+16 [SD 11] W) of HIIT (all P < 0.001), with no difference in increase between the groups. There were no changes in any parameter in the control group. Conclusion: Improvements in exercise tolerance from HIIT precede changes in CRF. Just 4 weeks of a well-tolerated, reduced-exertion HIIT protocol are required to produce significant changes in AT, with a further 2 weeks of training also eliciting improvements in VO2 peak.

Background: Hypertension is a risk factor for both cardiovascular and cerebrovascular disease, with an increasing incidence with advancing patient age. Exercise interventions have the potential to reduce blood pressure in older adults, however, rates of exercise uptake and adherence are low, with 'lack of time' a commonly cited reason. As such, there remains the need for time-efficient physical activity interventions to reduce blood pressure in older adults. Objective: To compare the effect of three, novel time-efficient physical activity interventions on resting blood pressure in older adults. Methods: Forty-eight, healthy, community-dwelling older adults (mean age: 71 years) were recruited to a 6-week randomised control trial. Resting blood pressure was measured before and after one of three supervised, time-efficient interventions: high-intensity interval training (HIIT) on a cycle ergometer; isometric handgrip training (IHG); unilateral, upper limb remote ischaemic preconditioning (RIPC) or non-intervention control. Results: Both HIIT and IHG led to a statistically significant reduction in resting systolic blood pressure (SBP) of 9 mmHg, with no significant change in the RIPC or control groups. There was no change in diastolic blood pressure or pulse pressure in any group. Conclusions: Supervised HIIT or IHG using the protocols described in this study can lead to statistically significant and clinically relevant reductions in resting SBP in healthy older adults in just 6 weeks.

OBJECTIVES: There is a need to improve efficiency in healthcare delivery without compromising quality of care. One approach is the development and evaluation of behavioural strategies to reduce unnecessary use of common tests. However, there is an absence of evidence on patient attitudes to the use of such approaches in the delivery of care. Our objective was to explore patient acceptability of a nudge-type intervention that aimed to modify blood test requests by hospital doctors. STUDY DESIGN: Single-centre qualitative study. METHODS: The financial costs of common blood tests were presented to hospital doctors on results reports for 1 year at a hospital. Focus group discussions were conducted with recent inpatients at the hospital using a semi-structured question schedule. Discussions were transcribed and analysed using qualitative content analysis to identify and prioritise common themes explaining attitudes to the intervention approach. RESULTS: Three focus groups involving 17 participants were conducted. Patients were generally apprehensive about the provision of blood test cost feedback to doctors. Attitudes were organised around themes representing beliefs about blood tests, the impact on doctors and their autonomy, and beliefs about unnecessary testing. Patients thought that blood tests were important, powerful and inexpensive, and cost information could place doctors under additional pressure. CONCLUSION: The findings identify predominantly positive beliefs about testing and negative attitudes to the use of financial costs in the decision-making of hospital doctors. Public discussion and education about the possible overuse of common tests may allow more resources to be allocated to evidence-based healthcare, by reducing the perception that such strategies to improve healthcare efficiency negatively impact on quality of care.

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD -2.0; 95% CI -2.38, -1.61; p < 0.00001) and permanent (SMD -1.54; 95% CI -2.38, -1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD -1.63; 95% CI -1.97, -1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4-9/10); Egger's test suggested publication bias (p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.

BACKGROUND: A novel loaded self-managed exercise programme that includes pain education and self-management strategies may result in better outcomes for people with patellofemoral pain (PFP). However, establishing program feasibility is an essential first step before testing efficacy. The purpose of this study was to evaluate the feasibility and acceptability of conducting a definitive RCT which will evaluate the clinical and cost-effectiveness of a loaded self-managed exercise programme for people with PFP compared with usual physiotherapy. METHODS: In a mixed methods, pragmatic, randomised controlled feasibility study, 60 participants with PFP (57% female; mean age 29 years) were recruited from a physiotherapy clinic within a large UK teaching hospital. They were randomly allocated to receive either a loaded self-managed exercise programme (n = 30) or usual physiotherapy (n = 30). Feasibility indicators of process, resources, and management were collected through follow-up of standardised questionnaires six months after recruitment and semi-structured interviews with 20 participants and physiotherapists. RESULTS: Recruitment rate was 5 participants per month; consent rate was 99%; adherence to intervention appointments was 87%; completeness of questionnaire data was 100%; and adherence to intervention delivery was 95%. Three exercise diaries were returned at six months (5%). At six months, 25 questionnaire booklets were returned (9 in the loaded self-managed group, 16 in the usual physiotherapy group), with a total retention rate of 42%. At six months, 56% (5/9) of respondents in the loaded self-managed group and 56% (9/16) in the usual physiotherapy group were classified as 'recovered'. Both groups demonstrated improvements in average pain (VAS), kinesiophobia, pain catastrophizing, general self-efficacy and EQ-5D-5 L from baseline to six months. CONCLUSION: The results of this feasibility study confirm that it is feasible and acceptable to deliver a loaded self-managed exercise programme to adults with PFP in an NHS physiotherapy outpatient setting. However, between group differences in lost to follow up and poor exercise diary completion mean we are uncertain on vsome feasibility aspects. These methodological issues need addressing prior to vconducting a definitive RCT. TRIAL REGISTRATION: ISRCTN 35272486 . Registered 19th December 2016.